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Severe pediatric COVID‑19:a review from the clinical and immunopathophysiological perspectives

World Journal of Pediatrics 2024年第4期20卷 307-324页

作者： Yi‑Kan Sun Can Wang Pei‑Quan Lin Lei Hu Jing Ye Zhi‑Gang Gao Ru Lin Hao‑Min Li Qiang Shu Li‑Su Huang Lin‑Hua Tan Children's hospital Zhejiang University School f MedicineHangzhou 310052China The Second Affiliated hospital Zhejiang University School of MedicineHangzhou 310030China Surgical Intensive Care Unit Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of General Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiopulmonary and Extracorporeal Life Support Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Clinical Data Center Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiac Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China National Clinical Research Center for Child Health Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Infectious Diseases Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background Coronavirus disease 2019(COVID-19)tends to have mild presentations in children.However,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from clinicians.Meanwhile,the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood.Data sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang databases.Searched keywords included“COVID-19 in children”,“severe pediatric COVID-19”,and“critical illness in children with COVID-19”.Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status.Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be seen.Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways,whose dysregulation in severe and critical diseases translates into adverse clinical manifestations.Multisystem inflammatory syndrome in children(MIS-C),a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure,denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity.Despite the considerable dissimilarities between the pediatric and adult immune systems,clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines.Conclusions Severe pediatric COVID-19 can affect multiple organ systems.The dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the pediatric immune system and highlight the immun

关键词： Immunopathophysiology MIS-C Pediatric critical care Severe pediatric COVID-19

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Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 385-392页

作者： Min-Zhi Chen Ping Xie Xiao-Chang Wu Zhen-Hua Tan Hai Qian Zhi-Hong Ma Xing Yao Department of Hepatopancreatobiliary Surgery Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhou 313000China Huzhou Key Laboratory of Molecular Medicine Huzhou Central HospitalAffiliated Huzhou HospitalZhejiang University School of MedicineHuzhou 313000China

Background:Obesity is a common public health issue and is currently deemed a disease.Research has shown that the risk of gallstones in individuals with obesity is elevated.This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight.Methods:Bile samples from 20 patients(10 with obesity and 10 with normal body weight)who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT)and liquid chromatography-tandem mass spectrometry(LC-MS/MS),followed by further bioinformatic analysis.Results:Among the differentially expressed proteins,23 were upregulated and 67 were downregulated.Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development,inflammatory responses,glycerolipid metabolic processes,and protein activation cascades.In addition,the activity of the peroxisome proliferator-activated receptor(PPAR,a subfamily of nuclear receptors)signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Two downregulated proteins in the PPAR signaling pathway,APO A-I and APO A-II,were confirmed using enzyme-linked immunosorbent assay.Conclusions:The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity.Furthermore,biliary proteomics profiling of gallstones patients with obesity is revealed,providing a reference for future research.

关键词： Proteome profiling Gallstones Obesity-associated gallstones Tandem mass tag labeling PPAR signaling

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Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

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World Journal of Pediatrics 2024年第3期20卷 259-271页

作者： Yi-Long Wang Meng-Ying Zhu Zhe-Feng Yuan Xiao-Yan Ren Xiao-Tong Guo Yi Hua Lu Xu Cong-Ying Zhao Li-Hua Jiang Xin Zhang Guo-Xia Sheng Pei-Fang Jiang Zheng-Yan Zhao Feng Gao Department of Neurology Children's HospitalZhejiang University School of MedicineHangzhou 310052China Children's hospital Zhejiang University School of MedicineHangzhou 310052China Children's hospital National Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhou 310052China

Background Myelin oligodendrocyte glycoprotein(MOG)antibody-associated disease(MOGAD)is an autoimmune demy-elinating disorder of the central nervous system.Methods Extracted proteins from 34 cerebrospinal fluid(CSF)samples[patients with MOGAD(MOG group,n=12);healthy controls(HC group,n=12);patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases(IND group,n=10)]were processed and subjected to label-free quantitative proteomics.Supervised partial least squares-discriminant analysis(PLS-DA)and orthogonal PLS-DA(O-PLS-DA)models were also performed based on proteomics data.Functional analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and Genomes.An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD.Results Four hundred and twenty-nine DEPs(149 upregulated and 280 downregulated proteins)were identified in the MOG group compared to the HC group according to the P value and fold change(FC).Using the O-PLS-DA model,872 differentially abundant proteins were identified with variable importance projection(VIP)scores>1.Five proteins(gamma-glutamyl hydrolase,cathepsin F,interalpha-trypsin inhibitor heavy chain 5,latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1)overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired.Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades,cell adhesion,axon guidance,and glycosphingolipid biosynthesis compared to the HC group.Conclusion The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

关键词： Acute disseminated encephalomyelitis Cerebrospinal fluid Complement cascades Myelin oligodendrocyte glycoprotein-associated disease Proteomics

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Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

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Science China(Life Sciences) 2024年第1期67卷 113-121页

作者： Hui Zhu Taishun Li Peizhen Xu Lijun Ding Xianghong Zhu Bin Wang Xiaoqiu Tang Juan Li Pengfeng Zhu Huiyan Wang Chenyan Dai Haixiang Sun Jianwu Dai Yali Hu Department of Obstetrics and Gynecology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Biostatistics Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Gynecology Changzhou Maternal and Child Health Care HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China Clinical Center for Stem Cell Research Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Hematology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100190China

Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively

关键词： intrauterine adhesion Asherman’s syndrome uterine infertility autologous bone marrow stem cells transplantation endometrial regeneration ongoing pregnancy rate

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Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage

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Neural Regeneration Research 2024年第4期19卷 825-832页

作者： Jiatong Zhang Qi Zhu Jie Wang Zheng Peng Zong Zhuang Chunhua Hang Wei Li Department of Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University Department of Neurosurgery Nanjing Drum Tower HospitalClinical College of Nanjing Medical University

The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.

关键词： mitochondrial biogenesis mitochondrial dynamics mitochondrial dysfunction mitochondrial fission and fusion mitochondrial quality control mitophagy subarachnoid hemorrhage

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Animal models of hepatitis E infection: Advances and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 171-180页

作者： Ze Xiang Xiang-Lin He Chuan-Wu Zhu Jia-Jia Yang Lan Huang Chun Jiang Jian Wu Chinese Consortium for the Study of Hepatitis E(CCSHE) Zhejiang University school of Medicine Hangzhou 310030China Department of Infectious Diseases The Fifth People’s Hospital of SuzhouSuzhou 215007China Department of Infection Management The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China Department of Clinical Laboratory The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China 不详

Hepatitis E virus(HEV)is one of the leading causes of acute viral hepatitis worldwide.Although most of HEV infections are asymptomatic,some patients will develop the symptoms,especially pregnant women,the elderly,and patients with preexisting liver diseases,who often experience anorexia,nausea,vom-iting,malaise,abdominal pain,and jaundice.HEV infection may become chronic in immunosuppressed individuals.In addition,HEV infection can also cause several extrahepatic manifestations.HEV exists in a wide range of hosts in nature and can be transmitted across species.Hence,animals susceptible to HEV can be used as models.The establishment of animal models is of great significance for studying HEV transmission,clinical symptoms,extrahepatic manifestations,and therapeutic strategies,which will help us understand the pathogenesis,prevention,and treatment of hepatitis E.This review summarized the animal models of HEV,including pigs,monkeys,rabbits,mice,rats,and other animals.For each animal species,we provided a concise summary of the HEV genotypes that they can be infected with,the cross-species transmission pathways,as well as their role in studying extrahepatic manifestations,prevention,and treatment of HEV infection.The advantages and disadvantages of these animal models were also emphasized.This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

关键词： Hepatitis E virus Animal models Pathogenesis Prevention Treatment

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Design,synthesis,and biological evaluation of novel chrysin derivatives as poly(ADP-ribose)polymerase 1(PARP1)inhibitors for the treatment of breast cancer

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Chinese Journal of Natural Medicines 2024年第5期22卷 455-465页

作者： YANG Yao TONG Jing XIE Xianshun CAO Hong FU Yong LUO Yong LIU Shan CHEN Wen YANG Ning Hengyang Medical school University of South ChinaHengyang 421200China Emergency Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hengyang Medical school The Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hemato-oncology Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Department of Breast and Thyroid Surgery Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China

In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

关键词： Chrysin derivatives PARP1 Antitumor DNA damage Small molecules

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Effect of Guanxin Danshen Dripping Pills on Coronary Heart Disease Comorbid with Depression or Anxiety: The ADECODE-Real World Study

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Chinese Journal of Integrative Medicine 2024年第5期30卷 443-448页

作者： WU Shi-hao SHI Wei-qi LI Yu-hang LIU Ru-hui HU Da-yi ZHENG Li-qiang MA Wen-lin Department of Geriatric Medicine Tongji HospitalSchool of MedicineTongji UniversityShanghai 200065China Department of Cardiology Tongji HospitalSchool of MedicineTongji UniversityShanghai 200065China Department of Cardiology Peking University People's HospitalBeijing 100044China school of Public Health Shanghai Jiao Tong UniversityShanghai 200030China

Objective: To evaluate the efficacy of Guanxin Danshen Dripping Pill(GXDSDP) in treating anxiety and depression in patients with coronary heart disease(CHD). Methods: A total of 1,428 patients diagnosed with CHD screened for anxiety, depression, and quality of life(QOL) at baseline received 0.4 g of GXDSDP treatment 3 times per day and returned for monthly reassessment. Patients were recruited after stable treatment for CHD and received assessment of General Anxiety Disorder-7(GAD-7), Patient Health Questionnaire-9(PHQ-9), and Seattle Angina Questionnaire(SAQ) for evaluating anxiety, depression, and QOL.Patients were followed up 3 times, once every 4 weeks, during outpatient visits for 12 weeks. Results: At the third follow-up(F3), the anxiety symptom of 63.79%(673/1,055) of the patients improved to sub-clinical level, and the GAD-7 score improved significantly(8.11 vs. 3.87, P<0.01);57.52%(585/1,017) patients' depressive symptoms improved to sub-clinical level, with a significant improvement in PHQ-9 score(8.69 vs. 4.41, P<0.01) at F3. All aspects of QOL significantly improved at the end of treatment compared to those at baseline(all P<0.01) as assessed by SAQ: physical limitation(31.17 vs. 34.14), anginal stability(2.74 vs. 4.14), anginal frequency(8.16vs. 9.10), treatment satisfaction(13.43 vs. 16.29), and disease perception(8.69 vs. 11.02). Conclusions: A fixed dosage of GXDSDP may be a potential treatment option for CHD patients comorbid with anxiety or depression.(Registration No. ChiCTR2100051523)

关键词： Guanxin Danshen Dripping Pill coronary heart disease depression anxiety quality of life Chinese medicine

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Clinical pathological characteristics of“crawling-type”gastric adenocarcinoma cancer:A case report

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1660-1667页

作者： Yong-Wei Xu Yan Song Jun Tian Ba-Cui Zhang Yu-Sheng Yang Jing Wang Department of Gastroenterology Songjiang HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 201600China Department of Pathology Songjiang HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 201600China

BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.

关键词： Clinicopathological Crawling-type gastric Pathology Gastric cancer Gastric adenocarcinoma cancer Case report

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Increased N6-methyladenosine is related to the promotion of the methyltransferase METTL14 in ovarian aging

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Genes & Diseases 2024年第3期11卷 151-154页

作者： Chunfeng Qian Zhenxing Liu Yonghong Qian Jie Ding Rulei Chen Han Su Minghong Shen Hong Li Boxian Huang State Key Laboratory of Reproductive Medicine and Offspring Health Suzhou Affliated Hospital of Nanjing Medicine and Offspring HealthSuzhou Affiliated Hospital of Nanjing Medical UniversitySuzhouMunicipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215002China Department of Gynecology Affliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China Department of Pathology Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China

The ovary is a vital female reproductive organ that functions to produce oocyte gametes and cyclically expressed sex hormones to maintain reproductive capacity and hormone homeostasis.Ovarian aging,characterized by declines in follicle quantity and oocyte quality,leads to premature ovarian failure,premature ovarian insufficiency,or diminished ovarian reserve,thus contributing to female infertility.Distinct gene-expression signatures from RNA transcriptional level and post-transcriptional regulation are relative to oocyte quality and reproductive age.

关键词： promotion signature maintain

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