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Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2025年第1期 103-115页

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State Key Laboratory for Diagnosis and treatment of Severe Zoonotic Infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Basic MedicineJilin University State Key Laboratory for Diagnosis and treatment of Severe Zoonotic Infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Veterinary MedicineJilin University College of Mathematics Jilin University Bioinformatic Lab School of MathematicsShandong University department of Cardiology China-Japan Union HospitalJilin University

The coronavirus disease 2019（COVID-19） outbreak caused by the severe acute respiratory syndrome coronavirus-2（SARS-CoV-2） developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality（CAC）, and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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Management of recurrent hepatitis C virus after liver transplantation

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World Journal of Gastroenterology 2014年第44期20卷 16409-16417页

作者： Miguel Jiménez-Pérez Rocío González-Grande Francisco Javier Rando-Mu?oz Liver transplantation and hepatology unit UGC de Aparato Digestivo Hospital Regional Universitario department of abdominal diseases Hospital Nij Smellinghe Ziekenhuis

Chronic hepatitis C virus (HCV) infection is the leading cause of death from liver disease and the leading indication for liver transplantation (LT) in the United States and Western Europe. LT represents the best therapeutic alternative for patients with advanced chronic liver disease caused by HCV or those who develop hepatocarcinoma. Reinfection by HCV of the graft is universal and occurs in 95% of transplant patients. This reinfection can compromise graft function and patient survival. In a few cases, the histological recurrence is minimal and non-progressive; however, in most patients it follows a more rapid course than in immunocompetent persons, and frequently evolves into cirrhosis with graft loss. In fact, the five-year and ten-year survival of patients transplanted because of HCV are 75% and 68%, respectively, compared with 85% and 78% in patients transplanted for other reasons. There is also a pattern of recurrence that is very severe, but rare (treatment have better survival. Many studies published over recent years have shown that antiviral treatment of post-transplant HCV hepatitis carried out during the late phase is the best option for improving the prognosis of these patients. Until 2011, PEGylated interferon plus ribavirin was the standard of care, resulting in a sustained virological response in around 30% of recipients. The addition of protease inhibitors, such as boceprevir or telaprevir, to the standard of care, or the use of other direct-acting antiviral drugs may involve therapeutic changes in the context of HCV recurrence. This may result a better prognosis for these patients, particularly those with severe recurrence or factors predicting rapid progression of fibrosis. However, the use of these agents in LT still requires clarification in terms of safety and efficacy.

关键词： Hepatitis C virus Liver transplantation Recurrence treatment

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit

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Science China Life Sciences 2025年

作者： Ruyu Wang Tianxiao Wang Ziyu Chen Jiandong Jiang Yifei Du Hua Yuan Yongchu Pan Yuli Wang department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University department of Stomatology Chongzhou People's Hospital Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular diseases Ministry of Education International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical University Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College department of Orthodontic The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University

Delayed tooth extraction socket(TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils(ANs), and neutrophil extracellular traps(NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium(CM) collected from berberine-treated human bone marrow mesenchymal stem cells(BBR-HB-CM) accelerated TES healing. BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2, impeded the formation of ANs and NETs, and modulated M2 macrophage efferocytosis in vivo and in vitro. Mechanistically, BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy. The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM. Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus. Overall, our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

Alpha-fetoprotein and 18F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis:Preliminary experience

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Hepatobiliary & Pancreatic diseases International 2020年第3期19卷 229-234页

作者： Zhe Yang Fang-Zhou Luo Shuo Wang Jan Lerut Li Zhuang Qi-Yong Li Xiao Xu Shu-Sen Zheng department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhouChina Division of Hepatobiliary Pancreatic Surgery First Affiliated HospitalZhejiang University School of MedicineHangzhouChina National Clinical Research Center of Infectious diseases HangzhouChina Starzl Unit of abdominal transplantation University Hospitals Saint LucUniversitécatholique LouvainBrusselsBelgium

Background:Portal vein tumor thrombosis(PVTT)is regarded as a contraindication for liver transplantation(LT)in hepatocellular carcinoma(HCC).However,some of these patients may have a favorable prognosis after *** this study,we evaluated the biological behavior of HCC with PVTT using tumor biomarker(alpha-fetoprotein,AFP)and 18 F-FDG positron emission tomography(tumor standard uptake value)to identify a subset of patients who may be suitable for ***:Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were *** pre-transplant prognostic factors were identified by univariate and multivariate *** status was identified following Vp classification(Vp1-Vp4).Results:Three-year recurrence-free survival and overall survival rates were 40%and 65.4%in Vp2-Vp3 PVTT patients,21.4%and 30.6%in Vp4 PVTT patients(P8 cm,pretransplant AFP level>1000 ng/m L and intrahepatic tumor maximal standard uptake value(SUVmaxtumor>5)were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT *** risk patients were defined as total tumor diameter≤8 cm;or if total tumor diameter more than 8 cm,with both pre-transplant AFP level less than 1000 ng/m L and intrahepatic tumor SUVmax less than 5,***-two Vp2-3 PVTT HCC patients(46.8%)were identified as low risk patients,and their 3-year recurrence-free and overall survival rates were 67.6%and 95.2%,***:Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18 F-FDG SUVmax might be suitable for LT.

关键词： Hepatocellular carcinoma Liver transplantation Portal vein tumor thrombosis Alpha-fetoprotein Standard uptake value

Trimming the fat myth: adipose tissue’s role in liver regeneration

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 727-731页

作者： Andrea Peloso Nicolas Golse Hepato-Biliary Center Paul-Brousse HospitalAssistance Publique-Hôpitaux de ParisVillejuifFrance Division of transplantation and abdominal Surgery Department of SurgeryGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland UMRS 1193 Paris-Saclay UniversityInsermPathogenesis and Treatment of Liver DiseasesFHU HepatinovVillejuifFrance

We read with great interest the paper from Jena(Germany)recently published in Hepatobiliary Surgery and Nutrition by Deeb et al.,which caught our attention,given its clinical *** fact,post-hepatectomy liver failure(PHLF)remains nowadays a significant clinical challenge,occasionally leading to death or potentially requiring,in highly selected cases,rescue liver transplantation(1).Within quaternary care centers,the incidence of PHLF fluctuates from 5%to 20%,depending on the criteria employed,the underlying liver parenchyma quality and the type of hepatectomy(2).Hence,liver regeneration(LR)holds paramount importance in hepatic surgery as it directly impacts post-operative outcomes(3):it is a strictly orchestrated phenomenon that entails the activation of hepatocytes and hepatic progenitor cells,as well as the regulation of cell-cycle genes and growth *** contributing to PHLF include pre-operative,intra-operative and post-operative elements,leading to careful patient selection(4).

关键词： Liver regeneration(LR) adipose tissue liver living-donor transplantation

Malaria after living donor liver transplantation:report of two cases

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Hepatobiliary & Pancreatic diseases International 2008年第2期7卷 210-213页

作者： Durgatosh Pandey Kan-Hoe Lee Sin-Yew Wong Kai-Chah Tan department of Hepatobiliary Surgery and Liver transplantation Asian Centre for Liver diseases and transplantation Gleneagles Hospital Singapore department of Respiratory Medicine and Intensive Care Asian Centre for Liver diseases and transplantation Gleneagles Hospital Singapore department of Infectious diseases Asian Centre for Liver diseases and transplantation Gleneagles Hospital Singapore

BACKGROUND:Infectious complications are common during the postoperative course of a liver transplant recipient. Malaria, however, is a rare complication in such a setting. METHOD:We report post-transplantation malaria causing elevation of liver enzymes in two recipients. RESULTS:Both patients who had undergone living donor liver transplantation showed elevated levels of liver enzymes and fever during the postoperative course. Investigations (including liver biopsy in one patient) were initially inconclusive in determining the cause of liver dysfunction. The diagnosis of malaria was established in both cases by peripheral blood smear. Liver function transiently worsened with antimalarial treatment but subsequently became normal. CONCLUSION:This report highlights the importance of excluding such uncommon causes of post-transplantation liver dysfunction, especially when either the recipient or the donor comes from a region endemic for malaria.

关键词： liver transplantation malaria recipient

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

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World Journal of Clinical Oncology 2025年第1期16卷 1-4页

作者： Emad Qayed department of Medicine Division of Digestive DiseasesEmory University School of MedicineAtlantaGA 30303United States

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with *** propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse *** study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

关键词： Gastric cancer Overt bleeding Systemic therapy Endoscopic therapy Hemostasis