OBJECTIVE:To study the effect of Bushen Jiangzhi formula(BSJZF)on atherosclerosis(AS)in apolipoprotein E knockout(apoE^-/-)mice and the underlying mechanism.METHODS:We used a high fat diet to induce AS in apoE^-/- mic...OBJECTIVE:To study the effect of Bushen Jiangzhi formula(BSJZF)on atherosclerosis(AS)in apolipoprotein E knockout(apoE^-/-)mice and the underlying mechanism.METHODS:We used a high fat diet to induce AS in apoE^-/- mice.The mice were randomly divided into four groups:model,BSJZF,atorvastatin,and 3-methyladenine groups.Syngeneic C57BL/6 mice of the same age were used for the control group.Autophagosomes in the aorta were examined by transmission electron microscopy.Morphology,lipid accumulation,and collagen deposition in the aorta were examined by hematoxylin and eosin,Oil Red O,and Masson's staining,respectively.Serum levels of tumor necrosis factor alpha(TNF-α),interferon gamma(IFN-γ),and interleukin 10(IL-10)were measured by enzyme-linked immunoassays.Protein expression of microtubule-associated protein light chain 3(LC3),Beclin 1,and p62 in the aorta were examined by Western blot analyses.RESULTS:ApoE^-/- mice fed a high fat diet exhibited AS symptoms including less autophagosomes in the aorta,higher serum levels of TNF-α,IFN-γ,and p62,and lower serum levels of IL-10,LC3,and Beclin 1.Treatment with BSJZF significantly reduced the area of the aortic plaque,decreased expression of TNF-α,IFN-γ,and p62,and increased expression of IL-10,LC3,and Beclin 1.CONCLUSION:Our findings suggest that BSJZF promotes autophagy and reduces inflammation by regulating the expression of autophagy-related proteins LC3,Beclin 1,and p62,thereby effectively treating AS.展开更多
OBJECTIVES:To analyze the distribution characteristics of Traditional Chinese Medicine(TCM)syndromes in patients with oxaliplatin-induced peripheral neuropathy(OIPN)and observe the clinical efficacy of Bushen Yiqi for...OBJECTIVES:To analyze the distribution characteristics of Traditional Chinese Medicine(TCM)syndromes in patients with oxaliplatin-induced peripheral neuropathy(OIPN)and observe the clinical efficacy of Bushen Yiqi formula(补肾益气方,BSYQF)in treating patients with OIPN.METHODS:A total of 89 patients with OIPN were enrolled in this study.The TCM syndrome characteristics were investigated by frequency analysis methodology after collecting and analyzing the TCM syndrome elements of the patients with the OIPN TCM syndrome element scale.Further,62 cases of cold-dampness obstruction syndrome and kidney-Qi deficiency and cold syndrome were selected and randomly divided into the control group(n=31)and the treatment group(n=31).The patients in the treatment group were treated with modified BSYQF,while those in the control group were treated with mecobalamin tablets for 3 weeks.The Levi sensory neurotoxicity score and the neuro-electrophysiological changes were observed before and after the treatment in both groups.RESULTS:The distribution of TCM syndrome types in 89 patients with OIPN were in order of kidney-Qi deficiency and cold syndrome(44 cases),cold-dampness obstruction syndrome(18 cases),Yin deficiency of liver and kidney syndrome(11 cases),blood stasis obstruction syndrome(7 cases),and dampness-heat obstruction syndrome(5 cases).Improvement in Levi sensory neurotoxicity score:After 3-week treatment,the total effective rate in the treatment group was higher than that in the control group(P<0.05).The subgroup analysis showed that the total effective rate in the treatment group of patients with kidney-Qi deficiency and cold syndrome was higher than that in the control group before and after treatment(P<0.05).Improvement in nerve conduction velocity:The sensory nerve conduction velocity of bilateral ulnar nerves improved in the control group after treatment compared with that before treatment(P<0.05).The sensory and motor nerve conduction velocities of the bilateral ulnar and bilateral peroneal nerves improved in the treatment group compared with those before treatment and after treatment in the control group(P<0.05).CONCLUSIONS:The modified BSYQF had a definite therapeutic effect on the OIPN in patients with kidney-Qi deficiency and cold syndrome and those with cold-dampness obstruction syndrome.It could effectively reduce the grade of peripheral nerve toxicity and improve nerve conduction velocity,and its curative effect was better than that of mecobalamin tablets.展开更多
Objective: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice....Objective: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice. Methods: Forty ICR mice were randomized into the normal control group, model group, Nimotop group and Chinese medicine group, 10 mice in each group. Tail intravenous injection of alloxan was applied to prepare diabetic model. Four weeks later, intragastric administration of Bushen Huoxue Formula for the Chinese medicine group, Nimotop for the Nimotop group, and isometric distilled water for the other two groups were respectively given for 8 weeks. The changes in the blood sugar level were observed; the learning and memory function was detected by Morris labyrinth test; and the contents of norepinephrine (NE), dopamine (DA), 5-hydroxyltryptamine (5-HT) and 5-hydroxyl indole acetic acid (5-HIAA) in cerebral cortex were determined in mice of all the groups. Results: The blood sugar levels in the diabetic model mice significantly increased as compared with those of the normal control group determined 72 h and 12 weeks later (P<0.05 or P<0.01). Latencies for Morris labyrinth test in the Nimotop group and the Chinese medicine group were significantly shortened as compared with that in the model group (P<0.01). The contents of cortical NE in the Chinese medicine group was significantly higher than that in the model group (P<0.01). Conclusion: Bushen Huoxue Formula can improve the learning and memory function in the diabetic mice, and the mechanism is possibly related with change of the cortical NE content.展开更多
OBJECTIVE:To investigate the effect of Bushen Jianpi formula(BSJP)therapy on survival of the patients with moderate and advanced hepatocellular carcinoma(HCC).METHODS:This was a five-year retrospective study,enrolling...OBJECTIVE:To investigate the effect of Bushen Jianpi formula(BSJP)therapy on survival of the patients with moderate and advanced hepatocellular carcinoma(HCC).METHODS:This was a five-year retrospective study,enrolling 209 adult patients with moderate and advanced HCC patients.Log-rank test,Cox regression analysis and Kaplan-Meier analysis was applied to analyze the data.RESULTS:The outcome of single-factor Kaplan-Meier analysis and Log-rank test showed that stage of Barcelona-clinic liver cancer(BCLC),locoregional therapy and BSJP therapy were three factors that dominantly influenced the survival of moderate and advanced HCC patients(P<0.05).In Cox multiple-factor regression analysis,lower BCLC staging(RR=2.016;P=0.000),locoregional therapy(RR=0.611;P=0.011)and BSJP therapy(RR=0.684;P=0.044)were the independent protective factors affecting survival of patients,and BSJP exerted a more significant effect on patients at BCLC-C stage(RR=0.513;P=0.002).CONCLUSION:BSJP therapy and locoregional therapy both contributed to prolonged survival for moderate and advanced HCC patients.展开更多
OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focus...OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focuses on the etiology and pathogenesis of AD for treating both cause and symptoms.In this research,the pharmacodynamic study protocol of Bushen Yizhi formula was designed according to the characteristics and indications function of herbs in the formula,and was conformed to preclinical pharmacological research of traditional Chinese medicine for AD,The Technical Requirements of Pharmacology and Toxicology Research in New Drug Development Enacted by State Food and Drug administration also was guiding principle.METHODS A preliminary randomized double-blind clinical trail with 141 cases of AD showed that the efficiency of Bushen Yizhi formula was 61.9%and the increased mean of MMSE was 3.17,but the specific mechanism remains unclear.This study was aimed to reveal the preventive and therapeutic effect of Bushen Yizhi formula on AD rats and its related mechanism.In this research,forebrain-injected IBO-induced AD rats(cholinergic neuron lesion),senescence accelerated mouse,scopolamineinduced learning and memory deficiency rats(mild cognitive impairment)were all established.The learning and memory ability was tested with Morris water maze.Then formation of age pigment,extent of neuronal loss,activation of astrocytes,content of NTFs and degree of oxidized stress damage were determined by morphology,mmunohistochemical and molecular biology methods.RESULTS As the application of Bushen Yizhi formula,the learning and memory ability in all three groups were significantly improved,the formation of age pigment and the content of ACH in cortex and hippocampus were reduced,the activation of astrocytes and release of inflammatory factor(TNF-αand IL-1β)were inhibited,and the antioxidases(CAT,SOD,GSH-PX)were up-regulated and MDA was down-regulated.CONCLUSION Bushen Yizhi formula can prevent and treat AD rats,which might be achieved by anti-inflammatory,antioxidant and protecting cholinergic neuron.展开更多
While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amylo...While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.展开更多
Objective:To investigate the effect of Qihuang Bushen Xiezhuo Formula on the expression of the nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway of human glomerular mesangial ...Objective:To investigate the effect of Qihuang Bushen Xiezhuo Formula on the expression of the nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway of human glomerular mesangial cells(HMC)in high glucose medium and its protective effect on oxidative stress.Methods:The HMC were cultured in vitro to prepare normal rat serum.The rats were intragastrically administered with irbesartan and Qihuang Bushen Xiezhuo Formula.The serum containing the drugs was prepared after the blood concentration was reached.The rats were divided into the control group,the high glucose group,the irbesartan group and the Qihuang Bushen Xiezhuo Formula group.The HMC of the control group was cultured with normal rat serum(10%serum concentration)medium,while that of the high glucose group was cultured with high glucose medium of rat serum(10%serum concentration).The irbesartan group and the Qihuang Bushen Xiezhuo Formula group were respectively treated with 10%irbesartan and 10%Qihuang Bushen Xiezhuo Formula in serum high glucose medium.After 48 h of culture,the relevant indicators were collected and detected.The mRNA expression levels of Nrf2,gamma-glutamylcysteine synthetase(γ-GCS)and superoxide dismutase(SOD)in each group were detected by real-time PCR.The expressions ofγ-GCS and SOD were detected by immunohistochemistry.The protein expressions ofγ-GCS and SOD in HMC of each group were observed by Western Blot.Results:The expressions of Nrf2,γ-GCS,SOD mRNA and protein in experimental cells of each group were low in the control group,while those in the high glucose group were decreased as compared with the control group(P<0.05).After interference of irbesartan and Qihuang Bushen Xiezhuo Formula the expressions were increased,and the increase in Qihuang Bushen Xiezhuo Formula group was more significant(P<0.05).Conclusion:Qihuang Bushen Xiezhuo Formula can improve HMC oxidative stress injury in high glucose culture,and its mechanism may be achieved by activating Nrf2 and its related downstream proteinsγ-GCS and SOD.展开更多
Objective:To study the effective compound action target signal pathway of Peiyuan bushenan taifang(PYBSATF)has achieved good clinical efficacy in the treatment of recurrent spontaneous abortion(RSA),but its mechanism ...Objective:To study the effective compound action target signal pathway of Peiyuan bushenan taifang(PYBSATF)has achieved good clinical efficacy in the treatment of recurrent spontaneous abortion(RSA),but its mechanism has not been clarified because of its complex components.In this study,network pharmacology is applied to study the effective compounds,targets and signal pathways of PYBSATF in the treatment of RSA,so as to reveal its pharmacological mechanism of action in the treatment of recurrent spontaneous abortion.Methods:The Traditional Chinese Medicine Systems Pharmacology database(TCMSP)and CNKI are used to obtain the main compounds and drug action targets of PYBSATF.Genecards and the Online Mendelian Inheritance of Man databases(OMIM)are searched to collect the known genes related to RSA,so as to construct compound-target network and screen out the common target proteins and main active compounds.We also use string database to construct a visual protein-protein interaction network(PPI).Cluster Profiler and R software were used to analyze the common targets of drugs and diseases for GO function analysis and KEGG pathway enrichment analysis.Finally,the compound and the protein sequences were conducted according to the node parameters,so that the core protein and core compounds are used to perform molecular docking.Results:186 potential active components and 65 predicted action targets of PYBSATF were screened out.At the same time,1658 genes were also screened out to be closely related to RSA,among which 65genes overlaped with PYBSATF targets and were considered to be related to way of treatment.PPI network showed that VEGFA,IL6,EGFR,MAPK8 and ESR1were the core targets of PYBSATF for the treatment of RSA.GO and KEGG enrichment analysis obtained 93 biological processes of cells(P<0.01)and 87 signaling pathways(P<0.01).PYBSATF played a pharmacological role through a variety of pathways including anti-inflammatory,anti-apoptosis,promoting proliferation and angiogenesis.Molecular docking showed that most active components and key targets of PYBSATF had strong efficiency.Conclusion:Through the study of network pharmacology,it predicted that PYBSATF might treat RSA through multiple targets and multiple signal pathways.Significantly,the predictive targets may be potential targets for treatment of RSA.展开更多
When gene expression profile is used for gene detection,the probe on the chip can emit fluorescence with different wavelengths.Under the action of confocal laser scanner,a clear gene change image can be obtained,by wh...When gene expression profile is used for gene detection,the probe on the chip can emit fluorescence with different wavelengths.Under the action of confocal laser scanner,a clear gene change image can be obtained,by which the gene changes of the sample to be tested can be observed directly.First,the knee osteoarthritis(KOA)models of mice are established by the method of collateral ligament and meniscus resection(MLI-OA).Then,Bushen Huoxue formula is given by gavage,and ribonucleic acid(RNA)is routinely extracted and purified.Finally,the gene expression changes of KOA tissues of mice are detected by Agilent SurePrint G3 Mouse GE V2.0 gene expression profile.The results show that Bushen Huoxue formula has significant regulation effect on gene expression of KOA tissue.Among the genes with significant up-regulation effect of Bushen Huoxue formula,there are 56 genes of traditional Chinese medicine(TCM)groups up-regulated more than twice compared with model groups.Among the genes with significant down-regulation effect,there are 119 genes of TCM groups down-regulated more than twice compared with model groups.The experimental results indicate that Bushen Huoxue formula may promote the metabolism of arthritic factors and delay cartilage degeneration to treat KOA by regulating genes that are currently unknown in the pathological process of KOA.展开更多
Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting ...Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCMv2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidateBZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-kB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.展开更多
Background The side effects of chemotherapy-induced nausea and vomiting(CINV)and myelosuppression reduce the cancer patients’adherence to chemotherapy.Many Chinese patients choose Chinese medicine(CM)during chemother...Background The side effects of chemotherapy-induced nausea and vomiting(CINV)and myelosuppression reduce the cancer patients’adherence to chemotherapy.Many Chinese patients choose Chinese medicine(CM)during chemotherapy to reduce side effects;however,the evidence is lacking.The efficacy of a CM herbal treatment protocol,Jianpi Bushen Sequential Formula(健脾补肾续贯方,JBSF)will be evaluated on chemotherapy completion rate among patients with colon cancer.Methods A multi-center double-blind randomized controlled trial(RCT)will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine(CAPEOX).Patients will be randomized 1:1 to receive the JBSF or placebo formula.The primary outcome is the overall chemotherapy completion rate.The secondary outcomes include individual chemotherapy completion rate,4-cycle completion rate of chemotherapy,time to treatment failure,relative dose intensity and treatment toxicity.Follow-up visits will be scheduled before every and after last chemotherapy.Discussion This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer.(Trial registration:Clinical Trials.gov,No.NCT03716518)。展开更多
Objective:To assess the efficacy and safety of Bushen Huoxue Formula(BSHXF)for the treatment of discogenic low-back pain(DLBP).Methods:This was a parallel,double-blind,randomized,clinical trial performed between May 2...Objective:To assess the efficacy and safety of Bushen Huoxue Formula(BSHXF)for the treatment of discogenic low-back pain(DLBP).Methods:This was a parallel,double-blind,randomized,clinical trial performed between May 2019 and June 2020.Seventy patients were assigned by computerized random number table to the treatment group(lumbar traction and BSHXF,35 cases)or the control group(lumbar traction and placebo,35 cases).The patients received intervention for 3 weeks.Assessment was conducted before treatment and at week 1,2,3 during treatment.Primary outcome was the self-reported score of Oswestry Disability Index(ODI).Secondary outcomes included Visual Analog Scale(VAS),clinical efficacy rate by minimal clinically important difference(MCID)as well as lumbar tenderness,muscle tone and lumbar spine mobility.Adverse reactions were recorded.Follow-up was performed at 1 and 3 months after the end of treatment.Results:In the treatment group,ODI score was significantly decreased compared with baseline(P<0.05)and the control group at 2-and 3-week treatment.Similarly,VAS score decreased compared with the baseline(P<0.05)and was lower than that in the control group at 2-and 3-week treatment(P<0.05).The clinical efficacy rate of the treatment group was higher than that of the control group after treatment[32.35%(11/34)vs.3.13%(1/32),P<0.05].Moreover,the tenderness,and muscle tone,as well as the back extension and left flexion in lumbar spine mobility in the treatment group at 3-week treatment were significantly improved compared with the control group(P<0.05).Follow-up showed that at 1-month after treatment,the treatment group had better outcomes than the control group with regard to a total score of ODI and VAS scores,as well as clinical efficacy rate(all P<0.05).Moreover,VAS score was still significantly lower than the control group at 3-month follow-up(P<0.05).No adverse reactions were reported during the study.Conclusion:BSXHF combined with lumbar traction can significantly improve the clinical symptoms including pain intensity,functionality,muscle tone,and lumbar spine mobility in DLBP patients.(Registration No.Chi CTR1900027777).展开更多
基金grants from the National Natural Science Foundation of China(Bushen Jiangzhi formula Protects Against Atherosclerosis via miR-27a-mediated PCSK9/ABCA1 Pathway,No.81873348)National Traditional Chinese Medicine Innovation Talent Training Project[Letter(2019)No.128]Shanghai Health and Family Planning Commission Fund(Effect of Bushen Jiangzhi Formula Intervention on the Atherosclerosis in ApoE^-/-knockout Mice Based on mTOR signaling pathway of Autophagy System,No.201640217)。
文摘OBJECTIVE:To study the effect of Bushen Jiangzhi formula(BSJZF)on atherosclerosis(AS)in apolipoprotein E knockout(apoE^-/-)mice and the underlying mechanism.METHODS:We used a high fat diet to induce AS in apoE^-/- mice.The mice were randomly divided into four groups:model,BSJZF,atorvastatin,and 3-methyladenine groups.Syngeneic C57BL/6 mice of the same age were used for the control group.Autophagosomes in the aorta were examined by transmission electron microscopy.Morphology,lipid accumulation,and collagen deposition in the aorta were examined by hematoxylin and eosin,Oil Red O,and Masson's staining,respectively.Serum levels of tumor necrosis factor alpha(TNF-α),interferon gamma(IFN-γ),and interleukin 10(IL-10)were measured by enzyme-linked immunoassays.Protein expression of microtubule-associated protein light chain 3(LC3),Beclin 1,and p62 in the aorta were examined by Western blot analyses.RESULTS:ApoE^-/- mice fed a high fat diet exhibited AS symptoms including less autophagosomes in the aorta,higher serum levels of TNF-α,IFN-γ,and p62,and lower serum levels of IL-10,LC3,and Beclin 1.Treatment with BSJZF significantly reduced the area of the aortic plaque,decreased expression of TNF-α,IFN-γ,and p62,and increased expression of IL-10,LC3,and Beclin 1.CONCLUSION:Our findings suggest that BSJZF promotes autophagy and reduces inflammation by regulating the expression of autophagy-related proteins LC3,Beclin 1,and p62,thereby effectively treating AS.
基金the Innovative Research Team of High-Level Local University in Shanghaithe Discipline Construction and Talent Training Project in Qingpu District of Shanghai:the Fourth Round of Key Discipline Construction in Qingpu District (No.WZ2019-04)+1 种基金the Fourth Round of Discipline Leader Training Plan in Qingpu District (WD2019-17/39 and WT-2019-02)the Project of Qingpu District Science and Technology Committee:Study on the Mechanism of Icariin Regulating GR in the Treatment of OIPN (No.QKY2020-34)
文摘OBJECTIVES:To analyze the distribution characteristics of Traditional Chinese Medicine(TCM)syndromes in patients with oxaliplatin-induced peripheral neuropathy(OIPN)and observe the clinical efficacy of Bushen Yiqi formula(补肾益气方,BSYQF)in treating patients with OIPN.METHODS:A total of 89 patients with OIPN were enrolled in this study.The TCM syndrome characteristics were investigated by frequency analysis methodology after collecting and analyzing the TCM syndrome elements of the patients with the OIPN TCM syndrome element scale.Further,62 cases of cold-dampness obstruction syndrome and kidney-Qi deficiency and cold syndrome were selected and randomly divided into the control group(n=31)and the treatment group(n=31).The patients in the treatment group were treated with modified BSYQF,while those in the control group were treated with mecobalamin tablets for 3 weeks.The Levi sensory neurotoxicity score and the neuro-electrophysiological changes were observed before and after the treatment in both groups.RESULTS:The distribution of TCM syndrome types in 89 patients with OIPN were in order of kidney-Qi deficiency and cold syndrome(44 cases),cold-dampness obstruction syndrome(18 cases),Yin deficiency of liver and kidney syndrome(11 cases),blood stasis obstruction syndrome(7 cases),and dampness-heat obstruction syndrome(5 cases).Improvement in Levi sensory neurotoxicity score:After 3-week treatment,the total effective rate in the treatment group was higher than that in the control group(P<0.05).The subgroup analysis showed that the total effective rate in the treatment group of patients with kidney-Qi deficiency and cold syndrome was higher than that in the control group before and after treatment(P<0.05).Improvement in nerve conduction velocity:The sensory nerve conduction velocity of bilateral ulnar nerves improved in the control group after treatment compared with that before treatment(P<0.05).The sensory and motor nerve conduction velocities of the bilateral ulnar and bilateral peroneal nerves improved in the treatment group compared with those before treatment and after treatment in the control group(P<0.05).CONCLUSIONS:The modified BSYQF had a definite therapeutic effect on the OIPN in patients with kidney-Qi deficiency and cold syndrome and those with cold-dampness obstruction syndrome.It could effectively reduce the grade of peripheral nerve toxicity and improve nerve conduction velocity,and its curative effect was better than that of mecobalamin tablets.
基金supported by the Foundation of Peking Union Medical College Hospital, China (XH-020042)
文摘Objective: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice. Methods: Forty ICR mice were randomized into the normal control group, model group, Nimotop group and Chinese medicine group, 10 mice in each group. Tail intravenous injection of alloxan was applied to prepare diabetic model. Four weeks later, intragastric administration of Bushen Huoxue Formula for the Chinese medicine group, Nimotop for the Nimotop group, and isometric distilled water for the other two groups were respectively given for 8 weeks. The changes in the blood sugar level were observed; the learning and memory function was detected by Morris labyrinth test; and the contents of norepinephrine (NE), dopamine (DA), 5-hydroxyltryptamine (5-HT) and 5-hydroxyl indole acetic acid (5-HIAA) in cerebral cortex were determined in mice of all the groups. Results: The blood sugar levels in the diabetic model mice significantly increased as compared with those of the normal control group determined 72 h and 12 weeks later (P<0.05 or P<0.01). Latencies for Morris labyrinth test in the Nimotop group and the Chinese medicine group were significantly shortened as compared with that in the model group (P<0.01). The contents of cortical NE in the Chinese medicine group was significantly higher than that in the model group (P<0.01). Conclusion: Bushen Huoxue Formula can improve the learning and memory function in the diabetic mice, and the mechanism is possibly related with change of the cortical NE content.
基金the Action three years plan for Shanghai Chinese medicine industry(No.ZY3-LCPT-1-1001,ZY3-RCPY-3-1011)National Natural Science Foundation of China(No.81302891)。
文摘OBJECTIVE:To investigate the effect of Bushen Jianpi formula(BSJP)therapy on survival of the patients with moderate and advanced hepatocellular carcinoma(HCC).METHODS:This was a five-year retrospective study,enrolling 209 adult patients with moderate and advanced HCC patients.Log-rank test,Cox regression analysis and Kaplan-Meier analysis was applied to analyze the data.RESULTS:The outcome of single-factor Kaplan-Meier analysis and Log-rank test showed that stage of Barcelona-clinic liver cancer(BCLC),locoregional therapy and BSJP therapy were three factors that dominantly influenced the survival of moderate and advanced HCC patients(P<0.05).In Cox multiple-factor regression analysis,lower BCLC staging(RR=2.016;P=0.000),locoregional therapy(RR=0.611;P=0.011)and BSJP therapy(RR=0.684;P=0.044)were the independent protective factors affecting survival of patients,and BSJP exerted a more significant effect on patients at BCLC-C stage(RR=0.513;P=0.002).CONCLUSION:BSJP therapy and locoregional therapy both contributed to prolonged survival for moderate and advanced HCC patients.
基金The project supported by National Natural Science Foundation of China(81273817)Shandong Province Natural Science Foundation of China(ZR2013HL062)by Foundation of Overseas Distinguished Taishan Scholars of Shandong Province
文摘OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focuses on the etiology and pathogenesis of AD for treating both cause and symptoms.In this research,the pharmacodynamic study protocol of Bushen Yizhi formula was designed according to the characteristics and indications function of herbs in the formula,and was conformed to preclinical pharmacological research of traditional Chinese medicine for AD,The Technical Requirements of Pharmacology and Toxicology Research in New Drug Development Enacted by State Food and Drug administration also was guiding principle.METHODS A preliminary randomized double-blind clinical trail with 141 cases of AD showed that the efficiency of Bushen Yizhi formula was 61.9%and the increased mean of MMSE was 3.17,but the specific mechanism remains unclear.This study was aimed to reveal the preventive and therapeutic effect of Bushen Yizhi formula on AD rats and its related mechanism.In this research,forebrain-injected IBO-induced AD rats(cholinergic neuron lesion),senescence accelerated mouse,scopolamineinduced learning and memory deficiency rats(mild cognitive impairment)were all established.The learning and memory ability was tested with Morris water maze.Then formation of age pigment,extent of neuronal loss,activation of astrocytes,content of NTFs and degree of oxidized stress damage were determined by morphology,mmunohistochemical and molecular biology methods.RESULTS As the application of Bushen Yizhi formula,the learning and memory ability in all three groups were significantly improved,the formation of age pigment and the content of ACH in cortex and hippocampus were reduced,the activation of astrocytes and release of inflammatory factor(TNF-αand IL-1β)were inhibited,and the antioxidases(CAT,SOD,GSH-PX)were up-regulated and MDA was down-regulated.CONCLUSION Bushen Yizhi formula can prevent and treat AD rats,which might be achieved by anti-inflammatory,antioxidant and protecting cholinergic neuron.
基金supported by the National Natural Science Foundation of China[81904266,82004309].
文摘While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.
基金General Project of Natural Science Foundation of Heilongjiang Province(No.H2016066)Young Chinese Medicine Science and Technology Innovation Project of Heilongjiang Chinese Medicine Association(No.ZHY19-023)。
文摘Objective:To investigate the effect of Qihuang Bushen Xiezhuo Formula on the expression of the nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway of human glomerular mesangial cells(HMC)in high glucose medium and its protective effect on oxidative stress.Methods:The HMC were cultured in vitro to prepare normal rat serum.The rats were intragastrically administered with irbesartan and Qihuang Bushen Xiezhuo Formula.The serum containing the drugs was prepared after the blood concentration was reached.The rats were divided into the control group,the high glucose group,the irbesartan group and the Qihuang Bushen Xiezhuo Formula group.The HMC of the control group was cultured with normal rat serum(10%serum concentration)medium,while that of the high glucose group was cultured with high glucose medium of rat serum(10%serum concentration).The irbesartan group and the Qihuang Bushen Xiezhuo Formula group were respectively treated with 10%irbesartan and 10%Qihuang Bushen Xiezhuo Formula in serum high glucose medium.After 48 h of culture,the relevant indicators were collected and detected.The mRNA expression levels of Nrf2,gamma-glutamylcysteine synthetase(γ-GCS)and superoxide dismutase(SOD)in each group were detected by real-time PCR.The expressions ofγ-GCS and SOD were detected by immunohistochemistry.The protein expressions ofγ-GCS and SOD in HMC of each group were observed by Western Blot.Results:The expressions of Nrf2,γ-GCS,SOD mRNA and protein in experimental cells of each group were low in the control group,while those in the high glucose group were decreased as compared with the control group(P<0.05).After interference of irbesartan and Qihuang Bushen Xiezhuo Formula the expressions were increased,and the increase in Qihuang Bushen Xiezhuo Formula group was more significant(P<0.05).Conclusion:Qihuang Bushen Xiezhuo Formula can improve HMC oxidative stress injury in high glucose culture,and its mechanism may be achieved by activating Nrf2 and its related downstream proteinsγ-GCS and SOD.
基金National natural science foundation of China(No.81473721)。
文摘Objective:To study the effective compound action target signal pathway of Peiyuan bushenan taifang(PYBSATF)has achieved good clinical efficacy in the treatment of recurrent spontaneous abortion(RSA),but its mechanism has not been clarified because of its complex components.In this study,network pharmacology is applied to study the effective compounds,targets and signal pathways of PYBSATF in the treatment of RSA,so as to reveal its pharmacological mechanism of action in the treatment of recurrent spontaneous abortion.Methods:The Traditional Chinese Medicine Systems Pharmacology database(TCMSP)and CNKI are used to obtain the main compounds and drug action targets of PYBSATF.Genecards and the Online Mendelian Inheritance of Man databases(OMIM)are searched to collect the known genes related to RSA,so as to construct compound-target network and screen out the common target proteins and main active compounds.We also use string database to construct a visual protein-protein interaction network(PPI).Cluster Profiler and R software were used to analyze the common targets of drugs and diseases for GO function analysis and KEGG pathway enrichment analysis.Finally,the compound and the protein sequences were conducted according to the node parameters,so that the core protein and core compounds are used to perform molecular docking.Results:186 potential active components and 65 predicted action targets of PYBSATF were screened out.At the same time,1658 genes were also screened out to be closely related to RSA,among which 65genes overlaped with PYBSATF targets and were considered to be related to way of treatment.PPI network showed that VEGFA,IL6,EGFR,MAPK8 and ESR1were the core targets of PYBSATF for the treatment of RSA.GO and KEGG enrichment analysis obtained 93 biological processes of cells(P<0.01)and 87 signaling pathways(P<0.01).PYBSATF played a pharmacological role through a variety of pathways including anti-inflammatory,anti-apoptosis,promoting proliferation and angiogenesis.Molecular docking showed that most active components and key targets of PYBSATF had strong efficiency.Conclusion:Through the study of network pharmacology,it predicted that PYBSATF might treat RSA through multiple targets and multiple signal pathways.Significantly,the predictive targets may be potential targets for treatment of RSA.
基金National Natural Science Foundation of China(No.81673782)Shanghai Putuo District Health System“315”Project Talent Training Program(No.14Q-RC-11)。
文摘When gene expression profile is used for gene detection,the probe on the chip can emit fluorescence with different wavelengths.Under the action of confocal laser scanner,a clear gene change image can be obtained,by which the gene changes of the sample to be tested can be observed directly.First,the knee osteoarthritis(KOA)models of mice are established by the method of collateral ligament and meniscus resection(MLI-OA).Then,Bushen Huoxue formula is given by gavage,and ribonucleic acid(RNA)is routinely extracted and purified.Finally,the gene expression changes of KOA tissues of mice are detected by Agilent SurePrint G3 Mouse GE V2.0 gene expression profile.The results show that Bushen Huoxue formula has significant regulation effect on gene expression of KOA tissue.Among the genes with significant up-regulation effect of Bushen Huoxue formula,there are 56 genes of traditional Chinese medicine(TCM)groups up-regulated more than twice compared with model groups.Among the genes with significant down-regulation effect,there are 119 genes of TCM groups down-regulated more than twice compared with model groups.The experimental results indicate that Bushen Huoxue formula may promote the metabolism of arthritic factors and delay cartilage degeneration to treat KOA by regulating genes that are currently unknown in the pathological process of KOA.
基金the Key Project of the National Natural Science Foundation of China (No. 82030122&82474548)Sanming Project of Medicine in Shenzhen (No. SZZYSM202311020)。
文摘Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCMv2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidateBZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-kB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.
文摘Background The side effects of chemotherapy-induced nausea and vomiting(CINV)and myelosuppression reduce the cancer patients’adherence to chemotherapy.Many Chinese patients choose Chinese medicine(CM)during chemotherapy to reduce side effects;however,the evidence is lacking.The efficacy of a CM herbal treatment protocol,Jianpi Bushen Sequential Formula(健脾补肾续贯方,JBSF)will be evaluated on chemotherapy completion rate among patients with colon cancer.Methods A multi-center double-blind randomized controlled trial(RCT)will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine(CAPEOX).Patients will be randomized 1:1 to receive the JBSF or placebo formula.The primary outcome is the overall chemotherapy completion rate.The secondary outcomes include individual chemotherapy completion rate,4-cycle completion rate of chemotherapy,time to treatment failure,relative dose intensity and treatment toxicity.Follow-up visits will be scheduled before every and after last chemotherapy.Discussion This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer.(Trial registration:Clinical Trials.gov,No.NCT03716518)。
基金Supported by National Natural Science Foundation of China(No.81930118)Central Public Welfare Research Institutes(No.ZZ13-YQ-038)+1 种基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202003)National Key R&D Program of China(No.2021YFC1712800)。
文摘Objective:To assess the efficacy and safety of Bushen Huoxue Formula(BSHXF)for the treatment of discogenic low-back pain(DLBP).Methods:This was a parallel,double-blind,randomized,clinical trial performed between May 2019 and June 2020.Seventy patients were assigned by computerized random number table to the treatment group(lumbar traction and BSHXF,35 cases)or the control group(lumbar traction and placebo,35 cases).The patients received intervention for 3 weeks.Assessment was conducted before treatment and at week 1,2,3 during treatment.Primary outcome was the self-reported score of Oswestry Disability Index(ODI).Secondary outcomes included Visual Analog Scale(VAS),clinical efficacy rate by minimal clinically important difference(MCID)as well as lumbar tenderness,muscle tone and lumbar spine mobility.Adverse reactions were recorded.Follow-up was performed at 1 and 3 months after the end of treatment.Results:In the treatment group,ODI score was significantly decreased compared with baseline(P<0.05)and the control group at 2-and 3-week treatment.Similarly,VAS score decreased compared with the baseline(P<0.05)and was lower than that in the control group at 2-and 3-week treatment(P<0.05).The clinical efficacy rate of the treatment group was higher than that of the control group after treatment[32.35%(11/34)vs.3.13%(1/32),P<0.05].Moreover,the tenderness,and muscle tone,as well as the back extension and left flexion in lumbar spine mobility in the treatment group at 3-week treatment were significantly improved compared with the control group(P<0.05).Follow-up showed that at 1-month after treatment,the treatment group had better outcomes than the control group with regard to a total score of ODI and VAS scores,as well as clinical efficacy rate(all P<0.05).Moreover,VAS score was still significantly lower than the control group at 3-month follow-up(P<0.05).No adverse reactions were reported during the study.Conclusion:BSXHF combined with lumbar traction can significantly improve the clinical symptoms including pain intensity,functionality,muscle tone,and lumbar spine mobility in DLBP patients.(Registration No.Chi CTR1900027777).
