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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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Preliminary exploration of animal models of congenital choledochal cysts

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World Journal of Gastroenterology 2024年第10期30卷 1420-1430页

作者： Shu-Hao Zhang Yue-Bin Zhang Duo-Te Cai Tao Pan Ken Chen Yi Jin Wen-Juan Luo Zong-Wei Huang Qing-Jiang Chen zhi-gang gao Department of General Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing *** surgical techniques can achieve satisfactory outcomes for treatment of ***,recent studies have focused more on clinical issues rather than basic ***,we need appropriate animal models to further basic *** To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of *** Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile *** reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human *** Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical *** levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after *** of the biochemical indices gradually decreased to normal ranges 28 d after *** protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC *** The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.

关键词： Choledochal cyst Animal model Partial ligation Cystic and fusiform dilation Juvenile rats

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Schedulability analysis for linear transactions under fixed priority hybrid scheduling

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2008年第6期9卷 776-785页

作者： zhi-gang gao Zhao-hui WU School of Computer Science and Technology Zhejiang University Hangzhou 310027 China

In hard real-time systems, schedulability analysis is not only one of the important means of guaranteeing the timelines of embedded software but also one of the fundamental theories of applying other new techniques, such as energy savings and fault tolerance. However, most of the existing schedulability analysis methods assume that schedulers use preemptive scheduling or non-preemptive scheduling. In this paper, we present a schedulability analysis method, i.e., the worst-case hybrid scheduling (WCHS) algorithm, which considers the influence of release jitters of transactions and extends schedulability analysis theory to timing analysis of linear transactions under fixed priority hybrid scheduling. To the best of our knowledge, this method is the first one on timing analysis of linear transactions under hybrid scheduling. An example is employed to demonstrate the use of this method. Experiments show that this method has lower computational complexity while keeping correctness, and that hybrid scheduling has little influence on the average worst-case response time (WCRT), but a negative impact on the schedulability of systems.

关键词：可调度性分析线性分析实时系统响应时间计算机技术

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Management of foreign bodies ingestion in children

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World Journal of Pediatrics 2022年第12期18卷 854-860页

作者： Qing-Jiang Chen Lin-Yan Wang Yi Chen Jia-Jin Xue Yue-Bin Zhang Li-Feng Zhang Yun-Zhong Qian Qi-Xing Xiong zhi-gang gao Department of Pediatric General Surgery National Center for Clinical Medicine of Children’s Health and DiseaseChildren’s HospitalZhejiang University School of MedicineNational Children’s Regional Medical Center3333 Binsheng RoadBinjiang DistrictHangzhou310052China

Foreign bodies(FBs)ingestion in children is one of the common presentations to the emergency *** majority of FBs ingestion occurs in children younger than 3 years,with males showing a slight predominance[1].Although most FBs pass through the gastrointestinal tract spontaneously,some FBs need urgent medical intervention and even surgical management owing to the complications of obstruction or perforation and a potential risk to children’s health[2].Therefore,timely diagnosis and rational treatment are crucial for reducing FBs ***,optimal indications and/or timing of surgery remain *** this study,we discussed the characteristics of FBs ingestion in children and summarized our experience in its management.

关键词： diagnosis younger children

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： gang Zhou Siyuan Pang Yongning Li Jun gao Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of International Medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in *** emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past *** literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal ***,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional *** qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue *** utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord ***,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational *** of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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A novel alternative for pyrogen detection based on a transgenic cell line

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1221-1229页

作者： Qing He Chuan-Fei Yu gang Wu Kai-Qin Wang Yong-Bo Ni Xiao Guo zhi-Hao Fu Lan Wang De-Jiang Tan Hua gao Can Wang gang Chen Xu-Hong Chen Bo Chen Jun-zhi Wang National Institutes for Food and Drug Control BeijingChina School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyangChina Shanghai Institute for Food and Drug Control ShanghaiChina KeyMed Biosciences Inc. ChengduChina

Pyrogen,often as a contaminant,is a key indicator affecting the safety of almost all parenteral drugs(including biologicals,chemicals,traditional Chinese medicines and medical devices).It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted‘reduction,replacement and refinement’principle,which has been highly considered by regulatory agencies from different *** used NF-κB,a central signalling molecule mediating inflammatory responses,as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence ***,we show that this test can quantitatively and sensitively detect endotoxin(lipopolysaccharide from different strains)and nonendotoxin(lipoteichoic acid,zymosan,peptidoglycan,lectin and glucan),has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals(group A&C meningococcal polysaccharide vaccine;basiliximab;rabies vaccine(Vero cells)for human use,freeze-dried;Japanese encephalitis vaccine(Vero cells),inactivated;insulin aspart injection;human albumin;recombinant human erythropoietin injection(CHO Cell)).The within-laboratory reproducibility of the test in three independent laboratories was 85%,80%and 80%and the interlaboratory reproducibility among laboratories was 83.3%,95.6%and 86.7%.The sensitivity(true positive rate)and specificity(true negative rate)of the test were 89.9%and 90.9%,*** summary,the test provides a novel alternative for pyrogen detection.

关键词： pyrogen rabbit replace

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Diagnosis,treatment,and prevention of severe acute hepatitis of unknown etiology in children

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World Journal of Pediatrics 2022年第8期18卷 538-544页

作者： Ying‑Hu Chen Jin‑Gan Lou Zi‑Hao Yang Qing‑Jiang Chen Chun‑Zhen Hua Sheng Ye Chen‑Mei Zhang Jie Chen Zong‑Wei Huang Jin‑Dan Yu zhi‑gang gao Qiang Shu Infectious Disease Department National Clinical Research Center for Child HealthChildren’s HospitalZhejiang University School of MedicineHangzhou 310052China Gastroenterology Department National Clinical Research Center for Child HealthChildren’s HospitalZhejiang University School of MedicineHangzhou 310052China PICU National Clinical Research Center for Child HealthChildren’s HospitalZhejiang University School of MedicineHangzhou 310052China General Surgery Department National Clinical Research Center for Child HealthChildren’s HospitalZhejiang University School of MedicineBinsheng Road 3333Hangzhou 310052China

Background Severe acute hepatitis of unknown etiology in children has recently exhibited a global trend of concentrated *** review aimed to summarize the current available information regarding the outbreak of severe acute hepatitis and introduce our hospital’s previous experiences with the diagnosis and treatment of severe acute hepatitis for *** sources Websites including the UK Health Security Agency,European Centre for Disease Prevention and Control,CDC,WHO,and databases including PubMed/Medline,Cochrane Library,Embase and Web of Science were searched for articles on severe acute hepatitis in *** As of May 26,2022,a total of 650 cases have been reported in 33 countries;at least 38(6%)children required liver transplantation,and nine(1%)*** are predominantly aged between 3 and 5 years old,and there are no epidemiological links among *** common manifestations are jaundice,vomiting and pale *** tested positive in most cases,and SARS-CoV-2 and other viruses were detected in a few cases,but virus particles were not found in liver *** immunohistochemistry showed immunoreactivity in the intrasinusoidal lumen from some liver *** hierarchical treatment includes symptomatic and supportive therapy,management of coagulation disorders and hepatic encephalopathy,artifcial liver support,and liver transplantation(approximately 6%–10%of cases require liver transplant).Conclusions The etiology of this severe acute hepatitis in children is not *** clinical features are severe acute hepatitis with signifcantly elevated liver *** need to be alert to children with hepatitis.

关键词： Acute Hepatitis Diagnosis Epidemiology Pediatrics Treatment

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Preliminary Outcome of Individualized Abdominoperineal Excision for Locally Advanced Low Rectal Cancer

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Chinese Medical Journal 2018年第11期131卷 1268-1274页

作者： Yi Zheng Jia-gang Han Zhen-Jun Wang zhi-gang gao Guang-Hui Wei zhi-Wei Zhai Bao-Cheng Zhao Department of General Surgery Beijing Chaoyang Hospital Capital Medical University Beijing 100020 China

Background： The introduction of individualized abdominoperineal excision （APE） may minimize operative trauma and reduce the rate of complications. The purpose of this study was to evaluate the safety and efficacy of individualized APE for low rectal cancer. Methods： Fifty-six patients who underwent individualized APE from June 2011 to June 2015 were evaluated retrospectively in Beijing Chaoyang Hospital, Capital Medical University. The main outcome measures were circumferential resection margin （CRM） involvement, intraoperative perforation, postoperative complications, and local recurrence. Statistical analysis was performed using SPSS version 16.0. Results： Fifty （89%） patients received preoperative chemoradiotherapy： 51 （91%） patients were treated with the sacrococcyx preserved; 27 （48%） patients with the levator ani muscle partially preserved bilaterally; 20 （36%） patients with the levator ani muscle partially preserved unilaterally and the muscle on the opposite side totally preserved; 7 （13%） patients with intact levator ani muscle and part of the ischioanal fat bilaterally dissected; and 2 （4%） patients with part of the ischioanal fat and intact lavator ani muscle dissected unilaterally and the muscle on the opposite side partially preserved. The most common complications included sexual dysfunction （12%）, perineal wound complications （13%）, urinary retention （7%）, and chronic perineal pain （5%）. A positive CRM was demonstrated in 3 （5%） patients, and intraoperative perforations occurred in 2 （4%） patients. On multiple logistic regression analysis, longer operative time （P = 0.032） and more intraoperative blood loss （P = 0.006） were significantly associated with perineal procedure-related complications. The local recurrence was 4% at a median follow-up of 53 months （range： 30–74 months）. Conclusion： With preoperative chemoradiotherapy, individualized APE may be a relatively safe and feasible approach for low rectal cancer with acceptable oncological outcomes.

关键词： Abdominoperineal Excision Complications Individualized Low Rectal Cancer Recurrence

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The effects of cool materials,façade orientation,and morphological parameters on energy consumption at the residential neighborhood scale

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Building Simulation 2024年第4期17卷 525-542页

作者： Fusuo Xu Dongdong Tian zhi gao Jianshun Jensen Zhang Department of Mechanical and Aerospace Engineering Syracuse UniversitySyracuseNY13210USA School of Architecture and Urban Planning Nanjing University22 Hankou RoadNanjingJiangsu Province210093China

Building surface cool materials are novel materials that can reduce urban heat island intensity and decrease building energy *** study investigated the impact of radiative properties of materials,façade orientation,and morphological parameters on energy consumption in six typical residential neighborhoods in Nanjing,*** neighborhood energy consumption of 16 application schemes considering the façade orientation factor is compared to determine the best energy-saving *** and annual energy-saving rates,savings in electricity costs,and the price ceiling for materials per unit area are *** results show that for low-rise buildings,using cool materials only on the roof can reduce the annual energy consumption by 1%.When cool or super cool materials are also used on the building façade,the annual energy saving rate can be up to 3.4%and 4.3%,*** cool materials on the south façade of buildings is not recommended due to significant heat loss in *** savings in electricity costs and the price ceiling for materials per unit area,the price of cool and super cool materials should be less than 3.0 and 3.7 RMB/m2,respectively,assuming a lifespan of eight years in Nanjing.

关键词： cool materials building energy saving neighborhood morphology façade orientation

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Spatial covariant gravity with two degrees of freedom in the presence of an auxiliary scalar field:Perturbation analysis

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Chinese Physics C 2024年第8期48卷 198-212页

作者： zhi-Chao Wang Xian gao School of Physics and Astronomy Sun Yat-sen UniversityZhuhai 519082China

We investigate a class of gravity theories respecting only spatial covariance,termed spatially covariant gravity,in the presence of an auxiliary scalar *** examine the conditions on the Lagrangian required to eliminate scalar degrees of freedom,allowing only two tensorial degrees of freedom to *** of strict constraint analysis,in this paper,we employ the perturbation method and focus on the necessary conditions to evade the scalar mode at the linear order in perturbations around a cosmological *** with a general action and solving the auxiliary perturbation variables in terms of a would-be dynamical scalar mode,we derive the condition to remove its kinetic term,thus ensuring that no scalar mode *** an application of the general condition,we study a polynomial-type Lagrangian as a concrete example,in which all monomials are spatially covariant scalars containing two *** find that the auxiliary scalar field is essential,and new terms in the Lagrangian are *** analysis provides insights into constructing gravity theories with two degrees of freedom in the extended framework of spatially covariant gravity.

关键词： modified gravity cosmological perturbation theory gravitational theory

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