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Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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Analysis of surgical and perioperative complications in seventy-five right hepatectomies for living donor liver transplantation

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World Journal of Gastroenterology 2008年第20期14卷 3159-3164页

作者： Salvatore Gruttadauria James Wallis Marsh Giovan Battista Vizzini Fabrizio di Francesco Angelo Luca Riccardo Volpes Amadeo Marcos Bruno Gridelli department of abdominal Transplant surgery Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione department of abdominal Transplant surgery University of Pittsburgh Medical Center

AIM: To present an analysis of the surgical and perioperative complications in a series of seventy- five right hepatectomies for living-donation (RHLD) performed in our center. METHODS: From January 2002 to September 2007, we performed 75 RHLD, defined as removal of a portion of the liver corresponding to Couinaud segments 5-8, in order to obtain a graft for adult to adult living-related liver transplantation (ALRLT). Surgical complications were stratified according to the most recent version of the Clavien classification of postoperative surgical complications. The perioperative period was defined as within 90 d of surgery. RESULTS: No living donor mortality was present in this series, no donor operation was aborted and no donors received any blood transfusion. Twenty- three (30.6%) living donors presented one or more episodes of complication in the perioperative period. Seven patients (9.33%) out of 75 developed biliary complications, which were the most common complications in our ***: The need to define, categorize and record complications when healthy individuals, such as living donors, undergo a major surgical procedure, such as a right hepatectomy, reflects the need for prompt and detailed reports of complications arising in this particular category of patient. Perioperative complications and post resection liver regeneration are not influenced by anatomic variations or patient demographic.

关键词： Right hepatectomy surgery Living-relatedliver transplantation Surgical complications

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Transanal total mesorectal excision:Towards standardization of technique

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World Journal of Gastroenterology 2015年第44期21卷 12686-12695页

作者： Albert M Wolthuis Gabriele Bislenghi Anthony de Buck van Overstraeten André D'Hoore department of abdominal surgery University Hospital Leuven

AIM: To describe the role of Transanal total mesorectal excision(Ta TME) in minimally invasive rectal cancer surgery, to examine the differences in patient selection and in reported surgical techniques and their impactson postoperative outcomes and to discuss the future of Ta TME. METHODS: MEDLINE(Pub Med), EMBASE, and The Cochrane Library were systematically searched through the 1st of March 2015 using a predefined search strategy. RESULTS: A total of 20 studies with 323 patients were included. Most studies were single-arm prospective studies with fewer than 100 patients. Multiple transanal access platforms were used, and the laparoscopic approach was either multi- or single port. The procedure was initiated transanally or transabdominally. If a simultaneous approach with 2 operating surgeons was chosen, the operative time was significantly reduced. CONCLUSION: Ta TME was also associated with better TME specimens and a longer distal resection margin. Ta TME is thus feasible in expert hands, but the learning curve and safety profile are not well defined. Longterm follow-up regarding anal function and oncological outcomes should be performed in the future.

关键词： Laparoscopy Colorectal surgery Rectal cancer Total

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Genetic signatures of ERCC1 and ERCC2 expression,along with SNPs variants,unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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Oncology Research 2025年第1期33卷 45-55页

作者： ENRICO CALIMAN SARA FANCELLI FEDERICO SCOLARI ADRIANO PASQUI CLARA MANNESCHI DANIELE LAVACCHI FRANCESCA MAZZONI FRANCESCA GENSINI VALERIA PASINI CAMILLA EVA COMIN LUCA VOLTOLINI SERENA PILLOZZI LORENZO ANTONUZZO Clinical Oncology Unit Careggi University HospitalFlorence50134Italy department of Experimental and Clinical Medicine University of FlorenceFlorence50134Italy department of Health Sciences University of FlorenceFlorence50134Italy Medical Oncology Unit Careggi University HospitalFlorence50134Italy department of Experimental and Clinical Biomedical Sciences“Mario Serio” University of FlorenceFlorence50134Italy Section of Anatomic Pathology Department of Health SciencesUniversity of FlorenceFlorence50139Italy Section of surgery Histopathology and Molecular PathologyUniversity of FlorenceFlorence50139Italy Thoracic surgery Unit Careggi University HospitalFlorence50134Italy

Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum *** in this repair mechanism may affect patients’*** and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to *** expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor ***:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy *** with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant ***:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： Small cell lung cancer(SCLC) Nucleotide excision repair(NER)pathway ERCC genes Single nucleotide polymorphisms(SNPs) Platinumchemotherapy(CT)

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Three-dimensional models:from cell culture to Patient-Derived Organoid and its application to future liposarcoma research

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Oncology Research 2025年第1期33卷 1-13页

作者： SAYUMI TAHARA SYDNEY RENTSCH FERNANDA COSTAS CASAL DE FARIA PATRICIA SARCHET ROMA KARNA FEDERICA CALORE RAPHAEL E.POLLOCK department of surgery Division of Surgical OncologyThe James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA department of Cancer Biology and Genetics The James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA

Liposarcoma is one of the most common soft tissue sarcomas,however,its occurrence rate is still rare compared to other *** to its rarity,in vitro experiments are an essential approach to elucidate liposarcoma *** cell culture-based research(2D cell culture)is still playing a pivotal role,while several shortcomings have been recently under *** vivo,mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell ***,they do not fully recapitulate human dedifferentiated liposarcoma(DDLPS)***,three-dimensional(3D)culture systems have been the recent research focus in the cell biology field with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fill in the gap between *** the liposarcoma rarity,we believe that 3D cell culture techniques,including 3D cell cultures/co-cultures,and Patient-Derived tumor Organoids(PDOs),represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy *** this review,we first provide a general overview of 3D cell cultures compared to 2D cell *** then focus on one of the recent 3D cell culture applications,Patient-Derived Organoids(PDOs),summarizing and discussing several PDO ***,we discuss the current and future applications of PDOs to sarcoma,particularly in the field of liposarcoma.

关键词： Cell culture Liposarcoma Patient-Derived Organoid(PDO) Spheroid Three-dimensional(3D)cell culture

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Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

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World Journal of Clinical Cases 2025年第2期13卷 14-20页

作者： Aikaterini Mastoraki Maria Tsamopoulou Foivos-Konstantinos Stamatis Alexios Strimpakos Ero Mouchtouri Christiana Panagi Evgenia Mela Sotiria Mastoraki Aristotelis Kechagias Dimitrios Schizas department of surgery National and Kapodistrian University of AthensLaikon General HospitalAthens 11527Greece department of surgery National and Kapodistrian University of AthensAthens 11527Greece department of Medical Oncology Hygeia HospitalAthens 15123Greece department of Radiology Henry Dunant Hospital CenterAthens 11526Greece department of surgery Athens Metropolitan HospitalAthens 15562Greece

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast *** is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition *** cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic *** recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative *** CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always ***,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone ***,surgical removal of breast CS does not necessarily ensure patient’s long-term ***,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is ***,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment *** aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological *** features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

关键词： Carcinosarcoma Breast Diagnostic approach Therapeutic management Prognostic parameters

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Gardner's syndrome:Genetic testing and colonoscopy are indicated in adolescents and young adults with cranial osteomas:A case report

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World Journal of Gastroenterology 2007年第28期13卷 3900-3903页

作者： Dubravko Smud Goran Augustin Tihomir Kekez Emil Kinda Mate Majerovic Zeljko Jelincic department of surgery Division of Abdominal SurgeryClinical Hospital Center ZagrebZagrebCroatia

We present a case of a 25-year-old female with diagnosed familial adenomatous polyposis and elevated carcinoembryonic antigen with negative family history. The suspicion of Gardner's syndrome was raised because extirpation of an osteoma of the left temporo-occipital region was made 10 years ago. Restorative procto-colectomy and ileal pouch anal anastomosis was made but histology delineated adenocarcinoma of the rectum (Dukes C stage). We conclude that cranial osteomas often precede gastrointestinal manifestations of familial adenomatous polyposis or Gardner's syndrome and such patients should be evaluated with genetic testing followed by colonoscopy if results are positive to prevent the development of colorectal carcinoma. If the diagnosis is positive all family members should be evaluated for familial adenomatous polyposis.

关键词： Gardner's syndrome Familial adenomatous polyposis Restorative proctocolectomy Ileal pouch anal anastomosis Cranial osteoma

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Can intraluminal devices prevent or reduce colorectal anastomotic leakage:A review

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World Journal of Gastroenterology 2011年第40期17卷 4461-4469页

作者： Annelien N Morks Klaas Havenga Rutger J Ploeg Division of abdominal surgery department of surgery University Medical Center Groningen 9700 RB Groningen The Netherlands

Colorectal anastomotic leakage is a serious complication of colorectal surgery, leading to high morbidity and mortality rates. In recent decades, many strategies aimed at lowering the incidence of anastomotic leakage have been examined. The focus of this review will be on mechanical aids protecting the colonic anastomosis against leakage. A literature search was performed using MEDLINE, EMBASE, and The Cochrane Collaborative library for all papers related to prevention of anastomotic leakage by placement of a device in the colon. Devices were categorised as decompression devices, intracolonic devices, and biodegradable devices. A decompression device functions by keeping the anal sphincter open, thereby lowering the intraluminal pressure and lowering the pressure on the anastomosis. Intracolonic devices do not prevent the formation of dehiscence. However, they prevent the faecal load from contacting the anastomotic site, thereby preventing leakage of faeces into the peritoneal cavity. Many attempts have been made to find a device that decreases the incidence of AL;however, to date, none of the devices have been widely accepted.

关键词： Anastomotic leakage Colorectal surgery Complication Rectum Device

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Various approaches of laparoscopic common bile duct exploration plus primary duct closure for choledocholithiasis:A systematic review and meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2018年第3期17卷 183-191页

作者： Ming-Yan He Xia-Dong Zhou Hao Chen Peng Zheng Fa-Zhan Zhang Wei-Wei Ren department of the Third abdominal surgery Gansu Province Cancer Hospital department of General surgery Second Hospital of Lanzhou University

Background： Common bile duct （CBD） stones may occur in up to 3%–14.7% of all patients with *** approaches of laparoscopic CBD exploration plus primary duct closure （PDC） are the most commonly used and the best methods to treat CBD stone. This systematic review was to comparethe effectiveness and safety of the various approaches of laparoscopic CBD exploration plus PDC forcholedocholithiasis

关键词： Laparoscopy Choledocholithiasis Common bile duct exploration Primary duct closureMeta-analysis

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Laparoscopic appendectomy for elemental mercury sequestration in the appendix: A case report

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World Journal of Clinical Cases 2019年第9期7卷 1038-1042页

作者： Gregor Nor?i? ?an ?ebron Primo? Sever Jan Grosek Ale? Toma?i? department of abdominal surgery University Medical Centre Ljubljana

BACKGROUND Despite negligible absorption of elemental mercury after acute ingestion,retention in the appendix with subsequent local and systemic complications is possible. We present a case of elemental mercury sequestration in the appendix,managed by laparoscopic *** SUMMARY A 57-year-old Caucasian female was found unconscious following application of long-lasting insulin detemir and ingestion of elemental mercury in a suicidal attempt. Diagnostic investigations revealed several radiopaque collections in the gastrointestinal(GI) tract and elevated mercury levels in the blood. Much of the ingested elemental mercury was eliminated from the GI tract with stools stimulated by several enemas. However, a significant amount of mercury remained sequestrated in the appendix despite all conservative ***, following deliberations by an interdisciplinary team of specialists,laparoscopic appendectomy was performed 29 d after the mercury ingestion. The surgery itself and postoperative course were *** Since conservative measures are often unsuccessful in the management of mercury retention in the appendix, surgery remains a compelling option to prevent possible associated complications.

关键词： Mercury poisoning Appendix Mercury ingestion Mercury retention Appendectomy Case report

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