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 7th day after the removal of the seton, all animals had persistent lumens on EUS imaging, showing continuous full-thickness 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.

A Risk Stratification Model for Predicting Overall Survival and Surgical Benefit in Triple-Negative Breast Cancer Patients With de novo Distant Metastasis.

Background and Aims: This research aimed to construct a novel model for predicting overall survival (OS) and surgical benefit in triple-negative breast cancer (TNBC) patients with de novo distant metastasis. Methods: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database for TNBC patients with distant metastasis between 2010 and 2016. Patients were excluded if the data regarding metastatic status, follow-up time, or clinicopathological information were incomplete. Univariate and multivariate analyses were applied to identify significant prognostic parameters. By integrating these variables, a predictive nomogram and risk stratification model were constructed and assessed with C-indexes and calibration curves. Results: A total of 1,737 patients were finally identified. Patients enrolled from 2010 to 2014 were randomly assigned to two cohorts, 918 patients in the training cohort and 306 patients in the validation cohort I, and 513 patients enrolled from 2015 to 2016 were assigned to validation cohort II. Seven clinicopathological factors were included as prognostic variables in the nomogram: age, marital status, T stage, bone metastasis, brain metastasis, liver metastasis, and lung metastasis. The C-indexes were 0.72 [95% confidence interval [CI] 0.68-0.76] in the training cohort, 0.71 (95% CI 0.68-0.74) in validation cohort I and 0.71 (95% CI 0.67-0.75) in validation cohort II. Calibration plots indicated that the nomogram-based predictive outcome had good consistency with the recoded prognosis. A risk stratification model was further generated to accurately differentiate patients into three prognostic groups. In all cohorts, the median overall survival time in the low-, intermediate- and high-risk groups was 17.0 months (95% CI 15.6-18.4), 11.0 months (95% CI 10.0-12.0), and 6.0 months (95% CI 4.7-7.3), respectively. Locoregional surgery improved prognosis in both the low-risk [hazard ratio [HR] 0.49, 95% CI 0.41-0.60, P < 0.0001] and intermediate-risk groups (HR 0.55, 95% CI 0.46-0.67, P < 0.0001), but not in high-risk group (HR 0.73, 95% CI 0.52-1.03, P = 0.068). All stratified groups could prognostically benefit from chemotherapy (low-risk group: HR 0.50, 95% CI 0.35-0.69, P < 0.0001; intermediate-risk group: HR 0.34, 95% CI 0.26-0.44, P < 0.0001; and high-risk group: HR 0.16, 95% CI 0.10-0.25, P < 0.0001). Conclusion: A predictive nomogram and risk stratification model were constructed to assess prognosis in TNBC patients with de novo distant metastasis; these methods may provide additional introspection, integration and improvement for therapeutic decisions and further studies.

The Emergence, Epidemiology, and Etiology of Haff Disease.

Haff disease is a type of human rhabdomyolysis characterized by the sudden onset of unexplained muscular rigidity and an elevated serum creatine kinase level within 24 h after consuming cooked aquatic products. Here, we reviewed a previous study on Haff disease and summarized the clinical manifestations, epidemiological characteristics, and etiological data to confirm the incidence and global epidemiology of the disease and identify the most common seafood vectors. Future directions for Haff disease study will include further prospective etiological studies and the development of prevention and control strategies.

Effects of the fenugreek extracts on high-fat diet-fed and streptozotocin-induced type 2 diabetic mice.

BACKGROUND: To study the antidiabetic effects and mechanisms of the fenugreek extracts in streptozotocin (STZ)-induced type 2 diabetic (T2DM) mice fed a high-fat diet (HFD). METHODS: We established C57BL/6J mice model of T2DM using HFD-fed and STZ-induced method. Then, the mice were administered with two types of fenugreek extracts (E1, flavonoid and E2, stilbene glycoside) for 4 weeks and the effects on fasting blood glucose (FBG), weight, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and pathological indexes were investigated. RESULTS: Administration of fenugreek extracts decreased the FBG level compared with that of the model group. Comparatively, the high-dose E2 decreased the FBG more significantly than the other treatments did. Both extracts showed an obvious antioxidant effect by increasing serum SOD and CAT activities and decreasing the MDA content. Furthermore, the high-dose E1 showed a significant difference (P < .01) compared with the model group in the three investigated indexes. CONCLUSION: Our study demonstrated that both the flavonoid and stilbene glycoside extracts of fenugreek improved the hyperglycemia in the T2DM mice model. Moreover, the antidiabetic effects of both extracts might be due to their antioxidant activity in vivo.