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Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi Genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance Center for Brain Health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

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Matching donor to recipient in liver transplantation: Relevance in clinical practice

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World Journal of Hepatology 2013年第11期5卷 603-611页

作者： Mettu Srinivas Reddy Joy Varghese Jayanthi Venkataraman Mohamed Rela institute of liver diseases and transplantation Global Hospital and Health City Department of Hepatology and transplantation Institute of Liver Diseases and Transplantation Global Hospital and Health City

Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor,graft and recipient *** the cohort of patients waiting for a transplant,better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation.A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age,gender,ethnicity,viral serology;graft factors such as size and quality,recipient factors such as age,size,gender and transplant factors such as major or minor blood group incompatibility and immunological *** also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’clinical *** donor and recipient factors impact graft survival after liver *** matching based on donor-organ-recipient variables,modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.

关键词： liver transplantation Donor-recipient mismatch Immunological mismatch Viral serology mismatch

Novel en-bloc resection of locally advanced hilar cholangiocarcinoma: the Rex recess approach

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Hepatobiliary & Pancreatic diseases International 2014年第1期13卷 93-97页

作者： Mohamed Rela Rajesh Rajalingam Vivekanandan Shanmugam Adrian O' Sullivan Mettu S Reddy Nigel Heaton institute of liver Studies King's College Hospital institute of liver Surgery and transplantation Global Hospital and Health City

Loco-regional recurrence after potentially curative resection remains a problem in hilar cholangiocarcinoma. Hilar dissection risks local spillage of tumor cells leading to suboptimal disease free survival. We have developed a new technique of radical resection for hilar cholangiocarcinoma based on the distinctive anatomy of the Rex recess of the liver, which has been assessed in two patients with locally advanced hilar cholangiocarcinoma. This technique included a right hepatectomy with en-bloc resection of the hepatoduodenal ligament and portal venous reconstruction to the left portal vein at the Rex recess. Both patients had R0 resection and have been disease-free for 26 and 38 months, respectively.

关键词： cholangiocarcinoma vascular resection no-touch technique Rex recess

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Laparoscopic VS open hepatectomy for hepatolithiasis: An updated systematic review and meta-analysis

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World Journal of Gastroenterology 2017年第43期23卷 7791-7806页

作者： Hui Li Jun Zheng Jian-Ye Cai Shi-Hui Li Jun-Bin Zhang Xiao-Ming Wang Gui-Hua Chen Yang Yang Gen-Shu Wang Department of Hepatic Surgery and liver transplantation Center of the Third Affiliated Hospital Organ Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong Province Guangdong Key Laboratory of liver disease Research Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutesthe Third Affiliated Hospital of Sun Yat-sen University Department of Hepatobiliary Surgery Yijishan Hospital affiliated to Wannan Medical College

AIM To perform a meta-analysis on laparoscopic hepatectomy VS conventional liver resection for treating *** We conducted a systematic literature search on Pub Med,Embase,Web of Science and Cochrane Library,and undertook a meta-analysis to compare the efficacy and safety of laparoscopic hepatectomy V S conventional open liver resection for local hepatolithiasis in the left or right lobe. Intraoperative and postoperative outcomes(time,estimated blood loss,blood transfusion rate,postoperative intestinal function recovery time,length of hospital stay,postoperative complication rate,initial residual stone,final residual stone and stone recurrence) were analyzed *** A comprehensive literature search retrieved 16 publications with a total of 1329 cases. Meta-analysis of these studies showed that the laparoscopic approach for hepatolithiasis was associated with significantly less intraoperative estimated blood loss [weighted mean difference(WMD): 61.56,95% confidence interval(CI): 14.91-108.20,P = 0.01],lower blood transfusion rate [odds ratio(OR): 0.41,95%CI: 0.22-0.79,P = 0.008],shorter intestinal function recovery time(WMD: 0.98,95%CI: 0.47-1.48,P = 0.01),lower total postoperative complication rate(OR: 0.52,95%CI: 0.39-0.70,P < 0.0001) and shorter stay in hospital(WMD: 3.32,95%CI: 2.32-4.32,P < 0.00001). In addition,our results showed no significant differences between the two groups in operative time(WMD: 21.49,95%CI: 0.27-43.24,P = 0.05),residual stones(OR: 0.79,95%CI: 0.50-1.25,P = 0.31) and stone recurrence(OR: 0.34,95%CI: 0.11-1.08,P = 0.07). Furthermore,with subgroups analysis,our results proved that the laparoscopic approach for hepatolithiasis in the left lateral lobe and left side could achieve satisfactory therapeutic effects. CONCLUSION The laparoscopic approach is safe and effective,with less intraoperative estimated blood loss,fewer postoperative complications,reduced length of hospital stay and shorter intestinal funct

关键词： Hepatolithiasis Laparoscopic hepatectomy Conventional liver resection Systematic review Metaanalysis

Major complications of adult right lobe living liver donors

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Hepatobiliary & Pancreatic diseases International 2015年第2期14卷 150-156页

作者： Necdet Guler Onur Yaprak Yusuf Gunay Murat Dayangac Murat Akyildiz Fisun Yuzer Yildiray Yuzer Yaman Tokat liver transplantation Center Florence Nightingale Hospital

BACKGROUND：The right lobe of the liver is generally preferred for living donor liver transplantation in adult patients with end-stage liver *** is important to know the preoperative factors relating to the major postoperative *** therefore evaluated the possible risk factors for predicting postoperative complications in right lobe liver ***：Data from 378 donors who had undergone right lobe hepatectomy at our center were evaluated retrospectively. The factors we evaluated induded donor age, gender, body mass index （BMI）, remnant liver volume, operation time, history of previous abdominal surgery, inclusion of the middle hepatic vein and variations in the portal and bile systems. RESUEI＇S： Of the 378 donors, 219 were male and 159 female. None of the donors died, but 124 （32.8%） donors experienced complications including major complications （Clavien scores III and IV） in 27 （7.1%）. Univariate analysis showed that complica- tions were significantly associated with male gender and higher BMI （P〈0.05）, but not with donor age, remnant liver volume, operation time, graft with middle hepatic vein, variations in the portal and bile systems and previous abdominal surgery （P〉0.05）. Multivariate logistic regression analysis showed that major complications were significantly associated with male gender （P=0.005） and higher BMI （P=0.029）. Moreover, the Chi- square test showed that there were significant relationships between major complications and male gender （P=0.010,Z2=6.614, df=l） and BMI 〉25 kg/m2 （P=-0.031, Z2=8.562, df-1）. Of the 96 male donors with BMI 〉25 kg/m2, 14 （14.6%） with major complications had significantly smaller mean remnant liver volume than those （82, 85.4%） without major complications （32.50%± 4.45% vs 34.63%±3.11%, P=0.029）.CONCLUSION： Male donors with BMI 〉25 kg/m2 and a remnant liver volume 〈32.50% had a significantly increased risk for major complications.

关键词： living donor right lobe liver donor major complications risk factors

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Targeting angiogenesis for liver cancer: Past, present, and future

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Genes & diseases 2020年第3期7卷 328-335页

作者： Xiao-Dong Zhu Zhao-You Tang Hui-Chuan Sun Department of liver Surgery and transplantation Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghai200032China

liver cancer,mostly hepatocellular carcinoma(HCC),is the second leading cause of cancer mortality *** patients were diagnosed at an advanced stage,and systemic therapy is the standard of *** the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling *** and lenvatinib are the first-line treatment,and regorafenib,ramucirumab,and cabozantinib are second-line treatment *** anti-PD-1 antibodies,including nivolumab and pembrolizumab,demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials,both failed in phase III ***-angiogenic treatment remains the backbone of systemic therapy for *** this review,we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy,including combination therapy with other treatments,and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies.

关键词： Anti-angiogenic therapy Combinational therapy Hepatocellular carcinoma Molecular targeted therapy Systemic therapy

Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu Department of Hepatobiliary and Pancreatic Surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ transplantation Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of Medicine Department of Urology The Second Affiliated HospitalZhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Adjuvant therapies after curative treatments for hepatocellular carcinoma: Current status and prospects

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Genes & diseases 2020年第3期7卷 359-369页

作者： Xiao-Dong Zhu Kang-Shuai Li Hui-Chuan Sun Department of liver Surgery and transplantation Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghai200032China

Tumor recurrence rate after surgery or ablation of hepatocellular carcinoma(HCC)is as high as 70%.However,there are no widely accepted adjuvant therapies;therefore,no treatment has been recommended by guidelines from the American Association for the Study of liver disease or the European Association for the Study of the *** the registered trials failed to find any treatment to prolong recurrence-free survival,which is the primary outcome in most studies,including *** investigator-initiated studies revealed that antihepatitis B virus agents,interferon-a,transcatheter chemoembolization,chemokine-induced killer cells,and other treatments prolonged patient recurrence-free survival or overall survival after curative *** this review,we summarize the current status of adjuvant treatments for HCC and explain the challenges associated with designing a clinical trial for adjuvant *** new treatments being used as adjuvant therapy,especially anti-PD-1 antibodies,are also discussed.

关键词： Adjuvant therapy Anti-PD-1 antibody Clinical trial Hepatocellular carcinoma Molecular targeted therapy Recurrence-free survival

Pathological,molecular,and clinical characteristics of cholangiocarcinoma:A comprehensive review

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 607-627页

作者： Mukul Vij Yogesh Puri Ashwin Rammohan Gowripriya G Rajesh Rajalingam Ilankumaran Kaliamoorthy Mohamed Rela Department of Pathology Dr Rela Institute and Medical centerChennai 600044Tamil NaduIndia institute of liver disease and transplantation Dr Rela Institute and Medical CenterChennai 600044Tamil NaduIndia

Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary *** is a wide geographical variation with regards to its incidence,and risk-factor associations which may include liver fluke infection,primary sclerosing cholangitis,and hepatolithiasis amongst *** tumours are classified into intrahepatic,perihilar and distal based on their anatomical ***,intrahepatic cholangiocarcinomas are further sub-classified into small and large duct *** and distal cholangiocarcinomas are usually mucin-producing tubular *** develop through a multistep carcinogenesis and are preceded by dysplastic and in situ *** clinical characteristics and management of these tumours have been extensively elucidated in literature,their ultra-structure and tumour biology remain relatively *** review focuses on the current knowledge of pathological characteristics,molecular alterations of cholangiocarcinoma,and its precursor lesions(including biliary intraepithelial neoplasia,intraductal papillary neoplasms of the bile duct,intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).

关键词： Cholangiocarcinoma Classification Pathology Molecular features Precursors lesions Treatment