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Clinically, diabetes mellitus is closely associated with and induces certain cardiovascular diseases. The aim of this study was to investigate endoplasmic reticulum (ER) stress-associated apoptosis of diabetic cardiomyopathy (DCM), and explore the protective mechanism of liraglutide. The DCM model was established with a high-fat diet and streptozotocin (STZ). Cardiac function was detected by echocardiogram examination and hematoxylin-eosin staining. ER stress unfolded protein response (UPR) hallmarks [inositol-requiring enzyme-α (IRE-α), p-Perk and ATF6] and transcription factors were detected with western blotting. Apoptosis inducers CHOP, c-Jun amino terminal kinase (JNK) and casapse-12 were also examined with western blotting. The results indicated that liraglutide is capable of improving cardiac function in DCM rats (P<0.05). IRE-α expression was significantly increased in the DCM group compared with the control group (P<0.05), and liraglutide is capable of decreasing IRE-α expression. X-box transcription factor-1 (XBP-1) was significantly spliced in the model group, and downregulated in the liraglutide-treated group. CHOP protein was upregulated in the DCM group, but inactivated by liraglutide treatment. In conclusion, liraglutide is capable of protecting DCM and blocking CHOP-mediated ER stress by inhibiting the IRE-α UPR pathway.

In the present study, we investigated the potential pathogenesis of coxsackievirus B3 (CVB3)-induced viral myocarditis and the promising protective effect of silencing RNA (small interfering RNA, siRNA). One hundred and twenty mice were included in the study, and 30 mice were intraperitoneally inoculated with CVB3 to establish an acute viral myocarditis model. The survival rate was observed for the CVB3-infected mouse model (MOD), and myocardial injury was examined by HE (hematoxylin and eosin) staining assay. Real-time PCR (RT-PCR) and Western blot assay were selected to detect the toll-like receptor 4 (TLR4) expression in myocardial tissues. The TLR4 gene was silenced for the MOD mice, and the effects of this treatment were observed. The results indicate that the expression of TLR4 mRNA and the protein significantly and persistently increased during the progression of CVB3-induced myocarditis. The activities of cardiac enzymes including CK, LDH, AST, and CK-MB were also enhanced in CVB3-induced myocardial tissues. Interestingly, when the TLR4 gene was silenced, the CVB3-induced TLR4 production was significantly decreased and the severity of myocarditis was significantly lessened. In conclusion, CVB3 may induce viral myocarditis by upregulating toll-like receptor 4 expression. The viral myocarditis can be ameliorated by silencing the TLR4 gene in the CVB3 viral myocarditis model, which may be a feasible therapeutic method for treatment of viral myocarditis.

Introduction:Passing the National Physical Therapy Examination (NPTE) is a necessary step in progressing into a professional career. The purpose of this study was to identify student factors that predicted failure on the first attempt of the NPTE in graduates of a blended Doctor of Physical Therapy (DPT) program.Review of Literature:Student factors that may affect NPTE outcomes have been studied in traditional physical therapist education programs but have not been studied in blended programs. Blended instruction is a delivery format that combines distance asynchronous learning and face-to-face synchronous learning in a complementary way.Subjects:Two hundred ten graduates from 6 consecutive cohorts of a DPT program taught in a blended format.Methods.Retrospective observational cohort design. Demographic, preadmission, and in-program academic data and NPTE pass/fail status were collected. Variables were analyzed with forward stepwise logistic regression for their ability to predict first-time NPTE failure. Receiver operating characteristic curves were plotted to determine cut points of predictive variables.Results.Two regression analyses were conducted. First, an analysis of all variables identified 3 significant predictors: comprehensive examination score, cumulative third-year grade point average, and Graduate Record Examination Verbal Reasoning (GRE-V) score, which explained 43.2% of the variance. The second analysis excluded variables occurring late in matriculation to identify early occurring predictors. This yielded 2 early predictive variables, GRE-V score and academic difficulty, which explained 29.5% of the variance.Discussion and Conclusion.To our knowledge, this is the first study of predictors of NPTE outcomes in blended DPT program graduates. Like previous studies, a mix of preadmission and in-program factors predicted first-time NPTE failure. These findings may help inform admissions policies, academic advising processes, and academic warning policies in blended programs. Future research is needed to explore factors unique to blended educational settings and the qualities of the students they attract.

Background Ivabradine improves cardiac function and clinical outcomes in chronic heart failure (HF) by reducing heart rate (HR), but there is a lack of real-world data on its effectiveness and safety in Chinese patients. Methods We designed a prospective, multicenter, observational study of Chinese adults with HF and left ventricular systolic dysfunction, resting HR ≥ 75 beats per minute (bpm), and an indication for ivabradine treatment. An interim analysis was performed using a cut-off date of 31 October 2019. The primary outcome was change in HR at 6 months after the initiation of ivabradine. Secondary endpoints included change in New York Heart Association (NYHA) functional class; quality of life (QoL), measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ); and adverse events (AEs). Results Overall, 655 subjects were included in the interim analysis. Mean reduction in HR from baseline was 13.2 (95% confidence interval [CI] 11.2-15.2) bpm at Month 1, and 14.5 (95% CI 11.8-17.2) bpm at Month 6 (p < 0.001 for both changes). NYHA functional class and KCCQ scores improved significantly over time (p < 0.001 for all comparisons with baseline), indicating amelioration of symptoms and better QoL, respectively. Forty-four subjects (6.7%) reported a total of 60 ivabradine-related AEs, most frequently phosphenes and bradycardia (both n = 6, 0.9%). Conclusion Treatment with ivabradine for 6 months effectively reduced HR and improved functional class and QoL in Chinese patients with chronic HF. Treatment was well tolerated. Clinical Trial Registration ISRCTN11703380; registered on