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Participant Heterogeneity of Systemic Scleroderma Interventional Trials Worldwide

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International Journal of Dermatology and Venereology 2024年第2期7卷 99-107页

作者： Li-Qing Shi Shi-Hang Zhou Ping-Lang Ruan Bo Zhang Yue Xin Cheng Zhao Xu Yao Jing-Ru Tian Qian-Jin Lu Hospital for Skin Diseases(Institute of Dermatology) Chinese Academy of Medical Sciences and Peking Union Medical CollegeNanjingJiangsu 210042China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases Chinese Academy of Medical SciencesNanjingJiangsu 210042China Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs NanjingJiangsu 210042China Department of Dermatology Hunan Key Laboratory of Medical Epigenomicsthe Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

Objective:Heterogeneity of participants in clinical trials distorts intervention ***,factors associated with participant heterogeneity in randomized clinical trials(RCTs)focusing on systemic sclerosis(SSc)are not *** conducted this systematic review to establish normative standards for future research and help develop management ***:Three databases and 4 registries were searched to identify characteristics of SSc RCTs across different *** of bias was assessed by the Cochrane Collaboration’s tool and logistic regression was performed to calculate crude and adjusted odds ***:In total,261 trials met our inclusion *** quality of SSc RCTs worldwide was relatively poor,with no trend of improvement in recent years,and only 12.2%were ranked as having a low risk of *** with a low risk of bias as well as single-center,single-country,or open-label trials tended to have better participant adherence than trials with a high risk of bias and multiple-center,multiple-country,or double-blind ***,trial registration and primary outcome definition contributed to high *** income was also relevant;participant adherence in high-income countries,but not in upper-and lower-middle-income countries,was significantly altered by different ***:Overall,the risk of bias,national income,and trial design may lead to participant heterogeneity of SSc RCTs and ultimately confound the general clinical utility of the *** with a rigorous design and transparent conduction protocol are crucial for obtaining unbiased data that can serve as a reference and for maintaining the fundamental repeatability of SSc RCTs.

关键词： systemic sclerosis randomized clinical trials heterogeneity participant adherence national income risk of bias

Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

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Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan Fang Somaira Nowsheen Ye-Xiong Li Zhenkun Lou Min Deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor *** is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy *** studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic *** this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)*** found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM *** regulation of AMPK requires the Hippo kinases but not LKB1/*** kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM ***,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival *** activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC ***,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

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Neuroscience Bulletin 2024年第4期40卷 439-450页

作者： Xiaotong Wu Yali Liu Xiaomeng Wang Lu Zheng Libiao Pan Hao Wang Department of Neurosurgery of Second Affiliated Hospital and School of Brain science and Brain Medicine Key Laboratory for Biomedical Engineering of Education MinistryZhejiang University School of MedicineHangzhou310058China Nanhu Brain-computer Interface Institute Hangzhou311100China NHC and CAMS Key Laboratory of medical Neurobiology MOE Frontier Science Center for Brain Research and Brain Machine IntegrationKey Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain ***,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was *** showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm *** synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and *** results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

关键词： Fragile X syndrome Synaptic refinement VPm Sensory over-reactivity

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical ***:ASPA was identified as a novel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

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Protein & Cell 2024年第6期15卷 403-418页

作者： Song Xue Yuru Han Fan Wu Qiao Wang Key Laboratory of medical Molecular Virology (MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecurityShanghai Frontiers Science Center of Pathogenic Microorganisms and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation *** mutations,particularly those within the receptor binding domain(RBD)of SARS-CoV-2 spike(S)protein,lead to the functional alteration in both receptor engagement and monoclonal antibody(mAb)***,we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune *** single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding ***,this weakened effect could be largely compensated by specific epistatic mutations,such as N501Y,thus maintaining the overall ACE2 affinity for the spike protein of all major *** predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two ***,this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained,emphasizing the significance of comprehensive assessment of spike mutations.

关键词： ACE2 affinity maintained

Development and performance evaluation of a culture-independent nanopore amplicon-based sequencing method for accurate typing and antimicrobial resistance profiling in Neisseria gonorrhoeae

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science China(Life sciences) 2024年第2期67卷 421-423页

作者： Chi Zhang Lulu Zhang Feng Wang Yaling Zeng Liying Sun Di Wang Yamei Li Liqin Wang Junping Peng NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100176China Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical SciencesBeijing 100730China Shenzhen Center for Chronic Disease Control Shenzhen 518020China

Dear Editor,Bacterial antimicrobial resistance(AMR)poses a serious threat to global human health(Antimicrobial Resistance Collaborators,2022).Comprehensive profiling of AMR and accurate molecular typing are important for tracking and controlling the emergence and dissemination of antibiotic-resistant bacteria(Yahara et al.,2021).We previously developed a multiplex amplicon sequencing-based method for directly sequencing AMR-related loci in *** from clinical samples(Zhang et al.,2021).

关键词： gonorrhoeae resistance

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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Laparoscopic sacrocolpopexy for treatment of pelvic organ prolapse,a prospective observation cohort with follow-up time over 7 years

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chinese medical Journal 2024年第12期137卷 1477-1479页

作者： Jianbin Guo Xiaochen Song Shuo Liang Yuan Wang Yang Ye Qianqian Gao Juan Chen Lan Zhu Department of Obstetrics and Gynecology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeNational Clinical Research Center for Obstetric&Gynecologic DiseasesBeijing 100730China

To the Editor:Pelvic organ prolapse(POP)is a common pelvic floor disorder in older women and is responsible for a significant decrease in health-related quality of *** the increased longevity of women,POP is becoming a major health concern.[1]Laparoscopic sacrocolpopexy(LSC)is a common mesh-based surgical approach for severe prolapse,and a high cure rate and few complications have been reported.[2]To our knowledge,the long-term durability,complications,and pelvic floor symptoms after LSC have not been fully evaluated in detail.A few studies assessed the 5-year outcome after LSC,but these reports were limited by their retrospective design,uneven follow-up time,or inconsistent outcome assessment.

关键词： prolapse pelvic Laparoscopic

Percutaneous transhepatic stenting for acute superior mesenteric vein stenosis after pancreaticoduodenectomy with portal vein reconstruction:A case report

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1195-1202页

作者： Chen Lin Zi-Yan Wang Liang-Bo Dong Zhi-Wei Wang Ze-Hui Li Wei-Bin Wang Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of General Surgery Peking Union Medical College HospitalBeijing 100730China Interventional Section Department of RadiologyPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China

BACKGROUND Percutaneous transhepatic stent placement has become a common strategy for the postoperative treatment of portal vein(PV)/superior mesenteric veins(SMV)stenosis/*** has been widely used after liver transplantation surgery;however,reports on stent placement for acute PV/SMV stenosis after pancreatic surgery within postoperative 3 d are *** SUMMARY Herein,we reported a case of intestinal edema and SMV stenosis 2 d after pancreatic *** patient was successfully treated using stent *** the stenosis resolved after stent placement,complications,including bleeding,pancreatic fistula,bile leakage,and infection,made the treatment highly *** use of anticoagulants was adjusted multiple times to prevent venous thromboembolism and the risk of *** careful treatment,the patient stabilized,and stent placement effectively managed postoperative PV/SMV *** Stent placement is effective and feasible for treating acute PV/SMV stenosis after pancreatic surgery even within postoperative 3 d.

关键词： Pancreaticoduodenectomy Portal vein reconstruction Portal vein stenosis Portal vein stent Case report