Multicenter case-control study of the risk factors for ulcerative colitis in China

AIM:To evaluate potential risk factors in the development of ulcerative colitis(UC) in China.METHODS:A total of 1308 patients with UC and 1308 age-matched and sex-matched controls were prospectively studied in China.The UC cases were collected from 17 hospitals in China from April 2007 to April 2010.Uniform questionnaires were designed to investigate risk factors including smoking,appendectomy,stress,socio-economic conditions,nonsteroidal antiinflammatory drugs(NSAIDs),oral contraceptives,diet,breastfeeding,infections and family sanitary conditions.Group comparisons by each factor were done using simple logistic regression analysis.Conditional logistic regression was used for multivariate analysis.RESULTS:By univariate analysis,the variables predictive of UC included feeling stress,light and heavy alcoholic drinking,spicy food,sugar consumption and infectious diarrhea,while heavy tea intake and tap water consumption were protective against UC.On multivariate analysis,the protective factor for UC was tap water consumption [odds ratios(OR) = 0.424,95%CI:0.302-0.594,P < 0.001];while the potential risk factors for UC were heavy sugar consumption(OR = 1.632,95%CI:1.156-2.305,P < 0.001),spicy food(light intake:OR = 3.329,95%CI:2.282-4.857,P < 0.001;heavy intake:OR = 3.979,95%CI:2.700-5.863,P < 0.001),and often feeling stress(OR = 1.981,95%CI:1.447-2.711,P < 0.001).Other factors,such as smoking habit,appendectomy,breastfeeding,a history of measles,rural or urban residence,education,oral contraceptives,and NSAID use have not been found to have a significant association with the development of UC in the present study.CONCLUSION:Our study showed tap water consumption was a protective factor for UC,while spicy food,heavy sugar consumption and often feeling stress were risk factors for UC in this Chinese population.

Investigation of immune escape-associated mutations of hepatitis B virus in patients harboring hepatitis B virus drug-resistance mutations

It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen(HBsAg)are associated with nucleoside/nucleotide analog resistance.AIM To evaluate the association between immune escape-associated mutations and nucleoside/nucleotide analog resistance mutations.METHODS In total,19440 patients with chronic hepatitis B virus infection,who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between July 2007 and December 2017,were enrolled.As determined by sequence analysis,6982 patients harbored a virus with resistance mutations and 12458 harbored a virus lacking resistance mutations.Phenotypic analyses were performed to evaluate HBsAg production,replication capacity,and drug-induced viral inhibition of patient-derived drug-resistant mutants with or without the coexistence of sA159V.RESULTS The rate of immune escape-associated mutation was significantly higher in 9 of the 39 analyzed mutation sites in patients with resistance mutations than in patients without resistance mutations.In particular,these mutations were sQ101H/K/R,sS114A/L/T,sT118A/K/M/R/S/V,sP120A/L/Q/S/T,sT/I126A/N/P/S,sM133I/L/T,sC137W/Y,sG145A/R,and sA159G/V.Among these,sA159V was detected in 1.95%(136/6982)of patients with resistance mutations and 1.08%(134/12,458)of patients lacking resistance mutations(P<0.05).The coexistence of sA159V with lamivudine(LAM)and entecavir(ETV)-resistance mutations in the same viral genome was identified during follow-up in some patients with drug resistance.HBsAg production was significantly lower and the replication capacity was significantly higher,without a significant difference in LAM/ETV susceptibility,in sA159V-containing LAM/ETV-resistant mutants than in their sA159V-lacking counterparts.CONCLUSION In summary,we observed a close link between the increase in certain immune escape-associated mutations and the development of resistance mutations.sA159V might increase the fitness of LAM/ETV-resistant mutants under environmental pressure in some cases.

The Involvement of Ca^2＋ Signal Pathways in Distal Colonic Myocytes in a Rat Model of Dextran Sulfate Sodium-induced Colitis

Background： Disrupted Ca2＋ homeostasis contributes to the development of colonic dysmotility in ulcerative colitis （UC）, but the underlying mechanisms are unknown. This study aimed to examine the alteration of colonic smooth muscle （SM） Ca2＋ signaling and Ca2＋ handling proteins in a rat model of dextran sulfate sodium （DSS）-induced UC. Methods： Male Sprague-Dawley rats were randomly divided into control （n = 18） and DSS （n = 17） groups. Acute colitis was induced by 5% DSS in the drinking water for 7 days. Contractility of colonic SM strips （controls, n = 8 and DSS, n = 7） was measured in an organ bath. Cytosolic resting Ca2＋ levels （n = 3 in each group） and Ca2＋ transients （n = 3 in each group） were measured in single colonic SM cells. Ca2＋ handling protein expression was determined by Western blotting （n = 4 in each group）. Differences between control and DSS groups were analyzed by a two-sample independent t-test. Results： Average tension and amplitude of spontaneous contractions of colonic muscle strips were significantly enhanced in DSS-treated rats compared with controls （1.25 ± 0.08 g vs. 0.96 - 0.05 g, P = 0.007; and 2.67 - 0.62 g vs. 0.52 ±0.10 g, P= 0.013）. Average tensions of carbachol-evoked contractions were much weaker in the DSS group （1.08 ±0.10 g vs. 1.80 ±0.19 g, P = 0.006）. Spontaneous Ca2＋ transients were observed in more SM cells from DSS-treated rats （15/30 cells） than from controls （5/36 cells）. Peak caffeine-induced intracellular Ca2＋ release was lower in SM cells of DSS-treated rats than controls （0.413 ±0.046 vs. 0.548 ±0.041, P = 0.033）. Finally, several Ca2＋ handling proteins in colonic SM were altered by DSS treatment, including sarcoplasmic reticulum calcium-transporting ATPase 2a downregulation and phospholamban and inositol 1,4,5-trisphosphate receptor 1 upregulation. Conclusions： Impaired intracellular Ca2＋ signaling of colonic SM, caused by alteration of Ca2＋ handing proteins, contribute to colonic dysmotility in DSS-induced UC.

Screening Safflower Injection for Constituents with Activity against Stroke Using Comprehensive Chemical Profiling Coupled with Network Pharmacology

Objective:This study aimed to explore safflower injection(SI)for constituents with activity against ischemic stroke using a combination of chemical analysis and a network pharmacology strategy.Materials and Methods:The main ingredients of SI were comprehensively identified using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry,and the core targets and pathways associated with stroke were predicted using PharmMapper and Kyoto Encyclopedia of Genes and Genomes analysis.Cytoscape software was used to visualize and analyze the active compound-target-pathway network of SI regulating ischemic stroke.Results:A total of76 chemical compounds were identified from the SI sample,including 63,which regulated 88 targets that were ultimately enriched in 12 key ischemia stroke-related signaling pathways.Kaempferol-3-O-sophoroside,kaempferol-3-O-rutinoside,carthamoside B6,neoeriocitrin,and6-hydroxykaempferol-3-O-rutinoside-6-O-glucoside were determined to be important for stroke treatment because they had a higher degree value in the network than other constituents did.Moreover,the characteristic components isolated from SI showed protective effect mainly by acting on multiple targets including AKT1,epidermal growth factor receptor,transforming growth factor-beta receptor(TGFBR),Ras homolog,mTORC1 binding,caspase 3,and glycogen synthase kinase 3 beta,which were involved in different signaling pathways including phosphoinositide 3-kinase-Akt,mitogen-activated protein kinase,neurotrophin,ErbB,mechanistic target of rapamycin,and tumor necrosis factor.Conclusions:This study proposed a network pharmacology and chemical component profiling strategy for the systematic understanding of the therapeutic material basis of using SI against ischemic stroke.

A Simple High-Performance Liquid Chromatography Method for the Assay of Flavonoids in Ginkgo biloba Leaves

Objective:Ginkgo biloba leaves,as an herbal medicine or dietary supplement,have been widely used worldwide.In this study,an integrated analytical method was established for the comprehensive analysis of flavonoids in G.biloba leaves.Materials and Methods:A practical chromatographic method combining high-performance liquid chromatography fingerprint analysis and quantitation was used to simultaneously determine 11 flavonoids(6 flavonol glycosides and 5 biflavones)in G.biloba leaves from different regions.Results:A total of 11 characteristic peaks were identified accurately,and the similarity of fingerprints ranged from 0.944 to 0.996.Methodology validation revealed appropriate linearity(R^(2)≥0.9997),precision,repeatability,stability,and recovery.The total contents of the six flavonol glycosides and five biflavones were within the range of 2.142-8.378 mg/g and 3.759-5.675 mg/g in 19 batches of samples,respectively.Among them,two coumaroyl flavonol glycosides were the predominant components.Conclusions:In this study,a convenient and reliable approach was successfully employed for the comprehensive evaluation of flavonoids in G.biloba leaves,which also provided a reference for its quality standard.