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The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 doctor medical program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue Zhang Liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China medical doctor program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain *** evidence implicates N6-methyladenosine(m6A)modification in ALS *** RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication *** of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in *** proteome analysis demonstrated the role of dysregulated immune cell migration in *** type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were *** communication between neurons and glial cells was selectively altered in ALS *** integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome:A Systematic Review and Meta-Analysis

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Chinese medical Sciences Journal 2024年第2期39卷 122-130页

作者： Xia-Xiao Yan Yue-Lun Zhang Yu-Pei Zhang Ying-Yun Yang Dong Wu Department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Eight-Year medical doctor program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and *** We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September ***-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were *** estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the *** Four studies were *** pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for ***,limited high-quality data make the results'validity and applicability *** is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.

关键词： irritable bowel syndrome bowel sound analysis diagnostic accuracy systematic review meta-analysis

Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up

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Science China(Life Sciences) 2024年第5期67卷 1061-1068页

作者： Zhibo Zhang Jianbin Guo Weijie Tian Ye Zhang Yuelun Zhang Tianshu Sun Jiali Duan Xinmiao Bao Yuan Wang Yang Ye Qianqian Gao Honghui Shi Abraham Nick Morse Juan Chen Lan Zhu Departmentof Obstetrics and Gynecology Peking Union MedicalCollege HospitalChinese Academyof Medical Sciences&Peking Union MedicalCollegeNational Clinical Research Center for Obstetricand Gynecologic DiseasesBeijing 100730China Department of Gynecology Guizhou Provincial People’s HospitalMedical College of Guizhou UniversityGuiyang 550002China Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China medical doctor program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Pathology Peking Union Medical College HospitalBeijing 100730China Tufts University School of Medicine Boston MA 02111USA

Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance ***,reports with follow-up>10 years are ***,this study aimed to report outcomes in a prospective cohort with at least 10 years of *** with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary *** main outcome measure was symptomatic *** outcomes included anatomic failure,recurrence,patient satisfaction,complications,and *** Kaplan-Meier curve was used to estimate the cumulative failure *** the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 *** estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,*** estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,*** trimming resolved 80.0%of vaginal *** patients did not report decreased overall *** with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh *** rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,*** results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal *** mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.

关键词： complication efficacy long-term follow-up pelvic organ prolapse safety transvaginal mesh

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Zircon U-Pb ages in the Nuratau ophiolitic mélange in the southern Tianshan,Uzbekistan:Implication for the closure of Paleo-Asian Ocean

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China Geology 2024年第2期7卷 365-368,I0004-I0007页

作者： Kai Weng Ji-fei Cao Divayev-Farid Karibovich Jahongir-Jurabekovich Movlanov Bo Chen Zhong-ping Ma Xi’an Center of Geological Survey China Geological SurveyXi’an 710119China The Center for Geoinnovation Technologies doctor of Sciences in Geology and Mineralogy University of Geological ScienceTashkent 100060Uzbekistan

*** The Central Asian Orogenic Belt(CAOB),which is located between the European craton,Siberian craton,and Tarim-North China craton(Fig.1a),is the largest phanerozoic accretionary orogen in the *** resulted from the longterm subduction and accretion of the Paleo-Asian Ocean(PAO).The PAO has been in existence since at least the late Mesoproterozoic(about 1020 Ma).However,there has been debate about the closing time of the PAO.

关键词： Asian Paleo Tianshan

Tumor necrosis factor-alpha, transforming growth factor-beta, degree of lower urinary tract symptoms as predictors of erectile dysfunction in benign prostatic hyperplasia patients

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Asian Journal of Urology 2024年第2期11卷 280-285页

作者： Gede W.K.Duarsa Yeremia G.Kusumah Ronald Sugianto Pande M.W.Tirtayasa Tjokorda G.B.Mahadewa Department of Urology Faculty of MedicineUniversitas UdayanaProf.Dr.I.G.N.G Ngoerah General HospitalBaliIndonesia Department of General Surgery Faculty of MedicineUniversitas UdayanaProf.Dr.I.G.N.G Ngoerah General HospitalBaliIndonesia medical doctor Study program Faculty of MedicineUniversitas UdayanaBaliIndonesia Department of Urology Faculty of MedicineUniversitas UdayanaUniversitas Udayana Teaching HospitalBaliIndonesia Department of Neurosurgery Faculty of MedicineUniversitas UdayanaProf.Dr.I.G.N.G Ngoerah General HospitalBaliIndonesia

Objective: Erectile dysfunction (ED) is a condition of insufficient penile erection, consistently or recurrently, for sexual activity. Tumor necrosis factor-alpha (TNF-α) induces transforming growth factor-beta (TGF-β), which causes the transition of epithelial cells into mesenchymal cells that affect ED. This study aimed to evaluate the roles of TNF-α, TGF-β, degree of lower urinary tract symptoms, and prostatic volume for the presence of ED in benign prostatic hyperplasia (BPH) ***: Our study performed an analytic observational retrospective cohort study using secondary data from four hospitals in Bali, Indonesia, including medical records and other administrative data. The sample was BPH patients with several history ***: Our sample was 83 respondents, ranging from 50 years to 80 years, 61 respondents with ED and 22 with non-ED. The International Prostate Symptom Score showed a significant result, which indicates that ED is more common in patients with higher International Prostate Symptom Score (p=0.002). Moreover, the TNF-α of ≥43.9 pg/mg and TGF-β of ≥175.8 pg/mL were significantly associated with the presence of ED in BPH patients (p<0.0001). Despite these results, prostate volume is not significant with ED (p=0.947).Conclusion: TNF-α, TGF-β, and lower urinary tract symptoms severity can predict the occurrence of ED in BPH, while prostatic volume was not significant.

关键词： Prostate enlargement Biomarker Erectiledysfunction Riskfactor

Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies

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Journal of Traditional Chinese Medicine 2024年第3期44卷 417-426页

作者： ZHU Ruifang ZHANG Jun LYU Yaru CHEN Yulu HAN Shifan WANG Hongwei Key Laboratory for Molecular Diagnosis and Treatment of Hematologic Diseases Second Hospital of Shanxi Medical University Editorial Office First Hospital of Shanxi Medical University School of Nursing Shanxi Medical University

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins,flavones, and alkaloids on experimental animals with autoimmune diseases(AIDs).METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO(CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, Pub Med,Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases;consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum ***: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin(IL)-1β[standardized mean difference(SMD) =-1.94, 95%confidence interval(CI)(-2.99,-0.90), P = 0.0003], IL-6 [SMD =-1.65, 95% CI(-2.33,-0.97,) P < 0.000 01],IL-17 [SMD =-2.41, 95% CI(-3.61,-1.20), P <0.0001], tumor necrosis factor(TNF)-α [SMD =-1.84, 95%CI(-2.61,-1.06), P < 0.0001], and interferon(IFN)-γ[SMD =-1.54, 95% CI(-2.43,-0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI(0.15,2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI(1.39,2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD =-0.63, 95% CI(-1.82, 0.57), P = 0.30].CONCLUTIONS: Substances containing saponins,flavones, and alkaloids regulated the changes of immunerelated cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

关键词： Meta-analysis alkaloids autoimmune diseases flavones saponins system evaluation

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An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome

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Chinese Journal of Natural Medicines 2024年第3期22卷 249-264页

作者： ZHOU Jiangtao WANG Jun WANG Jiajing LI Deyun HOU Jing LI Jiankuan BAI Yun’e GAO Jianping School of Pharmaceutical Science Shanxi Medical UniversityJinzhong 030600China

Inulin-type fructan CP-A,a predominant polysaccharide in Codonopsis pilosula,demonstrates regulatory effects on immune activity and *** efficacy of CP-A in treating ulcerative colitis(UC)is,however,not *** study employed an in vitro lipopolysaccharide(LPS)-induced colonic epithelial cell model(NCM460)and an in vivo dextran sulfate sodium(DSS)-induced colitis mouse model to explore CP-A’s protective effects against experimental colitis and its underlying *** monitored the clinical symptoms in mice using various parameters:body weight,disease activity index(DAI),colon length,spleen weight,and histopathological ***,molecular markers were assessed through enzyme-linked immunosorbent assay(ELISA),quantitative real-time polymerase chain reaction(qRT-PCR),immunofluorescence(IF),immunohistochemistry(IHC),and Western blotting *** showed that CP-A significantly reduced reactive oxygen species(ROS),tumor necrosis factor-alpha(TNF-α),and interleukins(IL-6,IL-1β,IL-18)in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1,ZO-1,and occludin proteins in NCM460 ***,in vivo findings revealed that CPA administration markedly improved DAI,reduced colon shortening,and decreased the production of myeloperoxidase(MPO),malondialdehyde(MDA),ROS,IL-1β,IL-18,and NOD-like receptor protein 3(NLRP3)inflammasome-associated genes/proteins in UC ***-A treatment also elevated glutathione(GSH)and superoxide dismutase(SOD)levels,stimulated autophagy(LC3B,P62,Beclin-1,and ATG5),and reinforced Claudin-1 and ZO-1 expression,thereby aiding in intestinal epithelial barrier repair in colitis ***,the inhibition of autophagy via chloroquine(CQ)diminished CP-A’s protective impact against colitis in *** findings elucidate that CP-A’s therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagymediated N

关键词： Inulin-type fructan CP-A Codonopsis pilosula Ulcerative colitis NLRP3 inflammasome Autophagy

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-na?ve advanced pancreatic ductal adenocarcinoma

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Cancer Biology & Medicine 2023年第10期20卷 765-778页

作者： Zhou Zhu Hui Tang Jinrong Ying Yuejuan Cheng Xiang Wang Yingyi Wang Chunmei Bai Department of medical Oncology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China 4+4 medical doctor program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Objective:Gemcitabine plus nab-paclitaxel(GnP)is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma(PDAC).S-1,an oral fluoropyrimidine derivative,as compared with gemcitabine,is non-inferior in terms of overall survival(OS)and is associated with lower hematologic ***,S-1 is a convenient oral alternative treatment for advanced *** study was aimed at comparing the efficacy and safety of gemcitabine plus S-1(GS)*** as first-line chemotherapy for advanced ***:Patients with advanced PDAC who received first-line GS or GnP at the Peking Union medical College Hospital between March 2011 and November 2022 were ***:A total of 300 patients were assessed,of whom 84 received GS and 216 received *** chemotherapy completion rate was higher with GS than GnP(50.0%vs.30.3%,P=0.0028).The objective response rate(ORR)was slightly higher(14.3%vs.9.7%,P=0.35),and the median OS was significantly longer(17.9 months vs.13.3 months,P=0.0078),in the GS group than the GnP ***,the median progression-free survival(PFS)did not significantly differ between *** risk was significantly lower in the GS group than the GnP group(14.9%vs.28.1%,P=0.049).Conclusions:As first-line chemotherapy for advanced PDAC,the GS regimen led to a significantly longer OS than the GnP *** PFS,ORR,and incidence of severe adverse events were comparable between the GS and GnP groups.

关键词： Advanced pancreatic cancer first-line chemotherapy gemcitabine S-1 nab-paclitaxel