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Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 802-814页

作者： ye hu Chao {2. {3. Chen Yu-Dong Liu Jian-Gao Fan department of Gastroenterology Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina department of Geriatrics Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina department of Gastroenterology Changxing branch of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease(MASLD),the absence of licensed medications is striking.A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available *** therapies center on four major *** the close relationship between MASLD and type 2.diabetes,the first approach involves antidiabetic medications,including incretins,thiazolidinedione insulin sensitizers,and sodium-glucose cotransporter 2.*** second approach targets hepatic lipid accumulation and the resultant metabolic *** in this group include peroxisome proliferatoractivated receptor agonists(e.g.,pioglitazone,elafibranor,saroglitazar),bile acid-farnesoid X receptor axis regulators(obeticholic acid),de novo lipogenesis inhibitors(aramchol,NDI-010976),and fibroblast growth factor 2./19 *** third approach focuses on targeting oxidative stress,inflammation,and *** in this group include antioxi-dants(vitamin E),tumor necrosis factor a pathway regulators(emricasan,pentoxifylline,ZSP1601),and immune modulators(cenicriviroc,belapectin).The final group targets the gut(IMM-12.e,solithromycin).Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side *** review aimed to provide an update on these medications.

关键词： NAFLD MASLD Clinical trial Medication Hypoglycemic agents Intermediary metabolism

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Low temperature albitization in Caino-Mesozoic reservoir sandstones from North Tarim, and a discussion on the fluid origin

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Chinese Science Bulletin 1999年第S2期44卷 35-37页

作者： ye ying~1, hu shouxi~2.and sun jinggui~2.1. department of earth sciences, {2. University,{3., China 2. department of earth sciences, Nanjing University, Nanjing 2.0008, China department of earth {2. Zhejiang University Hangzhou 310027 China department of earth {2. Nanjing University Nanjing 210008 China

CAJNOZOIC and Mesozoic in North Tarim are predominantly a set of terrestrial detrital formations. In thereservoir sandstones in the area, albite is one of the widely developed authigenic mineral. Micro-structural evidence shows that diagenetic albite occurs as euhedral crystals in the pore, and replaces feldsparand other detritus along cleavage and micro-crack. EPMA analyzing found that some of the alteration product has a chemical composition between purealbite and the replaced detrital feldspar. For example, composition of replaced alkali feldspar is betweenmicrocline and albite, and content of altered plagioclase decreases continuously. This has been regardedas direct evidence for fluid replacement, for feldspar crystallized from solution or magma is usually withfixed chemical composition. Taking alkali feldspar as an example, although Kf and Ab forming completeisomorphous admixture in high temperature, they exsolved out as two relative pure phases while temperature decreases.

关键词： low temperature albitization sandstones fluid origin North Tarim.

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The Lanshantou Kyanite-bearing Eclogite with Coesite Inclusions in the Sulu Ultrahigh-Pressure Metamorphic Belt and Its PTt Path

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Acta Geologica Sinica(English Edition) 2001年第4期75卷 409-420页

作者： hu shouxi, {2. {3., LING Hongfei, ye ying, Fang Changquan and ZHAO Yiying department of earth sciences, Nanjing University, Nanjing 2.0008, Jiangsu department of earth sciences, zhejiang University, hangzhou 3.002., zhejiang department of earth {2. Zhejiang University Hangzhou 310027 Zhejiang [?]3.0} shouxi Born in 192. graduated from zhejiang University in 1952 now professor of geoscience at Nanjing University. His main research interests are mineral deposits and petrology. E-mail: hushouxi@***.

Coesite inclusions are found in kyanite from the Lanshantou eclogite in the Sulu ultrahigh-pressure (UHP) metamorphic belt. This discovery extends the stable region of kyanite to over 2.4 GPa. As an important UHP metamorphic belt in China, the Sulu eclogite belt is the product of A-subduction induced by strong compression of the yellow Sea terrane to the Jiaodong-northereastern Jiangsu terrane during the interaction of the Eurasian plate and Palaeo-Pacific plate in the Indosinian. It stretches about 3.0 km and contains over 1000 eclogite bodies. Most eclogites in this belt belong to Groups B and C in the classification of Coleman et al., and commonly contain kyanite, while the Lanshantou eclogite belongs to Group A and contains coesite. The MgO, CaO and FeO contents in garnet and pyroxene show regular variation from the core to the rim, which reveals the PTt paths of progressive metamorphism during the Early Mesozoic (2.0-2.0 Ma) and retrogressive metamorphism during the Late Mesozoic and Cenozoic exhumation.

关键词： coesite-bearing kyanite eclogite ultrahigh-pressure (UHP) metamorphic belt PTt path of subduction and exhumation

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Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory

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Neuroscience Bulletin 2024年第2期40卷 147-156页

作者： Minghong Su Kejia hu Wei Liu Yunhao Wu Tao Wang Chunyan Cao Bomin {2. Shikun Zhan Zheng {3. Institute of Psychology Chinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China department of Neurosurgery Center for Functional NeurosurgeryRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial *** stereoelectroencephalography(SEEG)study investigated how the dorsolateral prefrontal cortex(DLPFC)interacts with the hippocampus in the online processing of sequential *** patients with epilepsy(eight women,age 2..6±8.2.years)completed a line ordering task with SEEG recordings over the DLPFC and the *** showed longer thinking times and more recall errors when asked to arrange random lines clockwise(random trials)than to maintain ordered lines(ordered trials)before recalling the orientation of a particular ***,the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC(3.10 Hz).In particular,the hippocampal theta power increase correlated with the memory precision of line ***,theta phase coherences between the DLPFC and hippocampus were enhanced for ordering,especially for more precisely memorized ***,the theta band DLPFC→hippocampus influence was selectively enhanced for ordering,especially for more precisely memorized *** study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

关键词： Sequential working memory Hippocampus Dorsolateral prefrontal cortex Theta oscillations Stereoelectroencephalography(SEEG) Phase coherence Granger causality

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The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun Xu Kai Liu Cong Li Minghan Li Fangqi Liu Xiaoyan Zhou Menghong sun Megha Ranganathan Liying Zhang Sheng Wang Xin {2. {3. Xu department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China department of Pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA department of Pathology and Laboratory Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision Cancer Medical Center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 3.% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2.1. to December 2.1., we retrospectively enrolled 2.1.1 patients from 8,{3.0 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 46{3.pathogenic variants were detected in 19.3. of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of {3.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

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A Quasi-Linear Relationship between Planetary Outgoing Longwave Radiation and Surface Temperature in a Radiative-Convective-Transportive Climate Model of a Gray Atmosphere

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Advances in Atmospheric sciences 2024年第1期41卷 8-18页

作者： Jie sun Michael SECOR Ming CAI Xiaoming hu department of earth Oceanand Atmospheric ScienceFlorida State UniversityTallahasseeFlorida 32304USA School of Atmospheric sciences Sun Yat-sen University and Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Zhuhai 519082China Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies Zhuhai 519082China

In this study,we put forward a radiative-convective-transportive energy balance model of a gray atmosphere to examine individual roles of the greenhouse effect of water vapor,vertical convection,and atmospheric poleward energy transport as well as their combined effects for a quasi-linear relationship between the outgoing longwave radiation(OLR)and surface temperature(T_(S)).The greenhouse effect of water vapor enhances the meridional gradient of surface temperature,thereby directly contributing to a quasi-linear OLR-T_(S) *** atmospheric poleward energy transport decreases the meridional gradient of surface *** a result of the poleward energy transport,tropical(high-latitude)atmosphere-surface columns emit less(more)OLR than the solar energy input at their respective locations,causing a substantial reduction of the meridional gradient of the *** combined effect of reducing the meridional gradients of both OLR and surface temperature by the poleward energy transport also contributes to the quasi-linear OLR-T_(S) *** convective energy transport reduces the meridional gradient of surface temperature without affecting the meridional gradient of OLR,thereby suppressing part of the reduction to the increasing rate of OLR with surface temperature by the greenhouse effect of water vapor and poleward energy *** of the nature of the energy balance in the climate system,such a quasi-linear relationship is also a good approximation for the relationship between the annual-mean net downward solar energy flux at the top of the atmosphere and surface temperature.

关键词： outgoing longwave radiation greenhouse effect poleward energy transport

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Clinical features, treatment strategies and outcomes of craniocervical junction arteriovenous fistulas: a cohort study of 193.patients

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Stroke & Vascular Neurology 2024年第1期9卷 18-29页

作者： Yongjie Ma Zihao Song Yinqing Wang Jiachen Wang Chuan He Guilin Li Peng Zhang Tao Hong Liyong sun Peng hu Ming {3. Hongqi Zhang department of Neurosurgery Xuanwu Hospital Capital Medical University

Background Craniocervical junction(CCJ)arteriovenous fistulas(AVFs)are *** current treatment strategies for AVFs with different angioarchitecture need to be *** present study aimed to analyse the correlation between angioarchitecture and clinical characteristics,share our experience in treating this disease and identify risk factors associated with subarachnoid haemorrhage(SAH)and poor *** A total of 198 consecutive patients with CCJ AVFs from our neurosurgical centre were retrospectively *** patients were grouped according to their clinical manifestations,and their baseline clinical characteristics,angioarchitecture,treatment strategies and outcomes were *** The patients’median age was 56 years(IQR 47–62.years).The majority of patients were men with 166(83.8%)*** most common clinical manifestation was SAH(52.0%),followed by venous hypertensive myelopathy(VHM)(45.5%).The most common CCJ AVFs type was dural AVF,with 13.1}63.5%)*** most frequent fistula location was C-1(68.7%)and dural branch of vertebral artery(70.2.)was the most involved arterial feeders for *** most common direction of venous drainage was descending intradural drainage(40.9%),followed by ascending intradural drainage(3..5%).Microsurgery was the most common treatment strategy applied for 151(76.3.)patients,15(7.6%)patients were treated with interventional embolisation only,and 2.(13.6%)received both interventional embolisation and microsurgical *** learning curve for microsurgery only was analysed by cumulative summation method,and the turning point was the 70th case,and blood loss in post-group was lower than that in pre-group(p=0.03.).At the last follow-up,there were 155(78.3.)patients with favourable outcomes(modified Rankin Scale(mRS)3..Age≥56(OR 2.03.,95%CI 1.03. to 3.998,p=0.03.),VHM as the clinical manifestation(OR 4.102.95%CI 2.1.8 to 7.982.p3.OR 3.12.,95%CI 1.617 to 6.047,p<0

关键词： patients treatment hypertensive

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A land surface model incorporated with soil freeze/thaw and its application in GAME/Tibet

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Science China earth sciences 2006年第12期49卷 1311-1322页

作者： hu Heping1, ye Baisheng2. ZHOU Yuhua3.& TIAN Fuqiang1 1. department of Hydraulic Engineering, Tsinghua University, Beijing 100084, China 2. Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of sciences, Lanzhou 73.000, China 3. department of Civil Engineering, Massachusetts Institute of Technology, USA 1. department of Hydraulic Engineering Tsinghua University Beijing 100084 China 2. Cold and Arid Regions Environmental and Engineering Research Institute Chinese Academy of Sciences Lanzhou 730000 China 3. department of Civil Engineering Massachusetts Institute of Technology USA

Land surface process is of great importance in global climate change, moisture and heat exchange in the interface of the earth and atmosphere, human impacts on the environment and eco- system, etc. Soil freeze/thaw plays an important role in cold land surface processes. In this work the diurnal freeze/thaw effects on energy partition in the context of GAME/Tibet are studied. A sophisti- cated land surface model is developed, the particular aspect of which is its physical consideration of soil freeze/thaw and vapor flux. The simultaneous water and heat transfer soil sub-model not only reflects the water flow from unfrozen zone to frozen fringe in freezing/thawing soil, but also demon- strates the change of moisture and temperature field induced by vapor flux from high temperature zone to low temperature zone, which makes the model applicable for various circumstances. The modified Picard numerical method is emplo{2.d to help with the water balance and convergence of the numerical scheme. Finally, the model is applied to analyze the diurnal energy and water cycle char- acteristics over the Tibetan Plateau using the Game/Tibet datasets observed in May and July of 1998. Heat and energy transfer simulation shows that: (i) There exists a negative feedback mechanism between soil freeze/thaw and soil temperature/ground heat flux; (ii) during freezing period all three heat fluxes do not vary apparently, in spite of the fact that the negative soil temperature is higher than that not considering soil freeze; (iii) during thawing period, ground heat flux increases, and sensible heat flux decreases, but latent heat flux does not change much; and (iv) during freezing period, soil temperature decreases, though ground heat flux increases.

关键词： land surface model,soil freeze/thaw,GAME/Tibet,simultaneous liquid,vapor and heat transfer.

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Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

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Chinese Journal of Cancer Research 2024年第3期36卷 257-269页

作者： Jian Li ye Xu Aimin Zang Yunong Gao Quanli Gao Yanqiao Zhang Dong Wang Jianming Xu ying Yuan Haiping Jiang Jieer ying C{3.nmei Shi Yanhong Deng Jing Wang Tians{3. Liu Yi {3.ang Xiaoping Qian Yueyin Pan ying Cheng Sheng {3. Jin Wang Mengyue Shi Ke Wang Han {3. Lin Shen State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China department of Oncology Fudan University Shanghai Cancer CenterShanghai 200032China department of Medical Oncology Affiliated Hospital of Hebei UniversityBaoding 071000China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of GynecologyPeking University Cancer Hospital&InstituteBeijing 100142China department of Immunotherapy Henan Cancer HospitalZhengzhou 450001China department of Gastrointestinal Oncology Affiliated Cancer Hospital of Harbin Medical UniversityHarbin 150086China department of Gastrointestinal Oncology Chongqing University Cancer HospitalChongqing 400030China department of Gastrointestinal Oncology the Fifth Medical CenterChinese PLA General HospitalBeijing 100048China department of Medical Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Medical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Medical Oncology Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China department of Medical Oncology Fujian Medical University Union HospitalFuzhou 350001China department of Oncology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China department of Medical Oncology Hunan Cancer HospitalChangsha 410013China department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China department of Immunotherapy Hubei Cancer HospitalWuhan 430079China department of Medical Oncology the Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China department of Medical Oncology Anhui Provincial HospitalHefei 230001China department of Medical Oncology Jilin Cancer Hospital

Objective:The open-label,phase II RATIONALE-2.9 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)***:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were *** received tislelizumab 2.0 mg intravenously every 3.*** response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at *** had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2.2.;median follow-up 15.2.months),overall ORR[46.7%;95%confidence interval(95%CI),3..1−58.6;one-sided P1]and ORR across tumor-specific subgroups[colorectal(n=46):3..1%(95%CI,2..1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,2..2.86.3.;others(n=2.):60.0%(95%CI,3..1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete *** DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2.2.;median follow-up 2..9 months).Tislelizumab was well tolerated with no unexpected safety ***-related adverse events(TRAEs)of grade≥3.occurred in 53.8%of patients;7.5%of patients discontinued treatment due to ***:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

关键词： Biomarkers DNA mismatch repair immune checkpoint inhibitors microsatellite instability phase II clinical trials programmed cell death 1 receptor

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

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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 {2. 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 2.1.(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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