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Current and future pharmacological therapies for managing cirrhosis and its complications

World Journal of Gastroenterology 2019年第8期25卷 888-908页

作者： David Kockerling Rooshi Nathwani Roberta Forlano Pinelopi Manousou Benjamin h Mullish Ameet Dhar Liver Unit/Division of Integrative Systems medicine and Digestive Disease Imperial College London

Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of *** article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future ***/medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of ***-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced *** observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial *** gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial *** remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory *** have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental *** initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated ***,statins are suggested to have protective effects upon fibrosis progression,decompensation and *** as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is *** evidence indicates that anticoa

关键词： Cirrhosis Beta-blockers Rifaximin Diuretics Statins Proton pump inhibitors Pharmacology

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Systematic review of anorectal leiomyosarcoma: Current challenges and recent advances

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World Journal of Gastrointestinal Surgery 2019年第8期11卷 334-341页

作者： mohammed O Nassif Razan A habib Luai Z Almarzouki Nora h Trabulsi Department of Surgery King Abdulaziz University

BACKGROUND The anorectal leiomyosarcoma (LMS) is an aggressive malignant neoplasm. Owing to the rarity of LMSs, an optimal treatment modality has yet to be determined. AIM To collect all published data on anorectal LMS characteristics, explore current treatment options, and review recent cases of postradiation LMS. METhODS A literature search of the Pubmed electronic database was conducted using the MeSh terms "rectal neoplasms","anus neoplasms" and "gastrointestinal neoplasms" combined with "leiomyosarcoma". The search was limited to English language and human studies. All available case reports and case series of anal or rectal LMSs that were published from the beginning of January 1996 to May 2017 were included if the diagnosis of LMS had been confirmed by histopathologic examination. Data were analyzed using simple statistics (mean, median, and standard deviation). Independent sample t-test was used to compare means for continuous variables. RESULTS A total of 27 articles reporting on 51 cases of anorectal LMS were identified. Among these cases, 11.7% had undergone previous pelvic radiotherapy (developing LMS at 13-35 years afterwards). Anorectal LMS affected the rectum in 92.2% of the cases, and no sex-based predominance was observed. Surgical resection with negative margins remains the mainstay of treatment, which can be accomplished with wide local excision or radical resection. The local recurrence rate was higher among cases who received wide local excision (30%), as compared to radical resection (20%);however, the overall rate of metastasis was 51.61% regardless of the treatment approach. The use of neoadjuvant radiation lowers the risk of local recurrence compared to adjuvant radiotherapy, and facilitates R0 resection of the tumor. Cases treated with adjuvant chemotherapy showed better rates of distant recurrence and overall survival. Nonetheless, multidisciplinary team discussion is necessary to determine the optimal management plan whilst considering pa

关键词： Leiomyosarcoma Rectal neoplasms Anal neoplasms Gastrointestinal neoplasms Soft tissue neoplasms

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Insights into Theranostic Properties of Titanium Dioxide for Nanomedicine

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Nano-Micro Letters 2020年第2期12卷 102-136页

作者： Morteza hasanzadeh Kafshgari Wolfgang hGoldmann Department of Engineering Physics Polytechnique MontreálMontrealQC H3C3A7Canada Department of Physics Biophysics GroupUniversity of Erlangen-Nuremberg91052 ErlangenGermany

Titanium dioxide(TiO2)nanostructures exhibit a broad range of theranostic properties that make them attractive for biomedical ***2 nanostructures promise to improve current theranostic strategies by leveraging the enhanced quantum confinement,thermal conversion,specific surface area,and surface *** review highlights certain important aspects of fabrication strategies,which are employed to generate multifunctional TiO2 nanostructures,while outlining post-fabrication techniques with an emphasis on their suitability for *** biodistribution,toxicity,biocompatibility,cellular adhesion,and endocytosis of these nanostructures,when exposed to biological microenvironments,are examined in regard to their geometry,size,and surface *** final section focuses on recent biomedical applications of TiO2 nanostructures,specifically evaluating therapeutic delivery,photodynamic and sonodynamic therapy,bioimaging,biosensing,tissue regeneration,as well as chronic wound healing.

关键词： TiO2 nanostructures Drug delivery systems Bioimaging Biosensing Tissue regeneration

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Transplantation tolerance that depends on regulatory T cells induced by TGF-beta-producing regulatory B cells

Transplantation tolerance that depends on regulatory T cells...

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2013中国器官移植大会

作者： Gaoping Zhao Kang Me Lee Ryan Scott Julie Soohoo Liang moh moh Lindsey Fitzgerald Ji Lei heidi Yeh Shaoping Deng James Markmann James Kim Department of Surgery Sichuan Provincial People's Hospital & Sichuan Academy of Medical Sciences Department of Surgery Massachusetts General HospitalHarvard Medical School

Regulatory B cells(Bregs)have been shown to play a critical role in immune homeostasis and in autoimmunity *** have recently demonstrated that combined anti-TIM-1 and anti-CD45RB antibody treatment generates regulatory B cells necessary for long- term mouse islet allograft survival in a full MhC-mismatch donor-recipient pair Lee KM,Kim JI,,Stott R,Soohoo J,O’Connor *** h, Zhao G,Eliades P,Fox C,Cheng N,Deng S,Markmann ***-CD45RB/anti-TIM-1-induced tolerance requires regulatory B cells. Am J Transplantation.2012;12:2072—2078).here we provide evidence that the induction of tolerance by regulatory B cells requires regulatory T ***,adoptive transfer of Bregs results in an increase in absolute number of Tregs in grafted recipients,and depletion of Tregs abrogates transplant tolerance conferred by adoptive transfer of regulatory B *** hypothesize that Bregs induce

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Cigarette smoking and the risk of endometrial cancer:A meta-analysis

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南京医科大学学报(自然科学版) 2008年第7期 939-939页

作者： Zhou,B. Yang,L. Sun,Q.M. Cong,R.h. Gu,h.J. Tang,N.P. Zhu,h.J. Wang,B.Nanjing med Univ,Dept Pharmacol,Key Lab Reproduct med,Nanjing 210029,Jiangsu,Peoples R China.Nanjing med Univ,Affiliated hosp 1,Dept Gen Surg,Nanjing 210029,Jiangsu,Peoples R China.Nanjing Univ,Sch med,Affiliated Drum Tower hosp,Nanjing 210008,Jiangsu,Peoples R China.

OBJECTIVE:Epidemiologic findings are inconsistent concerning the association of endometrial cancer risk with cigarette *** conducted a meta-analysis of epidemiologic studies to examine this ***:A systematic literature search up to June of 2007 was performed in medLINE and ***-specific risk estimates were pooled using a random-effects ***:Ten prospective and 24 case-control studies were included in the analysis of the effect of ever *** smoking was statistically significantly associated with a reduced risk of endometrial cancer among prospective studies(relative risk 0.81;95% confidence interval[CI],0.74-0.88) and case-control studies(odds ratio 0.72;95% CI,0.66-0.79).The inverse association was significant among current and former *** prospective and 6 case-control studies were included in the quantitative *** noted that an increase in smoking of 20 cigarettes per day was statistically significantly associated with 16% and 27% reduced risks of endometrial cancer in prospective and case-control studies,*** also found that cigarette smoking was significantly associated with a decreased risk of endometrial cancer among postmenopausal women(relative risk 0.71;95% CI,0.65-0.78) but not among premenopausal *** addition,the risk reduction seemed to be stronger among hormone replacement therapy users than ***:Cigarette smoking was found to be significantly associated with a reduced risk of endometrial cancer,especially among postmenopausal women.(C) 2008 Elsevier *** rights reserved.

关键词： cigarette smoking endometrial cancer meta-analysis risk hormone-replacement therapy dose-response data alcohol-consumption postmenopausal women trend estimation estrogen use life-style aarp diet follow-up cohort

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Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation

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南京医科大学学报(自然科学版) 2009年第7期 991-991页

作者： huang, S. M. Zhang, A. h. Ding, G. X. Chen, R. h. Nanjing med Univ, Nanjing Childrens hosp, Dept Nephrol, Nanjing, Peoples R China. Nanjing med Univ, Inst Pediat, Nanjing, Peoples R China.

huang S, Zhang A, Ding G, Chen R. Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation. Am J Physiol Renal Physiol 296: F1323-F1333, 2009. First published April 1, 2009; doi: 10.1152 / ajprenal. 90428.2008. -Aldosterone (Aldo) stimulates glomerular mesangial cell (MC) proliferation, in part, through an ERK1 / 2-dependent pathway. In this study, we examined whether Aldo activation of ERK1 / 2 in MC is mediated through redox-dependent EGF receptor (EGFR) transactivation, as well as the involvement of other signaling mechanisms in Aldo-induced MC proliferation. Aldo increased human MC proliferation, as determined by [h-3]thymidine incorporation and cell counts. This increase in proliferation was blocked by inhibition of the mineralocorticoid receptor (MR). Continuing our observations downstream in the signaling pathway, we examined the ability of Aldo to activate both the Ras / MAPK and the PI3K signaling pathways. Aldo increased Ki-RasA and Ki-RasA:GTP levels, and sequentially phosphorylated c-Raf, MAPK kinase (MEK1 / 2), and ERK1 / 2. Ki-RasA small interfering RNA (siRNA), the c-Raf inhibitor GW5074, and the MEK1 / 2 inhibitor PD98059 reduced Aldo-induced cell proliferation by similar to 65%. Aldo also increased phosphorylation of PI3K, Akt, the mammalian target of rapamycin (mTOR), and the 70-kDa ribosomal S6 kinase (p70S6K1). Inhibition of the PI3K pathways by the selective PI3K inhibitor LY 294002, an Akt inhibitor, or the mTOR inhibitor rapamycin reduced cell proliferation by 51% . Combining LY 294002 and PD98059 completely blocked Aldo-induced MC proliferation. Next, we confirmed that Aldo exerts its effect on MAPK and PI3K activation, as well as on cell proliferation, by activating the EGFR. Pretreatment with the EGFR antagonist AG1478 inhibited MC proliferation, as well as the activation of Ras / MAPK and PI3K / Akt, suggesting that Ras / MAPK and PI3K / Akt activation occur downstream of EGFR activation. Finally, we exa

关键词： reactive oxygen species PI3K hypertensive-rats phosphatidylinositol 3-kinase stimulates proliferation mesenchymal transition epithelial-cells nadph oxidase s6 kinase activation ras cascade

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Tribology of enzymatically degraded cartilage mimicking early osteoarthritis

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Friction 2023年第9期11卷 1724-1740页

作者： Ke REN Miguel Alejandro REINA mahEChA Maike hÜBNER Zhiwei CUI hans J.KAPER hugo C.VAN DER VEEN Prashant K.ShARMA Department of Biomedical Engineering University Medical Centre GroningenUniversity of GroningenGroningen 9713AVthe Netherlands Department of Mechanical Engineering Eindhoven University of TechnologyEindhoven 5600MBthe Netherlands Department of Orthopedic Surgery University Medical Centre GroningenUniversity of GroningenGroningen 9700RBthe Netherlands

healthy cartilage is a water-filled super lubricious *** type II provides it structural stability,and proteoglycans absorb water to keep the cartilage in a swollen condition,providing it the ability to creep and provide weeping ***(OA)is a degenerative and debilitating disorder of diarthrodial joints,where articular cartilage damage originates from enzymatic degradation and mechanical damage(wear).The objective of this research is to observe the level of cartilage damage present in knee arthroplasty patients and to understand the friction and creep behavior of enzymatically degraded bovine cartilage in ***(Lat)and medial(med)condylar cartilages from OA patients undergoing total knee arthroplasty showed signs of enzymatic degradation and mechanical *** cartilages were exposed to collagenase III and chondroitinase ABC to degrade collagen and proteoglycans,*** loss of proteoglycans or collagen network and morphological changes were observed through histology and the atomic force microscope(AFM),respectively.A significant effect on creep due to enzymatic treatment was not *** the enzymatic treatment was found to significantly decrease the coefficient of friction(COF)at 4 N,while higher COF was shown from chondroitinase ABC degraded cartilage at 40 *** III treatment leads to the release of intact proteoglycans at the sliding interface,while chondroitinase ABC treatment leads to the loss of chondroitin sulfate(CS)from the *** ABC-digested bovine cartilage mimicked patient samples the best because of the similar distributions of proteoglycans,collagen network,and friction behavior.

关键词： lubrication cartilage boundary lubrication osteoarthritis(OA)

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普通外科医对於颅及脑损伤之疗法

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中华医学杂志 1933年第1期19卷 87-91页

作者： E. h. Risley. New Engl. Journ. of med., March, 1932

近年来汽车肇祸日多一日,不但可伤及四肢,且颅脑等受伤者亦不少。此等损作之影响颇大,不仅有关於其本身,且与其家庭及社会均莫不有密切之关系。至於病人幸有头颅被击而未致命者,虽如此,但其中亦有脑受重伤者,致其肢瘫痪或

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Research on optimal immunization strategies for hepatitis B in different endemic areas in China

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World Journal of Gastroenterology 2000年第3期6卷 392-394页

作者： Li h Wang L Wang SS Gong J Zeng XJ Li RC Nong Y huang YK Chen XR huang ZN CAMS & PUMC Inst Basic Med Sci Dept Epidemiol Beijing 100005 Peoples R China

INTRODUCTION At present hepatitis B vaccine immunization is an unique effective measure for controlling hepatitis *** is important o determine optimal immunization

关键词： hepatitis B vaccine immunization strategy cost-benefit analysis china

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Abdominal pain among children re-evaluation of a diagnostic algorithm

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World Journal of Gastroenterology 2002年第5期8卷 947-951页

作者： Zhou, h Chen, YC Zhang, JZ Capital Univ med Sci Beijing Childrens Hosp Dept Pediat Surg Beijing 100045 Peoples R China

AIM: To re-evaluate the algorithm that has been used forover 40 years for diagnosis of acute abdominal pain ***: Among the 937 cases admitted to the surgicalemergency ward in 2000, 656 cases of acute appendicitiswere studied to evaluate the usefulness of the presentalgorithm for its colculated accuracy, false positive and falsenegative rates, the sensitivity and specificity in the instantdiagnosis of various types of acute appendicitis in differentage *** algorithm used was established in 1958and revisedror this study in 1999. It includes a 3-step analysisof clinical presentations, i.e.: firstly, a diagnosis of surgicalpain by definite organic abdominal signs; then a diagnosisof the subgroup of surgical condition by special signs; andfinally the diagnosis of the present disease by specific signs.A footnote describes a 'comparative technique″ of abdominalexamination in non-cooperative ***: The general accuracy of diagnosis was 92.8 %,overall mortality 0.1% among 973 cases of abdominal painin 2000. 373 attending surgeons and 241 residents includingtrainees joined the diagnosis and treatment with noremarkable difference in the results. The incidence of acuteappendicitis, 656 in 973 cases, was 67.4 % representingthe majority of abdominal pain. In the series of 656 cases,the accuracy of diagnosis of acute appendidtis was 93.6 %,false positive 6.4 %, false negative 0.9 %, sensitivity at firstvisit 82.7 %, specificity for appendicitis 98.0 %, no death ordocumentary ***: The present algorithm used for diagnosisof acute abdominal pain is effective and preferable inreducing misdiagnosis and maltreatment at emergency. Theuse of some modern technology should be further explored.

关键词：儿童腹痛鉴别诊断病因

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