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HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

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Virologica Sinica 2024年第1期39卷 81-96页

作者： Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang Department of Critical Care Medicine Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China Precision Research Center for Refractory Diseases Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm.However,the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated.Here,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells.Specifically,HIF-1αprotein expression is upregulated after H1N1 infection.Deficiency of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in vivo.In addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in vitro.Mechanistically,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and lactate.Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses.Further analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/βproduction.In conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

关键词： H1N1 Severe pneumonia Virus replication Hypoxia inducible factor-1α Glycolysis

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

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

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

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

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

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Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer

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World Journal of Gastroenterology 2024年第21期30卷 2734-2739页

作者： Shi-Yan Yan Jian-Gao Fan Department of Gastroenterology Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 200092China

In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the application of immune checkpoint inhibitors(ICIs)and microsatellite instability(MSI)in gastric cancer(GC).The four pillars of GC management have long been considered,including surgery,chemotherapy,radiotherapy and targeted therapy.However,immunotherapy has recently emerged as a“fifth pillar”,and its use is rapidly expanding.There are four principal strategies for tumor immunotherapy:ICIs,tumor vaccines,adoptive immunotherapy and nonspecific immunomodulators.Of them,ICIs are the most advanced and widespread type of cancer immunotherapy for GC.Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy.In particular,inhibition of the PD-1/PD-L1 axis with ICIs,including nivolumab and pembrolizumab,has emerged as a novel treatment strategy for advanced GC.Unfortunately,these therapies are sometimes associated with often subtle,potentially fatal immune-related adverse events(irAEs),including dermatitis,diarrhea,colitis,endocrinopathy,hepatotoxicity,neuropathy and pneumonitis.We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges,emergency department revisits,and downstream complications.Recent studies have revealed that MSI-high or mismatch-repair-deficient tumors,regardless of their primary site,have a promising response to ICIs.So,it is important to detect MSI before applying ICIs for treatment of GC.

关键词： Gastric cancer Immune checkpoint inhibitors Microsatellite instability Immunotherapy Immune-related adverse events

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Development and validation of a nomogram to predict allograft survival after pediatric liver transplantation

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World Journal of Pediatrics 2024年第3期20卷 239-249页

作者： Guang-Xiang Gu Shu-Ting Pan Yi-Chen Fan Chen Chen Qiang Xia Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineNo.160 Pujian RoadPudong New DistrictShanghai 200128China Department of Liver Transplantation Sun Yet-Sen Memorial HospitalSun Yat-Sen UniversityNo.107 Yanjiang West RoadGuangzhou 510080China Clinical Center for Investigation Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina Department of Anesthesiology Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina

Background Liver transplantation is the main treatment for cholestatic liver disease and some metabolic liver diseases in children.However,no accurate prediction model to determine the survival probability of grafts prior to surgery exists.This study aimed to develop an effective prognostic model for allograft survival after pediatric liver transplantation.Methods This retrospective cohort study included 2032 patients who underwent pediatric liver transplantation between January 1,2006,and January 1,2020.A nomogram was developed using Cox regression and validated based on bootstrap sampling.Predictive and discriminatory accuracies were determined using the concordance index and visualized using calibration curves;net benefits were calculated for model comparison.An online Shiny application was developed for easy access to the model.Results Multivariable analysis demonstrated that preoperative diagnosis,recipient age,body weight,graft type,preoperative total bilirubin,interleukin-1β,portal venous blood flow direction,spleen thickness,and the presence of heart disease and cholangitis were independent factors for survival,all of which were selected in the nomogram.Calibration of the nomogram indicated that the 1-,3-,and 5-year predicted survival rates agreed with the actual survival rate.The concordance indices for graft survival at 1,3,and 5 years were 0.776,0.757,and 0.753,respectively,which were significantly higher than those of the Pediatric End-Stage Liver Disease and Child-Pugh scoring systems.The allograft dysfunction risk of a recipient could be easily predicted using the following URL:https://aspelt.***.io/ASPELT/l Conclusion The allograft survival after pediatric liver transplantation(ASPELT)score model can effectively predict the graft survival rate after liver transplantation in children,providing a simple and convenient evaluation method for clinicians and patients.

关键词： Allograft survival Nomogram Pediatric liver transplantation

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Development of Fixture Layout Optimization for Thin-Walled Parts:A Review

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Chinese Journal of Mechanical Engineering 2024年第1期37卷 15-39页

作者： Changhui Liu Jing Wang Binghai Zhou Jianbo Yu Ying Zheng Jianfeng Liu School of Mechanical Engineering Tongji UniversityShanghai 201804China shanghai jiaotong university Shanghai 200240China shanghai Waigaoqiao Shipbuilding Co. Ltd.Shanghai 200137China

An increasing number of researchers have researched fixture layout optimization for thin-walled part assembly during the past decades.However,few papers systematically review these researches.By analyzing existing literature,this paper summarizes the process of fixture layout optimization and the methods applied.The process of optimization is made up of optimization objective setting,assembly variation/deformation modeling,and fixture layout optimization.This paper makes a review of the fixture layout for thin-walled parts according to these three steps.First,two different kinds of optimization objectives are introduced.Researchers usually consider in-plane variations or out-of-plane deformations when designing objectives.Then,modeling methods for assembly variation and deformation are divided into two categories:Mechanism-based and data-based methods.Several common methods are discussed respectively.After that,optimization algorithms are reviewed systematically.There are two kinds of optimization algorithms:Traditional nonlinear programming and heuristic algorithms.Finally,discussions on the current situation are provided.The research direction of fixture layout optimization in the future is discussed from three aspects:Objective setting,improving modeling accuracy and optimization algorithms.Also,a new research point for fixture layout optimization is discussed.This paper systematically reviews the research on fixture layout optimization for thin-walled parts,and provides a reference for future research in this field.

关键词： Thin-walled parts Assembly quality Fixture layout optimization Modeling methods Optimization algorithms

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Metabolic syndrome’s new therapy:Supplement the gut microbiome

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World Journal of Diabetes 2024年第4期15卷 793-796页

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

This letter to the editor discusses the publication on gut microbiome supple-mentation as therapy for metabolic syndrome.Gut microbiome dysbiosis disrupts intestinal bacterial homeostasis and is related to chronic inflammation,insulin resistance,cardiovascular diseases,type 2 diabetes mellitus,and obesity.Previous research has found that increasing the abundance of beneficial microbiota in the gut modulates metabolic syndrome by reducing chronic inflammation and insulin resistance.Prebiotics,probiotics,synbiotics,and postbiotics are often used as supplements to increase the number of beneficial microbes and thus the produc-tion of short-chain fatty acids,which have positive effects on the gut microbiome and metabolic syndrome.In this review article,the author summarizes the available supplements to increase the abundance of beneficial gut microbiota and reduce the abundance of harmful microbiota in patients with metabolic disorders.Our group is also researching the role of the gut microbiota in chronic liver disease.This article will be of great help to our research.At the end of the letter,the mechanism of the gut microbiota in chronic liver disease is discussed.

关键词： Gut microbiome Metabolic syndrome Diabetes mellitus Short-chain fatty acids Chronic liver disease

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Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study

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Chinese Journal of Integrative Medicine 2024年第6期30卷 489-498页

作者： CAO Ni-da ZHU Xiao-hong MA Fang-qi XU Yan DONG Jia-huan QIN Meng-meng LIU Tian-shu ZHU Chun-chao GUO Wei-jian DING Hong-hua GUO Yuan-biao LIU Li-kun SONG Jin-jie WU Ji-ping CHENG Yue-lei ZENG Lin ZHAO Ai-guang Oncology Department I Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghai200032China Oncology Department Zhongshan HospitalFudan UniversityShanghai200032China Gastrointestinal Surgery Department Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China Oncology Department Fudan University Shanghai Cancer CenterShanghai200032China Oncology Department Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080China Traditional Chinese Medicine Department Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China Oncology Department Shanxi Traditional Chinese Medicine HospitalTaiyuan030012China Oncology Department Xiyuan HospitalChina Academy of Chinese Medical ScienceBeijing102445China Oncology Department Yunnan Province Hospital of Traditional Chinese MedicineKunming650021China Oncology Department Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai201203China shanghai NewCore Biotechnology Co. Ltd.Shanghai200240China

Objective To describe the treatment patterns and survival status of advanced gastric cancer(AGC)in China in the past two decades,and objectively evaluate the impact of standardized Chinese medicine(CM)treatment on the survival of AGC patients.Methods This multicenter registry designed and propensity score analysis study described the diagnosis characteristics,treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1,2000 and July 31,2021.Overall survival(OS)was evaluated between non-CM cohort(standard medical treatment)and CM cohort(integrated standard CM treatment≥3 months).Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to adjust any difference in average outcomes for bias.Results A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled.Among them,1,607 received systemic chemotherapy,215(10.74%)accepted molecular targeted therapy,44(2.2%)received checkpoint inhibitor therapy,and 769(38.43%)received CM.Two-drug regimen was the main choice for first-line treatment,with fluoropyrimidine plus platinum as the most common regimen(530 cases,60.09%).While 45.71%(16 cases)of patients with HER2 amplification received trastuzumab in first-line.The application of apatinib increased(33.33%)in third-line.The application of checkpoint inhibitors has increased since 2020.COX analysis showed that Lauren mixed type(P=0.017),cycles of first-line treatment>6(P=0.000),CM(P=0.000),palliative gastrectomy(P=0.000),trastuzumab(P=0.011),and apatinib(P=0.008)were independent prognostic factors for the OS of AGC.After PSM and IPTW,the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months,respectively(P<0.001).Conclusions In real-world practice for AGC in China,therapy choices consisted with guidelines.Two-drug regimen was the main first-line choice.Standardized CM treatment was an independent prognostic factor and could prolong the OS of C

关键词： advancedgastriccancer real-world study treatment pattern survival analysis Chinese medicine

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Optimization of Band Gap of 1D Elastic Metamaterial Under Impact Load by Regulating Stiffness

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Acta Mechanica Solida Sinica 2024年第1期37卷 148-154页

作者： Tong Li Xianlong Jin Yongqiang Li Peizhong Yang School of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Mechanical System and Vibration Shanghai Jiaotong UniversityShanghai 200240China College of Science Northeastern UniversityShenyang 110819China

Designing materials that mitigate impacts effectively are crucial for protecting people and structures.Here,a single-resonator metamaterial with negative mass characteristics is proposed for impact mitigation,and numerical analysis of wave propagation shows explicitly how the spring stiffness and number of unit cells influence that mitigation.The results show clearly that a metamaterial with differing microstructural stiffness is better at mitigating the effect of a shock wave than one with a unique stiffness.Also,there is a critical number of unit cells beyond which the shock wave is not attenuated further,but the fabrication complexity increases.In the 40 groups of microstructural regions in this example,the attenuation effect no longer increases when there are more than 35 groups.This work offers guidance for microstructure designs in metamaterials and provides new ideas for using metamaterials to mitigate shock waves.

关键词： Elastic metamaterials Wave attenuation Stiffness Number of unit cells

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Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis

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Science China(Life Sciences) 2024年第5期67卷 865-878页

作者： Wei Jia Yitao Li Kenneth C.P.Cheung Xiaojiao Zheng School of Chinese Medicine Hong Kong Baptist UniversityHong KongChina Center for Translational Medicine and shanghai Key Laboratory of Diabetes Mellitus Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University School of MedicineShanghai 200233China

Bile acids(BAs)play a crucial role in nutrient absorption and act as key regulators of lipid and glucose metabolism and immune homeostasis.Through the enterohepatic circulation,BAs are synthesized,metabolized,and reabsorbed,with a portion entering the vascular circulation and distributing systemically.This allows BAs to interact with receptors in all major organs,leading to organ-organ interactions that regulate both local and global metabolic processes,as well as the immune system.This review focuses on the whole-body effects of BA-mediated metabolic and immunological regulation,including in the brain,heart,liver,intestine,eyes,skin,adipose tissue,and muscle.Targeting BA synthesis and receptor signaling is a promising strategy for the development of novel therapies for various diseases throughout the body.

关键词： bile acid whole body metabolism immunity

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Optimization of magnetic field design for Hall thrusters based on a genetic algorithm

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Plasma Science and Technology 2024年第7期26卷 82-92页

作者：谭睿杭观荣王平阳 School of Mechanical Engineering Shanghai Jiaotong UniversityShanghai 200240People’s Republic of China Division of Electric Propulsion Shanghai Institute of Space PropulsionShanghai 201112People’s Republic of China

Magnetic field design is essential for the operation of Hall thrusters.This study focuses on utilizing a genetic algorithm to optimize the magnetic field configuration of SPT70.A 2D hybrid PIC-DSMC and channel-wall erosion model are employed to analyze the plume divergence angle and wall erosion rate,while a Farady probe measurement and laser profilometry system are set up to verify the simulation results.The results demonstrate that the genetic algorithm contributes to reducing the divergence angle of the thruster plumes and alleviating the impact of high-energy particles on the discharge channel wall,reducing the erosion by 5.5%and 2.7%,respectively.Further analysis indicates that the change from a divergent magnetic field to a convergent magnetic field,combined with the upstream shift of the ionization region,contributes to the improving the operation of the Hall thruster.

关键词： magnetic field design genetic algorithm divergence angle erosion of discharge channel convergent magnetic field

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