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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of Experimental surgery The Second Affiliated Hospital of Air Force Medical University department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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“Hepatic hilum area priority,liver posterior first”:An optimized strategy in laparoscopic resection for type Ⅲ-Ⅳ hilar cholangiocarcinoma

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World Journal of Gastrointestinal surgery 2024年第7期16卷 2167-2174页

作者： Xiao-Si Hu Yong Wang Hong-Tao Pan Chao Zhu Shi-Lei Chen Shuai Zhou Hui-Chun Liu Qing Pang Hao Jin department of hepatopancreatobiliary surgery Anhui No.2 Provincial People's HospitalHefei 230041Anhui ProvinceChina

BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still worthy of further improvement and *** To summarize and share the application experience of the emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types Ⅲ and *** The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively *** Among the 6 patients,4 were males and 2 were *** average age was 62.2±11.0 years,and the median body mass index was 20.7(19.2-24.1)kg/m^(2).The preoperative median total bilirubin was 57.7(16.0-155.7)μmol/*** patient had Bismuth-Corlette type Ⅲa,4 patients had Bismuth-Corlette type Ⅲb,and 1 patient had Bismuth-Corlette type Ⅳ.All patients successfully underwent pure laparoscopic radical resection following the strategy of“hepatic hilum area dissection priority,liver posterior separation first”.The operation time was 358.3±85.0 minutes,and the intraoperative blood loss volume was 195.0±108.4 *** of the patients received blood transfusions during the perioperative *** median length of stay was 8.3(7.0-10.0)*** bile leakage occurred in 2 patients,and all patients were discharged without serious surgery-related *** The emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ.This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA,shortens the learning curve,and

关键词： Hilar cholangiocarcinoma Bismuth-Corlette typesⅢandⅣ Laparoscopy Radical resection Strategy

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"Five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in laparoscopic pancreaticoduodenectomy

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World Journal of Gastrointestinal surgery 2024年第2期16卷 503-510页

作者： Xiao-Si Hu Yong Wang Hong-Tao Pan Chao Zhu Shi-Lei Chen Hui-Chun Liu Qing Pang Hao Jin department of hepatopancreatobiliary surgery Anhui No.2 Provincial People’s HospitalHefei 230041Anhui ProvinceChina

BACKGROUND Although en bloc dissection of hepatic hilum lymph nodes has many advantages in radical tumor treatment,the feasibility and safety of this approach for laparo-scopic pancreaticoduodenectomy(LPD)require further clinical evaluation and *** To explore the application value of the"five steps four quadrants"modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in LPD *** A total of 52 patients who underwent LPD via the"five steps four quadrants"modularized en bloc dissection technique for hepatic hilum lymph nodes from April 2021 to July 2023 in our department were analyzed *** patients'body mass index(BMI),preoperative laboratory indices,intraoperative variables and postoperative complications were *** relationships between preoperative data and intraoperative lymph node dissection time and blood loss were also *** Among the 52 patients,36 were males and 16 were females,and the average age was 62.2±11.0 *** were 26 patients with pancreatic head cancer,16 patients with periampullary cancer,and 10 patients with distal bile duct *** BMI was 22.3±3.3 kg/m²,and the median total bilirubin(TBIL)concentration was 57.7(16.0-155.7)µmol/*** patients successfully underwent the"five steps four quadrants"modularized en bloc dissection technique without lymph node clearance-related complications such as postoperative bleeding or lymphatic *** analysis revealed significant associations between preoperative BMI(r=0.3581,P=0.0091),TBIL level(r=0.2988,P=0.0341),prothrombin time(r=0.3018,P=0.0297)and lymph node dissection ***,dissection time was significantly correlated with intraoperative blood loss(r=0.7744,P<0.0001).Further stratified analysis demonstrated that patients with a preoperative BMI≥21.9 kg/m²and a TIBL concentration≥57.7μmol/L had significantly longer lymph node dissection times(both P<0.05).CONCLUSION The"five steps four quadrants

关键词： Five steps four quadrants Hepatic hilum lymph node Modularized en bloc clearance Laparoscopic pancreaticoduodenectomy

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PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

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Oncology Research 2024年第6期32卷 1063-1078页

作者： KUN FENG HAO PENG QINGPENG LV YEWEI ZHANG hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Medical School Southeast UniversityNanjing210000China

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable *** dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment *** elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also ***,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of ***,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT *** findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer *** methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver ***,noteworthy associations were observed between PHLDA2 expression and immune infiltration in *** addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in *** vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy ***,we found that TGF-βinduced the expression of PHLDA2 in *** GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling *** study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

关键词： HCC Immune infiltration Drug resistance TME PHLDA2

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Surgically treating a rare and asymptomatic intraductal papillary neoplasm of the bile duct:A case report

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World Journal of Clinical Cases 2024年第2期12卷 367-373页

作者： Shen-Zhen Zhu Zhao-Feng Gao Xiao-Rong Liu Xiao-Guang Wang Fei Chen department of General surgery Jiaxing Second HospitalJiaxing 314000Zhejiang ProvinceChina department of Hepatobiliary surgery Jiaxing Second HospitalJiaxing 314000Zhejiang ProvinceChina

BACKGROUND Intraductal papillary neoplasms of the bile duct(IPNBs)are rare and characterized by papillary growth within the bile duct *** is similar to obstructive biliary *** this report,we present an unexpected case of asymptomatic IPNB and consolidate our findings with the relevant literature to augment our understanding of this *** relevant literature contributes to a more comprehensive understanding of the *** SUMMARY A 66-year-old Chinese male patient was admitted to our hospital for surgical intervention after gallstones were discovered during a routine physical *** imaging revealed a lesion on the left side of the liver,which raised the suspicion of IPNB.A laparoscopic left hemihepatectomy was performed,and subsequent histopathological examination confirmed the diagnosis of *** the 3-mo postoperative follow-up,the patient reported good recovery and no *** can manifest both latently and *** surgical resection is the most effective treatment for *** Hepatic and biliary masses,should be considered to diagnose *** surgery and vigilant follow-up are crucial in determining prognosis.

关键词： Intraductal papillary neoplasm of the bile duct Tumor Surgical treatment Prognosis Case report

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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

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Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

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World Journal of Gastroenterology 2024年第10期30卷 1295-1312页

作者： Hui Ma Qing-Zhu Yan Jing-Ru Ma Dong-Fu Li Jun-Ling Yang department of Clinical Laboratory The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina department of Ultrasound Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Digestive Diseases Center Department of Hepatopancreatobiliary MedicineThe Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina department of Respiratory and Critical Care Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease *** review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and *** delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive *** factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are ***,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease *** reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is *** strategies,including anti-viral and immunomodulatory approaches,are critically *** role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent *** conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV *** a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge *** more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient *** dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory *** role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

关键词： Hepatitis B virus reactivation Immunological mechanisms Disease progression Management strategies Immune response

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Role of gut microbiota in Crohn’s disease pathogenesis:Insights from fecal microbiota transplantation in mouse model

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World Journal of Gastroenterology 2024年第31期30卷 3689-3704页

作者： Qiang Wu Lian-Wen Yuan Li-Chao Yang Ya-Wei Zhang Heng-Chang Yao Liang-Xin Peng Bao-Jia Yao Zhi-Xian Jiang Geriatric surgery of department of General surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina

BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and *** To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in *** Intestinal tissue and MAT were collected from 12 patients with *** manifestations and protein expression levels were analyzed to determine lesion *** samples were collected from five recently treated CD patients and five control subjects and transplanted into *** intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control *** Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota *** microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD ***,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and ***,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced *** Gut microbiota play a critical role in the histopathology of *** MAT and creeping fat may therefore have potential in the treatment of patients with CD.

关键词： Mesenteric adipose tissue Crohn’s disease Fecal microbiota transplantation Intestinal fibrosis Intestinal barrier

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Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 370-375页

作者： Sheng-Yan Liu Lu-Hao Li Zhao-Chen Liu Su-Xin Li Xiao-Wei Dang department of hepatopancreatobiliary surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Budd-Chiari Syndrome Diagnosis and Treatment Center of Henan Province Zhengzhou 450052China

Background:Hepatocellular carcinoma(HCC)is a serious complication of hepatic vena cava Budd-Chiari syndrome(HVC-BCS)that significantly reduces the survival time of *** study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring ***:The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively ***-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the *** and multivariate Cox regression analyses were performed to analyze the influence of biochemical,tumor,and etiological characteristics on the total survival time of patients,and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical *** prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance ***:Multivariate analysis showed that serum albumin level7 cm(HR=8.623,95%CI:3.771-19.715,P<0.001),and inferior vena cava stenosis(HR=3.612,95%CI:1.646-7.928,P=0.001)were independent predictors of survival.A prognostic scoring system was developed according to the above-mentioned independent predictors,and patients were classified into grades A,B,C and *** differences in survival were found among the four ***:This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC,which is helpful for clinical evaluation of patient prognosis.

关键词： Budd-Chiari syndrome Hepatocellular carcinoma Prognostic factors Inferior vena cava stenosis Prognostic scoring system

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Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1564-1577页

作者： Sai-Nan Li Shan Yang Hao-Qi Wang Tian-Li Hui Meng Cheng Xi Zhang Bao-Kun Li Gui-Ying Wang The First department of surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina The second department of surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina department of General surgery The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality *** to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient *** noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain *** To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this *** Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin *** bioinformatics tools were employed to elucidate molecular *** expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain *** assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA *** between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream ***,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy *** LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)*** was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 *** expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing *** RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of *** PRNT/ZNF184

关键词： Colorectal cancer Oxaliplatin resistance Prion protein testis specific Zinc finger protein 184 Homeodomain interacting protein kinase 2

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