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Colostomy is a simple and effective procedure for severe chronic radiation proctitis

World Journal of Gastroenterology 2016年第24期22卷 5598-5608页

作者： Zi-Xu Yuan Teng-Hui Ma Huai-Ming Wang Qing-Hua Zhong Xi-Hu Yu Qi-Yuan Qin Jian-Ping Wang Lei Wang department of Colorectal Surgery The Sixth Affiliated Hospital of Sun Yat-Sen University clinical Research Division Fred Hutchinson Cancer Research Center University of Washington

AIM: To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis(CRP). METHODS: Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life beforetreatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during ***: Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission(94% vs 12%), especially in control of transfusion-dependent bleeding(100% vs 0%), and offered a better control of refractory perianal pain(100% vs 0%), and a lower score of bleeding(P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding(100% vs 21.5%, P = 0.002) and severe bleeding(100% vs 0%, P < 0.001), obtained a lower score of bleeding(0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels(P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammatio

关键词： Chronic radiation proctitis Rectal bleeding Diverting colostomy Quality of life Serious complication

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Bromophenols from Marine Algae with Potential Anti-Diabetic Activities

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Journal of Ocean University of China 2012年第4期11卷 533-538页

作者： LIN Xiukun LIU Ming department of pharmacology Capital Medical UniversityBeijing 100069P.R.China Institute of Oceanology Chi-nese Academy of ScienceQingdao 266071P.R.China

Marine algae contain various bromophenols with a variety of biological activities, including antimicrobial, anticancer, and anti-diabetic effects. Here, we briefly review the recent progress in researches on the biomaterials from marine algae, emphasizing the relationship between the structure and the potential anti-diabetic applications. Bromophenols from marine algae display their hyper- glycemic effects by inhibiting the activities of protein tyrosine phosphatase 1B, ct-glucosidase, as well as other mechanisms.

关键词： bromophenols marine algae type 2 diabetes mellitus

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Epigenetics of cutaneous T-cell lymphoma:biomarkers and therapeutic potentials

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Cancer Biology & Medicine 2021年第1期18卷 34-51页

作者： Pan Lai Yang Wang department of Dermatology and Venereology Peking University First HospitalBeijing Key Laboratory of Molecular Diagnosis on DermatosesNational Clinical Research Center for Skin and Immune DiseasesBeijing 100034China

Cutaneous T-cell lymphomas(CTCLs)are a heterogeneous group of skin-homing non-Hodgkin *** are limited options for effective treatment of patients with advanced-stage CTCL,leading to a poor survival *** plays a pivotal role in regulating gene expression without altering the DNA *** alterations are involved in virtually all key cancerassociated pathways and are fundamental to the genesis of *** recent years,the epigenetic hallmarks of CTCL have been gradually elucidated and their potential values in the diagnosis,prognosis,and therapeutic intervention have been *** this review,we summarize the current knowledge of the best-studied epigenetic modifications in CTCL,including DNA methylation,histone modifications,micro RNAs,and chromatin *** epigenetic regulators are essential in the development of CTCL and provide new insights into the clinical treatments of this refractory disease.

关键词： Epigenetics cutaneous T-cell lymphoma DNA methylation histone modification micro RNA chromatin-remodeling complex

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Effects of Jiazhu decoction in combination with cyclophosphamide on breast cancer in mice

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Journal of Traditional Chinese Medicine 2019年第5期39卷 642-648页

作者： Guan Huiting Xie Su Liu Shangyi Xie Qing Hou Shengkai Liu Huarong Zhang Yunjie Hu Yaqing Zhang Chenyu Academy of clinical Medicine Guizhou Medical UniversityGuiyang 550004China department of Chinese Medicine the Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China the First Affiliated Hospital of Guiyang University of Chinese Medicine Guiyang 550004 China department of Chinese Medicine the Maternity and Child Health Care of ZaozhuangZaozhuang 277100China Academy of clinical Medicine Guizhou Medical UniversityGuiyang 550004China

OBJECTIVE: To investigate the therapeutic effects of Jiazhu decoction (JZD) in combination with cyclophosphamide (CTX) on the growth of breast cancer in mice and to explore the possible molecular mechanisms of action. METHODS: BALB/c mice were randomly divided into four groups of 10 (untreated model group, JZD group, CTX group, and JZD + CTX group) and subcutaneously injected with 4T1 mouse breast cancer cells. Tumors were allowed to establish for ~7 d before initiation of treatment with CTX (100 mg/kg every week by intraperitoneal injection) and/or JZD (0.015 mL of 1.65 g/mL crude drug, administered daily by gavage). The model group received equivalent volumes of vehicle on the same schedules. Tumor volumes were measured every 3 d. Mice were sacrificed after 3 weeks of treatment, and tumors were excised and subjected to RT-qPCR and western blot analysis to evaluate expression of the Wnt/β-catenin signaling pathway components β-catenin, c-Myc, and cyclin D1 at the mRNA and protein levels. RESULTS: The mean tumor volume was smaller and the growth rate was slower in the CTX and JZD + CTX groups compared with the model group (P < 0.05), and in the JZD + CTX group compared with the CTX and JZD groups (P < 0.05). Tumor growth was inhibited by 35.4% and 48.1% by CTX and JZD + CTX treatment, respectively (P < 0.001). The expression of β-catenin, c-Myc, and cyclin D1 mRNA and protein in tumors was significantly lower in mice treated with JZD or JZD + CTX compared with the untreated mice (P < 0.05), and was significantly lower in mice treated with JZD + CTX compared with either JZD or CTX alone (P < 0.05). CONCLUSION: JZD inhibited the growth of mouse breast cancer cells in vivo, possibly by reducing the expression of β-catenin, c-Myc, and cyclin D1. Combination therapy with JZD plus CTX had a more potent inhibitory effect on breast cancer growth compared with either agent alone.

关键词： Breast neoplasms Cyclophosphamide Wnt signaling pathway Jiazhu decoction

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Endoscopic and pathological features of neoplastic transformation of gastric hyperplastic polyps:Retrospective study of 4010 cases

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World Journal of Gastrointestinal Oncology 2024年第11期16卷 4424-4435页

作者： Dong-Xue Zhang Zhan-Yue Niu Ye Wang Ming Zu Ya-Han Wu Yan-Yan Shi He-Jun Zhang Jing Zhang Shi-Gang Ding department of Gastroenterology Peking University Third HospitalBeijing 100191China Research Center of clinical Epidemiology Peking University Third HospitalBeijing 100191China

BACKGROUND Hyperplastic polyps,which represent 30%-93%of all gastric epithelial polyps,are the second most common type of gastric polyps after fundic gland *** were previously considered to have no risk of neoplastic ***,an increasing number of cases of gastric hyperplastic polyps(GHPs)combined with neoplastic changes have been reported;however,the specific mechanism underlying their transformation has not been thoroughly *** To investigate the clinical,endoscopic,and pathological characteristics of the neoplastic transformation of GHPs and explore the risk *** A retrospective analysis was performed on 4010 cases of GHPs diagnosed by gastroscopy and pathological examination at the hospital from 2005 to *** total,3874,119,and 17 cases were in the group without intraepithelial neoplasia(IN),with low-grade IN,and with high-grade IN,*** data analysis examined the association of endoscopic and pathological features with risk factors for neoplastic *** with significant differences were entered into univariate logistic regression,followed by multivariate logistic regression *** Univariate analysis revealed diameter,multiple polyp presence,redness,rough surface,lobulation,erosion,Yamada classification,location,and gastric mucosa were risk factors for neoplastic *** analysis showed that age>65 years[odds ratio(OR)=1.789;95%confidence interval(CI):1.227-2.609;P=0.003],male sex(OR=1.680;95%CI:1.158-2.438;P=0.006),multiple polyps(OR=1.851;95%CI:1.230-2.784;P=0.003),pedunculated or semi-pedunculated shape(OR=2.722;95%CI:1.689-4.388;P<0.001),and polyp diameter were significantly associated with GHPs that demonstrated neoplastic *** with chronic superficial gastritis,autoimmune gastritis,atrophic gastritis,and gastritis with IN were independent risk factors for neoplastic transformation[(OR=2.672;95%CI:1.559-4.579;P<0.001),(OR=1.876;95%CI:1.

关键词： Endoscopy Gastric hyperplastic polyps Neoplastic transformation Pathology Risk factors Tumour

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Modern drug discovery for inflammatory bowel disease: The role of computational methods

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World Journal of Gastroenterology 2023年第2期29卷 310-331页

作者： Titilayo Omolara Johnson Augustina Oduje Akinsanmi Stephen Adakole Ejembi Olugbenga Eyitayo Adeyemi Jane-Rose Oche Grace Inioluwa Johnson Abayomi Emmanuel Adegboyega department of Biochemistry University of JosJos 930222PlateauNigeria Faculty of clinical Sciences College of Health SciencesUniversity of JosJos 930222PlateauNigeria

Inflammatory bowel diseases(IBDs)comprising ulcerative colitis,Crohn’s disease and microscopic colitis are characterized by chronic inflammation of the gastrointestinal *** has spread around the world and is becoming more prevalent at an alarming rate in developing countries whose societies have become more *** therapy,intestinal microecology,apheresis therapy,exosome therapy and small molecules are emerging therapeutic options for ***,it is thought that low-molecular-mass substances with good oral bio-availability and the ability to permeate the cell membrane to regulate the action of elements of the inflammatory signaling pathway are effective therapeutic options for the treatment of *** small molecule inhibitors are being developed as a promising alternative for IBD *** use of highly efficient and time-saving techniques,such as computational methods,is still a viable option for the development of these small molecule *** computeraided(in silico)discovery approach is one drug development technique that has mostly proven *** approaches when combined with traditional drug development methodology dramatically boost the likelihood of drug discovery in a sustainable and cost-effective *** review focuses on the modern drug discovery approaches for the design of novel IBD drugs with an emphasis on the role of computational *** computational approaches to IBD genomic studies,target identification,and virtual screening for the discovery of new drugs and in the repurposing of existing drugs are discussed.

关键词： Inflammatory bowel disease Computer-aided drug design Janus Kinase Molecular docking Genome-wide association study Molecular dynamics simulation

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Licorice Extracts Attenuate Nephrotoxicity Induced by Brucine Through Suppression of Mitochondria Apoptotic Pathway and STAT3 Activation

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Current Medical Science 2019年第6期39卷 890-898页

作者： Min ZHANG Chao WANG Hua-lin CAI Jing WEN Ping-fei FANG department of Pharmacy the Second Xiangya HospitalCentral South UniversityChangsha 410011China Institute of clinical Pharmacy Central South UniversityChangsha 410011China

Licorice,one of the most widely used medicinal herbs in East Asia,has effects such as anti-inflammation,antioxidant,and *** study aimed to evaluate the protective effect of licorice on brucine-induced *** Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with *** content of blood urea nitrogen and creatinine in serum,the activities of superoxide dismutase and content of glutathione,malonaldehyde in kidney tissue were ***-eosin staining was employed to observe the histopathological changes of *** expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical *** results illustrated that treatment with licorice extracts(LE)significantly protected against the brucineinduced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine,attenuating pathologic *** unbalance of oxidative stress was repaired by LE via increasing the level of glutathione,promoting the activities of superoxide dismutase and decreasing the content of *** addition,LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3(STAT3)*** together,these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis *** importantly,the renoprotective effects may be mediated,at least partly,by preventing the activation of STAT3 protein.

关键词： licorice brucine nephrotoxicity apoptosis STAT3

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Biogenesis of Mammalian MicroRNAs:A Global View

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Genomics, Proteomics & Bioinformatics 2012年第5期10卷 239-245页

作者： Paul Graves Yan Zeng department of Radiation Oncology New York Methodist Hospital Weill Cornell Medical College Brooklyn NY 11215 USA department of pharmacology Masonic Cancer Center University of Minnesota Minneapolis MN 55455 USA

MicroRNAs （miRNAs） are approximately 22-nucleotide-long non-coding RNAs that are important regulators of gene expression in eukaryotes, miRNAs are first transcribed as long primary transcripts, which then undergo a series of processing steps to produce the single-stranded mature miRNAs. This article reviews our current knowledge of the mechanism and regulation of mammalian miRNA expression and points out areas of research that may enhance our understanding of how the specificity and efficiency of miRNA pro- duction is controlled in vivo.

关键词： MicroRNA expression MicroRNA processing Primary microRNA Drosha

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Celecoxib attenuates 5-fluorouracil-induced apoptosis in HCT-15 and HT-29 human colon cancer cells

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World Journal of Gastroenterology 2007年第13期13卷 1947-1952页

作者： Yun Jeong Lim Jong Chul Rhee Young Mee Bae Wan Joo Chun department of Internal Medicine Dongguk University International Hospital Dongguk University College of Medicine Goyang Korea Division of Gastroenterology Department of Internal Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea department of Parasitology Seoul National University College of Medicine Seoul Korea department of pharmacology Kangwon National University College of Medicine Chuncheon Korea

AIM： To investigate the combined chemotherapeutic effects of celecoxib when used with 5-FU in vitro. METHODS： Two human colon cancer cell lines （HCT-15 and HT-29） were treated with 5-FU and celecoxib, alone and in combination. The effects of each drug were evaluated using the MTT （3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide） assay, flow cytometry, and western blotting. RESULTS： 5-FU and celecoxib showed a dosedependent cytotoxic effect. When treated with 10-3 mol/L 5-FU （IC50） and celecoxib with its concentration ranging from 10.8 mol/L to 10.4 mol/L of celecoxib, cells showed reduced cytotoxic effect than 5-FU （10.3 mol/L） alone. Flow cytometry showed that celecoxib attenuated 5-FU induced accumulation of cells at subG1 phase. Western blot analyses for caspase-3 and poly （ADP-ribose） polymerase （PARP） cleavage showed that celecoxib attenuated 5-FU induced apoptosis. Western blot analyses for cell cycle molecules showed that G2/M arrest might be possible cause of 5-FU induced apoptosis and celecoxib attenuated 5-FU induced apoptosis via blocking of cell cycle progression to the G2/M phase, causing an accumulation of cells at the GI/S phase. CONCLUSION： We found that celecoxib attenuated cytotoxic effect of 5-FU. Celecoxib might act via inhibition of cell cycle progression, thus preventing apoptosis induced by 5-FU.

关键词： Antagonism Celecoxib Colorectal neoplasms Fluorouracil

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The key role of gut-liver axis in pyrrolizidine alkaloid-induced hepatotoxicity and enterotoxicity

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3820-3835页

作者： Yisheng He Jiang Ma Xiaoyu Fan Liang Ding Xinxin Ding Qing-Yu Zhang Ge Lin School of Biomedical Sciences Faculty of Medicinethe Chinese University of Hong KongHong Kong SAR 999077China department of pharmacology&Toxicology College of PharmacyUniversity of ArizonaTucsonAZ 85721USA

Pyrrolizidine alkaloids(PAs) are the most common phytotoxins with documented human *** require metabolic activation by cytochromes P450 to generate toxic intermediates which bind to proteins and form protein adducts,thereby causing *** study investigated the role of the gut-liver axis in PA intoxication and the underlying *** exposed mice to retrorsine(RTS),a representative PA,and for the first time found RTS-induced intestinal epithelium damage and disruption to intestinal barrier *** mice with tissue-selective ablation of P450 activity,we found that hepatic P450 s,but not intestinal P450 s,were essential for PA ***,in RTS-exposed,bile duct-cannulated rats,we found the liver-derived reactive PA metabolites were transported by bile into the intestine to exert *** impact of gut-derived pathogenic factors in RTS-induced hepatotoxicity was further studied in mice with dextran sulfate sodium(DSS)-induced chronic *** treatment increased the hepatic endotoxin level and depleted hepatic reduced glutathione,thereby suppressing the PA detoxification *** to RTS-exposed normal mice,the colitic mice displayed more severe RTS-induced hepatic vasculature damage,fibrosis,and ***,our findings provide the first mode-of-action evidence of PA-induced enterotoxicity and highlight the importance of gut barrier function in PA-induced liver injury.

关键词： Pyrrolizidine alkaloid Cytochrome P450 Inflammatory bowel disease Intestinal injury Liver injury Gut-liver axis

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