Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are current...Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.展开更多
OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(...OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(LPS)nasal drops and passive smoke exposure,followed by evaluation of SJGB decoction efficacy via lung function tests and histological analysis.Non-targeted liquid chromatography-mass spectrometry(LC-MS)-based metabolomics was used to explore the mechanisms of SJGB decoction in COPD.RESULTS:We found that the SJGB decoction effectively reduced inflammatory cell infiltration in the airways and lungs,and improved lung function in the COPD model mice.LC-MS-based metabolomics identified 86 biomarkers in COPD models.Compared to the model group,SJGB decoction significantly altered 34 metabolites.Prostaglandin E2 and DL-Citrulline were highlighted as two representative differential metabolites.MetaboAnalyst 5.0 highlighted glycerophospholipid and riboflavin metabolisms as key pathways affected by SJGB decoction.CONCLUSION:This study evaluated the protective effect of SJGB decoction against COPD and provided insights into its potential mechanisms in COPD treatment.展开更多
Background:Renshen Guben oral liquid(RGSB)has the ability to consolidate constitution,restore vitality,and delay the ageing process and the onset of geriatric diseases.RGSB also has potential therapeutic effects on in...Background:Renshen Guben oral liquid(RGSB)has the ability to consolidate constitution,restore vitality,and delay the ageing process and the onset of geriatric diseases.RGSB also has potential therapeutic effects on intervertebral disc degeneration(IVDD).This study investigated the therapeutic effects of RGSB on IVDD and explored the underlying mechanisms.Methods:Single-cell sequencing and network pharmacology analyses were conducted in combination to determine the mechanisms of IVDD.Thirty-two C57BL/6J mice were randomly assigned to four groups:the sham operation group,IVDD group,Ibuprofen(IB)group,and RGSB group.All groups except for the sham operation group underwent needle puncture of the caudal IVDs.Behavioral tests,ELISA,PCR,TUNEL staining,and immunohistochemical staining were performed to investigate the therapeutic mechanisms associated with IVDD.Results:Bioinformatics analysis revealed that apoptosis is involved in the development of IVDD and that RSGB might alleviate IVDD by inhibiting apoptosis.After needle puncture,the mice exhibited from thermal allodynia,a decrease in disc height,an increase in the Pfirrmann grade,and destruction of IVDs.Surgery to induce IVDD increased the levels of Matrix Metalloproteinase-3(MMP3),Caspase-6,and Cyt-c in nucleus pulposus cells and the periphery;serum levels of interleukin-1β(IL‐1β)and TNF‐α;and the mRNA levels of IL-6,TNF-α,and IL-1β.Moreover,IVDD decreased the IL-10 mRNA level and the expression of Col-I and BCL2.RSGB reversed these changes.Conclusion:RSGB alleviated IVDD by relieving inflammation and apoptosis and alleviating neuroinflammation.展开更多
Introduction:With the incidence of chronic kidney disease(CKD)increasing year by year,it is particularly important to intervene in the early stage of CKD(stages 1–3).Unfortunately,the effective drug treatment methods...Introduction:With the incidence of chronic kidney disease(CKD)increasing year by year,it is particularly important to intervene in the early stage of CKD(stages 1–3).Unfortunately,the effective drug treatment methods for CKD(stages 1–3)are lacking.Guben Tongluo Formula(GTF)is the experience formula of Professor Liqun He,a famous traditional Chinese medicine(TCM)doctor in Shanghai.Our previous studies demonstrated that GTF might effectively alleviate CKD via multi-mechanisms.As the first angiotensin-2 receptor antagonist for treating hypertension,losartan potassium(LP)could effectively reduce blood pressure,decrease cardiovascular risk,and delay the occurrence of end-stage renal disease.Thus,we design this clinical protocol of GTF combining LP to observe the efficacy and safety of GTF and try to provide a novel drug treatment method for treating CKD(stages 1–3)patients.Methods and analysis:This is a multicenter randomized controlled clinical trial.160 participants will be enrolled in this trial and divided into LP group,GTF group,LP+GTF group,and placebo group randomly assigning 1:1:1:1 principle.LP group will receive general treatments combining LP,GTF group will receive general treatments combining GTF,and the GTF+LP group will receive general treatments combining GTF and LP.Placebo group will receive general treatments combining placebo treatment.The primary evaluation index will be the change of serum creatinine after treatment.Secondary evaluation indexes include changes in blood urea nitrogen,serum uric acid,estimated glomerular filtration rate,etc.;immune indicators and renal fibrosis indicators,as well as TCM symptoms.Besides,vital sign indicators and adverse events will be closely observed.Ethics and dissemination:The protocol has been approved by the Ethics Committee of Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine(reference number:2024-7th-HIRB-094)and other ethics committees at each center.With the implementation of this clinical trial,it would offer a TCM formula for the treatment of CKD(stages 1–3)and clarify the underlying mechanism of GTF for alleviating CKD.Trial registration:This trial is registered with ChiCTR2400090125 and registered on September 24,2024.展开更多
Background:Guben Zhike decoction(GBZKD)is derived from the experience of Professor Enxiang Chao,an esteemed master of Chinese medicine,while treating chronic obstructive pulmonary disease(COPD).GBZKD reinforces the he...Background:Guben Zhike decoction(GBZKD)is derived from the experience of Professor Enxiang Chao,an esteemed master of Chinese medicine,while treating chronic obstructive pulmonary disease(COPD).GBZKD reinforces the healthy qi and consolidates defensive qi.This study explored the efficacy and potential mechanism of action of GBZKD in a COPD mouse model using proteomics.Methods:A COPD mouse model was established through cigarette smoke exposure and intranasal lipopolysaccharide administration.The model was verified through lung function test and lung histopathological observation.Label-free quantitative proteomics was used to detect the lung tissue proteins of mice from the GBZKD,COPD,and control groups.Results:GBZKD markedly improved the lung function and associated pathological conditions in the COPD mouse model.Proteomic analysis identified 4316 proteins,of which 3696 were quantitative proteins.We highlighted 287 and 184 proteins with significant regulatory roles in the lung tissues of COPD mice and GBZKD-treated mice,respectively.These proteins participated in multiple functions,including complement/coagulation cascade,immune response,and metabolic pathways.Conclusion:GBZKD exhibits multitarget and multipathway therapeutic effects in a COPD mouse model.展开更多
Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine prote...Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.展开更多
Objective:To observe the effect of tetradecylene naphthalene soft capsule combined with Yishen Gubenyutong Decoction on bone metabolism and bone turnover in patients with osteoporosis and its clinical efficacy.Methods...Objective:To observe the effect of tetradecylene naphthalene soft capsule combined with Yishen Gubenyutong Decoction on bone metabolism and bone turnover in patients with osteoporosis and its clinical efficacy.Methods:A total of 100 patients with primary osteoporosis(all were treated by our hospital from February 2017 to June 2018)were divided into two groups.The control group(50 cases)was given to menatetrenone capsules.Treatment,observation group(50 cases)combined with Yishen Gubenqiaotongtong on the basis of the treatment of the control group,6 months for a course of treatment.The bone metabolic markers,bone mineral density changes and clinical efficacy were measured before and after treatment.Results:The total effective rate of the observation group was higher than that of the control group.After treatment,the observation group showed serum calcium(Ca),serum alkaline phosphatase(ALP)and typeⅠcollagen.The level of cross-linked C-terminal peptide(CTX-1)was lower than that of the control group.After treatment,the osteocalcin(OC)in the observation group was higher than that in the control group,and the bone mineral density(BMD)of lumbar vertebrae L2-4,femoral neck and femur trochanter in the observation group were higher than those in the control group.Conclusion:Menatetrenone soft capsule combined with Yishen Gubenyutong Decoction has good clinical effect on osteoporosis patients and it is worth further promotion in clinic.展开更多
Objective:To investigate the mechanism of Renshen Guben oral liquid(RSGB)enhancing immune function.Materials and Methods:Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of...Objective:To investigate the mechanism of Renshen Guben oral liquid(RSGB)enhancing immune function.Materials and Methods:Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of immune regulation of RSGB.Results:A total of 112 active compounds of RSGB were found,and 501 targets were predicted.Furthermore,2974 immune targets were obtained from UniProt and NCBI Gene databases,and 111 common targets of RSGB and immunity were obtained.Among them,interleukin(IL)6,tumor necrosis factor,AKT1,VEGFA,STAT3,MAPK1,SRC,EGFR,IL1B,and PTGS2 might be the key targets for RSGB to improve immunity.ClueGO and Kyoto Encyclopedia of Genes and Genomes analysis showed that the immunoregulatory mechanism of RSGB may find a relation with the B cell receptor signaling pathway and T cell receptor signaling pathway.Furthermore,this study preliminarily explored the mechanism of RSGB improving menopausal syndrome,polycystic ovary syndrome,and cancer-related fatigue by enhancing immunity.Conclusions:RSGB can improve the body's immunity through multicomponent,multitarget,and multipathway.In addition,RSGB can also improve the immune capacity of the body to assist in the treatment of diseases,which has great potential as an immunomodulator.展开更多
Background:Even with long-term complete suppression of the virus through antiretroviral therapy(ART),people infected with HIV cannot attain optimal immune reconstitution.This phenomenon is called immune reconstitution...Background:Even with long-term complete suppression of the virus through antiretroviral therapy(ART),people infected with HIV cannot attain optimal immune reconstitution.This phenomenon is called immune reconstitution deficiency,there are no effective therapeutic interventions for immune reconstitution deficiency in modern medicine.Objective:To evaluate the efficacy and safety of ART with Shenling Guben Granules Traditional Chinese medicine in boosting immunological reconstitution compared with ART alone.Methods:This was a randomized,double-blind,placebo-controlled,multicenter clinical trial evaluating the efficacy and safety of ART combined with Chinese medicine.The individuals aged 18–65 years with poor immune reconstitution following ART were included in this trial.The primary outcome was a change in the absolute value of CD4^(+)T lymphocytes after 72 weeks of combined ART and Chinese medicine administration.Secondary outcomes included changes in CD4^(+)T lymphocyte functional subpopulations,activated T lymphocyte subpopulations,CD4^(+)T lymphocyte proliferation,and T lymphocyte apoptosis from baseline to after 72 weeks.We also evaluated efficacy at 24-and 48-week intervals to better understand the dynamics of the trial drug’s efficacy.Results:There was a significant increase in CD4^(+)cell counts in groups treated with the Shenling Guben Granules after 24,48,and 72 weeks of treatment(P<0.05),and the difference in CD4^(+)cell counts at 24 weeks of treatment was statistically significant(P=0.010).After 48 and 72 weeks of therapy,the CD4^(+)CD38^(+)cell counts in the Shenling Guben Granules group were significantly higher than in the control group(P<0.05).In the subgroup analysis of CD4^(+)cell counts≥200 cells/mm^(3),the CD4^(+)cell counts in the treatment group were higher than the control group after treatment for 24,48,and 72 weeks(P<0.05).Discussion:CD4 cell counts in HIV/AIDS patients with immunological reconstitution insufficiency can be improved to a certain extent using Shenling Guben Granules.The greater the CD4 cell count at the start,the better the therapy response.Furthermore,Shenling Guben Granules have the efficacy and safety to prevent aberrant immunological activation.A large sample size,long-term follow-up,and multiple efficacy indicators were employed to assess the therapy’s safety.Our findings will lead to new therapeutic alternatives for HIV/AIDS patients suffering from immune reconstitution deficiency.Clinical Trial Registry:Name of the registry:Sundy on promote the reconstruction of Inadequate responders in HIV/AIDS patients after combined antiretroviral therapy by Shen Ling Gu Ben Granules;Chictr.org.cn Identifier:ChiCTR1800015290,registered on March 21,2018(http://www.chictr.org.cn/registry.aspx).展开更多
基金supported by the Research Fund Project of the Education Department of Yunnan Province(No.2023Y0464)Research Project for Scientific Research Funds of Provincial Research Institutions in Heilongjiang Province(No.CZBZ2025ZR003).
文摘Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.
基金Supported by Traditional Chinese Medicine Science and Technology Development Plan of Jiangsu Province (No. MS2021013, ZD202215):Exploring the Efficacy and Mechanism of Professor Cao Shihong's Shenji Guben Decoction in Treating Chronic Obstructive Pulmonary Disease Based on Metabolomicsa Real-World Cohort Study on Traditional Chinese Medicine for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary DiseaseIntra-hospital Fund of Jiangsu Provincial Hospital of Traditional Chinese Medicine Development (No. Y2021ZR11):Investigating the Mechanism of Shenji Guben Decoction in Treating Chronic Obstructive Pulmonary Disease Based on Metabolomics
文摘OBJECTIVE:To investigate the mechanisms of the effect of Shenji Guben(SJGB)decoction(参吉固本方)on chronic obstructive pulmonary disease(COPD).METHODS:A murine model of COPD was established through lipopolysaccharide(LPS)nasal drops and passive smoke exposure,followed by evaluation of SJGB decoction efficacy via lung function tests and histological analysis.Non-targeted liquid chromatography-mass spectrometry(LC-MS)-based metabolomics was used to explore the mechanisms of SJGB decoction in COPD.RESULTS:We found that the SJGB decoction effectively reduced inflammatory cell infiltration in the airways and lungs,and improved lung function in the COPD model mice.LC-MS-based metabolomics identified 86 biomarkers in COPD models.Compared to the model group,SJGB decoction significantly altered 34 metabolites.Prostaglandin E2 and DL-Citrulline were highlighted as two representative differential metabolites.MetaboAnalyst 5.0 highlighted glycerophospholipid and riboflavin metabolisms as key pathways affected by SJGB decoction.CONCLUSION:This study evaluated the protective effect of SJGB decoction against COPD and provided insights into its potential mechanisms in COPD treatment.
基金supported by the National Natural Science Foundation of China(grant No.82405081)Guangdong Basic and Applied Basic Research Foundation(grant No.2025A1515011267)the National Postdoctoral Research Program(certificate number:GZC20230979)+4 种基金the China Postdoctoral Science Foundation(certificate numbers:2023TQ0135 and 2024M751136)Guangzhou Basic and Applied Basic Research(2025A04J3397)the Guangzhou Key Laboratory of Formula-Patterns of Traditional Chinese Medicine(No.202102010014)the Project of Administration of Traditional Chinese Medicine of Guangdong Province of China(No.20232179)the Fundamental Research Funds for the Central Universities(No.21624362).
文摘Background:Renshen Guben oral liquid(RGSB)has the ability to consolidate constitution,restore vitality,and delay the ageing process and the onset of geriatric diseases.RGSB also has potential therapeutic effects on intervertebral disc degeneration(IVDD).This study investigated the therapeutic effects of RGSB on IVDD and explored the underlying mechanisms.Methods:Single-cell sequencing and network pharmacology analyses were conducted in combination to determine the mechanisms of IVDD.Thirty-two C57BL/6J mice were randomly assigned to four groups:the sham operation group,IVDD group,Ibuprofen(IB)group,and RGSB group.All groups except for the sham operation group underwent needle puncture of the caudal IVDs.Behavioral tests,ELISA,PCR,TUNEL staining,and immunohistochemical staining were performed to investigate the therapeutic mechanisms associated with IVDD.Results:Bioinformatics analysis revealed that apoptosis is involved in the development of IVDD and that RSGB might alleviate IVDD by inhibiting apoptosis.After needle puncture,the mice exhibited from thermal allodynia,a decrease in disc height,an increase in the Pfirrmann grade,and destruction of IVDs.Surgery to induce IVDD increased the levels of Matrix Metalloproteinase-3(MMP3),Caspase-6,and Cyt-c in nucleus pulposus cells and the periphery;serum levels of interleukin-1β(IL‐1β)and TNF‐α;and the mRNA levels of IL-6,TNF-α,and IL-1β.Moreover,IVDD decreased the IL-10 mRNA level and the expression of Col-I and BCL2.RSGB reversed these changes.Conclusion:RSGB alleviated IVDD by relieving inflammation and apoptosis and alleviating neuroinflammation.
基金supported by grants from Pudong New Area Traditional Chinese Medicine Brand Multiplication Plan-Chronic Nephropathy(PDZY-2021-0302)Construction of He Liqun’s famous TCM studio(PDZY-2022-0703)+2 种基金Clinical Observation on the Efficacy of Guben Tongluo Formula in Treating Chronic Kidney Disease Phase 1-3(PW2022D-12)Pilot Project of Inheritance,Innovation and Development of Traditional Chinese Medicine in Pudong New Area(YC-2023-0602)Pudong New Area’s Peak and Plateau Discipline Development in Clinical Medicine for Novel and Special Diseases(2025-PWXZ-15).
文摘Introduction:With the incidence of chronic kidney disease(CKD)increasing year by year,it is particularly important to intervene in the early stage of CKD(stages 1–3).Unfortunately,the effective drug treatment methods for CKD(stages 1–3)are lacking.Guben Tongluo Formula(GTF)is the experience formula of Professor Liqun He,a famous traditional Chinese medicine(TCM)doctor in Shanghai.Our previous studies demonstrated that GTF might effectively alleviate CKD via multi-mechanisms.As the first angiotensin-2 receptor antagonist for treating hypertension,losartan potassium(LP)could effectively reduce blood pressure,decrease cardiovascular risk,and delay the occurrence of end-stage renal disease.Thus,we design this clinical protocol of GTF combining LP to observe the efficacy and safety of GTF and try to provide a novel drug treatment method for treating CKD(stages 1–3)patients.Methods and analysis:This is a multicenter randomized controlled clinical trial.160 participants will be enrolled in this trial and divided into LP group,GTF group,LP+GTF group,and placebo group randomly assigning 1:1:1:1 principle.LP group will receive general treatments combining LP,GTF group will receive general treatments combining GTF,and the GTF+LP group will receive general treatments combining GTF and LP.Placebo group will receive general treatments combining placebo treatment.The primary evaluation index will be the change of serum creatinine after treatment.Secondary evaluation indexes include changes in blood urea nitrogen,serum uric acid,estimated glomerular filtration rate,etc.;immune indicators and renal fibrosis indicators,as well as TCM symptoms.Besides,vital sign indicators and adverse events will be closely observed.Ethics and dissemination:The protocol has been approved by the Ethics Committee of Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine(reference number:2024-7th-HIRB-094)and other ethics committees at each center.With the implementation of this clinical trial,it would offer a TCM formula for the treatment of CKD(stages 1–3)and clarify the underlying mechanism of GTF for alleviating CKD.Trial registration:This trial is registered with ChiCTR2400090125 and registered on September 24,2024.
基金This study was supported by the National Natural Science Foundation of China(82074367).
文摘Background:Guben Zhike decoction(GBZKD)is derived from the experience of Professor Enxiang Chao,an esteemed master of Chinese medicine,while treating chronic obstructive pulmonary disease(COPD).GBZKD reinforces the healthy qi and consolidates defensive qi.This study explored the efficacy and potential mechanism of action of GBZKD in a COPD mouse model using proteomics.Methods:A COPD mouse model was established through cigarette smoke exposure and intranasal lipopolysaccharide administration.The model was verified through lung function test and lung histopathological observation.Label-free quantitative proteomics was used to detect the lung tissue proteins of mice from the GBZKD,COPD,and control groups.Results:GBZKD markedly improved the lung function and associated pathological conditions in the COPD mouse model.Proteomic analysis identified 4316 proteins,of which 3696 were quantitative proteins.We highlighted 287 and 184 proteins with significant regulatory roles in the lung tissues of COPD mice and GBZKD-treated mice,respectively.These proteins participated in multiple functions,including complement/coagulation cascade,immune response,and metabolic pathways.Conclusion:GBZKD exhibits multitarget and multipathway therapeutic effects in a COPD mouse model.
基金supported by the National Natural Science Foundation of China(No.81904124)the Scientific Project of Shanghai Sanitation and Health Committee(No.20204Y0191)the projects of Shanghai Science and Technology Commission(No.22Y31920200).
文摘Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.
基金Scientific Research Project of Guangdong Traditional Chinese Medicine Bureau(20191292).
文摘Objective:To observe the effect of tetradecylene naphthalene soft capsule combined with Yishen Gubenyutong Decoction on bone metabolism and bone turnover in patients with osteoporosis and its clinical efficacy.Methods:A total of 100 patients with primary osteoporosis(all were treated by our hospital from February 2017 to June 2018)were divided into two groups.The control group(50 cases)was given to menatetrenone capsules.Treatment,observation group(50 cases)combined with Yishen Gubenqiaotongtong on the basis of the treatment of the control group,6 months for a course of treatment.The bone metabolic markers,bone mineral density changes and clinical efficacy were measured before and after treatment.Results:The total effective rate of the observation group was higher than that of the control group.After treatment,the observation group showed serum calcium(Ca),serum alkaline phosphatase(ALP)and typeⅠcollagen.The level of cross-linked C-terminal peptide(CTX-1)was lower than that of the control group.After treatment,the osteocalcin(OC)in the observation group was higher than that in the control group,and the bone mineral density(BMD)of lumbar vertebrae L2-4,femoral neck and femur trochanter in the observation group were higher than those in the control group.Conclusion:Menatetrenone soft capsule combined with Yishen Gubenyutong Decoction has good clinical effect on osteoporosis patients and it is worth further promotion in clinic.
基金the National Nature Science Foundation of China(No.81673829)。
文摘Objective:To investigate the mechanism of Renshen Guben oral liquid(RSGB)enhancing immune function.Materials and Methods:Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of immune regulation of RSGB.Results:A total of 112 active compounds of RSGB were found,and 501 targets were predicted.Furthermore,2974 immune targets were obtained from UniProt and NCBI Gene databases,and 111 common targets of RSGB and immunity were obtained.Among them,interleukin(IL)6,tumor necrosis factor,AKT1,VEGFA,STAT3,MAPK1,SRC,EGFR,IL1B,and PTGS2 might be the key targets for RSGB to improve immunity.ClueGO and Kyoto Encyclopedia of Genes and Genomes analysis showed that the immunoregulatory mechanism of RSGB may find a relation with the B cell receptor signaling pathway and T cell receptor signaling pathway.Furthermore,this study preliminarily explored the mechanism of RSGB improving menopausal syndrome,polycystic ovary syndrome,and cancer-related fatigue by enhancing immunity.Conclusions:RSGB can improve the body's immunity through multicomponent,multitarget,and multipathway.In addition,RSGB can also improve the immune capacity of the body to assist in the treatment of diseases,which has great potential as an immunomodulator.
基金Supported by the State Major Science&Technology Specific Projects(2017ZX10205501)National Nature Science Foundation of China(82174221).
文摘Background:Even with long-term complete suppression of the virus through antiretroviral therapy(ART),people infected with HIV cannot attain optimal immune reconstitution.This phenomenon is called immune reconstitution deficiency,there are no effective therapeutic interventions for immune reconstitution deficiency in modern medicine.Objective:To evaluate the efficacy and safety of ART with Shenling Guben Granules Traditional Chinese medicine in boosting immunological reconstitution compared with ART alone.Methods:This was a randomized,double-blind,placebo-controlled,multicenter clinical trial evaluating the efficacy and safety of ART combined with Chinese medicine.The individuals aged 18–65 years with poor immune reconstitution following ART were included in this trial.The primary outcome was a change in the absolute value of CD4^(+)T lymphocytes after 72 weeks of combined ART and Chinese medicine administration.Secondary outcomes included changes in CD4^(+)T lymphocyte functional subpopulations,activated T lymphocyte subpopulations,CD4^(+)T lymphocyte proliferation,and T lymphocyte apoptosis from baseline to after 72 weeks.We also evaluated efficacy at 24-and 48-week intervals to better understand the dynamics of the trial drug’s efficacy.Results:There was a significant increase in CD4^(+)cell counts in groups treated with the Shenling Guben Granules after 24,48,and 72 weeks of treatment(P<0.05),and the difference in CD4^(+)cell counts at 24 weeks of treatment was statistically significant(P=0.010).After 48 and 72 weeks of therapy,the CD4^(+)CD38^(+)cell counts in the Shenling Guben Granules group were significantly higher than in the control group(P<0.05).In the subgroup analysis of CD4^(+)cell counts≥200 cells/mm^(3),the CD4^(+)cell counts in the treatment group were higher than the control group after treatment for 24,48,and 72 weeks(P<0.05).Discussion:CD4 cell counts in HIV/AIDS patients with immunological reconstitution insufficiency can be improved to a certain extent using Shenling Guben Granules.The greater the CD4 cell count at the start,the better the therapy response.Furthermore,Shenling Guben Granules have the efficacy and safety to prevent aberrant immunological activation.A large sample size,long-term follow-up,and multiple efficacy indicators were employed to assess the therapy’s safety.Our findings will lead to new therapeutic alternatives for HIV/AIDS patients suffering from immune reconstitution deficiency.Clinical Trial Registry:Name of the registry:Sundy on promote the reconstruction of Inadequate responders in HIV/AIDS patients after combined antiretroviral therapy by Shen Ling Gu Ben Granules;Chictr.org.cn Identifier:ChiCTR1800015290,registered on March 21,2018(http://www.chictr.org.cn/registry.aspx).
