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Reinfection and Risk Factors of SARS-CoV-2 during an Omicron Wave 2022 in Shanghai

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Biomedical and Environmental Sciences 2024年第2期37卷 204-209页

作者： WANG Pei Qin WANG Xiao Hang WANG Jian SHI Zhi Wen CHU Dong Mei WANG Zhi Fei ZHANG Mu Bai LIU Wei ZHOU Zi Jie XIE Wei Fen Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghai 200003China Health examination center Changzheng HospitalNaval Medical UniversityShanghai 200003China

Multiple waves of coronavirus disease 2019(COVID-19) outbreaks have affected numerous countries worldwide. The first case of SARS-CoV-2 reinfection was reported in Hong Kong in August 2020^([1]), leading to increased interest in the effectiveness of natural immunity acquired from primary infection. While data reports vary across countries, all findings indicate that prior SARS-CoV-2 infection provides substantial protection against reinfection^([2]). However, natural immunity from infection with previous non-Omicron or early Omicron sub-lineages offers lower levels of protection against Omicron reinfection, with rates below 60%^([3]) and approximately 75%[4], respectively.

关键词： immunity infection Omi

Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

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Neural Regeneration Research 2024年第8期19卷 1802-1811页

作者： Fudong Li Xiaofei Sun Kaiqiang Sun Fanqi Kong Xin Jiang Qingjie Kong Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Orthopedic Surgery Spine CenterShanghai Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Orthopedic Surgery Naval Medical CenterNaval Medical UniversityShanghaiChina Department of Anesthesiology Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina

Spinal cord injury-induced motor dysfunction is associated with *** have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic ***,the effects of lupenone on acute inflammation induced by spinal cord injury remain *** this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal *** also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord *** res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial ***,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B *** findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

关键词： inflammasome inflammation lupenone microglia polarization pyroptosis spinal cord injury

New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of Medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

Heparin is an effective treatment for preventing liver failure after hepatectomy

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World Journal of Gastroenterology 2024年第22期30卷 2881-2892页

作者： Zhi-Ying Xu Min Peng Ming-Ming Fan Qi-Fei Zou Yi-Ran Li Dong Jiang Hepatic Surgery IV Shanghai Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai 200433China Ultrasound Diagnosis PLA Naval Medical CenterShanghai 200437China Department of Ultrasound Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai 200433China

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver ***,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver *** To look at the safety and efficacy of heparin in preventing hepatic dysfunction after *** The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were *** statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU *** regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two *** In this study,1388 patients who underwent liver cancer hepatectomy were *** yielded 213 matched pairs from the heparin-treated and control *** univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched *** analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU *** Liver failure is an important hazard following hepatic *** ICU care heparin administration has been proved to decr

关键词： Liver resection Posthepatectomy liver failure Prophylactic treatment Heparin Prognosis of hepatectomy

Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie Lian Wenwu Liu Qin Hu Xiaohua Zhang Department of Neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine Department of Diving and Hyperbaric Medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability *** cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain *** mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of ***,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ***,the role of succinylation modification in cell metabolism after stroke and its regulation are not well *** aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after *** also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of *** succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by *** evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic ***,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic *** between succinylation and desuccinylation has been implicated in the pathophysiology of *** agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke ***,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

Assessment of the triglyceride glucose index in adult patients with chronic diarrhea and constipation

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World Journal of Clinical Cases 2024年第6期12卷 1094-1103页

作者： Jing-Yi Zhu Mu-Yun Liu Chang Sun Department of Gastroenterology The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of Gastroenterology Navy No.905 HospitalNaval Medical UniversityShanghai 200433China

BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and constipation,and the triglyceride glucose(TyG)index,a marker of IR,has not yet been *** To investigate the potential association between TyG and the incidence of chronic diarrhea and *** This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from *** was used as an exposure variable,with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables.A demographic investigation based on TyG quartile subgroups was *** application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG,chronic diarrhea,and *** analyses were performed to examine the stability of any potential *** In the chosen sample,chronic diarrhea had a prevalence of 8.00%,while chronic constipation had a prevalence of 8.04%.In multiple logistic regression,a more prominent positive association was found between TyG and chronic diarrhea,particularly in model 1(OR=1.45;95%CI:1.17-1.79,P=0.0007)and model 2(OR=1.40;95%CI:1.12-1.76,P=0.0033).No definite association was observed between the TyG levels and chronic *** weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63(OR=1.89;95%CI:1.05-3.41,P=0.0344),and another positive association with chronic constipation when it was greater than 8.2(OR=1.74;95%CI:1.02-2.95,P=0.0415).The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of *** Higher TyG levels were positively associated with abnormal bowel health.

关键词： Triglyceride glucose index National Health and Nutrition Examination Survey Chronic diarrhea Chronic constipation Cross-sectional study Bowel health

Knockdown of the nucleoporin Nup50 protects cells against ionizing radiation through enhancing DNA-PKcs-mediated DNA damage repair

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Radiation Medicine and Protection 2024年第3期5卷 194-200页

作者： Zhijie Wan Jingwen Gu Songyun Zhao Hang Jia Tingting Liu Yuanyuan Chen Yanyong Yang Department of Radiation Medicine Faculty of Naval MedicineNaval Medical UniversityShanghai200433China Department of Respiratory and Critical Care Medicine the Second Naval Hospital of Southern Theater CommandSanyaHainan572000China Department of Colorectal Surgery Changhai HospitalNaval Medical UniversityShanghai200433China

Objective:To investigate the effect and mechanism of Nup50 on radiation-induced DNA damage repair to radiation and explore the potential role of Nup50 as radioprotective ***:The Nup50 gene was knocked down in HUVEC cells using *** formation,CCK-8,and flow cytometry were performed to determine the viability,proliferation and apoptosis of HUVEC cells treated withγ-rays,*** extent of DNA damage was evaluated by using comet assay and immu-nofluorescence staining againstγ-*** addition,we explored the role of Nup50 in DNA damage response(DDR)pathways through western blotting ***,nuclear and chromatin fractionation were performed to determine the potential molecular mechanism underlying the radiation protection function of Nup50 ***:Nup50 knockdown increased the cellular resistance to ionizing *** CCK-8 data showed that cell viability was significantly increased in the Nup50 knockdown group after radiation(t=4.23,P<0.01).The Nup50 knockdown group also showed more survived colonies(t=10.06,P<0.001),less apoptosis rate(t=3.78,P<0.05)and less unrepaired DNA ***,Nup50 knockdown increased radiation-activated phosphorylation levels of DNA-PKcs in HUVEC ***,the nuclear and chromatin fractionation data showed that inhibiting Nup50 increased the recruitment of DNA-PKcs to chromatin after DNA ***:Our findings revealed that Nup50 knockdown promoted radioresistance in normal HUVEC cells by regulating DNA-PKcs pathway,suggesting Nup50 as a potential target for radiation protection.

关键词： damage protective p50

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography

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World Journal of Gastroenterology 2024年第25期30卷 3166-3178页

作者： Dong Jiang Yi Qian Yi-Jun Gu Ru Wang Hua Yu Hui Dong Dong-Yu Chen Yan Chen Hao-Zheng Jiang Bi-Bo Tan Min Peng Yi-Ran Li Department of Ultrasound Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of Pathology Shanghai Eastern Hepatobiliary Surgery HospitalThird Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of College of Art and Science Case Western Reserve UniversityClevelandOH 44106United States Ultrasound Diagnosis PLA Naval Medical CenterShanghai 200437China

BACKGROUND Integrating conventional ultrasound features with 2D shear wave elastography(2D-SWE)can potentially enhance preoperative hepatocellular carcinoma(HCC)*** To develop a 2D-SWE-based predictive model for preoperative identification of *** A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery *** patients were divided into the modeling group(n=720)and the control group(n=164).The study included conventional ultrasound,2D-SWE,and preoperative laboratory *** logistic regression was used to identify independent predictive factors for RESULTS In the modeling group analysis,maximal elasticity(Emax)of tumors and their peripheries,platelet count,cirrhosis,and blood flow were independent risk indicators for *** factors yielded an area under the curve of 0.77(95%confidence interval:0.73-0.81)with 84%sensitivity and 61%*** model demonstrated good calibration in both the construction and validation cohorts,as shown by the calibration graph and Hosmer-Lemeshow test(P=0.683 and P=0.658,respectively).Additionally,the mean elasticity(Emean)of the tumor periphery was identified as a risk factor for microvascular invasion(MVI)in malignant liver tumors(P=0.003).Patients receiving antiviral treatment differed significantly in platelet count(P=0.002),Emax of tumors(P=0.033),Emean of tumors(P=0.042),Emax at tumor periphery(P<0.001),and Emean at tumor periphery(P=0.003).CONCLUSION 2D-SWE’s hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions,correlating significantly with MVI and antiviral treatment efficacy.

关键词： Shear wave elastography Predicting model Microvascular invasion Antiviral treatment Hepatocellular carcinoma

An antibiotic-free platform for eliminating persistent Helicobacter pylori infection without disrupting gut microbiota

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3184-3204页

作者： Yongkang Lai Tinglin Zhang Xiaojing Yin Chunping Zhu Yiqi Du Zhaoshen Li Jie Gao Department of Gastroenterology Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China Department of Gastroenterology Ganzhou People’s Hospital Affiliated to Nanchang UniversityGanzhou 341000China National Key Laboratory of Immunity and Inflammation Naval Medical UniversityShanghai 200433China Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices Shanghai 200433China

Helicobacter pylori(***)infection remains the leading cause of gastric adenocarcinoma,and its eradication primarily relies on the prolonged and intensive use of two ***,antibiotic resistance has become a compelling health issue,leading to *** eradication treatment failure ***,the powerlessness of antibiotics against biofilms,as well as intracellular *** and the long-term damage of antibiotics to the intestinal microbiota,have also created an urgent demand for antibiotic-free ***,we describe an antibiotic-free,multifunctional copperorganic framework(HKUST-1)platform encased in a lipid layer comprising phosphatidic acid(PA),rhamnolipid(RHL),and cholesterol(CHOL),enveloped in chitosan(CS),and loaded in an ascorbyl palmitate(AP)hydrogel:AP@CS@Lip@*** platform targets inflammatory sites where *** aggregates through electrostatic ***,hydrolysis by matrix metalloproteinases(MMPs)releases CS-encased nanoparticles,disrupting bacterial urease activity and membrane ***,RHL disperses biofilms,while PA promotes lysosomal acidification and activates host autophagy,enabling clearance of intracellular ***,AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu^(2+) release while preserving the intestinal ***,this platform presents an advanced therapeutic strategy for eradicating persistent *** infection without inducing drug resistance.

关键词： Helicobacter pylori infection Antibiotic-free Biofilms Autophagy Gastric mucosal repair Drug resistance Intestinal microbiota Anti-inflammation