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Management of autoimmune hepatitis induced by hepatitis delta virus

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World Journal of Gastroenterology 2024年第8期30卷 799-805页

作者： Eleni Gigi Vasileios Lagopoulos Aris Liakos Hepatology Unit The Second Internal Medicine DepartmentAristotle University Medical SchoolHippokrateio General HospitalThessaloniki 54642Greece Department of Surgical AHEPA General Hospital of ThessalonikiThessaloniki 54636Greece Clinical Research and Evidence-Based Medicine Unit Second Medical DepartmentHippokratio General HospitalAristotle University ThessalonikiThessaloniki 54642Greece

Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most *** the past few decades,a correlation between viral hepatitis and autoimmune diseases has been ***,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been ***,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated ***,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with ***,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most ***,it remains uncertain whether autoimmunity is induced by HBV or delta ***,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated *** pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.

关键词： Autoimmune hepatitis Hepatitis delta virus Bulevirtide Prednisolone

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第19期30卷 2512-2522页

作者： Juan Jose Urquijo-Ponce Carlos Alventosa-Mateu Mercedes Latorre-Sánchez Inmaculada Castelló-Miralles Moisés Diago Hepatology Unit Department of Digestive Diseases Consorcio Hospital General Universitario of ValenciaValencia 46014Spain

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic *** therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at *** the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical *** systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of *** review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative *** also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative ***,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

关键词： Hepatocellular carcinoma Early stage Intermediate stage Neoadjuvant Adjuvant Systemic therapy

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 ***,the specific mechanisms triggering virus replication and cytokine storm are still not fully ***,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 ***,HIF-1αprotein expression is upregulated after H1N1 *** of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in *** addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in ***,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and *** of glycolysis significantly suppresses viral replication and inflammatory *** 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/β*** 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

Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

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Oncology Research 2024年第5期32卷 807-815页

作者： MARKO SKELIN BRUNA PERKOV-STIPIČIN SANJA VUŠKOVIĆ MARINAŠANDRK PLEHAČEK ANE BAŠIĆ DAVIDŠARČEVIĆ MAJA ILIĆ IVAN KREČAK Pharmacy Department General Hospital ofŠibenik-Knin CountyŠibenikCroatia Faculty of Medicine University of RijekaRijekaCroatia Undergraduate Study in Nursing University of Applied SciencesŠibenikCroatia Department of Oncology University Hospital Center ZagrebZagrebCroatia Pharmacies Joukhadar Sveta NedeljaCroatia Pharmacies Prima Pharme ZagrebCroatia Pharmacy Department General Hospital ZadarZadarCroatia Pharmacy Department General Hospital PulaPulaCroatia Department of Internal Medicine General Hospital ofŠibenik-Knin CountyŠibenikCroatia

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)***,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically *** study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer ***:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each *** examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer ***:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR ***,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous *** proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current *** the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)*** variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer ***:One-third of the current ESMO CPG recommendations are supported by the highest level of *** well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

关键词： ESMO guidelines Clinical practice guidelines Level of evidence Grade of recommendation

Identification of novel genes associated with atherosclerosis in Bama miniature pig

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Animal Models and Experimental Medicine 2024年第3期7卷 377-387页

作者： Dengfeng Ding Yuqiong Zhao Yunxiao Jia Miaomiao Niu Xuezhuang Li Xinou Zheng Hua Chen Laboratory Animal Center Chinese PLA General HospitalBeijingChina

Background:Atherosclerosis is a chronic cardiovascular disease of great ***,it is difficult to establish a direct connection between conventional small animal models and clinical *** pig's genome,physiology,and anatomy reflect human biology better than other laboratory animals,which is crucial for studying the pathogenesis of ***:We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis,and further used bioinformatic tools to filter and identify underlying candidate *** gene function prediction was performed using the online prediction tool STRING *** and immunofluorescence were used to detect the expression of proteins encoded by candidate ***:We mapped differential single nucleotide polymorphisms(SNPs)to genes and obtained a total of 102 differential genes,then we used GO and KEGG pathway enrichment analysis to identify four candidate genes,including SLA-1,SLA-2,SLA-3,and *** cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins,the primary structures of these two proteins have undergone amino acid changes,and the tertiary structures also show slight *** addition,immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner ***:We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis,highlighting the importance of antigen processing and immune response in atherogenesis.

关键词： atherosclerosis candidate genes genome-wide linkage analysis major histocompatibility complex whole genome sequencing

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

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Current Medical Science 2024年第3期44卷 485-493页

作者： Xia-hui HUANG Tian-xiang CHEN Hong-liang LIU Ming-wen HUANG Department of general Surgery The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the *** lesions have been recognized as one of the three major precancerous lesions in the biliary tract since *** 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 *** are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and *** a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 *** histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant *** to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging *** resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

关键词： intraductal papillary neoplasm of the bile duct subclassification neoplasms precancerous tissue prognosis

Efficacy and safety of clarithromycin for patients with sepsis or septic shock:a systematic review and meta-analysis

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Emergency and Critical Care Medicine 2024年第2期4卷 90-96页

作者： Pengyue Zhao Renqi Yao Jiaqi Yang Wei Wen Yongming Yao Xiaohui Du Department of general Surgery First Medical Center of the Chinese PLA General HospitalBeijingChina Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General HospitalBeijingChina Department of Burn Surgery the First Affiliated Hospital of Naval Medical UniversityShanghaiChina Department of general Surgery Hainan Hospital of Chinese PLA General HospitalSanyaHainanChina

Background:Clarithromycin exerts an immunomodulatory role in several human ***,whether this effect improves the prognosis in patients with sepsis remains controversial,and higher levels of clinical evidence are urgently *** the best of our knowledge,no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in ***:A comprehensive literature search of PubMed,EMBASE,and the Cochrane Library was conducted up to December 31,*** randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were *** were pooled by applying a fixed-effects model and a relative risk(RR)estimate with 95%confidence intervals(CIs)using Review Manager(version 5.3;Cochrane Collaboration,Copenhagen,Denmark).Results:Three randomized controlled trials involving a total of 910 patients were *** pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome(RR:1.51;95%CI:1.02-2.25;P=0.04;I^(2)=0%),28-day mortality(RR:1.09;95%CI:0.87-1.36;P=0.46;I^(2)=0%),and 90-day mortality(RR:0.86;95%CI:0.71-1.03;P=0.10;I^(2)=81%)in patients with sepsis or septic ***,there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group(RR:1.02;95%CI:0.87-1.19;P=0.83;I^(2)=18%).Conclusion:Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with ***,administration of clarithromycin did not increase the risk of adverse events.

关键词： Clarithromycin Meta-analysis Outcomes Sepsis Septic shock

Cemented vertebra and adjacent vertebra refractured in a chronic kidney disease-mineral and bone disorder patient: A case report

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World Journal of Clinical Cases 2024年第10期12卷 1804-1809页

作者： Ti-Dong Zhang Shuai Cao Hui-Yong Ren Yu-Min Li Yi-Ming Yuan Department of Orthopedics Civil Aviation General HospitalBeijing 100123China

BACKGROUND Although percutaneous vertebral augmentation(PVA)is a commonly used procedure for treating vertebral compression fracture(VCF),the risk of vertebral refracture should be *** kidney disease-mineral and bone disorder(CKD-MBD)is a systemic disease of mineral and bone *** is associated with an increased risk of *** studies have reported the use of PVA in patients with *** herein report a rare case wherein the cemented vertebra and the adjacent vertebra refractured simultaneously in a CKD-MBD patient after *** SUMMARY A 74-year-old man suffered from low back pain after taking a fall about 3 wk *** to physical examination,imaging and laboratory findings,diagnoses of T12 VCF,CKD-MBD,and chronic kidney disease stage 5 were *** then received percutaneous vertebroplasty at T12 *** weeks later,he presented with T12 and L1 vertebral refractures caused by lumbar *** again,he was given PVA which was optimized for the refractured *** the short-term postoperative effect was satisfactory,he reported chronic low back pain again at the 3-month *** It is necessary that patients with CKD-MBD who have received PVA are aware of the adverse effects of *** may increase the risk of vertebral ***,the PVA surgical technique needs to be optimized according to the condition of the *** medium-and long-term effects of PVA remain uncertain in patients with CKD-MBD.

关键词： Chronic kidney disease-mineral and bone disorder Percutaneous vertebral augmentation Vertebral compression fracture Vertebral refracture Cemented vertebra Adjacent vertebra Case report

Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

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Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： XIU Ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor