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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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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 *** 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 *** partial least squares-discriminant analysis(PLs-DA)and orthogonal PLs-DA(O-PLs-DA)models were also performed based on proteomics *** analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and *** enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with *** 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>*** 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 *** 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 *** 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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Delivering Microrobots in the Musculoskeletal system

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Nano-Micro Letters 2024年第11期16卷 585-617页

作者： Mumin Cao Renwang sheng Yimin sun Ying Cao Hao Wang Ming Zhang Yunmeng Pu Yucheng Gao Yuanwei Zhang Panpan Lu Gaojun Teng Qianqian Wang Yunfeng Rui Department of Orthopaedics Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsuPeople’s Republic of China school of medicine Southeast UniversityNanjing 210009People’s Republic of China Orthopaedic Trauma Institute(OTI) Southeast UniversityNanjing 210009People’s Republic of China Jiangsu Key Laboratory for Design and Manufacture of Micro‑Nano Biomedical Instruments School of Mechanical EngineeringSoutheast UniversityNanjing 210009People’s Republic of China Center of Interventional Radiology and Vascular surgery Department of RadiologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjing 210009People’s Republic of China

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited *** often suffer chronic pain and might eventually have to undergo end-stage ***,future treatments should focus on early detection and intervention of regional *** have been gradually used in organisms due to their advantages of intelligent,precise and minimally invasive targeted *** the combination of control and imaging systems,microrobots with good biosafety can be delivered to the desired area for *** the musculoskeletal system,microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the *** to traditional biomaterial and tissue engineering strategies,active motion improves the efficiency and penetration of local targeting of cells/*** review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal *** summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

关键词： Microrobot Musculoskeletal system Targeted delivery Microrobotic systems Magnetic actuation

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Multidimensional Analgesia of Acupuncture by Increasing Expression of MD2 in Central Nervous system

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Chinese Journal of Integrative medicine 2024年第11期30卷 1035-1044页

作者： LI Wan-rong REN Lu-lu ZHAO Tian-tian DAI Dan-qing GAO Xiao-fei LIANG Hua-zheng XIONG Li-ze shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Shanghai Fourth People's Hospital School of Medicine Tongji University Clinical Research Center for Anesthesiology and Perioperative medicine Shanghai Fourth People's Hospital School of Medicine Tongji University Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University Department of Anesthesiology and Perioperative medicine Shanghai Fourth People's Hospital School of Medicine Tongji University school of Rehabilitation Southwest Jiaotong University Monash suzhou Research Institute

Objective:To investigate changes of myeloid differentiation factor 2（MD2） in inflammationinduced pain and acupuncture-mediated ***:Mice were randomly divided into three groups by a random number table method:saline group（n=16）,complete Freund's adjuvant（CFA） group（n=24） and CFA+electroacupuncture（EA） group（n=26）.Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli（sT 36） to alleviate *** mice in the CFA+EA group received EA treatment（30 min/d for 2 weeks） 24 h after *** in the saline and CFA groups received sham ***-Frey test and Hargreaves test were used to assess the pain *** and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 ***:CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling（Ps+neurons was significantly increased in the dorsal horn of the spinal cord 7 and 14 days after EA,especially in laminae Ⅰ-Ⅱ_o（Psitive cells to the number of c-fos positive cells and the mean fluorescence intensity of MD2 neurons were also significantly increased in laminae Ⅰ-Ⅱ_o（Pstern blotting showed that the level of MD2 was significantly decreased by EA only in the hippocampus on day 7 and 14（both Psignificant changes were observed in the cortex,thalamus,cerebellum,or the brainstem（P>0.05）.Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray（PAG） and locus coeruleus（LC） after CFA injection on day 7（Psignificantly reversed this decrease（Psion:The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certai

关键词： dorsal horn electroacupuncture inflammation-induced pain locus coeruleus myeloid differentiation factor 2 periaqueductal gray

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EGFR-targeted and gemcitabine-incorporated chemogene for combinatorial pancreatic cancer treatment

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Nano Research 2024年第2期17卷 848-857页

作者： Miao Xie Qiushuang Zhang Yuanyuan Guo Lijuan Zhu Xinyuan Zhu Chuan Zhang school of Chemistry and Chemical Engineering Frontiers Science Center for Transformative MoleculesInstitute of Molecular MedicineSixth people’s HospitalSchool of MedicineShanghai Key Laboratory for Molecular Engineering of Chiral DrugsShanghai Jiao Tong UniversityShanghai 200240China Department of Radiology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200233China Institute of Molecular medicine Shanghai Jiao Tong University Affiliated Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Pancreatic cancer stands out as a recognized intractable tumor due to its high malignancy and mortality rates,which are largely attributed to the insensitivity of current clinical chemotherapies or *** chemo and gene therapy that integrates different therapeutic targets,may increase the chemosensitivity of pancreatic cancer and synergistically enhance the antitumor ***,conventional co-delivery of gene and chemo drugs is intensively dependent on complex nanoparticle delivery systems,thus would be limited by unstable drug packaging,nonspecific biodistribution,and biosafety ***,we rationally designed an epidermal growth factor-receptor(EGFR)-targeted and gemcitabine-incorporated oligonucleotide(termed as chemogene)with anti-Bcl-2 sequence,which achieves simple and precise integration of gemcitabine into a gene regulative agent,as well as the EGFR-targeted delivery for pancreatic cancer *** solid-phase synthesis,gemcitabine,as the first-line chemodrug for pancreatic cancer,is introduced to the antisense oligonucleotide to replace all cytosine nucleosides to obtain the gemcitabine-integrated chemogene(Ge-AsO^(Bcl-2)).Thereafter,Ge-AsO^(Bcl-2)is covalently coupled with EGFR nanobody to construct the final targeted chemogene without any exogenous ***,this nanobody-conjugated chemogene exhibits remarkable tumor targeting capability and antitumor effects both in vitro and in vivo,which initiates a first step toward the application of combinatorial chemo and gene therapy for future pancreatic cancer treatment.

关键词： antisense oligonucleotide chemogene nanobody drug delivery system pancreatic cancer

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Targeting CD47-sIRPα axis for Hodgkin and non-Hodgkin lymphoma immunotherapy

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Genes & Diseases 2024年第1期11卷 205-217页

作者： Pengcheng Zhao Longyan Xie Lei Yu Ping Wang school of Life sciences and medicine Shandong University of TechnologyZiboShandong 255000China Tongji university Cancer Center Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200092China

The interaction between cluster of differentiation 47(CD47)and signal regulatory proteinα(siRPa)protects healthy cells from macrophage attack,which is crucial for maintain-ing immune *** of CD47 occurs widely across various tumor cell types and transmits the"don't eat me"signal to macrophages to avoid phagocytosis through binding to *** of the CD47-sIRPa axis is therefore a promising approach for cancer *** is the most common hematological malignancy and is an area of unmet clin-ical *** review mainly described the current strategies targeting the CD47-sIRPa axis,including antibodies,siRPaFc fusion proteins,small molecule inhibitors,and peptides both in preclinical studies and clinical trials with Hodgkin lymphoma and non-Hodgkin lymphoma.

关键词： Cancer treatment CD47-sIRPαaxis Hodgkin lymphoma Immunotherapy Non-Hodgkin lymphoma

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Ketogenic diet therapy in children with epilepsy caused by sLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by sLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an sLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** six patients with sLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by sLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by sLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet sLC2A1

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Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1227-1235页

作者： Wen-Jing Hu Gang Bai Yan Wang Dong-Mei Hong Jin-Hua Jiang Jia-Xun Li Yin Hua Xin-Yu Wang Ying Chen Intensive Care Unit Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Department of Anesthesia and Perioperative medicine Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Department of Nursing Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Department of Thyroid Breast and Vascular SurgeryShanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China

BACKGROUND Postoperative delirium,particularly prevalent in elderly patients after abdominal cancer surgery,presents significant challenges in clinical *** To develop a synthetic minority oversampling technique(sMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer *** In this retrospective cohort study,we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between september 2020 and October *** incidence of postoperative delirium was recorded for 7 d *** were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not.A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative *** sMOTE technique was applied to enhance the model by oversampling the delirium *** model’s predictive accuracy was then *** In our study involving 611 elderly patients with abdominal malignant tumors,multivariate logistic regression analysis identified significant risk factors for postoperative *** included the Charlson comorbidity index,American society of Anesthesiologists classification,history of cerebrovascular disease,surgical duration,perioperative blood transfusion,and postoperative pain *** incidence rate of postoperative delirium in our study was 22.91%.The original predictive model(P1)exhibited an area under the receiver operating characteristic curve of *** comparison,the sMOTE-based logistic early warning model(P2),which utilized the sMOTE oversampling algorithm,showed a slightly lower but comparable area under the curve of 0.856,suggesting no significant difference in performance between the two predictive *** This study confirms that the sMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of tradi

关键词： Elderly patients Abdominal cancer Postoperative delirium synthetic minority oversampling technique Predictive modeling surgical outcomes

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Psychological Impact of the 2022 Round COVID-19 Pandemic on China's College students

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Journal of shanghai Jiaotong university(science) 2024年第1期29卷 141-149页

作者：洪冬羊王金霞张虹洋曹紫阳晏紫君邹琳 school of Pediatrics Shanghai Jiao Tong University School of MedicineShanghai 200001China Institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Children's HospitalShanghai Jiao Tong University School of MedicineShanghai 200062China Clinical Research Unit Shanghai Children's HospitalShanghai Jiao Tong University School of MedicineShanghai 200062China

In response to the new round of COVID-19 outbreaks since March 2022,universities with high outbreak rates around the country have taken quarantine measures to contain the *** from previous coronavirus outbreaks has shown that people under quarantine are at risk for mental health *** better understand the impacts of this round of COVID-19 quarantine on domestic college students and their responses,we conducted a systematic survey to assess the stress and anxiety,and to evaluate effective measurements in this *** searched relevant documents and literature,and designed a questionnaire from six aspects,including psychological status,epidemic situation,study,daily life,sports,and interpersonal communication,with 51 items in *** sent the questionnaire on the Wenjuanxing Web platform,from April 2 to 8,*** evaluated the mental status according to parts of the Generalized Anxiety Disorder-7(GAD-7)and Depression Anxiety stress scales-21(DAss-21),and investigated the influencing risk factors and *** analysis was performed by using the Chi-square test and multi-variable logistic *** total,508 college respondents were recruited in our survey,and the pooled prevalence of mild anxiety(GAD score≥5,or DAss-21 anxiety score≥8)or stress(DAss-21 pressure score≥14)caused by the new round of COVID-19 pandemic quarantine was 19.69%(100/508).The prevalence of the anxiety or stress in college students with COVID-19 quarantine between different genders,regions,and majors was not significantly *** risk factors for the mild anxiety or stress of undergraduates by COVID-19 quarantine included learning efficiency or duration[OR=1.36,95%CI(1.14—1.62),P=0.001],based on the combined analysis of Chi-square test analysis with multi-variable logistic regression ***,the mental well-beings before COVID-19 epidemic quarantine[OR=0.22,95%CI(0.130.36),Psity exercise[OR=0.36

关键词： COVID-19 psychological investigation college students anxiety stress

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Regenerative medicine strategies for chronic complete spinal cord injury

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Neural Regeneration Research 2024年第4期19卷 818-824页

作者： shogo Hashimoto Narihito Nagoshi Masaya Nakamura Hideyuki Okano Department of Orthopedic surgery Keio University School of Medicine Department of Physiology Keio University School of Medicine

spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various *** rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete ***,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental *** reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural ***,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe ***,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further ***,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

关键词： cell transplantation chronic phase complete transection regenerative medicine spinal cord injury

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