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Interplays of liver fibrosis-associated microRNAs:Molecular mechanisms and implications in diagnosis and therapy

Genes & Diseases 2023年第4期10卷 1457-1469页

作者： Hong Li Tingli Liu Yongchun Yang William C.Cho Robin J.Flynn Majid Fasihi Harandi Houhui Song Xuenong Luo Yadong Zheng State Key Laboratory of Veterinary Etiological Biology Key Laboratory of Veterinary Parasitology of Gansu ProvinceLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhouGansu 730046China Key Laboratory of Applied Technology on Green-Eco-healthy Animal Husbandry of Zhejiang Province Zhejiang Provincial Engineering Laboratory for Animal Health Inspection&Internet TechnologyZhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health ManagementChina-Australia Joint Laboratory for Animal Health Big Data AnalyticsCollege of Animal Science and Technology&College of Veterinary Medicine of Zhejiang A&F UniversityHangzhouZhejiang 311300China Department of clinical Oncology Queen Elizabeth HospitalHong Kong SAR 999077China Department of Infection Biology Institute of Infection and Global HealthUniversity of LiverpoolLiverpool L35RFUK Graduate Studies Office Department of ResearchInnovation and Graduate StudiesWaterford Institute of TechnologyX91 K0EKIreland Research Center for Hydatid Disease in Iran Kerman University of Medical SciencesKerman ***Iran

microRNAs(miRNAs)are a class of non-coding functional small RNA composed of 21e23 nucleotides,having multiple associations with liver ***-associated miRNAs are roughly classified into pro-fibrosis or anti-fibrosis *** former is capable of activating hepatic stellate cells(HSCs)by modulating pro-fibrotic signaling pathways,mainly including TGF-b/SMAD,WNT/b-catenin,and Hedgehog;the latter is responsible for maintenance of the quiescent phenotype of normal HSCs,phenotypic reversion of activated HSCs(aHSCs),inhibition of HSCs proliferation and suppression of the extracellular matrix-associated gene ***,several miRNAs are involved in regulation of liver fibrosis via alternative mechanisms,such as interacting between hepatocytes and other liver cells via exosomes and increasing autophagy of ***,understanding the role of these miRNAs may provide new avenues for the development of novel interventions against hepatic fibrosis.

关键词： Diagnosis Hepatic stellate cell Liver fibrosis miRNA Therapy

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Comparison of outcomes between immediate implantbased and autologous reconstruction: 15-year, single-center experience in a propensity score-matched Chinese cohort

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Cancer Biology & Medicine 2022年第9期19卷 1410-1421页

作者： Shanshan He Bowen Ding Gang Li Yubei Huang Chunyong Han Jingyan Sun Qingfeng Huang Jing Liu Zhuming Yin Shu Wang Jian Yin Department of Breast Reconstruction Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationSino‐Russian Joint Research Center for Oncoplastic Breast SurgeryTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China School of Pharmacy University College LondonLondon WC1N 1AXUK Department of Cancer Epidemiology and Biostatistics Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The number of immediate breast reconstruction(IBR)procedures has been increasing in *** study aimed to investigate the oncological safety of IBR,and to compare the survival and surgical outcomes between implant-based and autologous ***:Data from patients diagnosed with invasive breast cancer who underwent immediate total breast reconstruction between 2001 and 2016 were retrospectively ***-term breast cancer-specific survival(BCSS),disease-free survival(DFS),and locoregional recurrence-free survival(LRFS)were *** satisfaction with the breast was compared between the implantbased and autologous ***,DFS,and LRFS were compared between groups after propensity score matching(PSM).Results:A total of 784 IBR procedures were identified,of which 584 were performed on patients with invasive breast cancer(implantbased,n=288;autologous,n=296).With a median follow-up of 71.3 months,the 10-year estimates of BCSS,DFS,and LRFS were 88.9%[95%confidence interval(CI)(85.1%–93.0%)],79.6%[95%CI(74.7%–84.8%)],and 94.0%[95%CI(90.3%–97.8%)],respectively.A total of 124 patients completed the Breast-Q questionnaire,and no statistically significant differences were noted between groups(P=0.823).After PSM with 27 variables,no statistically significant differences in BCSS,DFS,and LRFS were found between the implant-based(n=177)and autologous(n=177)*** stratification according to staging,histological grade,lymph node status,and lymph-venous invasion status revealed no significant survival differences between ***:Both immediate implant-based and autologous reconstruction were reasonable choices with similar long-term oncological outcomes and patient-reported satisfaction among patients with invasive breast cancer in China.

关键词： Oncological safety immediate breast reconstruction implant-based autologous Chinese propensity-score matched

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Fibroblast growth factor receptor 4 single nucleotide polymorphism Gly388Arg in head and neck carcinomas

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World Journal of clinical Oncology 2019年第3期10卷 136-148页

作者： Eva Wimmer Stephan Ihrler Olivier Gires Sylvia Streit Wolfgang Issing Christoph Bergmann Department of Otorhinolaryngology Ludwig-Maximilians-University Institute of Pathology Ludwig-Maximilians-University clinical cooperation Group Personalized Radiotherapy of Head and Neck Tumors Department of Molecular Biology Max-Planck-Institute for Biochemistry ENT Department Freeman Hospital Department of Otorhinolaryngology University of Duisburg-Essen

BACKGROUND Head and neck squamous cell carcinoma(HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases(RTKs) and members of the fibroblast growth factor receptors(FGFR)-family. Singlenucleotide polymorphism(SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with *** To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was *** Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in *** were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by ***' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression *** Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high"(+++) in 74(26%),"intermediate"(++) in 103(36.3%), and "low"(+) in 107(36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors(33.8%), 84 of them(29.6%) having a heterozygous and 12(4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34%

关键词： Fibroblast growth factor receptor 4 Single-nucleotide polymorphism Head and neck squamous cell carcinoma Reduced survival Cancer progression Polymerase chain reaction Immunohistochemistry Outcome

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Associations of genetic polymorphisms of the transporters organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATE1),and ATP-binding cassette subfamily C member 2(ABCC2) with platinum-based chemotherapy response and toxicity in non-small cel

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Chinese Journal of Cancer 2016年第11期35卷 604-616页

作者： Chen-Yue Qian Yi Zheng Ying Wang Juan Chen Jun-Yan Liu Hong-Hao Zhou Ji-Ye Yin Zhao-Qian Liu Department of clinical Pharmacology Xiangya HospitalCentral South Uni-versityChangsha 410008HunanP.R.China. Institute of clinical Pharmacol-ogy Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangsha 410078HunanP.R.China. Hunan Province cooperation Innovation Center for Molecular Target New Drug Study Hengyang 421001HunanP.R.China. Key Laboratory of Hunan Province for Traditional Chinese Medicine in Obstetrics&Gynecology Research The Maternal and Child Health Hospital of Hunan ProvinceChangsha 410008HunanP.R.China. The affiliated Cancer Hospital of Xiangya School of Medicine Central South UniversityChangsha 410008HunanP.R.China. Xiangya School of Medicine Central South UniversityChangsha 410008HunanP.R.China.

Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this *** important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum *** study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC ***:A total of 403 Chinese NSCLC patients were recruited for this *** patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based *** tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was *** single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and ***:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor ***:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC *** registration Chinese clinical Trial Registry

关键词： OCT2 MATE1 ABCC2 Non-small cell lung cancer Platinum-based chemotherapy

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Research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer

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中国医学影像技术 2024年第8期40卷 1262-1265页

作者： LI Pengqiang LIU Nianjun ZHANG Yanli WANG Yanfei LAN Jinhui REN Huling DOU Yu LEI Junqiang The First clinical Medical College of Lanzhou University Lanzhou 730000China Department of Radiology the First Hospital of Lanzhou UniversityIntelligent Imaging Medical Engineering Research Center of Gansu ProvinceAccurate Image Collaborative Innovation International Science and Technology Cooperation Base of Gansu ProvinceRadiological Clinical Medicine Research Center of Gansu ProvinceIntelligent Imaging Medical Industry Technology Center of Gansu ProvinceLanzhou 730000China

Dual-layer spectral detector CT is a new spectrum CT imaging technology based on detector being able to obtain both images similar to true plain and spectral images in one time *** reconstructed multi-parameter spectral images can not only improve image quality,enhance tissue contrast,increase the visualization and detection ability of occult lesions,but also provide qualitative and quantitative analysis of the lesions,so as to provide more imaging information and multi-dimensional diagnostic *** research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer were reviewed in this article.

关键词： colorectal neoplasms tomography,X-ray computed

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T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients

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Genomics, Proteomics & Bioinformatics 2016年第6期14卷 338-348页

作者： Yin Tong Zhoufang Li Hua Zhang Ligang Xia Meng Zhang Ying Xu Zhanhui Wang Michael W.Deem Xiaojuan Sun Jiankui He Department of Biology South University of Science and Technology of ChinaShenzhen 518055China Department of Endocrinology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Department of Gastrointestinal Surgery Shenzhen People's Hospitalthe Second Clinical Medical College of Jinan UniversityShenzhen 518020China Department of Infectious Diseases and Hepatology unit Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Departments of Bioengineering and Physics&Astronomy Rice UniversityHoustonTX 77005USA Shenzhen Tumor Immune-Gene Therapy clinical Application Engineering Lab Biobank of the Second People's Hospitalthe First Affiliated Hospital of Shenzhen UniversityShenzhen 518035China

Type 1 diabetes mellitus （T1D） is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors （TCRs）, we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes （T2D） patients,and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients （P = 7.0E-08 for CD4＋ T cells, P = 1.4E-04 for CD8＋ T cells） and nondiabetic controls （P = 2.7E-09 for CD4＋ T cells, P = 7.6E-06 for CD8 ＋ T cells）. Moreover, T1D patients had significantly more highly-expanded T cell clones than T2D patients （P = 5.2E-06 for CD4＋ T cells, P = 1.9E-07 for CD8＋ T cells） and nondiabetic controls （P = 1.7E-07 for CD4＋ T cells, P =Y3E-03 for CD8＋ T cells）. Furthermore, we iden- tified a group of highly-expanded T cell receptor clones that are shared by more than two TID patients. Although further validation in larger cohorts is needed, our data suggest that T cell receptor diversity measurements may become a valuable tool in investigating diabetes, such as using the diversity as an index to distinguish different types of diabetes.

关键词： Diversity High-throughputsequencing Immune repertoire T cell receptor Type diabetes

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Vitamin D attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of RasGRP3

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BIOCELL 2023年第6期47卷 1243-1251页

作者： GUANQIONG HU RISHENG HUANG LUELUE LU QINSHI PAN XIAOXIN CHEN No.23 Ward of Nursing Department The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Thoracic Surgery Wenzhou Central HospitalDingli Clinical College of Wenzhou Medical UniversityWenzhouChina Department of clinical Laboratory The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina

Background:Transforming growth factor-β1(TGF-β1)is a pleiotropic cytokine that plays a central role in the pathogenesis of idiopathic pulmonary fibrosis(IPF).While previous studies have revealed a cross-talk between vitamin D and TGF-β1 signaling,it is still unclear how they interact with each other to regulate the progression of ***:In this work,we searched for a novel mediator of TGF-β1 activity in lung fibroblasts and examined its regulation by vitamin *** addition,we investigated the mechanism underlying the interaction between vitamin D and TGF-β1 signaling in lung fibroblast *** analysis was performed to identify TGF-β1 downstream target *** and overexpression expression experiments were conducted to determine gene function in the regulation of lung fibroblast proliferation and ***:Analysis of publicly available datasets revealed that RAS guanyl releasing protein 3(RasGRP3)was upregulated in TGF-β1-treated lung fibroblasts and lung tissues from IPF patients relative to healthy *** data confirmed the upregulation of RasGRP3 by TGF-β1 in human MRC5 lung *** of RasGRP3 enhanced MRC5 cell proliferation and *** of RasGRP3 blocked TGF-β1-induced MRC5 proliferation and *** D abolished TGF-β1-induced RasGRP3 upregulation,which was reversed by inhibition of the vitamin D receptor(VDR).Mechanistically,vitamin D promoted VDR enrichment and prevented mothers against decapentaplegic homolog(SMAD)2 and 3 occupancy at the promoter of ***,overexpression of RasGRP3 reversed the suppressive effect of vitamin D on MRC5 cell proliferation and ***:In conclusion,vitamin D antagonizes TGF-β1-induced lung fibroblast activation by repressing RasGRP3 transcription.

关键词： Lung fibrosis RasGRP3 TGF-β1 Vitamin D

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Novel insights into necrozoospermia from a single-center study:reference ranges,possible etiology,and impact on male fertility

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Asian Journal of Andrology 2024年第5期26卷 528-534页

作者： Er-Chen Zhang Xin-Yu Yin Zi-Yan Peng Zhi-Zhou Lai Liang Hu Yang-Qin Peng Huan Zhang Rui Ming Ge Lin Wei-Na Li NHC Key Laboratory of Human Stem Cell and Reproductive Engineering School of Basic Medical SciencesCentral South UniversityChangsha 410008China Laboratory of Zebrafish Genetics College of Life SciencesHunan Normal UniversityChangsha 410006China Hunan Guangxiu Hospital School of MedicineHunan Normal UniversityChangsha 410001China clinical Research Center for Reproduction and Genetics in Hunan Province Reproductive and Genetic Hospital of CITICXiangyaChangsha 410008China Hunan International Scientific and Technological cooperation Base of Development and Carcinogenesis Changsha 410008China Hunan Guangxiu Hi-tech Life Technology Co. Ltd.Changsha 410013China

Necrozoospermia is a poorly documented condition with a low incidence,and its definition and clinical significance are ***,we provide a reference range for necrozoospermia and discuss its possible etiology and impact on male fertility and assisted reproductive *** extracted relevant information from 650 Chinese male partners of infertile couples and statistically analyzed sperm *** was present in 3.4%(22/650)of our study population,and the lower cut-off value for sperm vitality was 75.3%.We compared two methods for assessing sperm vitality(eosin-nigrosin head staining and hypo-osmotic swelling test[HOST]),for which the percentage in the eosin-nigrosin group(mean±standard deviation[s.d.]:77.5%±10.5%)was significantly higher than that in the HOST group(mean±s.d.:58.1%±6.7%[5-10 min after incubation]and 55.6%±8.2%[25-30 min after incubation];both P<0.001).The incidence of necrozoospermia increased with age(odds ratio[OR]=1.116,95%confidence interval[CI]:1.048-1.189,P=0.001),while the percentage of normal sperm morphology and DNA fragmentation index(DFI)were significantly associated with necrozoospermia,with ORs of 0.691(95%CI:0.511-0.935,P=0.017)and 1.281(95%CI:1.180-1.390,P<0.001),*** the following 6 months,we recruited 166 patients in the nonnecrozoospermia group and 87 patients in the necrozoospermia group to compare intracytoplasmic sperm injection(ICSI)and pregnancy outcomes between the two *** necrozoospermia group had a significantly lower normal fertilization rate(74.7%vs 78.2%,P=0.041;OR=0.822;95%CI:0.682-0.992)than that in the nonnecrozoospermia *** study presents substantial information on necrozoospermia to establish comprehensive and applicable reference values for sperm vitality for spontaneous conception and artificially assisted reproductive management.

关键词： male fertility necrozoospermia reference ranges sperm vitality

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Auricular Acupuncture and Biomedical Research——A Promising Sino-Austrian Research cooperation

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Chinese Journal of Integrative Medicine 2015年第12期21卷 887-894页

作者：荣培晶赵敬军李宇清 Daniela Litscher 李少源 Ingrid Gaischek 翟煦 WANG Lu 罗曼 Gerhard Litscher Institute of Acupuncture-Moxibustion China Academy of Chinese Medical Sciences Traditional Chinese Medicine Research Center Graz Research Unit for Complementary and Integrative Laser MedicineResearch Unit of Biomedical Engineering in Anesthesia and Intensive Care MedicineMedical University of Graz

Treatment by auricular acupuncture has a long history. Ear-acupoint research has been advancing step by step in China and also in Europe. Auricles are rich in nerves, therefore a close relationship with different functions of the human body has been proved by the research teams of the two main authors of this article from China and Austria. In recent years, great progress has been made in the research of regulating human body functions through electroacupuncture at the auricular branch of the vagus nerve, which is part of auricular acupuncture therapy. It is well known that the auricular branch of the vagus nerve is the only peripheral pathway to the cerebral cortex. Studies of the Chinese team on hypertension, diabetes, epilepsy and depression have shown that the mechanism of auricular vagus nerve stimulation （VNS） may be comparable with cervical VNS in terms of pathways. Auricular VNS has a broad clinical application prospect.

关键词： auricular acupuncture biomedical research vagus nerve

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Parkinson’s disease and gut microbiota:from clinical to mechanistic and therapeutic studies

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Translational Neurodegeneration 2023年第1期12卷 1-30页

作者： Xuxiang Zhang Beisha Tang Jifeng Guo Department of Neurology Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangsha 410008China Hunan International Scientific and Technological cooperation Base of Neurodegenerative and Neurogenetic Diseases Changsha 410008China Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangsha 410008China Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha 410008China National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China

Parkinson’s disease(PD)is one of the most prevalent neurodegenerative *** typical symptomatology of PD includes motor symptoms;however,a range of nonmotor symptoms,such as intestinal issues,usually occur before the motor *** microorganisms inhabiting the gastrointestinal tract can profoundly influence the physiopathology of the central nervous system through neurological,endocrine,and immune system pathways involved in the microbiota-gut-brain *** addition,extensive evidence suggests that the gut microbiota is strongly associated with *** review summarizes the latest findings on microbial changes in PD and their clinical relevance,describes the underlying mechanisms through which intestinal bacteria may mediate PD,and discusses the correlations between gut microbes and anti-PD *** addition,this review outlines the status of research on microbial therapies for PD and the future directions of PD-gut microbiota research.

关键词： Gut microbiota Microbiota-gut-brain axis Mechanisms Alpha-synuclein Microbial therapy

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