New rabbit model for benign biliary stricture formation with repeatable administration

BACKGROUND The treatment of benign biliary strictures(BBS)is a challenging clinical problem.At present,there is a lack of ideal models for the study of BBS treatment.AIM To develop a novel animal model of BBS to simulate studies on the processes and mechanisms in the human condition.METHODS A rabbit model of benign bile duct stricture was established by surgical injury of the bile duct.After removal of the gallbladder,a drainage tube was placed th-rough the cystic duct at the stump,and a BBS model was induced by surgical injury at the lower end of the common bile duct.RESULTS Compared with the control group,the model rabbits showed gross jaundice,increased serum bilirubin,and decreased liver function.Cholangiography showed segmental bile duct stenosis in the model rabbits.Pathological staining showed inflammatory cell infiltration and fibrosis in the biliary tract of rabbits in the model group.This was consistent with the clinical manifestations of BBS.This model provided serology,imaging,pathology,and other aspects of BBS.CONCLUSION We have successfully established an animal model of benign stricture of the lower bile duct with repeatable administration,which is consistent with the clinical manifestations of BBS.

LM23 is a novel member of the Speedy/Ringo family at the ：rossroads of life and death of spermatogenic cell

LM23 is a gene specifically expressed in the testis of Rattus norvegicus, as previously reported by our laboratory. The aim of the study is to further investigate the biological function of LM23. Several bioinformatic tools were utilized, including PROSITE and BLAST. To determine the subcellullar localization of LM23, a polyclonal antibody specific for LM23 was generated via the immunization of rabbits. The LM23gene was cloned from rat testis tissue, and LM23 protein was expressed in Escherichia co/i. The biological function of LM23 was analyzed with microarray analysis and immunohistochemistry, using a rat model of LM23 gene knockdown. The results suggested that LM23 belongs to the Speedy/Ringo family. LM23 regulated the GI/S and G2/M transitions of the cell cycle during spermatogenesis. Downregulation of the LM23gene during spermatogenesis could lead to the activation of both the Fas-FasL pathway and the mitochondrial pathway. These novel findings indicate that LM23 has a diverse array of functions that are important in both the life and death of the spermatogenic cell.

Establishing a rabbit model of perianal fistulizing Crohn's disease

BACKGROUND Crohn’s disease(CD)is a chronic nonspecific intestinal inflammatory disease.The aetiology and pathogenesis of CD are still unclear.Anal fistula is the main complication of CD and is a difficult problem to solve at present.The main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness data.Therefore,an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal mucosa.AIM To improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing Crohn’s disease animal model to evaluate new treatment strategies.METHODS Twenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce proctitis.Group A was treated with an improved equal interval small dose increasing method.The dosage of group B was constant.Seven days later,the rabbits underwent surgical creation of a transsphincteric fistula.Then,three rabbits were randomly selected from each group every 7 d to remove the seton from the fistula.The rabbits were examined by endoscopy every 7 days,and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological analysis.The disease activity index(DAI),colonoscopy and histological scores were recorded.Perianal endoscopic ultrasonography(EUS)was used to evaluate the healing of fistulas.RESULTS Except for the DAI score,the colonoscopy and histological scores in group A were significantly higher than those in group B(P<0.05).In the ideal model rabbit group,on the 7 th day after the removal of the seton,all animals had persistent lumens on EUS imaging,showing continuous fullthickness high signals.Histological inspection of the fistula showed acute and chronic inflammation,fibrosis,epithelialization and peripheral proctitis of the adjoining rectum.CONCLUSION The improved method of CD colitis induction successfully established a rabbit perianal fistula CD preclinical model,which was confirmed by endoscopy and pathology.

Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease

Background：Renin-angiotensin system inhibitor and calcium channel blocker （CCB） are widely used in controlling blood pressure （BP） in patients with chronic kidney disease （CKD）.We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） and CCB （i.e.,ACEI/ARB ＋ CCB） with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods：Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials （RCTs） of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease （ESRD）,cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate （GFR）,and adverse events were extracted.Results：Based on seven RCTs with 628 patients,ACEI/ARB ＋ CCB did not show additional benefit for the incidence of ESRD （risk ratio [RR] =0.84;95% confidence interval [CI]：0.52-1.33） and cardiovascular events （RR =0.58;95% CI：0.21-1.63） significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP （weighted mean difference [WMD] =-1.28 mmHg;95% CI：-3.18 to-0.62）,proteinuria （standard mean difference =-0.55;95% CI：-1.41 to-0.30）,GFR （WMD =-0.32 ml/min;95% CI：-1.53 to-0.89）,and occurrence of adverse events （RR =1.05;95% CI：0.72-1.53）.However,ACEI/ARB ＋ CCB showed a greater reduction in systolic BP （WMD =-4.46 mmHg;95% CI：-6.95 to-1.97）,compared with ACEI/ARB monotherapy.Conclusion：ACEI/ARB ＋ CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.