Journal of Hainan Medical University
Volume 31,2025 Issue 23
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- Spatial‑temporal clustering of tuberculosis in Hainan Island from 2018 to 2022
- To optimize the salt process of Amomum longiligulare T.L.Wu based on entropy weight method combined with response surface method
- Network pharmacology research and experimental verification of Li Medicine Nauclea officinalis in the treatment of diabetic nephropathy
- The pyroptosis mechanism of pectic polysaccharides of Rauvolfia erticillata(Lour.) Baill.var. hainanensis Tsiang in regulating ulcerative colitis mice through MAPK/NF‑κB signaling pathway
- Drug resistance characteristics of 2020 strains of Mycobacterium tuberculosis in Hainan Province
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Journal of Hainan Medical University has been consecutively listed in Chinese Core Journals (Source Journal for Chinese Scientific and Technical Papers and Citations)
Dr. Dirk Engels (Former Director of Control of Neglected Tropical Diseases of WHO) joined HMU Press for academic exchanges
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Professor Jong-Yil Chai (Seoul University, Korea) come to visit our university
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Professor Adrin Angel Inchauspe, National University of La Plata, Argentina, made an academic visit to our journal
Professor Marcel Tanner, President of Swiss Academy of Natural Sciences, visited our university with Dr. Dirk Engels, Director of the Department of Prevention and Control of Neglected Tropical Diseases of the World Health Organization
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2025,31(23):1761-1769, DOI: 10.13210/j.cnki.jhmu.20250612.001
Abstract:
Objective:To observe the distribution and correlation characteristics of antibiotic resistance genes， virulence genes and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway in human and multi‑environmental media bacteria in coastal communities， and to provide evidence for further exploration of the interaction， mechanism and risk prevention between human and environmental microorganisms， based on the “One Health ”strategy. Methods:Human feces， beach and pig farm soil samples were collected aseptically. The second generation sequencing was performed in Majorbio Bio‑Pharm Technology Co.， Ltd. by shotgun metagenic method， annotation was performed by Comprehensive Antibiotic Resistance Database， Virulence Factors Database and KEGG database， and differential pathway analysis was performed by Linear Discriminant Analysis Effect Size and KEGG pathway enrichment method. The Spearman test was used for non‑parametric correlation analysis. Results:Multiple antibiotic resistances， tetracycline， macrolides， glycopeptides， and quinolones were mostly correlated with the human body and beach， soil （r=0.573‑0.783， P<0.05）， especially tetracycline and glycopeptides， but there was no correlation with the abundance of aminoglycosides and polymyxin resistance genes on the beach （P>0.05）. Linear Discriminant Analysis （LDA） indicated that the most common drug resistance mechanisms were antibiotic target change， target protection and decreased permeability. Beach A was the mechanism of antibiotic efflux pump， and the soil of pig farm was mainly replaced by antibiotic target （LDA>4）. The defensive virulence factor was more significant in human intestinal microbe. Attack virulence factors and non‑specific virulence factors were more significant in Beach B （LDA>4）. Two types of virulence genes strongly associated with beaches in human gut bacteria were defensive and regulatory virulence factors （r=0.727‒0.840， P<0.05）. KEGG enrichment analysis showed that the three KEGG Orthology pathways of human flora were the phosphotransferase system （PTS）， galactose， and ribosome， and only one PTS was more abundant in the human compared to the pig farm soil. The higher microbial pathways were carbon metabolism， methane metabolism， amino acid metabolism， and fatty acid metabolism， respectively. Escherichia coli biofilm had more up‑regulated pathways in humans， while Pseudomonas aeruginosa and Vibrio cholerae biofilm had more up‑regulated pathways in environment. Conclusion:The strong correlation of tetracycline and glycopeptide resistance between human and environment suggesting that it may be common or unreasonable usage of the antibiotics in human and animal. The strong correlation between two types of virulence factors in human and beach environmental flora. Differences in KEGG pathways were more pronounced between beach and human microbiomes than between soil and human microbiomes. It is necessary to further explore the interaction between the coastal environment and humans and animals from the perspective of One Health.
Objective:To observe the distribution and correlation characteristics of antibiotic resistance genes， virulence genes and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway in human and multi‑environmental media bacteria in coastal communities， and to provide evidence for further exploration of the interaction， mechanism and risk prevention between human and environmental microorganisms， based on the “One Health ”strategy. Methods:Human feces， beach and pig farm soil samples were collected aseptically. The second generation sequencing was performed in Majorbio Bio‑Pharm Technology Co.， Ltd. by shotgun metagenic method， annotation was performed by Comprehensive Antibiotic Resistance Database， Virulence Factors Database and KEGG database， and differential pathway analysis was performed by Linear Discriminant Analysis Effect Size and KEGG pathway enrichment method. The Spearman test was used for non‑parametric correlation analysis. Results:Multiple antibiotic resistances， tetracycline， macrolides， glycopeptides， and quinolones were mostly correlated with the human body and beach， soil （r=0.573‑0.783， P<0.05）， especially tetracycline and glycopeptides， but there was no correlation with the abundance of aminoglycosides and polymyxin resistance genes on the beach （P>0.05）. Linear Discriminant Analysis （LDA） indicated that the most common drug resistance mechanisms were antibiotic target change， target protection and decreased permeability. Beach A was the mechanism of antibiotic efflux pump， and the soil of pig farm was mainly replaced by antibiotic target （LDA>4）. The defensive virulence factor was more significant in human intestinal microbe. Attack virulence factors and non‑specific virulence factors were more significant in Beach B （LDA>4）. Two types of virulence genes strongly associated with beaches in human gut bacteria were defensive and regulatory virulence factors （r=0.727‒0.840， P<0.05）. KEGG enrichment analysis showed that the three KEGG Orthology pathways of human flora were the phosphotransferase system （PTS）， galactose， and ribosome， and only one PTS was more abundant in the human compared to the pig farm soil. The higher microbial pathways were carbon metabolism， methane metabolism， amino acid metabolism， and fatty acid metabolism， respectively. Escherichia coli biofilm had more up‑regulated pathways in humans， while Pseudomonas aeruginosa and Vibrio cholerae biofilm had more up‑regulated pathways in environment. Conclusion:The strong correlation of tetracycline and glycopeptide resistance between human and environment suggesting that it may be common or unreasonable usage of the antibiotics in human and animal. The strong correlation between two types of virulence factors in human and beach environmental flora. Differences in KEGG pathways were more pronounced between beach and human microbiomes than between soil and human microbiomes. It is necessary to further explore the interaction between the coastal environment and humans and animals from the perspective of One Health.
2025,31(23):1770-1777, DOI: 10.13210/j.cnki.jhmu.20250331.003
Abstract:
Objective:To explore the mechanism of Gubu Decoction （GBD） in improving the healing of diabetes foot ulcer （DFU） by regulating HIF‑1α/TGF‑β1/Smad3 pathway. Methods:The C57BL/6J mouse DFU model was constructed and randomly divided into a model group and GBD low， medium， and high dose groups， with 10 mice in each group. Another 10 mice were selected as the blank group， and all mice were treated continuously for 14 days. After administration， H&E staining and Masson staining were used to observe the pathological morphology and collagen deposition of ulcer tissue. EdU labeled immunofluorescence was used to detect fibroblast proliferation in ulcer tissue， TUNEL was used to detect fibroblast apoptosis in ulcer tissue， ELISA was used to detect the levels of inflammatory factors （TNF‑α， IL‑6， IL‑10） and oxidative stress （MDA， SOD， GSH‑PX） in ulcer tissue， and Western blot was used to detect the expression of HIF‑1α/TGF‑β1/Smad3 pathway related proteins. Results:Compared to the model group， GBD significantly reduced inflammatory cell infiltration in ulcer tissue， increased the number of collagen fibers， granulation tissue， and newly formed capillaries in ulcer tissue， reduced fibroblast proliferation rate， decreased ROS positive cell rate， fibroblast apoptosis， IL‑6， TNF‑α levels， MDA content， HIF‑1α， TGF‑β1， TβR1， and p‑Smad3 protein expression， increased IL‑10 levels， SOD， and GSH‑PX content （P<0.01）. Conclusion:GBD can reduce DFU inflammation and oxidative stress levels， activate the HIF‑1α/TGF‑β1/Smad3 pathway， promote fibroblast generation， and improve ulcer tissue healing.
Objective:To explore the mechanism of Gubu Decoction （GBD） in improving the healing of diabetes foot ulcer （DFU） by regulating HIF‑1α/TGF‑β1/Smad3 pathway. Methods:The C57BL/6J mouse DFU model was constructed and randomly divided into a model group and GBD low， medium， and high dose groups， with 10 mice in each group. Another 10 mice were selected as the blank group， and all mice were treated continuously for 14 days. After administration， H&E staining and Masson staining were used to observe the pathological morphology and collagen deposition of ulcer tissue. EdU labeled immunofluorescence was used to detect fibroblast proliferation in ulcer tissue， TUNEL was used to detect fibroblast apoptosis in ulcer tissue， ELISA was used to detect the levels of inflammatory factors （TNF‑α， IL‑6， IL‑10） and oxidative stress （MDA， SOD， GSH‑PX） in ulcer tissue， and Western blot was used to detect the expression of HIF‑1α/TGF‑β1/Smad3 pathway related proteins. Results:Compared to the model group， GBD significantly reduced inflammatory cell infiltration in ulcer tissue， increased the number of collagen fibers， granulation tissue， and newly formed capillaries in ulcer tissue， reduced fibroblast proliferation rate， decreased ROS positive cell rate， fibroblast apoptosis， IL‑6， TNF‑α levels， MDA content， HIF‑1α， TGF‑β1， TβR1， and p‑Smad3 protein expression， increased IL‑10 levels， SOD， and GSH‑PX content （P<0.01）. Conclusion:GBD can reduce DFU inflammation and oxidative stress levels， activate the HIF‑1α/TGF‑β1/Smad3 pathway， promote fibroblast generation， and improve ulcer tissue healing.
2025,31(23):1778-1785, DOI: 10.13210/j.cnki.jhmu.20240728.001
Abstract:
Objective:To analyze the effects of electroacupuncture on the relative abundance and diversity of intestinal microbiota species in controlled ovarian hyperstimulation （COH） mice through 16S rDNA high‑throughput sequencing， as well as to investigate its potential mechanism in enhancing the clinical pregnancy rate of in vitro fertilization‑embryo transplantation. Methods:A total of 27 cyclic regular female mice were randomly divided into the natural cycle group， the COH group， and the electroacupuncture group， with 9 mice in each group. The animal model was prepared using a controlled ovarian hyperstimulation protocol. In the electroacupuncture group， electroacupuncture treatment was performed on the day of human chorionic gonadotropin injection， targeting the Guanyuan， Zhongji， and Sanyinjiao acupoints with continuous waves at a frequency of 2 Hz， once a day for 15 min each time. The natural cycle group and COH group received no intervention. On the 4th day of pregnancy （the implantation window）， fecal samples from each group of mice were collected for 16S rDNA high‑throughput sequencing， followed by analysis of species relative abundance， alpha diversity， beta diversity， and predicted functional metabolism. Results:The numbers of operational taxonomic units in the natural cycle group， COH group， and electroacupuncture group were 1 083， 1 135， and 1 125， respectively. Compared to the natural cycle group， the relative abundance of Bacteroidota， Verrucomicrobiota， Parabacteroides， Bacteroides， and Alloprevotellain the COH group were increased， and the relative abundance of Firmicutes， Lactobacillus， and Alistipes were decreased. After the treatment of electroacupuncture， the above‑mentioned microorganisms showed different degrees of improvement in relative abundance. Compared to the natural cycle group， the Shannon， Simpson， and Chao1 indices of the COH group increased； compared to the COH group， the Shannon and Chao1 indices of the electroacupuncture group decreased， the difference were not statistically significant （P>0.05）. The functional prediction analysis found that electroacupuncture could regulate the functional genes involved in carbohydrate metabolism and amino acid metabolism. Conclusion:The administration of exogenous hormones alters the structural equilibrium of intestinal microbiota in mice， while electroacupuncture demonstrates the capability to regulate both the relative abundance of intestinal microbiota species and the overall diversity of microbiota in mice undergoing controlled ovarian hyperstimulation.
Objective:To analyze the effects of electroacupuncture on the relative abundance and diversity of intestinal microbiota species in controlled ovarian hyperstimulation （COH） mice through 16S rDNA high‑throughput sequencing， as well as to investigate its potential mechanism in enhancing the clinical pregnancy rate of in vitro fertilization‑embryo transplantation. Methods:A total of 27 cyclic regular female mice were randomly divided into the natural cycle group， the COH group， and the electroacupuncture group， with 9 mice in each group. The animal model was prepared using a controlled ovarian hyperstimulation protocol. In the electroacupuncture group， electroacupuncture treatment was performed on the day of human chorionic gonadotropin injection， targeting the Guanyuan， Zhongji， and Sanyinjiao acupoints with continuous waves at a frequency of 2 Hz， once a day for 15 min each time. The natural cycle group and COH group received no intervention. On the 4th day of pregnancy （the implantation window）， fecal samples from each group of mice were collected for 16S rDNA high‑throughput sequencing， followed by analysis of species relative abundance， alpha diversity， beta diversity， and predicted functional metabolism. Results:The numbers of operational taxonomic units in the natural cycle group， COH group， and electroacupuncture group were 1 083， 1 135， and 1 125， respectively. Compared to the natural cycle group， the relative abundance of Bacteroidota， Verrucomicrobiota， Parabacteroides， Bacteroides， and Alloprevotellain the COH group were increased， and the relative abundance of Firmicutes， Lactobacillus， and Alistipes were decreased. After the treatment of electroacupuncture， the above‑mentioned microorganisms showed different degrees of improvement in relative abundance. Compared to the natural cycle group， the Shannon， Simpson， and Chao1 indices of the COH group increased； compared to the COH group， the Shannon and Chao1 indices of the electroacupuncture group decreased， the difference were not statistically significant （P>0.05）. The functional prediction analysis found that electroacupuncture could regulate the functional genes involved in carbohydrate metabolism and amino acid metabolism. Conclusion:The administration of exogenous hormones alters the structural equilibrium of intestinal microbiota in mice， while electroacupuncture demonstrates the capability to regulate both the relative abundance of intestinal microbiota species and the overall diversity of microbiota in mice undergoing controlled ovarian hyperstimulation.
2025,31(23):1786-1792, DOI: 10.13210/j.cnki.jhmu.20241220.002
Abstract:
Objective:To investigate the biosafety of poly lactic‑co‑glycolic acid（PLGA） microparticles loaded with oxaliplatin in rats in vitro and in vivo， and to verify the feasibility of injection of PLGA microparticles loaded with oxaliplatin. Methods:The effect of microparticles on the proliferation rate of mouse epithelioid fibroblast cells L929 was detected by CCK‑8 to evaluate its in vitro safety. The microspheres were injected into the right posterior calf muscle of 200‒250 g SD female rats. Routine blood tests （WBC， HGB， PLT， and PCT） were performed， and blood biochemical indicators （ALT， AST， TP， ALB， ALP， BUN， Cre， CHO， and TBIL） were measured. Major organs' （liver， kidneys， bone marrow， and muscle） pathological sections were stained using H&E staining. The biosafety of the nanoparticles was verified in vivo. Results:In vitro cell proliferation experiments showed that PLGA drugs loaded with oxaliplatin may exhibit certain cytotoxicity due to the function of sustained release of oxaliplatin. In vivo experiments showed no obvious chronic toxicity in the rats. Pathological tissue section of H&E staining did not prompt important chronic tissue damage. Conclusion:PLGA particle loaded with oxaliplatin meets the requirements for injection， does not cause damage to the injection site， and does not cause obvious acute or chronic side effects after injection， which has a high safety， and is expected to be applied in clinical practice to provide a new method for the treatment of gastric cancer.
Objective:To investigate the biosafety of poly lactic‑co‑glycolic acid（PLGA） microparticles loaded with oxaliplatin in rats in vitro and in vivo， and to verify the feasibility of injection of PLGA microparticles loaded with oxaliplatin. Methods:The effect of microparticles on the proliferation rate of mouse epithelioid fibroblast cells L929 was detected by CCK‑8 to evaluate its in vitro safety. The microspheres were injected into the right posterior calf muscle of 200‒250 g SD female rats. Routine blood tests （WBC， HGB， PLT， and PCT） were performed， and blood biochemical indicators （ALT， AST， TP， ALB， ALP， BUN， Cre， CHO， and TBIL） were measured. Major organs' （liver， kidneys， bone marrow， and muscle） pathological sections were stained using H&E staining. The biosafety of the nanoparticles was verified in vivo. Results:In vitro cell proliferation experiments showed that PLGA drugs loaded with oxaliplatin may exhibit certain cytotoxicity due to the function of sustained release of oxaliplatin. In vivo experiments showed no obvious chronic toxicity in the rats. Pathological tissue section of H&E staining did not prompt important chronic tissue damage. Conclusion:PLGA particle loaded with oxaliplatin meets the requirements for injection， does not cause damage to the injection site， and does not cause obvious acute or chronic side effects after injection， which has a high safety， and is expected to be applied in clinical practice to provide a new method for the treatment of gastric cancer.
2025,31(23):1793-1801, DOI: 10.13210/j.cnki.jhmu.20250102.003
Abstract:
Objective:To explore the effect of Yifei Tongluo Formula on regulating IL‑17A in the model rats， constructing an animal model of pulmonary fibrosis using bleomycin tracheal instillation method. Methods:SD rat pulmonary fibrosis model was constructed using bleomycin tracheal instillation method， and randomly divided into the control group， the model group， the prednisone group， the low‑dose Yifei Tongluo Formula group， and the high‑dose Yifei Tongluo Formula group. Corresponding interventions were given for 14 days， and rat serum and lung tissue were taken for testing. The degree of pulmonary fibrosis in rats was evaluated by morphological observation of lung tissue， MicroCT imaging observation， H&E staining， and Masson staining. Immunohistochemistry was used to analyze the expression of pulmonary fibrosis related proteins such as α‑smooth muscle actin （α‑SMA） and vimentin protein （Vimentin）. Immunofluorescence was used to detected IL‑17A and other signaling molecule expressions. ELISA was used to detect the secretion level of hydroxyproline （HYP） in rat serum and the content of cytokines such as IL‑17A. PCR was used to detect the relative expression of IL‑17A mRNA. Western Blotting was used to detect the expression of IL‑17A protein. Results:Observation of the morphology of rat lung tissue shows that Yifei Tongluo Formula has a significant improvement effect on the appearance， color， lung lobe contour， and volume elasticity of both lungs in rats. Observation of chest MicroCT imaging showed that Yifei Tongluo Formula can reduce the degree of lung inflammation and improve fibrosis symptoms in rats. H&E staining of rat lung tissue showed that Yifei Tongluo Formula can alleviate pathological features such as inflammatory cell infiltration in lung tissue. Masson staining of rat lung tissue showed that Yifei Tongluo Formula can improve fibrosis and tissue proliferation in lung tissue. The immunohistochemical results showed that compared to the control group， the average positive area of α‑SMA and Vimentin in the lung tissue of the model group rats was significantly increased （P<0.05）. Compared to the model group， the average positive area of α‑SMA in the lung tissue of rats in the Yifei Tongluo Formula group was significantly reduced （P<0.01）， especially after high‑dose Yifei Tongluo Formula intervention， the average positive area of Vimentin in the lung tissue of rats was significantly reduced （P<0.05）. Immunofluorescence images showed that compared to the control group， the IL‑17A fluorescence intensity in the lung tissue of the model group rats was higher， and the fluorescence intensity was significantly reduced after intervention Yifei Tongluo Formula. The ELISA results showed that compared to the control group， the HYP and IL‑17A levels in the model group rats were significantly increased （P<0.05）. Compared to the model group， the levels of the above‑mentioned cytokines in the Yifei Tongluo Formula group of rats were significantly reduced （P<0.05）. The PCR results showed that compared to the control group， the model group rats significantly upregulated the relative expression of IL‑17A mRNA （P<0.05）. Compared to the model group， the relative expression of IL‑17A mRNA in the Yifei Tongluo Formula group rats was significantly reduced （P<0.05）. The Western blot test results showed that compared to the control group， the expression of IL‑17A protein in the lung tissue of the model group rats was significantly increased （P<0.05）. Compared to the model group， Yifei Tongluo Formula could significantly inhibit the expression of IL‑17A protein （P<0.05）. Conclusion:Yifei Tongluo Formula has a protective effect on bleomycin induced pulmonary fibrosis in rats. Yifei Tongluo Formula may improve rat pulmonary fibrosis by downregulating IL‑17A.
Objective:To explore the effect of Yifei Tongluo Formula on regulating IL‑17A in the model rats， constructing an animal model of pulmonary fibrosis using bleomycin tracheal instillation method. Methods:SD rat pulmonary fibrosis model was constructed using bleomycin tracheal instillation method， and randomly divided into the control group， the model group， the prednisone group， the low‑dose Yifei Tongluo Formula group， and the high‑dose Yifei Tongluo Formula group. Corresponding interventions were given for 14 days， and rat serum and lung tissue were taken for testing. The degree of pulmonary fibrosis in rats was evaluated by morphological observation of lung tissue， MicroCT imaging observation， H&E staining， and Masson staining. Immunohistochemistry was used to analyze the expression of pulmonary fibrosis related proteins such as α‑smooth muscle actin （α‑SMA） and vimentin protein （Vimentin）. Immunofluorescence was used to detected IL‑17A and other signaling molecule expressions. ELISA was used to detect the secretion level of hydroxyproline （HYP） in rat serum and the content of cytokines such as IL‑17A. PCR was used to detect the relative expression of IL‑17A mRNA. Western Blotting was used to detect the expression of IL‑17A protein. Results:Observation of the morphology of rat lung tissue shows that Yifei Tongluo Formula has a significant improvement effect on the appearance， color， lung lobe contour， and volume elasticity of both lungs in rats. Observation of chest MicroCT imaging showed that Yifei Tongluo Formula can reduce the degree of lung inflammation and improve fibrosis symptoms in rats. H&E staining of rat lung tissue showed that Yifei Tongluo Formula can alleviate pathological features such as inflammatory cell infiltration in lung tissue. Masson staining of rat lung tissue showed that Yifei Tongluo Formula can improve fibrosis and tissue proliferation in lung tissue. The immunohistochemical results showed that compared to the control group， the average positive area of α‑SMA and Vimentin in the lung tissue of the model group rats was significantly increased （P<0.05）. Compared to the model group， the average positive area of α‑SMA in the lung tissue of rats in the Yifei Tongluo Formula group was significantly reduced （P<0.01）， especially after high‑dose Yifei Tongluo Formula intervention， the average positive area of Vimentin in the lung tissue of rats was significantly reduced （P<0.05）. Immunofluorescence images showed that compared to the control group， the IL‑17A fluorescence intensity in the lung tissue of the model group rats was higher， and the fluorescence intensity was significantly reduced after intervention Yifei Tongluo Formula. The ELISA results showed that compared to the control group， the HYP and IL‑17A levels in the model group rats were significantly increased （P<0.05）. Compared to the model group， the levels of the above‑mentioned cytokines in the Yifei Tongluo Formula group of rats were significantly reduced （P<0.05）. The PCR results showed that compared to the control group， the model group rats significantly upregulated the relative expression of IL‑17A mRNA （P<0.05）. Compared to the model group， the relative expression of IL‑17A mRNA in the Yifei Tongluo Formula group rats was significantly reduced （P<0.05）. The Western blot test results showed that compared to the control group， the expression of IL‑17A protein in the lung tissue of the model group rats was significantly increased （P<0.05）. Compared to the model group， Yifei Tongluo Formula could significantly inhibit the expression of IL‑17A protein （P<0.05）. Conclusion:Yifei Tongluo Formula has a protective effect on bleomycin induced pulmonary fibrosis in rats. Yifei Tongluo Formula may improve rat pulmonary fibrosis by downregulating IL‑17A.
2025,31(23):1802-1811, DOI: 10.13210/j.cnki.jhmu.20241219.002
Abstract:
Objective:To explore the effects and mechanism of action of the classical formula of Pingchuanning （PCN） and MCC950 inhibitor on airway inflammation in asthmatic rats from the perspective of pyroptosis. Methods:A total of 70 SD rats were randomly divided into 7 groups： the normal group， the model group， the PCN group， the MCC950 group， the PCN+MCC950 inhibitor group， the dexamethasone group， and the Guilong Kechuanning group. A concentration of 10% ovalbumin （OVA） was injected subcutaneously via the abdominal cavity and the limbs to induce allergy， and the rat model of asthma was stimulated by the combination of 2% OVA nebulisation and cold air （2‒4 ℃）. The intervention was continued for 3 weeks with gavage and aerosolization of PCN （7.289 g/kg）， MCC950 （10 mg/kg）， PCN （7.289 g/kg）+MCC950 （10 mg/kg）， dexamethasone （0.405 mg/kg）， and Guilong Kechuanning （0.405 g/kg）. After the final stimulation， airway inflammation was observed by H&E and PAS staining in lung tissue of the rats. The levels of IL‑1β， IL‑18， and IL‑6 in serum and BALF were detected by ELISA， the mRNA expression levels of NEK7， NLRP3， ASC， and Caspase‑1 were detected by RT‑PCR， and the protein expression levels of NEK7， NLRP3， ASC， and Caspase‑1 were detected by Western blot. Results:Compared to the normal group， rats in the model group had reduced diet， weight loss， emotional irritability， shortness of breath， airway inflammatory cell infiltration， goblet cell proliferation， and there was a significant increase in IL‑1β， IL‑18， and IL‑6 inflammatory factors in the serum and BALF； mRNA and protein expression levels of NEK7， NLRP3， ASC， and Caspase‑1 were elevated. Compared to the model group， rats in the PCN， MCC950， and PCN+MCC950 groups showed a gradual improvement in diet， alleviation of asthma， significant reduction in airway inflammatory cell infiltration， and reduction of IL‑1β， IL‑18， and IL‑6 inflammatory factors in serum and BALF （P<0.001）， as well as suppression of NEK7， NLRP3， ASC， and Caspase‑1 mRNA and protein expression （P<0.001）. Conclusion:PCN and MCC950 inhibitor can significantly improve airway inflammation induced by OVA combined with cold stimulation in asthmatic rats and correlate with the NEK7/NLRP3/ASC signaling pathway and pyroptosis， in which the efficacy of PCN combined with MCC950 is more pronounced， suggesting that the combined treatment is more effective than a single compound or Western medicine.
Objective:To explore the effects and mechanism of action of the classical formula of Pingchuanning （PCN） and MCC950 inhibitor on airway inflammation in asthmatic rats from the perspective of pyroptosis. Methods:A total of 70 SD rats were randomly divided into 7 groups： the normal group， the model group， the PCN group， the MCC950 group， the PCN+MCC950 inhibitor group， the dexamethasone group， and the Guilong Kechuanning group. A concentration of 10% ovalbumin （OVA） was injected subcutaneously via the abdominal cavity and the limbs to induce allergy， and the rat model of asthma was stimulated by the combination of 2% OVA nebulisation and cold air （2‒4 ℃）. The intervention was continued for 3 weeks with gavage and aerosolization of PCN （7.289 g/kg）， MCC950 （10 mg/kg）， PCN （7.289 g/kg）+MCC950 （10 mg/kg）， dexamethasone （0.405 mg/kg）， and Guilong Kechuanning （0.405 g/kg）. After the final stimulation， airway inflammation was observed by H&E and PAS staining in lung tissue of the rats. The levels of IL‑1β， IL‑18， and IL‑6 in serum and BALF were detected by ELISA， the mRNA expression levels of NEK7， NLRP3， ASC， and Caspase‑1 were detected by RT‑PCR， and the protein expression levels of NEK7， NLRP3， ASC， and Caspase‑1 were detected by Western blot. Results:Compared to the normal group， rats in the model group had reduced diet， weight loss， emotional irritability， shortness of breath， airway inflammatory cell infiltration， goblet cell proliferation， and there was a significant increase in IL‑1β， IL‑18， and IL‑6 inflammatory factors in the serum and BALF； mRNA and protein expression levels of NEK7， NLRP3， ASC， and Caspase‑1 were elevated. Compared to the model group， rats in the PCN， MCC950， and PCN+MCC950 groups showed a gradual improvement in diet， alleviation of asthma， significant reduction in airway inflammatory cell infiltration， and reduction of IL‑1β， IL‑18， and IL‑6 inflammatory factors in serum and BALF （P<0.001）， as well as suppression of NEK7， NLRP3， ASC， and Caspase‑1 mRNA and protein expression （P<0.001）. Conclusion:PCN and MCC950 inhibitor can significantly improve airway inflammation induced by OVA combined with cold stimulation in asthmatic rats and correlate with the NEK7/NLRP3/ASC signaling pathway and pyroptosis， in which the efficacy of PCN combined with MCC950 is more pronounced， suggesting that the combined treatment is more effective than a single compound or Western medicine.
LI Jiongfen, HU Mengling, LIN Yong, ZENG Yangling, ZHANG Kan, ZHANG Riyun, WANG Tingshuai, WANG Minggang, MAO Dewen
2025,31(23):1812-1822, DOI: 10.13210/j.cnki.jhmu.20250103.002
Abstract:
Objective ： To investigate the causal relationship between coagulation factors （vWF， ADAMTS13， APTT， FⅧ， FⅪ， FⅦ， FⅩ， D⁃Dimer， Fibrinogen， Prothrombin， PAI⁃1， Protein C， Plasmin） and the risk of hepatocellular carcinoma （HCC） using a two⁃sample Mendelian randomization （MR） approach. Methods:Genetic data for 13 coagulation factors were obtained from published genome⁃wide association studies. The data for HCC came from the Finnish Biobank. The inverse variance weighted （IVW） method was used as the primary analysis approach， supplemented by the weighted median method， MR⁃Egger regression， simple mode， and weighted mode for analysis. Heterogeneity testing， horizontal pleiotropy analysis， and sensitivity analysis were also conducted. Multivariable MR analysis was performed to adjust for the effects of the 13 coagulation factors using the IVW method. Results:The univariate MR results showed a positive causal relationship between ADAMTS13， FⅪ， Prothrombin， PAI⁃1， and HCC， while Plasmin， vWF， APTT， and FⅦ showed a negative causal relationship with HCC. No causal relationship was found between other coagulation factors and the risk of HCC （P>0.05）. Sensitivity analysis indicated that the causal relationships were robust， and the MR⁃Egger intercept analysis did not detect potential horizontal pleiotropy. After multivariable MR adjustment， the negative correlation between APTT and HCC remained significant （OR=0.08， 95% CI： 0.01⁃0.87， P=0.037）， while ADAMTS13 showed an independent positive causal relationship with HCC （OR=1.84， 95% CI： 1.09⁃3.10， P=0.021）.IVW method result showed no causal relationship between HCC and the 13 coagulation factors（P>0.05）. Conclusion:This study elucidates the coagulation factors causally associated with HCC using genetic tools， providing potential targets for disease intervention and contributing to early screening and prevention.
Objective ： To investigate the causal relationship between coagulation factors （vWF， ADAMTS13， APTT， FⅧ， FⅪ， FⅦ， FⅩ， D⁃Dimer， Fibrinogen， Prothrombin， PAI⁃1， Protein C， Plasmin） and the risk of hepatocellular carcinoma （HCC） using a two⁃sample Mendelian randomization （MR） approach. Methods:Genetic data for 13 coagulation factors were obtained from published genome⁃wide association studies. The data for HCC came from the Finnish Biobank. The inverse variance weighted （IVW） method was used as the primary analysis approach， supplemented by the weighted median method， MR⁃Egger regression， simple mode， and weighted mode for analysis. Heterogeneity testing， horizontal pleiotropy analysis， and sensitivity analysis were also conducted. Multivariable MR analysis was performed to adjust for the effects of the 13 coagulation factors using the IVW method. Results:The univariate MR results showed a positive causal relationship between ADAMTS13， FⅪ， Prothrombin， PAI⁃1， and HCC， while Plasmin， vWF， APTT， and FⅦ showed a negative causal relationship with HCC. No causal relationship was found between other coagulation factors and the risk of HCC （P>0.05）. Sensitivity analysis indicated that the causal relationships were robust， and the MR⁃Egger intercept analysis did not detect potential horizontal pleiotropy. After multivariable MR adjustment， the negative correlation between APTT and HCC remained significant （OR=0.08， 95% CI： 0.01⁃0.87， P=0.037）， while ADAMTS13 showed an independent positive causal relationship with HCC （OR=1.84， 95% CI： 1.09⁃3.10， P=0.021）.IVW method result showed no causal relationship between HCC and the 13 coagulation factors（P>0.05）. Conclusion:This study elucidates the coagulation factors causally associated with HCC using genetic tools， providing potential targets for disease intervention and contributing to early screening and prevention.
2025,31(23):1823-1832, DOI: 10.13210/j.cnki.jhmu.20250327.004
Abstract:
Objective:To explore the potential mechanism of isobutyrylshikonin in the treatment of psoriasis by combining network pharmacology and untargeted metabolomics techniques. Methods:Network pharmacology was employed to screen the targets and pathways of isobutyrylshikonin in psoriasis treatment， followed by molecular docking verification. RAW264.7 cells and HaCaT cells were used as the research objects in vitro. The anti‑inflammatory activity of isobutyrylshikonin was investigated using a lipopolysaccharide （LPS）‑induced inflammatory model of M1 macrophages （pro‑inflammatory） and an interleukin‑4 （IL‑4）‑induced polarization model of M2 macrophages （anti‑inflammatory）. RT‑qPCR was conducted to detect the expression of TNF‑α， iNOS， CXCL9， CXCL10 in M1 macrophages， and CD206， TGF‑β， Arg‑1， IL‑10 in M2 macrophages. Nitric oxide （NO） and reactive oxygen species （ROS） levels in macrophages were measured by Griess regent method and fluorescence staining method. Western blot was used to detect the expression levels of proteins related to the JAK/STAT signaling pathway. Immunofluorescence was employed to investigate the nuclear translocation of p‑STAT3 protein. UPLC‑Q‑TOF/MS technology was utilized to detect the differential metabolites and metabolic pathways associated with isobutyrylshikonin in IL‑17A‑induced HaCaT cell inflammation. Results:Network pharmacology and molecular docking results indicated that isobutyrylshikonin mainly acts on the JAK/STAT pathway and can spontaneously bind to the key target STAT3 with a binding energy of <-5 kJ/mol. Compared to the control group， isobutyrylshikonin upregulated the mRNA expression levels of CD206， TGF‑β， Arg‑1， and IL‑10. Compared to the model group， isobutyrylshikonin downregulated the mRNA expression levels of TNF‑α， iNOS， CXCL9， and CXCL10 in M1 macrophages， reduced the levels of NO and ROS， inhibited the expression of p‑JAK2 and p‑STAT3 proteins in the JAK/STAT signaling pathway， and suppressed the nuclear translocation of p‑STAT3 protein， with statistically significant differences observed （P<0.05）. The results of untargeted metabolomics suggested that isobutyrylshikonin may regulate the inflammatory level of IL‑17A‑induced HaCaT cells through the glutathione metabolism pathway. Conclusion:Isobutyrylshikonin may inhibit LPS‑induced inflammation in RAW264.7 cells through the JAK/STAT signaling pathway and regulate the inflammatory of HaCaT cells through the glutathione metabolism pathway.
Objective:To explore the potential mechanism of isobutyrylshikonin in the treatment of psoriasis by combining network pharmacology and untargeted metabolomics techniques. Methods:Network pharmacology was employed to screen the targets and pathways of isobutyrylshikonin in psoriasis treatment， followed by molecular docking verification. RAW264.7 cells and HaCaT cells were used as the research objects in vitro. The anti‑inflammatory activity of isobutyrylshikonin was investigated using a lipopolysaccharide （LPS）‑induced inflammatory model of M1 macrophages （pro‑inflammatory） and an interleukin‑4 （IL‑4）‑induced polarization model of M2 macrophages （anti‑inflammatory）. RT‑qPCR was conducted to detect the expression of TNF‑α， iNOS， CXCL9， CXCL10 in M1 macrophages， and CD206， TGF‑β， Arg‑1， IL‑10 in M2 macrophages. Nitric oxide （NO） and reactive oxygen species （ROS） levels in macrophages were measured by Griess regent method and fluorescence staining method. Western blot was used to detect the expression levels of proteins related to the JAK/STAT signaling pathway. Immunofluorescence was employed to investigate the nuclear translocation of p‑STAT3 protein. UPLC‑Q‑TOF/MS technology was utilized to detect the differential metabolites and metabolic pathways associated with isobutyrylshikonin in IL‑17A‑induced HaCaT cell inflammation. Results:Network pharmacology and molecular docking results indicated that isobutyrylshikonin mainly acts on the JAK/STAT pathway and can spontaneously bind to the key target STAT3 with a binding energy of <-5 kJ/mol. Compared to the control group， isobutyrylshikonin upregulated the mRNA expression levels of CD206， TGF‑β， Arg‑1， and IL‑10. Compared to the model group， isobutyrylshikonin downregulated the mRNA expression levels of TNF‑α， iNOS， CXCL9， and CXCL10 in M1 macrophages， reduced the levels of NO and ROS， inhibited the expression of p‑JAK2 and p‑STAT3 proteins in the JAK/STAT signaling pathway， and suppressed the nuclear translocation of p‑STAT3 protein， with statistically significant differences observed （P<0.05）. The results of untargeted metabolomics suggested that isobutyrylshikonin may regulate the inflammatory level of IL‑17A‑induced HaCaT cells through the glutathione metabolism pathway. Conclusion:Isobutyrylshikonin may inhibit LPS‑induced inflammation in RAW264.7 cells through the JAK/STAT signaling pathway and regulate the inflammatory of HaCaT cells through the glutathione metabolism pathway.
2025,31(23):1833-1840, DOI: 10.13210/j.cnki.jhmu.20250627.002
Abstract:
Demyelinating diseases are characterized by demyelination， accompanied by abnormal nerve conduction caused by neuronal and axonal injury. In the central nervous system， oligodendrocytes are responsible for myelin formation， and their dysfunction is closely related to the pathological aggregation of α‑synuclein. The soluble protein misfolds under pathological conditions， interferes with oligodendrocyte function through oligomerization deposition， and then causes demyelination and white matter damage. This article focuses on the molecular mechanism of α‑synuclein misfolding and its pathological aggregation in oligodendrocytes， and discusses the mechanism of the influence of related hypotheses on the occurrence and development of demyelinating diseases， in order to provide new intervention targets for clinical treatment.
Demyelinating diseases are characterized by demyelination， accompanied by abnormal nerve conduction caused by neuronal and axonal injury. In the central nervous system， oligodendrocytes are responsible for myelin formation， and their dysfunction is closely related to the pathological aggregation of α‑synuclein. The soluble protein misfolds under pathological conditions， interferes with oligodendrocyte function through oligomerization deposition， and then causes demyelination and white matter damage. This article focuses on the molecular mechanism of α‑synuclein misfolding and its pathological aggregation in oligodendrocytes， and discusses the mechanism of the influence of related hypotheses on the occurrence and development of demyelinating diseases， in order to provide new intervention targets for clinical treatment.
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2021,27(13):1036-1040, DOI: 10.13210/j.cnki.jhmu.20200706.001
Abstract:
Hepatic fibrosis is a common pathological basis for all chronic liver diseases， and a necessary stage for the progression of chronic liver disease into cirrhosis. Since various cells and cytokines， as pathogenic factors， play a major role in hepatic fibrosis， the pathogenesis of hepatic fibrosis is extremely complicated. This review focuses on the role of different cells and cytokines （macrophages， natural killer cells and natural killer T cells， tumor necrosis factor， IL-22， transforming growth factor beta， connective tissue growth factor， vascular endothelial growth factor） in the progression of hepatic fibrosis.
Hepatic fibrosis is a common pathological basis for all chronic liver diseases， and a necessary stage for the progression of chronic liver disease into cirrhosis. Since various cells and cytokines， as pathogenic factors， play a major role in hepatic fibrosis， the pathogenesis of hepatic fibrosis is extremely complicated. This review focuses on the role of different cells and cytokines （macrophages， natural killer cells and natural killer T cells， tumor necrosis factor， IL-22， transforming growth factor beta， connective tissue growth factor， vascular endothelial growth factor） in the progression of hepatic fibrosis.
2021,27(21):1672-1676, DOI: 10.13210/j.cnki.jhmu.20200904.005
Abstract:
Parkinson's disease （PD） is a neurodegenerative disorder due to gradual loss of dopaminergic neurons in the substantia nigra in the midbrain， however， the pathogenesis is unclear. There is a correlation between the excitability of striatal neurons and PD. Ion channels are important to maintain membrane potential and regulate excitability of neurons， but ionic mechanisms for modulation of neurons excitability are not fully understood. This article reviews the relationship between ion channels and excitability of striatal neurons in PD and ion channel changes in the pathogenesis of PD， in order to find new targets to treatment PD by intervening ion channels.
Parkinson's disease （PD） is a neurodegenerative disorder due to gradual loss of dopaminergic neurons in the substantia nigra in the midbrain， however， the pathogenesis is unclear. There is a correlation between the excitability of striatal neurons and PD. Ion channels are important to maintain membrane potential and regulate excitability of neurons， but ionic mechanisms for modulation of neurons excitability are not fully understood. This article reviews the relationship between ion channels and excitability of striatal neurons in PD and ion channel changes in the pathogenesis of PD， in order to find new targets to treatment PD by intervening ion channels.
2021,27(17):1350-1354, DOI: 10.13210/j.cnki.jhmu.20200814.002
Abstract:
Cytokines play an important role in the pathological process of atherosclerosis （AS）， affecting the progression and prognosis of AS-related cerebrovascular diseases. Cytokines mainly include C-reactive protein， interleukin， tumor necrosis factor， chemotactic cytokines， matrix metalloproteinases， etc. These cytokines promote or inhibit the inflammatory response and plaque formation during AS process through different targets and mechanisms. A comprehensive understanding of the cytokines in the occurrence and development of AS is conducive to search for new therapeutic targets and drugs.
Cytokines play an important role in the pathological process of atherosclerosis （AS）， affecting the progression and prognosis of AS-related cerebrovascular diseases. Cytokines mainly include C-reactive protein， interleukin， tumor necrosis factor， chemotactic cytokines， matrix metalloproteinases， etc. These cytokines promote or inhibit the inflammatory response and plaque formation during AS process through different targets and mechanisms. A comprehensive understanding of the cytokines in the occurrence and development of AS is conducive to search for new therapeutic targets and drugs.
2021,27(17):1307-1311, DOI: 10.13210/j.cnki.jhmu.20200715.005
Abstract:
Objective： To explore the expression and prognostic significance of ADHs in hepatocellular carcinoma （HCC）.Methods： The clinical data in this study were retrieved from The Cancer Genome Atlas （TCGA）. The expression of ADHs was differentially analyzed in normal liver tissues and HCC by using the Metabolic gEne RApid Visualizer and the TCGA database， and the differentially expressed ADHs were selected for Kaplan‑Meier survival analysis. Cox analysis was performed to select factors that may influence the prognosis of HCC and to verify independent risk factors for HCC patients. The interaction among ADHs was explored at the gene level and protein expression level through GeneMAMIA and STRING， and the functional enrichment analysis of ADH family was carried out by using DAVID bioinformatics resources. Results： The expression levels of ADH1A， ADH1B， ADH1C， ADH4 and ADH7 in HCC were low. Patients with low expression level of ADH1A， ADH1B， ADH1C and ADH4 had poor survival rates， which may be related to the poor prognosis of HCC. Univariate Cox regression analysis showed that the expression levels of ADH1A， ADH1C and ADH4， as well as the clinical stage， T stage and M stage of the tumor were closely related to the overall survival rate of the patients. Multivariate Cox regression analysis further suggested that the low expression of ADH1A， ADH1C and ADH4 were independent risk factors affecting the prognosis of HCC patients. There was a pathway between ADH1A‑ADH1B， ADH1B‑ADH1C and ADH1A‑ADH1C， and ADHs were closely related to esterase D and aldehyde dehydrogenase. The ADHs were mainly involved in biological processes such as ethanol oxidation and retinol metabolism， and played a biological role in glycolysis/gluconeogenesis， chemical carcinogenesis and metabolism of xenobiotics by cytochrome P450. Conclusion： ADH1A， ADH1C and ADH4 may be biomarkers for the prognosis of HCC， providing reference value for the practical application of ADHs in HCC.
Objective： To explore the expression and prognostic significance of ADHs in hepatocellular carcinoma （HCC）.Methods： The clinical data in this study were retrieved from The Cancer Genome Atlas （TCGA）. The expression of ADHs was differentially analyzed in normal liver tissues and HCC by using the Metabolic gEne RApid Visualizer and the TCGA database， and the differentially expressed ADHs were selected for Kaplan‑Meier survival analysis. Cox analysis was performed to select factors that may influence the prognosis of HCC and to verify independent risk factors for HCC patients. The interaction among ADHs was explored at the gene level and protein expression level through GeneMAMIA and STRING， and the functional enrichment analysis of ADH family was carried out by using DAVID bioinformatics resources. Results： The expression levels of ADH1A， ADH1B， ADH1C， ADH4 and ADH7 in HCC were low. Patients with low expression level of ADH1A， ADH1B， ADH1C and ADH4 had poor survival rates， which may be related to the poor prognosis of HCC. Univariate Cox regression analysis showed that the expression levels of ADH1A， ADH1C and ADH4， as well as the clinical stage， T stage and M stage of the tumor were closely related to the overall survival rate of the patients. Multivariate Cox regression analysis further suggested that the low expression of ADH1A， ADH1C and ADH4 were independent risk factors affecting the prognosis of HCC patients. There was a pathway between ADH1A‑ADH1B， ADH1B‑ADH1C and ADH1A‑ADH1C， and ADHs were closely related to esterase D and aldehyde dehydrogenase. The ADHs were mainly involved in biological processes such as ethanol oxidation and retinol metabolism， and played a biological role in glycolysis/gluconeogenesis， chemical carcinogenesis and metabolism of xenobiotics by cytochrome P450. Conclusion： ADH1A， ADH1C and ADH4 may be biomarkers for the prognosis of HCC， providing reference value for the practical application of ADHs in HCC.
2021,27(17):1281-1284, DOI: 10.13210/j.cnki.jhmu.20210716.002
Abstract:
The outbreak of COVID‑19 caused by severe acute respiratory syndrome coronavirus type 2 （SARS‑CoV‑2） in 2019 threatens global public health. In the early stage， respiratory symptoms are the most common in patients with new coronal pneumonia， but with the spread of the disease around the world， gastrointestinal symptoms such as diarrhea， nausea and vomiting have attracted more and more attention. And some patients take diarrhea as the first symptom， which is easy to cause missed diagnosis. This paper expounds the close relationship between COVID‑19 and gastrointestinal tract， and reviews the research progress of COVID‑19's effect on gastrointestinal tract.
The outbreak of COVID‑19 caused by severe acute respiratory syndrome coronavirus type 2 （SARS‑CoV‑2） in 2019 threatens global public health. In the early stage， respiratory symptoms are the most common in patients with new coronal pneumonia， but with the spread of the disease around the world， gastrointestinal symptoms such as diarrhea， nausea and vomiting have attracted more and more attention. And some patients take diarrhea as the first symptom， which is easy to cause missed diagnosis. This paper expounds the close relationship between COVID‑19 and gastrointestinal tract， and reviews the research progress of COVID‑19's effect on gastrointestinal tract.
2024,30(6):475-480, DOI: 10.13210/j.cnki.jhmu.20230804.003
Abstract:
Hepatocellular carcinoma （HCC） is one of the most common malignant tumors in the world. Its formation is a complex process， and the specific mechanism of its formation hasn't been cleared yet. Due to the fact that most HCC patients are diagnosed in the late stage， and they often lose good surgical opportunities. The emergence of targeted drugs has brought new hope to current HCC patients and can also serve as one of the measures for postoperative treatment， playing a huge role in treating HCC. Sorafenib is the first targeted drug used to treat HCC. It can induce apoptosis of liver tumor cells and inhibit proliferation and angiogenesis of liver tumor cells， so it can improve the survival rate of some patients. However， according to current research， 50% ⁃60% of HCC patients experience a decrease in sensitivity to the drug. It is mainly because Sorafenib will inhibit relevant signaling pathways in vivo after using， which leads to the occurrence of drug resistance， so further exploring the mechanism of Sorafenib resistance and reversing Sorafenib resistance have extremely important clinical value for improving the prognosis of liver cancer treatment. In recent years， many scholars have devoted themselves to studying the close relationship between Sorafenib mediated autophagy and drug resistance through Hippo/YAP and PI3K/Akt/mTOR signaling pathways. And exploring the molecular mechanisms of drug resistance has led to significant development in this field. Therefore， this article mainly discusses the relationship between Hippo/YAP and PI3K/Akt/mTOR signaling pathways and autophagy， as well as the mechanism of drug resistance mediated by them， so as to provide a reliable Scientific theory basis for drug resistance of Sorafenib in the treatment of liver cancer.
Hepatocellular carcinoma （HCC） is one of the most common malignant tumors in the world. Its formation is a complex process， and the specific mechanism of its formation hasn't been cleared yet. Due to the fact that most HCC patients are diagnosed in the late stage， and they often lose good surgical opportunities. The emergence of targeted drugs has brought new hope to current HCC patients and can also serve as one of the measures for postoperative treatment， playing a huge role in treating HCC. Sorafenib is the first targeted drug used to treat HCC. It can induce apoptosis of liver tumor cells and inhibit proliferation and angiogenesis of liver tumor cells， so it can improve the survival rate of some patients. However， according to current research， 50% ⁃60% of HCC patients experience a decrease in sensitivity to the drug. It is mainly because Sorafenib will inhibit relevant signaling pathways in vivo after using， which leads to the occurrence of drug resistance， so further exploring the mechanism of Sorafenib resistance and reversing Sorafenib resistance have extremely important clinical value for improving the prognosis of liver cancer treatment. In recent years， many scholars have devoted themselves to studying the close relationship between Sorafenib mediated autophagy and drug resistance through Hippo/YAP and PI3K/Akt/mTOR signaling pathways. And exploring the molecular mechanisms of drug resistance has led to significant development in this field. Therefore， this article mainly discusses the relationship between Hippo/YAP and PI3K/Akt/mTOR signaling pathways and autophagy， as well as the mechanism of drug resistance mediated by them， so as to provide a reliable Scientific theory basis for drug resistance of Sorafenib in the treatment of liver cancer.
2021,27(1):71-74, DOI: 10．13210／j．cnki．jhmu．20200430．003
Abstract:
Endometriosis is not only a common disease in gynecology，but also a chronic and intractable disease in gy－ necology．In recent years，with the increase of cesarean section rate and the increase of artificial abortion and hysteroscopic op－ eration，the incidence of endometriosis has increased significantly，which impacts on women＇s health and quality of life．Treat－ ments of endometriosis by western medicine mainly include hormone therapy and surgical treatment，which have many limita－ tions and adverse reactions．In recent years，traditional Chinese medicine has shown more and more unique advantages，with di－ versification．We summarized literatures about the treatment of endometriosis with traditional Chinese medicine in recent years．
Endometriosis is not only a common disease in gynecology，but also a chronic and intractable disease in gy－ necology．In recent years，with the increase of cesarean section rate and the increase of artificial abortion and hysteroscopic op－ eration，the incidence of endometriosis has increased significantly，which impacts on women＇s health and quality of life．Treat－ ments of endometriosis by western medicine mainly include hormone therapy and surgical treatment，which have many limita－ tions and adverse reactions．In recent years，traditional Chinese medicine has shown more and more unique advantages，with di－ versification．We summarized literatures about the treatment of endometriosis with traditional Chinese medicine in recent years．
2021,27(11):872-875, DOI: 10.13210/j.cnki.jhmu.20200714.001
Abstract:
Drug resistance is a major problem when using molecular targeted drugs for tumors. Currently， functional gene screening is the most common strategy for screening drug resistance genes. In recent years， CRISPR‑Cas9 gene‑editing technology has been widely used in functional studies on tumor‑related genes because of its high accuracy， simplicity， and efficiency. In this paper， the principle of CRISPR‑Cas9 library screening technology and its application in functional gene screening are reviewed. At the same time， the application prospect of the CRISPR‑Cas9 technology is forecasted.
Drug resistance is a major problem when using molecular targeted drugs for tumors. Currently， functional gene screening is the most common strategy for screening drug resistance genes. In recent years， CRISPR‑Cas9 gene‑editing technology has been widely used in functional studies on tumor‑related genes because of its high accuracy， simplicity， and efficiency. In this paper， the principle of CRISPR‑Cas9 library screening technology and its application in functional gene screening are reviewed. At the same time， the application prospect of the CRISPR‑Cas9 technology is forecasted.
2021,27(7):555-560, DOI: 10.13210/j.cnki.jhmu.20200930.003
Abstract:
Ulcerative colitis （UC） is a type of chronic inflammatory recurrent disease. The etiology and pathogenesis are still unclear by now. Among them， immune factors are usually considered to be the final link in the pathogenesis of UC. Due to the increasing incidence， long course of the disease， and difficult recovery， the relevant research is gradually deepened， and related research on intestinal flora， immunity， genetics， etc. has become a hot spot. A large amount of evidence indicates that regulatory T cells （Treg）， helper T cells 17 （Th17）， Th17/Treg immune axis and intestinal microbiota in UC patients play an important role in regulating the development of diseases. There is also a certain correlation between the bacterial flora and the Th17/Treg immune axis. Therefore， this article examines Th17/Treg cells， intestinal microbiota and the relationship between them by consulting a large number of relevant data at home and abroad in recent years. The formation of the immune axis and other issues are briefly summarized， with a view to providing more practical basis for clinical targeted therapy.
Ulcerative colitis （UC） is a type of chronic inflammatory recurrent disease. The etiology and pathogenesis are still unclear by now. Among them， immune factors are usually considered to be the final link in the pathogenesis of UC. Due to the increasing incidence， long course of the disease， and difficult recovery， the relevant research is gradually deepened， and related research on intestinal flora， immunity， genetics， etc. has become a hot spot. A large amount of evidence indicates that regulatory T cells （Treg）， helper T cells 17 （Th17）， Th17/Treg immune axis and intestinal microbiota in UC patients play an important role in regulating the development of diseases. There is also a certain correlation between the bacterial flora and the Th17/Treg immune axis. Therefore， this article examines Th17/Treg cells， intestinal microbiota and the relationship between them by consulting a large number of relevant data at home and abroad in recent years. The formation of the immune axis and other issues are briefly summarized， with a view to providing more practical basis for clinical targeted therapy.
LI Peng?yu, CUI Fu?yan, HUANG Jin?yue, TANG Meng, JIANG Jia?xin, MA Ying, XIA Nian?tong, YANG Bo, WANG Zhi?gang
2023,29(6):22-27, DOI: 10.13210/j.cnki.jhmu.20230217.001
Abstract:
Objective： A chiral resolution method for enantiomers of two chiral nitrogen⁃containing metabolites R⁃gentiandiol and S⁃gentiandiol of swertiamarin in plasma was developed， and the pharmacokinetics of the metabolites were studied. Methods： The metabolites of swertiamarin in vivo were detected by LC⁃MS/MS using Astec Cyclobond Ⅱ Cyclodextrin column （4.6 mm×100 mm， 5 μm）， gradient elution with acetonitrile⁃water as mobile phase， and monitored by multiple reaction monitoring （MRM） method in positive mode. The ion pairs for quantitative analysis are R⁃gentiandiol （m/z 210.04→192.06）， S⁃gentiandiol （m/z 210.04→192.06） and gentianone （m/z 192.02→162.08）. Results： The linear correlation coefficients of the method developed were greater than 0.999， the precision was less than 7.00%， the recovery was 99.57%⁃102.65 %， and the matrix effect was 90.94%⁃91.34 %. The peak tmax of R⁃gentiandiol and S⁃gentiandiol in rat plasma after oral administration of swertiamarin were （1.63±0.23 h and （1.58 ± 0.21） h， t1/2 was （6.23±0.52） h and （5.46±0.38） h， Cmax was （86.79±20.81） ng/mL and （60.72±18.95） ng/mL， and the AUC0⁃24 were （1 094.58±86.37）） （ng·h）/mL and （724.67±58.38） （ng·h）/mL， respectively. Conclusion： The method was highly sensitive with good accuracy and precision， and it was successfully applied for chiral resolution and pharmacokinetics study of R⁃gentiandiol and S⁃gentiandiol in plasma. The method developed and experimental results will provide scientific basis for the study of pharmacodynamics and pharmacodynamic material basis of swertiamarin， and lay a foundation for clinical application and resource development of TCM monomer.
Objective： A chiral resolution method for enantiomers of two chiral nitrogen⁃containing metabolites R⁃gentiandiol and S⁃gentiandiol of swertiamarin in plasma was developed， and the pharmacokinetics of the metabolites were studied. Methods： The metabolites of swertiamarin in vivo were detected by LC⁃MS/MS using Astec Cyclobond Ⅱ Cyclodextrin column （4.6 mm×100 mm， 5 μm）， gradient elution with acetonitrile⁃water as mobile phase， and monitored by multiple reaction monitoring （MRM） method in positive mode. The ion pairs for quantitative analysis are R⁃gentiandiol （m/z 210.04→192.06）， S⁃gentiandiol （m/z 210.04→192.06） and gentianone （m/z 192.02→162.08）. Results： The linear correlation coefficients of the method developed were greater than 0.999， the precision was less than 7.00%， the recovery was 99.57%⁃102.65 %， and the matrix effect was 90.94%⁃91.34 %. The peak tmax of R⁃gentiandiol and S⁃gentiandiol in rat plasma after oral administration of swertiamarin were （1.63±0.23 h and （1.58 ± 0.21） h， t1/2 was （6.23±0.52） h and （5.46±0.38） h， Cmax was （86.79±20.81） ng/mL and （60.72±18.95） ng/mL， and the AUC0⁃24 were （1 094.58±86.37）） （ng·h）/mL and （724.67±58.38） （ng·h）/mL， respectively. Conclusion： The method was highly sensitive with good accuracy and precision， and it was successfully applied for chiral resolution and pharmacokinetics study of R⁃gentiandiol and S⁃gentiandiol in plasma. The method developed and experimental results will provide scientific basis for the study of pharmacodynamics and pharmacodynamic material basis of swertiamarin， and lay a foundation for clinical application and resource development of TCM monomer.
WEI Wu?jun, WANG Chun?fang, JIANG Qi, XU Gui?dan, HUANG Jing?jing, LIN Cheng, HU Ren?tong, CHANG Zheng?yi
2023,29(6):8-14, DOI: 10.13210/j.cnki.jhmu.20221221.001
Abstract:
Objective： To investigate the effect of mir⁃3168 on the malignant transformation and cisplatin resistance of AGS and AGS/DDP gastric cancer cells， and to verify its target gene. Methods： The expression of mir⁃3168 in AGS and AGS/DDP gastric cancer cells was detected by qPCR， and mir⁃3168 mimic， inhibitor and negative control were synthesized. They were transfected into AGS and AGS/DDP gastric cancer cells， respectively. The expression of mir⁃3168 and TP53 mRNA was detected by qPCR. Cell viability was detected by CCK8 under gradient cisplatin treatment and non treatment， apoptosis was detected by flow cytometry， cell invasion was detected by Transwell， and TP53 protein expression was detected by western blot， The database predicted the binding sites of mir⁃3168 and TP53. According to the binding sites， the double luciferase experiment was used to verify the binding of mir⁃3168 and TP53. Results： Compared with cisplatin sensitive gastric cancer cell AGS， mir⁃3168 was significantly overexpressed in cisplatin resistant gastric cancer cell AGS/DDP； mir⁃3168 mimic promotes cisplatin resistance， proliferation and invasion of AGS and AGS/DDP gastric cancer cells， and inhibits apoptosis of AGS and AGS/DDP gastric cancer cells； mir⁃3168 inhibitor inhibits cisplatin resistance， proliferation and invasion of AGS and AGS/DDP gastric cancer cells， and promotes apoptosis of AGS and AGS/DDP gastric cancer cells； mir⁃3168 mimic inhibits the expression of TP53 mRNA and protein， and mir⁃3168 inhibitor promotes the expression of TP53 mRNA and protein； Targetscan database predicted that there was a binding point between mir⁃3168 and TP53， and the double luciferase experiment suggested that mir⁃3168 was bound to TP53 through the predicted binding site. Conclusion： mir⁃3168 may promote the malignant transformation of AGS and AGS/DDP gastric cancer cells and cisplatin resistance by targeting TP53.
Objective： To investigate the effect of mir⁃3168 on the malignant transformation and cisplatin resistance of AGS and AGS/DDP gastric cancer cells， and to verify its target gene. Methods： The expression of mir⁃3168 in AGS and AGS/DDP gastric cancer cells was detected by qPCR， and mir⁃3168 mimic， inhibitor and negative control were synthesized. They were transfected into AGS and AGS/DDP gastric cancer cells， respectively. The expression of mir⁃3168 and TP53 mRNA was detected by qPCR. Cell viability was detected by CCK8 under gradient cisplatin treatment and non treatment， apoptosis was detected by flow cytometry， cell invasion was detected by Transwell， and TP53 protein expression was detected by western blot， The database predicted the binding sites of mir⁃3168 and TP53. According to the binding sites， the double luciferase experiment was used to verify the binding of mir⁃3168 and TP53. Results： Compared with cisplatin sensitive gastric cancer cell AGS， mir⁃3168 was significantly overexpressed in cisplatin resistant gastric cancer cell AGS/DDP； mir⁃3168 mimic promotes cisplatin resistance， proliferation and invasion of AGS and AGS/DDP gastric cancer cells， and inhibits apoptosis of AGS and AGS/DDP gastric cancer cells； mir⁃3168 inhibitor inhibits cisplatin resistance， proliferation and invasion of AGS and AGS/DDP gastric cancer cells， and promotes apoptosis of AGS and AGS/DDP gastric cancer cells； mir⁃3168 mimic inhibits the expression of TP53 mRNA and protein， and mir⁃3168 inhibitor promotes the expression of TP53 mRNA and protein； Targetscan database predicted that there was a binding point between mir⁃3168 and TP53， and the double luciferase experiment suggested that mir⁃3168 was bound to TP53 through the predicted binding site. Conclusion： mir⁃3168 may promote the malignant transformation of AGS and AGS/DDP gastric cancer cells and cisplatin resistance by targeting TP53.
2023,29(6):51-61, DOI: 10.13210/j.cnki.jhmu.20210713.001
Abstract:
Objective： To evaluate the clinical efficacy and safety of cinobufagin injection in the treatment of liver cancer. Methods： PubMed database， Embase database and Cochrane Library database， CNKI， Wanfang database， VIP database and Sinomed database were used to search for the randomized controlled trials of cinobufagin injection combined with Western medicine in the treatment of primary liver cancer. The retrieval time was from the establishment to December 15， 2020. Two independent researchers conducted systematic screening， literature inclusion and quality assessment of the articles according to the inclusion criteria， respectively. Meta‑analysis of the data was performed using RevMan 5.4 software. Results： A total of 30 studies with a total of 2 355 patients were included. Compared with conventional western medicine treatment， the clinical effective rate of Hububutin injection combined with western medicine was significantly higher ［RR=1.16，95%CI=（1.11，1.22），P<0.000 01］. It could effectively reduce the tumor size ［RR=1.33，95%CI=（1.17，1.51），P<0.000 01］， prolong the survival time of patients ［RR=1.41，95%CI=（1.31，1.52），P<0.000 01］， improve the quality of life ［RR=1.37，95%CI=（1.19，1.57），P<0.000 01］， improve the liver function of patients ［RR=-14.52，95%CI=（-16.15，-12.88），P<0.000 01］， and reduce the occurrence of adverse reactions ［RR=0.94，95%CI=（0.85，1.42），P=0.25］ such as bone marrow suppression ［RR=0.44，95%CI=（0.31，0.62），P<0.000 01］. Conclusion： Cinobufagin injection combined with western medicine therapy can effectively improve the clinical symptoms of primary liver cancer， and the safety is good. However， the methodological quality of the included literature is low， which affects the objectivity of the outcome， and it still needs to be verified by multi‑sample， multi‑center， randomized double‑blind controlled trial.
Objective： To evaluate the clinical efficacy and safety of cinobufagin injection in the treatment of liver cancer. Methods： PubMed database， Embase database and Cochrane Library database， CNKI， Wanfang database， VIP database and Sinomed database were used to search for the randomized controlled trials of cinobufagin injection combined with Western medicine in the treatment of primary liver cancer. The retrieval time was from the establishment to December 15， 2020. Two independent researchers conducted systematic screening， literature inclusion and quality assessment of the articles according to the inclusion criteria， respectively. Meta‑analysis of the data was performed using RevMan 5.4 software. Results： A total of 30 studies with a total of 2 355 patients were included. Compared with conventional western medicine treatment， the clinical effective rate of Hububutin injection combined with western medicine was significantly higher ［RR=1.16，95%CI=（1.11，1.22），P<0.000 01］. It could effectively reduce the tumor size ［RR=1.33，95%CI=（1.17，1.51），P<0.000 01］， prolong the survival time of patients ［RR=1.41，95%CI=（1.31，1.52），P<0.000 01］， improve the quality of life ［RR=1.37，95%CI=（1.19，1.57），P<0.000 01］， improve the liver function of patients ［RR=-14.52，95%CI=（-16.15，-12.88），P<0.000 01］， and reduce the occurrence of adverse reactions ［RR=0.94，95%CI=（0.85，1.42），P=0.25］ such as bone marrow suppression ［RR=0.44，95%CI=（0.31，0.62），P<0.000 01］. Conclusion： Cinobufagin injection combined with western medicine therapy can effectively improve the clinical symptoms of primary liver cancer， and the safety is good. However， the methodological quality of the included literature is low， which affects the objectivity of the outcome， and it still needs to be verified by multi‑sample， multi‑center， randomized double‑blind controlled trial.
The mechanism and application of specialized phagocytic cell burial function in chronic wound repair
2024,30(13):1035-1040, DOI: 10.13210/j.cnki.jhmu.20240005.001
Abstract:
Chronic wounds， as a long‑term wasting disease， are a long‑term clinical problem that is difficult to solve. Dysfunction of efferocytosis prevents apoptotic cells from being cleared from the wound in time， resulting in secondary cell necrosis and release of pro‑inflammatory cytokines， making it difficult for the wound to transition from the inflammatory phase to the proliferative phase. Macrophages and dendritic cells， as professional phagocytes， are the main bearers of efferocytosis. This article reviews the mechanism of action of these two types of professional phagocytes in the wound healing process and finds that in addition to efferocytosis‑related receptors， macrophages and dendritic cells also play a role in cytosis by acting on signaling molecules such as ICAM‑1， NK‑4， MIR‑21， CD36， etc.， to accelerate the healing of chronic wounds. In addition， the efferocytosis function of dendritic cells may be limited by SLC7A11. Removing or inhibiting SLC7A11 can significantly enhance the efferocytosis of dendritic cells and promote chronic wound healing. This study is of great significance to further elucidating the healing process of chronic refractory wound and the development of new treatmentss.
Chronic wounds， as a long‑term wasting disease， are a long‑term clinical problem that is difficult to solve. Dysfunction of efferocytosis prevents apoptotic cells from being cleared from the wound in time， resulting in secondary cell necrosis and release of pro‑inflammatory cytokines， making it difficult for the wound to transition from the inflammatory phase to the proliferative phase. Macrophages and dendritic cells， as professional phagocytes， are the main bearers of efferocytosis. This article reviews the mechanism of action of these two types of professional phagocytes in the wound healing process and finds that in addition to efferocytosis‑related receptors， macrophages and dendritic cells also play a role in cytosis by acting on signaling molecules such as ICAM‑1， NK‑4， MIR‑21， CD36， etc.， to accelerate the healing of chronic wounds. In addition， the efferocytosis function of dendritic cells may be limited by SLC7A11. Removing or inhibiting SLC7A11 can significantly enhance the efferocytosis of dendritic cells and promote chronic wound healing. This study is of great significance to further elucidating the healing process of chronic refractory wound and the development of new treatmentss.
2023,29(6):1-7, DOI: 10.13210/j.cnki.jhmu.20230106.001
Abstract:
Objective：To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH‑SY5Y cells. Methods： SH‑SY5Y cells were randomly divided into control （D‑galactose 0 mmol/L group）， D‑galactose （25 mmol/L， 50 mmol/L， 100 mmol/L， 200 mmol/L， 400 mmol/L） groups， and treated with corresponding concentrations of D‑galactose for 48 h. The changes of cell morphology， β‑galactosidase， the cell morphology， β‑galactosidase activity by microscopic observation， cell proliferation rate by EdU kit and cell survival rate by CCK‑8 assay were used to determine the decaying concentration of D‑galactose and to establish the senescence model. The senescent SH‑SY5Y cells were randomly divided into control group （oxygen glucose deprivation without treatment group）， oxygen glucose deprivation treatment （0.5 h， 1 h， 1.5 h， 2 h） group， followed by re‑glucose reoxygenation for 24 h， and CCK‑8 assay for the survival rate of senescent SH‑SY5Y cells. Results： There were no significant changes in cell morphology and β‑gal activity in the 25 mmol/L and 50 mmol/L groups compared with the control group （P>0.05）， cytosolic hypertrophy was seen in the cells of the 100 mmol/L group， chromatin fixation in the cells of the 200 mmol/L group， and massive vacuolization in the cells of the 400 mmol/L group； the positive rate of β‑galactosidase staining in the cells of the （100-400 mmol/L） group was significantly higher compared with the control group （P< 0.05）， with little difference between the 100 mmol/L and 200 mmol/L groups （P>0.05）； the cell proliferation ability of the （100-400 mmol/L） group was significantly decreased in a concentration‑dependent manner （P<0.05）； the cell survival rate was decreased in a concentration‑dependent manner （P<0.05）， with IC50 between 100 mmol/L and 200 mmol/L. The survival of senescent SH‑SY5Y cells showed a time‑dependent decrease in oxygen‑glucose deprivation （P<0.05）， with an IC50 close to 1 h. Conclusion： D‑gal concentration of 100 mmoL/L and 48 h of cell action could establish a survival rate of about 50% of senescent SH‑SY5Y cells， and oxygen glucose deprivation of senescent SH‑SY5Y cells for 1 h and reperfusion for 24 h could establish an oxygen glucose deprivation/reperfusion model of senescent SH‑SY5Y cells with a survival rate close to 50%.
Objective：To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH‑SY5Y cells. Methods： SH‑SY5Y cells were randomly divided into control （D‑galactose 0 mmol/L group）， D‑galactose （25 mmol/L， 50 mmol/L， 100 mmol/L， 200 mmol/L， 400 mmol/L） groups， and treated with corresponding concentrations of D‑galactose for 48 h. The changes of cell morphology， β‑galactosidase， the cell morphology， β‑galactosidase activity by microscopic observation， cell proliferation rate by EdU kit and cell survival rate by CCK‑8 assay were used to determine the decaying concentration of D‑galactose and to establish the senescence model. The senescent SH‑SY5Y cells were randomly divided into control group （oxygen glucose deprivation without treatment group）， oxygen glucose deprivation treatment （0.5 h， 1 h， 1.5 h， 2 h） group， followed by re‑glucose reoxygenation for 24 h， and CCK‑8 assay for the survival rate of senescent SH‑SY5Y cells. Results： There were no significant changes in cell morphology and β‑gal activity in the 25 mmol/L and 50 mmol/L groups compared with the control group （P>0.05）， cytosolic hypertrophy was seen in the cells of the 100 mmol/L group， chromatin fixation in the cells of the 200 mmol/L group， and massive vacuolization in the cells of the 400 mmol/L group； the positive rate of β‑galactosidase staining in the cells of the （100-400 mmol/L） group was significantly higher compared with the control group （P< 0.05）， with little difference between the 100 mmol/L and 200 mmol/L groups （P>0.05）； the cell proliferation ability of the （100-400 mmol/L） group was significantly decreased in a concentration‑dependent manner （P<0.05）； the cell survival rate was decreased in a concentration‑dependent manner （P<0.05）， with IC50 between 100 mmol/L and 200 mmol/L. The survival of senescent SH‑SY5Y cells showed a time‑dependent decrease in oxygen‑glucose deprivation （P<0.05）， with an IC50 close to 1 h. Conclusion： D‑gal concentration of 100 mmoL/L and 48 h of cell action could establish a survival rate of about 50% of senescent SH‑SY5Y cells， and oxygen glucose deprivation of senescent SH‑SY5Y cells for 1 h and reperfusion for 24 h could establish an oxygen glucose deprivation/reperfusion model of senescent SH‑SY5Y cells with a survival rate close to 50%.
YAN Dong?ming, LIANG Jian?tang, LIU Xiao?qian, LI Meng?yongwei, DING Shun, MENG Qing?wen, ZHANG Si?yuan, TANG Cai?ying, LIU Qi?bing, YANG Kun
2023,29(6):28-36, DOI: 10.13210/j.cnki.jhmu.20221125.001
Abstract:
Objective： To investigate the prognostic value of ORMDL2 in human glioma and its relationship with immune invasion. Methods： The clinical survival data from TCGA – LGG&GBM， CGGA and GEO were used to evaluate the clinical prognostic value of ORMDL2. The cut off value of ORMDL2 was detected with pROC package to draw ROC curve to prove its value in differential diagnosis of glioma. The first 300 genes with the most significant positive correlation with ORMDL2 were selected to establish PPI network through STRING database and conduct GO and pathway analysis. The relationship between the expression of ORMDL2 mRNA and immune cell infiltration was investigated by using ssGSEA and TIMER2.0 databases. Results： The expression of ORMDL2 mRNA in glioma was significantly higher than that in adjacent normal tissues， and the difference was most significant in high‑grade glioma. The expression of ORMDL2 was increased in human glioma， which was related to the clinicopathological characteristics and poor prognosis of glioma patients. In addition， the increased expression of ORMDL2 was associated with a series of immune infiltrating cells， including macrophages. Conclusion： ORMDL2 plays an important role in glioma immune cell infiltration and is a biomarker of prognosis of glioma patients.
Objective： To investigate the prognostic value of ORMDL2 in human glioma and its relationship with immune invasion. Methods： The clinical survival data from TCGA – LGG&GBM， CGGA and GEO were used to evaluate the clinical prognostic value of ORMDL2. The cut off value of ORMDL2 was detected with pROC package to draw ROC curve to prove its value in differential diagnosis of glioma. The first 300 genes with the most significant positive correlation with ORMDL2 were selected to establish PPI network through STRING database and conduct GO and pathway analysis. The relationship between the expression of ORMDL2 mRNA and immune cell infiltration was investigated by using ssGSEA and TIMER2.0 databases. Results： The expression of ORMDL2 mRNA in glioma was significantly higher than that in adjacent normal tissues， and the difference was most significant in high‑grade glioma. The expression of ORMDL2 was increased in human glioma， which was related to the clinicopathological characteristics and poor prognosis of glioma patients. In addition， the increased expression of ORMDL2 was associated with a series of immune infiltrating cells， including macrophages. Conclusion： ORMDL2 plays an important role in glioma immune cell infiltration and is a biomarker of prognosis of glioma patients.
CHEN Huan?xiong, HE Xian?bo, LI Guo?jun, TANG Song?jie, ZHONG Zhen?hao，, HUANG Tao, LIN You?cai, LIN Su?yu, MENG Zhi?bin
2023,29(6):43-50, DOI: 10.13210/j.cnki.jhmu.20230116.001
Abstract:
Objective： To study the position and the grade of screw perforation in the apical region of adolescent idiopathic scoliosis （AIS） surgery using a calibration technique for the intraoperative navigation error， and to analyze the related factors of navigation deviation and the clinical significance of the calibration technique. Methods： From 2017 to 2020， a total of 60 Lenke 1 AIS surgical cases were enrolled in this research. The 30 cases received surgery using the intraoperative navigation system （Navigation group） and another 30 cases were assisted with intraoperative navigation system with calibration technique （Calibration group） for the intraoperative navigation error. The basic information and radiological data of the both groups were all recorded. According to the Fu Chang⁃feng’s pedicle channel classification system， the pedicle on the apical region of the two groups was classified. And then the accuracy of screw placement of the two groups was evaluated according to the Rao’s classification. Results： A total of 600 screws were placed in the two groups. The 297 and 303 pedicle screws were implanted in the navigation group and the calibration group， respectively. In the apical region of the calibration group， the rates of the grade 0 screw placement in type A， B and C pedicle were 95.7%， 86.7% and 68.9% respectively. It was a statistically significant difference from the 73.9%， 66.9% and 30.0% in the navigation group respectively （P<0.05）. In the calibration group， the rates of the medial cortical perforation in the type A， B， C and D pedicle were 0%， 1.6%， 1.6% and 0%， respectively. The corresponding rates were 16.3%， 16.9%， 30.0% and 47.6% in the navigation group， respectively. Moreover， in the concave side of the apical region of the calibration group， the rates of the medial cortical perforation in the type A， B， C and D pedicle were 0%， 3.6%， 2.6% and 0%， respectively. Compared with the calibration group， the corresponding rates were higher in the navigation group （34.4%， 25.9%， 37.2% and 60.0%， respectively）. No serious complications such as spinal cord or neurovascular injury occurred for the two groups. Conclusion： Compared with the intraoperative navigation system， the calibration technique for the intraoperative navigation error could provide the higher accuracy of pedicle screw placement in the apical region of the major curve， the lower medial cortical perforation rate， the less screws misplacement rate on the concave side and the less complication rate of the severe Lenke 1 AIS patients.
Objective： To study the position and the grade of screw perforation in the apical region of adolescent idiopathic scoliosis （AIS） surgery using a calibration technique for the intraoperative navigation error， and to analyze the related factors of navigation deviation and the clinical significance of the calibration technique. Methods： From 2017 to 2020， a total of 60 Lenke 1 AIS surgical cases were enrolled in this research. The 30 cases received surgery using the intraoperative navigation system （Navigation group） and another 30 cases were assisted with intraoperative navigation system with calibration technique （Calibration group） for the intraoperative navigation error. The basic information and radiological data of the both groups were all recorded. According to the Fu Chang⁃feng’s pedicle channel classification system， the pedicle on the apical region of the two groups was classified. And then the accuracy of screw placement of the two groups was evaluated according to the Rao’s classification. Results： A total of 600 screws were placed in the two groups. The 297 and 303 pedicle screws were implanted in the navigation group and the calibration group， respectively. In the apical region of the calibration group， the rates of the grade 0 screw placement in type A， B and C pedicle were 95.7%， 86.7% and 68.9% respectively. It was a statistically significant difference from the 73.9%， 66.9% and 30.0% in the navigation group respectively （P<0.05）. In the calibration group， the rates of the medial cortical perforation in the type A， B， C and D pedicle were 0%， 1.6%， 1.6% and 0%， respectively. The corresponding rates were 16.3%， 16.9%， 30.0% and 47.6% in the navigation group， respectively. Moreover， in the concave side of the apical region of the calibration group， the rates of the medial cortical perforation in the type A， B， C and D pedicle were 0%， 3.6%， 2.6% and 0%， respectively. Compared with the calibration group， the corresponding rates were higher in the navigation group （34.4%， 25.9%， 37.2% and 60.0%， respectively）. No serious complications such as spinal cord or neurovascular injury occurred for the two groups. Conclusion： Compared with the intraoperative navigation system， the calibration technique for the intraoperative navigation error could provide the higher accuracy of pedicle screw placement in the apical region of the major curve， the lower medial cortical perforation rate， the less screws misplacement rate on the concave side and the less complication rate of the severe Lenke 1 AIS patients.
2023,29(6):15-21, DOI: 10.13210/j.cnki.jhmu.20211221.002
Abstract:
Objective： To investigate whether "Fuzheng Qingretonglin" decoction can reduce urinary tract damage caused by complex urinary tract infection caused by drug resistant Escherichia coli by regulating Nod‑like receptor pyrin domain3 inflammasome， and to explore the feasibility of this decoction combined with levofloxacin in the treatment of complex urinary tract infection caused by drug resistant bacteria. Methods： SD rats were divided into five groups： sham group， model group， levofloxacin group（Lev group）， levofloxacin+Fuzheng Qingre Tonglin decoction group（FZ+lev group）， and Fuzheng Qingre Tonglin decoction group（FZQRTL group）. After the experiment， urine was taken for bacterial culture to determine the urinary tract infection of rats in each group； HE staining was used to observe the pathological changes of kidney and bladder tissues in rats； The expression of NLRP3 in kidney and bladder tissues was detected by immunohistochemistry； The expression of IL‑1β and IL‑18 in serum of rats was detected by ELISA； The expressions of NLRP3，ASC and Caspase‑1 were detected by Western blotting. Results： The positive rate of urine bacteria culture in the sham group was 0%， the positive rate of urine bacteria culture in the model group was 100%； and the positive rate of urine bacteria culture in the FZ+lev group was 37.50%， which was statistically different from that in the model group（P<0.05）. A large number of inflammatory cells were observed in the kidney and bladder tissues of the model group by HE staining， while the number of inflammatory cells in the kidney and bladder tissues of the Lev group and FZQRTL group was significantly reduced compared with that of the model group. The FZ+lev group in the number and structure of inflammatory cells in kidney and bladder were similar to the sham group. The NLRP3 immunohistochemistry of kidney and bladder tissue in FZ+lev groups and FZQRTL groups was significantly different from that in model group（P<0.001）. The levels of IL‑1β and IL‑18 in serum of Lev group，FZQRTL group and FZ+lev group were significantly decreased by ELISA compared with model group（P<0.001）. The levels of IL‑1β and IL‑18 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group， and the differences were statistically significant（P<0.05）. The protein expressions of NLRP3， ASC and Caspase‑1 in the Lev group， FZQRTL group and FZ+lev group were significantly lower than those in the model group（P<0.001）. The protein expressions of NLRP3， ASC and Caspase‑1 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group， and the differences were statistically significant（P<0.05）. Conclusion： "Fuzheng Qingretonglin" decoction may have a protective effect on the kidney and bladder of rats with complex urinary tract infection caused by drug‑resistant Escherichia coli by inhibiting the activation of NLRP3 inflammatory bodies， and TCM combined with levofloxacin has a better therapeutic effect than TCM or levofloxacin alone.
Objective： To investigate whether "Fuzheng Qingretonglin" decoction can reduce urinary tract damage caused by complex urinary tract infection caused by drug resistant Escherichia coli by regulating Nod‑like receptor pyrin domain3 inflammasome， and to explore the feasibility of this decoction combined with levofloxacin in the treatment of complex urinary tract infection caused by drug resistant bacteria. Methods： SD rats were divided into five groups： sham group， model group， levofloxacin group（Lev group）， levofloxacin+Fuzheng Qingre Tonglin decoction group（FZ+lev group）， and Fuzheng Qingre Tonglin decoction group（FZQRTL group）. After the experiment， urine was taken for bacterial culture to determine the urinary tract infection of rats in each group； HE staining was used to observe the pathological changes of kidney and bladder tissues in rats； The expression of NLRP3 in kidney and bladder tissues was detected by immunohistochemistry； The expression of IL‑1β and IL‑18 in serum of rats was detected by ELISA； The expressions of NLRP3，ASC and Caspase‑1 were detected by Western blotting. Results： The positive rate of urine bacteria culture in the sham group was 0%， the positive rate of urine bacteria culture in the model group was 100%； and the positive rate of urine bacteria culture in the FZ+lev group was 37.50%， which was statistically different from that in the model group（P<0.05）. A large number of inflammatory cells were observed in the kidney and bladder tissues of the model group by HE staining， while the number of inflammatory cells in the kidney and bladder tissues of the Lev group and FZQRTL group was significantly reduced compared with that of the model group. The FZ+lev group in the number and structure of inflammatory cells in kidney and bladder were similar to the sham group. The NLRP3 immunohistochemistry of kidney and bladder tissue in FZ+lev groups and FZQRTL groups was significantly different from that in model group（P<0.001）. The levels of IL‑1β and IL‑18 in serum of Lev group，FZQRTL group and FZ+lev group were significantly decreased by ELISA compared with model group（P<0.001）. The levels of IL‑1β and IL‑18 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group， and the differences were statistically significant（P<0.05）. The protein expressions of NLRP3， ASC and Caspase‑1 in the Lev group， FZQRTL group and FZ+lev group were significantly lower than those in the model group（P<0.001）. The protein expressions of NLRP3， ASC and Caspase‑1 in the FZ+lev groups were significantly lower than in the Lev group and FZQRTL group， and the differences were statistically significant（P<0.05）. Conclusion： "Fuzheng Qingretonglin" decoction may have a protective effect on the kidney and bladder of rats with complex urinary tract infection caused by drug‑resistant Escherichia coli by inhibiting the activation of NLRP3 inflammatory bodies， and TCM combined with levofloxacin has a better therapeutic effect than TCM or levofloxacin alone.
2021,27(21):1652-1658, DOI: 10.13210/j.cnki.jhmu.20210609.001
Abstract:
Objective： To further understand the pathogenesis of psoriasis based on bioinformatics， gene set enrichment analysis （GSEA） and immune infiltration analysis were carried out on the microarray data of psoriasis expression profile. Methods： GSE6710 chip data were obtained from gene expression database （GEO）， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed using GSEA software. A total of 22 kinds of immune cell gene expression matrices and R packages were downloaded from CIBERSOFT official website， and the immune cell infiltration matrix was obtained by R software and related graphs were drawn. Results： The pathways related to cell proliferation and innate immunity were highly expressed in psoriatic lesions， and some cancer‑related pathways were highly expressed in psoriatic lesions. Immunized cell infiltration analysis showed that activated memory T cells， follicular helper T cells， M0 macrophages and activated dendritic cells were up‑regulated in the psoriatic skin lesion group， and inactive mast cells were down‑regulated in the psoriatic skin lesion group. Activated dendritic cells were positively correlated with follicular helper T cells， activated mast cells were positively correlated with M0 macrophages. Inactivated mast cells were negatively correlated with activated memory T cells， M1 macrophages were negatively correlated with regulatory T cells， M0 macrophages were negatively correlated with inactive mast cells.Conclusion： Cell proliferation and innate immunity are of great significance in the pathogenesis of psoriasis. Immune cell infiltration analysis is generally consistent with the current psoriasis pathogenesis model. Macrophages and mast cells also play a certain role in psoriasis.
Objective： To further understand the pathogenesis of psoriasis based on bioinformatics， gene set enrichment analysis （GSEA） and immune infiltration analysis were carried out on the microarray data of psoriasis expression profile. Methods： GSE6710 chip data were obtained from gene expression database （GEO）， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed using GSEA software. A total of 22 kinds of immune cell gene expression matrices and R packages were downloaded from CIBERSOFT official website， and the immune cell infiltration matrix was obtained by R software and related graphs were drawn. Results： The pathways related to cell proliferation and innate immunity were highly expressed in psoriatic lesions， and some cancer‑related pathways were highly expressed in psoriatic lesions. Immunized cell infiltration analysis showed that activated memory T cells， follicular helper T cells， M0 macrophages and activated dendritic cells were up‑regulated in the psoriatic skin lesion group， and inactive mast cells were down‑regulated in the psoriatic skin lesion group. Activated dendritic cells were positively correlated with follicular helper T cells， activated mast cells were positively correlated with M0 macrophages. Inactivated mast cells were negatively correlated with activated memory T cells， M1 macrophages were negatively correlated with regulatory T cells， M0 macrophages were negatively correlated with inactive mast cells.Conclusion： Cell proliferation and innate immunity are of great significance in the pathogenesis of psoriasis. Immune cell infiltration analysis is generally consistent with the current psoriasis pathogenesis model. Macrophages and mast cells also play a certain role in psoriasis.
2023,29(6):73-78, DOI: 10.13210/j.cnki.jhmu.20210701.001
Abstract:
Coronary no‑reflow phenomenon belongs to a type of coronary microcirculation disturbance， and its main pathogenic factors are vascular endothelial cell injury， microembolism and inflammatory reaction， which are corresponding to the pathogenesis of choroid injury， blood stasis and heat toxin in traditional Chinese medicine， such as NO， ET‑1， chemokine， IL and other cytokines. The degree of improvement of patients' symptoms and laboratory examination data provide a basis for traditional Chinese medicine compound prescription， monomer and traditional Chinese medicine characteristic therapy for the treatment of no-reflow phenomena（NRP）. Combined with related factors， the author summarizes the research progress of traditional Chinese medicine treatment of NRP in recent years， in order to provide clinical reference.
Coronary no‑reflow phenomenon belongs to a type of coronary microcirculation disturbance， and its main pathogenic factors are vascular endothelial cell injury， microembolism and inflammatory reaction， which are corresponding to the pathogenesis of choroid injury， blood stasis and heat toxin in traditional Chinese medicine， such as NO， ET‑1， chemokine， IL and other cytokines. The degree of improvement of patients' symptoms and laboratory examination data provide a basis for traditional Chinese medicine compound prescription， monomer and traditional Chinese medicine characteristic therapy for the treatment of no-reflow phenomena（NRP）. Combined with related factors， the author summarizes the research progress of traditional Chinese medicine treatment of NRP in recent years， in order to provide clinical reference.
2021,27(7):481-487, DOI: 10.13210/j.cnki.jhmu.20200914.003
Abstract:
Objective： To investigate to the effect of hypoxia and hypoxia/reoxygenation on ROS， MAPKs and cell apoptosis in H9c2 cardiomyocytes. Methods： H9c2 cells were treated with cobalt chloride （CoCl2） at different concentrations （150， 300， 450， 600， 900， 1 200， 2 400 µmol/L） for 4-48 h to establish the hypoxia and hypoxia/reoxygenation-induced cardiomyocyte injury model. H9c2 cell viability was detected by MTT， and the intracellular ROS level was measured by 2'，7'-dichlorofluorescin diacetate and dihydroethidium. In addition， the expression level of mitogen-activated protein kinases （MAPKs） （including phosphorylated JNK， ERK and p38） and caspase-3 was determined by Western blotting. Results： At 300-12 00 µmol/L， CoCl2 inhibited the cell viability in H9c2 cells in a concentration and time-dependent manner （P<0.01）. Compared with the control group， the ROS levels under hypoxia condition were significantly increased （P<0.05） at 4 and 16 h. Moreover， the expression levels of p-JNK， p-p38 and caspase-3 were increased （P<0.05）. However， the expression of p-ERK remained unchanged. Furthermore， the expression levels of ROS， p-JNK， p-ERK1/2， p-p38 and caspase-3 in the hypoxia/reoxygenation group were significantly increased compared with the hypoxia group （P<0.01）. Conclusion： Reoxygenation further aggravates hypoxia-induced oxidative stress injury in cardiomyocyte by activating ROS/MAPKs signaling pathway， suggesting the role of myocardial ischemia/reperfusion injury in the pathogenesis of ischemic heart disease.
Objective： To investigate to the effect of hypoxia and hypoxia/reoxygenation on ROS， MAPKs and cell apoptosis in H9c2 cardiomyocytes. Methods： H9c2 cells were treated with cobalt chloride （CoCl2） at different concentrations （150， 300， 450， 600， 900， 1 200， 2 400 µmol/L） for 4-48 h to establish the hypoxia and hypoxia/reoxygenation-induced cardiomyocyte injury model. H9c2 cell viability was detected by MTT， and the intracellular ROS level was measured by 2'，7'-dichlorofluorescin diacetate and dihydroethidium. In addition， the expression level of mitogen-activated protein kinases （MAPKs） （including phosphorylated JNK， ERK and p38） and caspase-3 was determined by Western blotting. Results： At 300-12 00 µmol/L， CoCl2 inhibited the cell viability in H9c2 cells in a concentration and time-dependent manner （P<0.01）. Compared with the control group， the ROS levels under hypoxia condition were significantly increased （P<0.05） at 4 and 16 h. Moreover， the expression levels of p-JNK， p-p38 and caspase-3 were increased （P<0.05）. However， the expression of p-ERK remained unchanged. Furthermore， the expression levels of ROS， p-JNK， p-ERK1/2， p-p38 and caspase-3 in the hypoxia/reoxygenation group were significantly increased compared with the hypoxia group （P<0.01）. Conclusion： Reoxygenation further aggravates hypoxia-induced oxidative stress injury in cardiomyocyte by activating ROS/MAPKs signaling pathway， suggesting the role of myocardial ischemia/reperfusion injury in the pathogenesis of ischemic heart disease.
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