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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 of 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 ***,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from ***,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 *** sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang *** 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 *** respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be *** 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 *** 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 *** 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 *** Severe pediatric COVID-19 can affect multiple organ *** dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the

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

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Cell replacement with stem cell-derived retinal ganglion cells from different protocols

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Neural Regeneration Research 2024年第4期19卷 807-810页

作者： Ziming Luo Kun-Che Chang Spencer Center for Vision Research Byers Eye InstituteStanford University School of Medicine Department of Ophthalmology Louis J.Fox Center for Vision RestorationUniversity of Pittsburgh School of Medicine Department of Neurobiology Center of NeuroscienceUniversity of Pittsburgh School of Medicine

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness *** is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after *** stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative *** this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation ***,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and *** review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

关键词： cell clumps cell suspension cell transplantation differentiation direct-induced protocol glaucoma optic neuropathy regenerative medicine retinal ganglion cell retinal organoids stem cells

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A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections

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Frontiers of medicine 2024年第1期18卷 169-179页

作者： Xu Hao Zhiyao Bao Ranran Dai Xiaojing Wu Xin Li Muyin Zhang Hao Li Lili Xu Panpan Qiao Xuefei Liu Weiting Hu Ze Zhang Jie Fang Min Zhou Weiming Wang Jieming Qu Department of Nephrology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Department of Pulmonary and Critical Care medicine Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Institute of Respiratory Diseases Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Pharmacy Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were *** parameters and chest CT(computed tomography)imaging were *** treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic *** serious adverse reactions or safety events were *** control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P<0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day ***,83.3%of the patients in the treatment group and 57.1%of the patients in the control group turned negative within 22 *** the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day *** therapy showed a potential therapeutic effect with good tolerance in hemodialysis *** optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

关键词： Paxlovid hemodialysis SARS-CoV-2 viral load chest CT scan

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Dietary cooking oils and cardiometabolic measurements in an elderly Chinese population

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Journal of Geriatric Cardiology 2024年第6期21卷 642-650页

作者： Xin-Yu WANG Chao-Ying MIAO Xiao-Fei YE Wen-Yuan-Yue WANG Jia-Bo ZHU Yi ZHOU Yan LI Ji-Guang WANG school of Public Health Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Cardiovascular medicine Centre for Epidemiological Studies and Clinical TrialsThe Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese *** The elderly(≥65 years)participants for this study were recruited from two community health centers in the urban area of Shanghai.A questionnaire was administered to collect information on dietary oil consumption(low,medium and high)and cooking styles(fry or stir-fry ***)and the composition of fatty acids(poly-unsaturated ***-unsaturated).The cardiometabolic measurements included anthropometry,blood pressure,fasting plasma glucose and serum *** The 1186 study participants had a mean age of 70.9±5.4 *** mean dietary oil consumption was 35.0 g/d,being low(<25 g/d),medium(25-49 g/d)and high(≥50 g/d)in 485,467 and 234 participants,*** proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4%and 27.4%,*** before and after adjustment for sex,age,current smoking and alcohol intake,dietary oil consumption was significantly(P≤0.02)and positively associated with the prevalence of treated hypertension and fasting plasma glucose *** similar adjustments as above and additional adjustment for dietary oil consumption,the fry or stir-fry cooking style was significantly(P≤0.048)and positively associated with body mass index,but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol,and the dietary intake of oils rich in mono-unsaturated fat acids was significantly(P≤0.02)and positively associated with diastolic blood pressure,serum triglycerides,total cholesterol and low-density lipoprotein cholesterol,and the prevalence of hypertriglyceridemia and *** This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to sev

关键词： cooking elderly unsaturated

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AZGP1P2/UBA1/RBM15 Cascade Mediates the Fate Determinations of Prostate Cancer Stem Cells and Promotes Therapeutic Effect of Docetaxel in Castration-Resistant Prostate Cancer via TPM1 m6A Modification

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Research 2024年第3期6卷 151-167页

作者： Hong Wang Jj Liu Xiaojun Zhu Bin Yang Zuping He Xudong Yao Department of Urology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina Urologic Cancer Institute School of MedicineTongji UniversityShanghaiChina. Department of Urology Surgery The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotChina. The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province School of MedicineHunan Normal UniversityThe Engineering Research Center of Reproduction and Translational Medicine of Hunan ProvinceChangshaChina Shanghai Key Laboratory of Reproductive medicine Shanghai Jiao Tong University School of MedicineShanghaiChina.

Prostate cancer(PCa)is a common malignant tumor with high morbidity and mortality *** prostate cancer stem cell(PCSC)model provides novel insights into the pathogenesis of PCa and its therapeutic ***,the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be *** this study,we have explored the expression,function,and mechanism of AZGP1P2,a pseudogene of AZGP1,in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer(CRPC).We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs,while it was positively associated with progression-free *** of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their *** pull-down associated with mass spectrometry analysis,co-immunoprecipitation assay,and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a“writer”of methyltransferase to form a ***1,an E1 ubiquitin-activating enzyme,contributed to RBM15 protein degradation via ubiquitination *** RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A ***,a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in ***,these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.

关键词： Prostate TPM1 m6A

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Long-Term Survival Trend of Gynecological Cancer:A Systematic Review of Population-Based Cancer Registration Data

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Biomedical and Environmental Sciences 2024年第8期37卷 897-921页

作者： Xiaohui Zhou Danni Yang Yixin Zou Dandan Tang Jun Chen Zhuoying Li Qiuming Shen Qun Xu Yongbing Xiang Department of Epidemiology&State Key Laboratory of Systems medicine for Cancer Shanghai Cancer InstituteRenji HospitalShanghai Jiaotong University School of MedicineShanghai 200032China school of Public Health Shanghai Jiaotong University School of MedicineShanghai 200025China school of Public Health Fudan UniversityShanghai 200025China Health Management Center Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200127China

Gynecological cancer significantly affect the health of *** review aimed to describe the global patterns and trends in the survival of patients with gynecological *** searched PubMed,Embase,Web of Science,SinoMed,and SEER for survival analyses of cancer registration data of cervical,endometrial,and ovarian cancers published between 1980 and ***,the highest 5-year observed survival rate for cervical cancer was 76.5% in Anshan,Liaoning,China(2008-2017).The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland(1995-1999,82.5%)and Singapore(1988-1992,62.0%).The 5-year relative survival rate of cervical cancer patients was higher in Haining,Zhejiang,China(2011-2014,85.8%).Korea ranked first at 89.0% and 64.5% for endometrial and ovarian cancers,*** rates have improved for cervical,endometrial,and ovarian *** aged≥75 years and those with advancedstage disease had the worst 5-year survival *** rates were better for squamous cell carcinoma in cervical cancer,for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer,and for germ cell and sex-cord stromal tumors in ovarian *** the past four decades,the survival rates of gynecological cancers have increased globally,with notable increases in cervical and endometrial *** rates are higher in developed countries,with a slow-growing *** studies should focus on improving survival,especially in ovarian cancer patients.

关键词： Survival Cancer globally

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Targeted delivery of factors and cells for improving cardiac tissue regeneration and heart function following myocardial infarction

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Engineered Regeneration 2024年第2期5卷 210-227页

作者： Kamila Raziyeva Zharylkasyn Zharkinbekov Yevgeniy Kim Arman Saparov school of medicine Nazarbayev UniversityAstana 010000Kazakhstan

Following myocardial infarction(MI),cardiac tissue undergoes irreversible cellular alterations,with cardiomy-ocytes being replaced by fibrotic *** order to improve tissue regeneration,a previously characterized chitosan-based cryogel,which was designed by our group,was *** treatment regimen involved the sequen-tial delivery of the cryogel loaded with specific cytokines and growth factors,followed by a separate injection of pre-differentiated ***,the cryogel loaded with interleukin-10 and transforming growth factor-βwas injected into infarcted tissue immediately after MI induction,targeting the acute inflammatory *** day four post-MI,a second injection was administered,this time utilizing cryogel loaded with vascular endothelial growth factor and fibroblast growth factor-2,aimed at promoting tissue regeneration and ***-quently,on day six post-MI,the experimental group received cardiomyocyte-like cells,smooth muscle cells,and endothelial *** purpose of these cells,in synergy with cytokines and growth factors,was to repopulate the lost cellular populations,thereby enhancing myocardial *** treatment improved myocardial tissue regeneration,increased cardiac output,ejection fraction,and reduced fibrotic ***,the chitosan-based cryogel,enriched with anti-inflammatory and proangiogenic factors and supplemented with pre-differentiated cells,offers a promising platform for controlled release of therapeutics,promoting substantial tissue repair and regeneration following MI.

关键词： Myocardial infarction Tissue regeneration Cryogel Growth factors Stem cells

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Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution

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Journal of Traditional Chinese medicine 2024年第1期44卷 188-196页

作者： ZHU Linghui SUN Ziwei GUAN Yuanyuan LIU Meiyi ZHENG Yi YU Ruoxi WANG Qi LI Lingru school of Chinese medicine Beijing University of Chinese MedicineBeijing 102488China National Institute of TCM Constitution and Preventive medicine Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study *** clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome *** differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were ***:There were no statistical differences found in the baseline *** vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial *** are 66 differentially expressed serum proteins between the two *** A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with ***:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese ***,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD.

关键词： obesity phlegm-dampness constitution vascular endothelial function proteome reactive hyperemia index

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Intranasal administration of stem cell-derived exosomes for central nervous system diseases

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Neural Regeneration Research 2024年第6期19卷 1249-1255页

作者： Shuho Gotoh Masahito Kawabori Miki Fujimura Department of Neurosurgery Hokkaido University Graduate School of MedicineHokkaidoJapan

Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular *** nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive *** findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system *** exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic ***,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug ***,researchers have turned their attention to exosomes as a novel therapeutic ***,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical *** overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous *** exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain ***,exosomes,owing to their small size,can readily access the nerve pathways using this *** a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased *** this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system ***,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

关键词： central nervous system disease exosome extracellular vesicle intranasal administration stem cell

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CRISPR-Cas9 gene editing strengthens cuproptosis/chemodynamic/ferroptosis synergistic cancer therapy

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4059-4072页

作者： Xiaoyu Wu Zijun Bai Hui Wang Hanqing Wang Dahai Hou Yunzhu Xu Guanqun Wo Haibo Cheng Dongdong Sun Weiwei Tao Department of Surgical Oncology Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China school of Integrated medicine Nanjing University of Chinese MedicineNanjing 210023China Jiangsu Collaborative Innovation Center of Traditional Chinese medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjing 210023China school of Pharmacology Nanjing University of Chinese MedicineNanjing 210023China school of Pharmacology Ningxia Medical UniversityYinchuan 750004China

Copper-based nanomaterials demonstrate promising potential in cancer *** efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione,initiating chemical dynamic therapy(CDT)and ***,a newly identified cell death modality that represents a great prospect in cancer therapy,is ***,active homeostatic systems rigorously keep copper levels within cells exceptionally low,which hinders the application of cooper nanomaterials-based ***,a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is *** Cu2O and organosilica shell would degrade under the high level of glutathione and weak acidic environment,further releasing RNP and *** liberated Cut triggered a Fenton-like reaction for CDT and partially transformed to Cu2t,consuming intracellular GSH and initiating cuproptosis and ferroptosis ***,the release of RNP effectively reduced the expression of copper transporter ATP7A,subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT,cuproptosis,and *** tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis.

关键词： GSH-and pH-responsive Effective copper delivery CRISPR-Cas9 ATP7A Cuproptosis Chemodynamic Ferroptosis Synergistic therapy

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