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Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATACseq and scRNA-seq

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Zoological Research 2024年第3期45卷 601-616页

作者： Hai-Quan wang Xiao-Long wu Jing zhang Si-Ting wang Yong-juan Sang Kang li Chao-Fan Yang Fei sun Chao-Jun li State Key Laboratory of Reproductive Medicine and Offspring Health Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Medical School Nanjing UniversityNanjingJiangsu 210093China Zhejiang University School of Medicine HangzhouZhejiang 310016China Department of Urology and Andrology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouZhejiang 310000China Model Animal Research Center of Medical School Nanjing UniversityNanjingNanjingJiangsu 210093China liangzhu Laboratory Zhejiang UniversityHangzhouZhejiang 311121China

Meiosis is a highly complex process significantly influenced by transcriptional ***,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are ***,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene *** event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional ***,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this *** suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these *** results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.

关键词： Single-cell RNA-seq Single-cell ATAC-seq Spermatogenesis Meiosis Transcriptional reprogramming Cell-cell communication

First-line penpulimab(an anti-PD1 antibody)and anlotinib(an angiogenesis inhibitor)with nab-paclitaxel/gemcitabine(PAAG)in metastatic pancreatic cancer:a prospective,multicentre,biomolecular exploratory,phase II trial

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2960-2969页

作者： Huizi Sha Fan Tong Jiayao Ni Yi sun Yahui Zhu liang Qi Xiaoqin li Wei li Yan Yang qing Gu Xing zhang Xiaoxuan wang Chan Zhu Dongsheng Chen Baorui liu juan Du The Comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University&Clinical Cancer Institute of Nanjing UniversityNanjingChina The Comprehensive Cancer Center Nanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina Department of Oncology The Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of Oncology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjingChina National Institute of Healthcare Data Science at Nanjing University NanjingChina State Key Laboratory of Neurology and Oncology Drug Development Jiangsu Simcere Diagnostics Co.Ltd.Nanjing Simcere Medical Laboratory Science Co.Ltd.NanjingChina

Metastatic pancreatic cancer(mPC)has a dismal ***,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and *** 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,*** 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer ***,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable *** conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for *** biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

关键词： CA724 prospective centre

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer malignant behaviors by activation of target of rapamycin kinase/autophagy signaling

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World Journal of Gastroenterology 2024年第26期30卷 3229-3246页

作者： juan sun Jin-Xiu zhang Meng-Shi li Meng-Bin Qin Ruo-Xi Cheng qing-Ru wu Qiu-ling Chen Dan Yang Cun liao Shi-Quan liu Jie-An Huang Department of Gastroenterology The Second Affiliated Hospital of Guangxi Medical UniversityNanning 530007Guangxi Zhuang Autonomous RegionChina Department of Colorectal&Anal Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human *** To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC *** overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were *** cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro *** MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC *** of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC *** the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO *** contrast,the opposite results were observed in tumor cells with MOB3B *** nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell *** Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

关键词： Colorectal cancer Monopolar spindle-binding protein 3B Mechanistic target of rapamycin kinase Autophagy Prognosis

From Perspective of Hippocampal Plasticity:Function of Antidepressant Chinese Medicine Xiaoyaosan

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Chinese Journal of Integrative Medicine 2024年第8期30卷 747-758页

作者： zhang wu-jing GUO Ze-xuan wang Yi-di FANG Shao-yi WAN Chun-miao YU Xiao-long GUO Xiao-fang CHEN Yue-yue ZHOU Xuan HUANG Jun-qing li Xiao-juan CHEN Jia-xu FAN li-li Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine School of Traditional Chinese MedicineJinan UniversityGuangzhou510632China

The hippocampus is one of the most commonly studied brain regions in the context of *** volume of the hippocampus is significantly reduced in patients with depression,which severely disrupts hippocampal ***,antidepressant therapies that target hippocampal neuroplasticity have not been identified as *** medicine(CM)can slow the progression of depression,potentially by modulating hippocampal ***(XYS)is a CM formula that has been clinically used for the treatment of *** is known to protect Gan(liver)and Pi(Spleen)function,and may exert its antidepressant effects by regulating hippocampal *** this review,we have summarized the association between depression and aberrant hippocampal ***,we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against *** results of this review can aid future research on XYS for the treatment of depression.

关键词： depression hippocampal neuroplasticity Xiaoyaosan Chinese medicine

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science China(life Sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui zhang Pan wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia Yan Hong-Wei Fan Ming-Ming zhang Yu Qiao Xiao-Die liu Bao-juan li Ming-Hui wang Hai-Long Dong Hao-Hong li Peng-Cheng Huang Yun-qing li wu-Gang Hou Jin-lian li Tao Chen Department of Anatomy and K.K.Leung Brain Research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical Sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China School of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier Research Center of Brain&Brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China Department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Department of Anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as ***,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely *** we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression *** determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA ***,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic *** of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic *** study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients:A 12-week randomized placebo-controlled phase III trial with long-term extension

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Chinese Medical Journal 2024年第10期137卷 1190-1198页

作者： Chen Yu Songmei Geng Bin Yang Yunhua Deng Fuqiu li Xiaojing Kang Mingye Bi Furen zhang Yi Zhao Weili Pan Zhongwei Tian Jinhua Xu Zhenghua zhang Nan Yu Xinsuo Duan Shuping Guo qing sun Weiquan li juan Tao Zhijun liu Yuanyuan Yin Gang wang Department of Dermatology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China Department of Dermatology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710004China Department of Dermatology Dermatology Hospital of Southern Medical UniversityGuangzhouGuangdong 510091China Department of Dermatology Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Dermatology The Second Hospital of Jilin UniversityChangchunJilin 130041China Department of Dermatology People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqiXinjiang 830001China Department of Dermatology Wuxi People’s Hospital of Wuxi CityWuxiJiangsu 214023China Department of Dermatology Shandong Provincial Hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and VenereologyShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China Department of Dermatology Beijing Tsinghua Changgung HospitalBeijing 102218China Department of Dermatology Zhejiang Provincial People’s HospitalHangzhouZhejiang 310014China Department of Dermatology The First Affiliated Hospital of Xinxiang Medical CollegeXinxiangHenan 453100China Department of Dermatology Huashan Hospital Affiliated to Fudan UniversityShanghai 200040China Department of Dermatology General Hospital of Ningxia Medical UniversityYinchuanNingxia 750000China Department of Dermatology Affiliated Hospital of Chengde Medical UniversityChengdeHebei 067000China Department of Dermatology The First Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China Department of Dermatology Qilu Hospital of Shandong UniversityJinanShandong 250012China Department of Dermatology Yuebei People’s HospitalShaoguanGuangdong 512026China Department of Dermatology Union Hospital Tongji Medical Collage Huazhong University of Science and TechnologyWuhanHubei 430022China Department of Dermatology and Venereal Diseases The First Affiliated Hospit

Background:There is a need for effective and safe therapies for psoriasis that provide sustained *** aim of this study was to assess the efficacy and safety of tildrakizumab,an anti-interleukin-23p19 monoclonal antibody,for treating moderate-to-severe plaque psoriasis in Chinese ***:In this multi-center,double-blind,phase III trial,patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned(1:1)to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and *** initially assigned to placebo were switched to receive tildrakizumab at weeks 12,16,and every 12 weeks *** in the tildrakizumab group continued with tildrakizumab at week 16,and every 12 weeks until week *** primary endpoint was the Psoriasis Area and Severity Index(PASI 75)response rate at week ***:At week 12,tildrakizumab demonstrated significantly higher PASI 75 response rates(66.4%[73/110]vs.12.7%[14/110];difference,51.4%[95%confidence interval(CI),40.72,62.13];P<0.001)and Physician’s Global Assessment(60.9%[67/110]vs.10.0%[11/110];difference,49.1%[95%CI,38.64,59.62];P<0.001)compared to *** 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups,reaching maximal efficacy after 28 weeks(86.8%[92/106]vs.82.4%[89/108])and maintained up to 52 weeks(91.3%[95/104]vs.87.4%[90/103]).Most treatment-emergent adverse events were mild and not related to ***:Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque *** registration:***,NCT05108766.

关键词： Tildrakizumab Interleukin 23 Plaque psoriasis Chinese Randomized controlled trial

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian li Mengxin Xu Jingyi Yang li Zhou lin liu Min li Shasha wang Mei-Qin liu Zhixiang Huang Zhen zhang Shuning liu Yunqi Hu Haofeng lin Bowen liu Ying sun qingguo wu Zheng-li Shi Ke Lan Yu Chen Huimin Yan Yao-qing Chen wuhan Institute of Virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation

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Protein & Cell 2024年第7期15卷 512-529页

作者： Kai-Hui zhang Fei-Fei zhang Zhi-ling zhang Ke-Fei Fang Wen-Xing sun Na Kong Min wu Hai-Ou liu Yan liu Zhi li qing-qing Cai Yang wang Quan-Wei Wei Peng-Cheng lin Yan lin Wei Xu Cong-Jian Xu Yi-Yuan Yuan Shi-Min Zhao The Obstetrics&Gynecology Hospital of Fudan University State Key Laboratory of Genetic EngineeringFudan UniversityShanghai 200090China Shanghai Key Laboratory of Metabolic Remodeling and Children’s Hospital of Fudan UniversityShanghai 200032China School of life Sciences and Institutes of Biomedical Sciences Fudan UniversityShanghai 200438China Department of Nutrition and Food Hygiene School of Public HealthNantong UniversityNantong 226019China Reproductive Medicine Center The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Shanghai Fifth People’s Hospital of Fudan University Fudan UniversityShanghai 200240China Department of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210014China Key Laboratory for Tibet Plateau Phytochemistry of qinghai Province College of PharmacyQinghai University for NationalitiesXining 810007China Pediatric Research Institute Children’s Hospital Affiliated to Shandong University(Jinan Children’s Hospital)Jinan 250022China

Polycystic ovary syndrome(PCOS)is the leading cause of anovulatory *** understanding of the ovulation drivers hinders PCOS ***,we report that follicle stimulating hormone(FSH)controls follicular fluid(FF)glutamine levels to determine *** ovulation starts from FF-exposing granulosa cell(GC)*** glutamine,which decreases in pre-ovulation porcine FF,elevates in PCOS patients ***-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal,metabolic,and morphologic PCOS ***,follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine,which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic *** and glutamine inhibit the rapture of cultured murine *** removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or *** suggest that glutamine,FSH,and ASK1-JNK pathway are targetable to alleviate PCOS.

关键词： ovulation glutamine granulosa cells PCOS FSH

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy:A Multicenter Double-Blind Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第3期30卷 195-202页

作者： HUANG Hao-yue liN Yu-ping WEI Hua FU Yu ZHOU Yue-hong FANG Zhao-hui QIU Xiao-tang wang Mei li qing-bo li Shan-shan wang Shi-dong DAI Fang liU Zhen-jie ZHAO ling WEN Jian-xuan wu li-yan ZENG Hui-yan zhang Jin-ming LU Qi-yun HE liu SONG Wei sun Lu LUO Lu-lu HE Jia-li XIE Wen-wen liANG qing-shun HUANG Yuan ZHU Sheng-ling LONG Jie-er GAO Zhi-juan WEN Ze-huai li Chun-ji OUYANG Wen-wei li Geng wu Ming-hui li An-xiang HUANG Jin-zhu Sanjoy K Paul TANG Xian-yu FAN Guan-jie Department of Endocrinology Guangdong Provincial Hospital of Chinese MedicineGuangzhou510120China The Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou510120China Department of Endocrinology The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China Guangdong Provincial Academy of Chinese Medical Sciences Guangzhou510120China Department of Endocrinology The First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Department of Endocrinology Liuyang Hospital of Chinese MedicineChangsha410000China Department of Endocrinology The First Affiliated Hospital of Anhui University of Chinese MedicineHefei230000China Department of Endocrinology Hainan Provincial Hospital of Traditional Chinese MedicineHaikou570100China Department of Endocrinology The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang110000China Department of Geriatric Luoyang No.1 Hospital of Traditional Chinese MedicineLuoyangHenan Province471000China Department of Endocrinology The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Department of Endocrinology Beijing University of Chinese Medicine Affiliated Dongzhimen HospitalBeijing100000China Department of Endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Melbourne EpiCentre The University of Melbourne and Melbourne HealthMelbourne3013Australia

Objective:To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction(TW)in treating patients with diabetic peripheral neuropathy(DPN).Methods:It is a multicenter double-blinded randomized controlled *** with DPN were recruited between November 18,2016 and May 30,2018 from 8 hospitals in *** patients received basic treatments for glycemic *** received foot baths with TW herbal granules either 66.9 g(intervention group)or 6.69 g(control group)for 30 min once a day for 2 weeks and followed by a 2-week rest,as a therapeutic *** the Toronto Clinical Scoring System total score(TCSS-TS)6 points,the patients received a total of 3 therapeutic courses(for 12 weeks)and were followed up for 12 *** primary outcome was change in TCSS-TS score at 12 and 24 *** outcomes included changes in bilateral motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of the median and common peroneal *** was also ***:Totally 632 patients were enrolled,and 317 and 315 were randomized to the intervention and control groups,*** the 12-week intervention,patients in both groups showed significant declines in TCSSTS scores,and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment(P0.05),and no serious adverse event was related with ***:Treatment of TW foot baths was safe and significantly benefitted patients with DPN.A low dose of TW appeared to be more effective than a high dose.(Registry *** CTR-IOR-16009331)

关键词： diabetic peripheral neuropathy herbal medicine foot baths Chinese medicine randomized controlled trial Tangbi Waixi Decoction