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Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1

chinese Journal of Natural Medicines 2023年第5期21卷 359-370页

作者： LIN Yiyou WEI Jiale ZHANG Yehui HUANG Junhao WANG Sichen LUO Qihan YU Hongxia JI Liting ZHOU Xiaojie LI Changyu School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Academy of chinese medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China

Renal interstitial fibrosis(RIF)is the crucial pathway in chronic kidney disease(CKD)leading to the end-stage renal failure.However,the underlying mechanism of Shen Qi Wan(SQW)on RIF is not fully understood.In the current study,we investigated the role of Aquaporin 1(AQP1)in SQW on tubular epithelial-to-mesenchymal transition(EMT).A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo.Subsequently,the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown.The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine,increased the protein expression of E-cadherin and AQP1 expression,and decreased the expression of vimentin andα-smooth muscle actin(α-SMA).Similarly,treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells.The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1.AQP1 knockdown also increased the mRNA expression of vimentin andα-SMA,and decreased the expression of E-cadherin.The protein expression of vimentin increased,while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells.These results revealed that AQP1 knockdown promoted EMT.Furthermore,AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells.In sum,SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

关键词： Shen Qi Wan Chronic kidney disease Renal interstitial fibrosis Epithelial to mesenchymal transition Aquaporin 1

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Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz.and Paeonia lactiflora Pall.in the treatment of functional constipation and its verification

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Animal Models and Experimental Medicine 2022年第2期5卷 120-132页

作者： Yuxiao Meng Xiaojun Li Xiaoting Wang Lu Zhang Jiaqi Guan School of Pharmacy Zhejiang Chinese Medical UniversityZhejiangChina

Background:We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz.(AMK)and Paeonia lactiflora Pall.(PLP).Methods:The main active ingredients of AMK and PLP were screened by the Traditional chinese Medicine Systems Pharmacology(TCMSP)platform.A database of functional constipation targets was established by GeneCard and OMIM.An“ingredient-target”network map was constructed with Cytoscape software(version 3.7.1),and molecular docking analysis was performed on the components and genes with the highest scores.The rats in the normal group were given saline,and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days.The serum and intestinal tissue levels of adenosine monophosphate(cAMP),protein kinase A(PKA),and adenylyl cyclase(AC)of the rats and aquaporin(AQP)1,AQP3,and AQP8 were measured.Results:AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.After treatment with AMK,PLP,or mosapride,the serum and intestinal tissue levels of AC,cAMP,and PKA were significantly downregulated.Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1,AQP3,and AQP8 to varying degrees.Conclusion:Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.Studies have confirmed that AMK and PLP can also affect AC,cAMP,and PKA.AC,cAMP,and PKA in model rats were significantly downregulated.AQP expression is closely related to AC,cAMP,and PKA.AMK and PLP can reduce the expression of AQP1,AQP3,and AQP9 in the colon of constipated rats.

关键词： coupling of AMK and PLP functional constipation mechanism network pharmacology

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Cooperative coordination-mediated multi-component self-assembly of“all-in-one”nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3710-3725页

作者： Xiaojie Chen Xudong Fan Yue Zhang Yinghui Wei Hangsheng Zheng Dandan Bao Hengwu Xu Ji-Gang Piao Fanzhu Li Hongyue Zheng School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Neuropharmacology and Translational Medicine of zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China Libraries of Zhejiang Chinese Medical University Zhejiang Chinese Medical UniversityHangzhou 310053China Department of Dermatology&Cosmetology The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou 310006China Academy of chinese medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Department of Pharmacy Jinhua People's HospitalJinhua 321000China

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation,high drug-loading efficiency,and excellent therapeutic efficacy.Herein,MnAs-ICG nanospike was generated by self-assembly of indocyanine green(ICG),manganese ions(Mn^(2+)),and arsenate(AsO_(4)^(3−))based on electrostatic and coordination interactions,effectively integrating the bimodal imaging ability of magnetic resonance imaging(MRI)and fluorescence(FL)imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an“all-in-one”theranostic nano-platform.The as-prepared MnAs-ICG nanospike had a uniform size,well-defined nanospike morphology,and impressive loading capacities.The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability,enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components.In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect,prolonged blood circulation and increased tumor accumulation compared to their individual components,effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect.Taken together,this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

关键词： Carrier-free nanodrugs Self-assembly Nanospike Magnetic resonance imaging Tumor microenvironment-responsive Deep penetration Synergistic therapy Breast cancer

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Traditional chinese medicine treatment for COVID-19:An overview of systematic reviews and meta-analyses

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Journal of Integrative Medicine 2022年第5期20卷 416-426页

作者： Han-ting Wu Cong-hua Ji Rong-chen Dai Pei-jie Hei Juan Liang Xia-qiu Wu Qiu-shuang Li Jun-chao Yang Wei Mao Qing Guo School of Public Health Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina The First Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou 310006Zhejiang ProvinceChina

Background:Coronavirus disease 2019(COVID-19)is a rapidly spreading disease that has caused an extensive burden to the world.Consequently,a large number of clinical trials have examined the efficacy of traditional chinese medicine(TCM)for treating and preventing COVID-19,with coinciding proliferation of reviews summarizing these studies.Objective:This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM.Search strategy:Seven electronic databases,including PubMed,Cochrane Library,Web of Science,China National Knowledge Infrastructure,Chongqing VIP,Wanfang Data and SinoMed,were searched for systematic reviews and meta-analyses in October 2021.Search terms such as“chinese medicine,”“Lianhua Qingwen”and“COVID-19”were used.Inclusion criteria:Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included.Data extraction and analysis:A Measurement Tool to Assess Systematic Reviews Version 2.0(AMSTAR 2)was used to evaluate the methodological quality.The quality of evidence was graded using the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)system.Data extraction and analysis were performed by two reviewers independently.Results:There were 17 meta-analyses included in our overview.The intervention group was defined as TCM combined with Western medicine,while the control group was Western medicine alone.The methodological quality of all the included studies was moderate to poor.A total of 89 outcome indicators were evaluated,of which,8 were rated as moderate quality,39 as low quality,and 41 as very low quality.Only one outcome measure was graded as being of high quality.The moderate quality of evidence indicated that,for the treatment of COVID-19,the clinical efficacy of TCM in combination with Western medicine was better,in terms of lung recovery,rate of conversion to severe/critical cases,symptom scores,duration of symptoms,mortality,and len

关键词： Medicine chinese traditional Integrative medicine COVID-19 Systematic review Meta-analysis

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Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment

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Acta Pharmaceutica Sinica B 2021年第1期11卷 271-282页

作者： Xiaojie Chen Jiafeng Zou Ke Zhang Jingjing Zhu Yue Zhang Zhihong Zhu Hongyue Zheng Fanzhu Li Ji-Gang Piao College of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Libraries of Zhejiang Chinese Medical University Zhejiang Chinese Medical UniversityHangzhou 310053China

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer.In present study,nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2(MMP-2)dual-responsive,tumor targeting,and size-variability were designed for enhancing the antitumor efficacy and achieving"on-demand"drug release markedly.Based on the thermal sensitivity of gelatin,we designed a size-variable gelatin nanoparticle(GNP)to encapsulate indocyanine green(ICG)and doxorubicin(DOX).Under an 808 nm laser irradiation,GNP-DOX/ICG responded photothermally and swelled in size from 71.58?4.28 to 160.80?9.51 nm,which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics.Additionally,GNP-DOX/ICG showed a size reduction of the particles to 33.24?4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor.In the subsequently performed in vitro experiments,it was confirmed that GNP-DOX/ICG could provide a therapeutic effect that was enhanced and synergistic.Consequently,GNP-DOX/ICG could efficiently suppress the growth of 4 T1 tumor in vivo.In conclusion,this study may provide a promising strategy in the rational design of drug delivery nanosystems based on gelatin for chemo-photothermal therapy to achieve synergistically enhanced therapeutic efficacy against breast cancer.

关键词： Breast cancer Gelatin Indocyanine green Doxorubicin Nanoparticle Size-variable Chemoephotothermal therapy MMP-2

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Low Grip Strength and Increased Mortality Hazard among Middle-Aged and Older chinese Adults with Chronic Diseases

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Biomedical and Environmental Sciences 2023年第3期36卷 213-221页

作者： XIE Kai Hong HAN Xiao ZHENG Wei Jun ZHUANG Su Fang School of Nursing Zhejiang Chinese Medical UniversityHangzhou 311400ZhejiangChina School of health humanities Peking UniversityBeijing 100000China School of Public Health Zhejiang Chinese Medical UniversityHangzhou 311400ZhejiangChina Office of Disciplinary Inspection and Supervision The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 311006ZhejiangChina

Objective This study aims to evaluate the association between lower grip strength and mortality hazard.Methods We selected 10,280 adults aged 45 to 96 years old from the China Health and Retirement Longitudinal Study and used multivariate Cox proportional hazard models to assess the association of grip strength with mortality hazard.In addition,we explored the possibility of a nonlinear relationship using a 4-knot restricted spline regression.Results We found that elevated grip strength was associated with lower mortality up to a certain threshold.The baseline quartile values of grip strength were 30,37,and 44 kg for males and 25,30,and35 kg for females.After adjusting for confounders,with category 1 as the reference group,the adjusted HRs were 0.58(0.42-0.79)in males and 0.70(0.48-0.99)in females(category 4).We also found a linear association between grip strength values and all-cause death risk(males,P=0.274;females,P=0.883)using restricted spline regression.For males with a grip strengthchinese adults with chronic diseases.

关键词： Grip strength Death Chronic disease

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Mechanisms of liver injuries caused by traditional chinese medicines

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 310-312页

作者： Shui-Fang Jin Qi Pan Jin-Peng Zhou Xiao-Ping Pan Intensive Care Unit The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou 310006China Institute of Liver Diseases College of Basic Medical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China The Second Clinical medical College of Zhejiang Chinese Medical University Hangzhou 310056China

Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The chinese medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].

关键词： drugs tuberculosis TCM

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Effects of Aromatherapy on Physical and Mental Health of Cancer Patients Undergoing Radiotherapy and/or Chemotherapy: A Meta-Analysis

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chinese Journal of Integrative Medicine 2024年第5期30卷 449-457页

作者： XIE Shuang-ran MA Liang XU Xin-yu ZHOU Shu XIE Hui-miao XIE Chang-sheng The First Clinical medical College Zhejiang Chinese Medical UniversityHangzhou 310053China Department of medical Oncology Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical UniversityHangzhou 310007China Department of Dermatology the Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Famous chinese Medicine Clinic the Second Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310005China Department of medical Oncology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China

Backgroup:Currently,aromatherapy is being increasingly utilized in clinical practice,particularly in managing the side effects associated with radiotherapy and chemoradiotherapy.However,it remains to be established whether aromatherapy can effectively alleviate these symptoms.Objective:To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and chemotherapy.Methods:Seven databases were researched from inception until September 29,2023,including PubMed,Scopus,and Web of Science,chinese National Knowledge Infrastructure,Wanfang database,China Biology Medicine disc and VIP chinese medical Journal Database.Review Manager version 5.3 was utilized for data analysis.The Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the study.Evidence quality rating was assessed using the Grading of Recommendations Assessment,Development,and Evaluation(GRADE) approach through the GRADEpro GDT online tool.Results:Nineteen studies involving 1,541 patients were included.Aromatherapy can alleviate nausea [relative risk(RR)=0.64,95% confidence interval(CI):0.53 to 0.78,P<0.05,I^(2)=46%;standardized mean difference(SMD)=-0.86,95% CI:-1.21 to-0.51,P<0.05,I^(2)=64%] and vomiting(RR=0.54,95% CI:0.42 to 0.69,P<0.05,I^(2)=35%;SMD=-1.28,95% CI:-1.52 to-1.03,P<0.05,I^(2)=92%),improve sleep disorders [mean difference(MD)=-3.39,95% CI:-3.95 to-2.84,P<0.05,I^(2)=0%],relieve pain(SMD=-1.58,95% CI:-1.96 to-1.21,P<0.05,I^(2)=0%),mitigate fatigue(SMD=-1.28,95% CI:-2.44 to-0.11,P<0.05,I^(2)=93%) and enhance quality of life(SMD=0.50,95% CI:0.22 to 0.79,P<0.05,I^(2)=0%) in cancer patients after radiotherapy and chemotherapy,but it may not have a significant effect on anxiety.The risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2,and no studies were considered to be of high grade according to the GRADE system.Conclusions:Aromatherapy is an efficacious,safe and economic adjunctive therapy for cancer patien

关键词： aromatherapy cancer chemoradiotherapy physical psychological

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Metabolomics: A useful tool for ischemic stroke research

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Journal of Pharmaceutical Analysis 2023年第9期13卷 968-983页

作者： Wentao Li Chongyu Shao Chang Li Huifen Zhou Li Yu Jiehong Yang Haitong Wan Yu He School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou310053China School of Basic Medicine Sciences Zhejiang Chinese Medical UniversityHangzhou310053China

Ischemic stroke(IS)is a multifactorial and heterogeneous disease.Despite years of studies,effective strategies for the diagnosis,management and treatment of stroke are still lacking in clinical practice.Metabolomics is a growing field in systems biology.It is starting to show promise in the identification of biomarkers and in the use of pharmacometabolomics to help patients with certain disorders choose their course of treatment.The development of metabolomics has enabled further and more biological applications.Particularly,metabolomics is increasingly being used to diagnose diseases,discover new drug targets,elucidate mechanisms,and monitor therapeutic outcomes and its potential effect on precision medicine.In this review,we reviewed some recent advances in the study of metabolomics as well as how metabolomics might be used to identify novel biomarkers and understand the mechanisms of IS.Then,the use of metabolomics approaches to investigate the molecular processes and active ingredients of chinese herbal formulations with anti-IS capabilities is summarized.We finally summarized recent developments in single cell metabolomics for exploring the metabolic profiles of single cells.Although the field is relatively young,the development of single cell metabolomics promises to provide a powerful tool for unraveling the pathogenesis of IS.

关键词： Metabolomics Ischemic stroke Biomarker Precision medicine Single cell metabolomics

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Lignin-assisted construction of sub-10 nm supramolecular self-assembly for photothermal immunotherapy and potentiating anti-PD-1 therapy against primary and distant breast tumors

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Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 713-727页

作者： Xudong Fan Tianxiang Yue Aidi Liu Xiaowei Xie Weixiang Fang Yinghui Wei Hangsheng Zheng Hongyue Zheng Meiqi Zhou Jigang Piao Fanzhu Li School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Neuropharmacology and Translational Medicine of zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China Libraries of Zhejiang Chinese Medical University Zhejiang Chinese Medical UniversityHangzhou 310053China Department of Breast Surgery Key Laboratory of Cancer Prevention and InterventionChina National Ministry of EducationSecond Hospital of ZhejiangUniversity College of MedicineHangzhou 310009China Academy of chinese medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China

Photothermal therapy(PTT)has brought hope for cancer treatments,with hyperthermia-induced immunogenic cell death(ICD),which is a critical part of therapeutically induced antitumor immune responses.Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation,therefore demonstrating urgent requirements for ICD amplifier.Herein,a sub-10 nm supramolecular nanoassembly was formed by coassembly of clinically approved aluminum adjuvant and commonly used indocyanine green(ICG)under the assistance of lignosulfonate(LS,a green and sustainable multifunctional lignin derivative)for localized photothermal-immunotherapy of breast cancer.The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD,efficiently eliciting solid immune responses through dendritic cells(DCs)activation and cytotoxic T-cell responses initiation for tumor killing.Moreover,anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity.The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy,which shows promise for delivering other therapeutics in biomedical applications.

关键词： Lignin Supramolecular self-assembly Photothermal-immunotherapy Anti-PD-1

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