TRAIL inhibits HBV replication and expression by down-regulating liver-enriched transcription factors.

BACKGROUND AND STUDY AIMS: To investigate the role of low-concentration TRAIL on HBV replication and expression. MATERIAL AND METHODS: MTT assay was performed to determine the minimum concentrations of TRAIL protein in HepG2 cell apoptosis. HepG2 cells were transfected by HBV replication plasmid pHBV4.1. After the treatment with low concentration of TRAIL, the culture supernatant was collected to detect HBsAg and HBeAg by ELISA. Proteins were extracted from the resulted cells, followed by total RNA and HBV DNA intermediate replication. Southern Blot and Northern Blot were carried out to detect HBV RNA and HBV DNA replication intermediates, respectively. RT-PCR and Western Blot were carried out to detect gene and protein expressions for HNF4α, PPARα, and RXRα, respectively. RESULTS: 50 ng/ml of TRAIL protein led to significant decline on the secretions of HBsAg and HBeAg. Expression levels of HBV RNA and HBV DNA replication intermediates were significantly decreased too. In addition, gene and protein expressions of HNF4α, PPARα and RXRα also dropped, especially for PPARα whose expressions significantly decreased. CONCLUSION: TRAIL could inhibit HBV replication and expression by downregulating the expressions of liver-enriched transcription factors HNF4α, PPARα, and RXRα.

Safety and effectiveness of a Tai Chi-based cardiac rehabilitation programme for chronic coronary syndrom patients: study protocol for a randomised controlled trial.

INTRODUCTION: Preliminary evidence from clinical observations suggests that Tai Chi exercise may offer potential benefits for patients with chronic coronary syndrom (CCS). However, the advantages for CCS patients to practice Tai Chi exercise as rehabilitation have not been rigorously tested and there is a lack of consensus on its benefits. This study aims to develop an innovative Tai Chi Cardiac Rehabilitation Program (TCCRP) for CCS patients and to assess the efficacy, safety and acceptability of the programme. METHODS AND ANALYSIS: We propose to conduct a multicentre randomised controlled clinical trial comprising of 150 participants with CCS. The patients will be randomly assigned in a 1:1 ratio into two groups. The intervention group will participate in a supervised TCCRP held three times a week for 3 months. The control group will receive supervised conventional exercise rehabilitation held three times a week for 3 months. The primary and secondary outcomes will be assessed at baseline, 1 month, 3 months after intervention and after an additional 3-month follow-up period. Primary outcome measures will include a score of 36-Item Short Form Survey and Chinese Perceived Stress Scale. The secondary outcome measures will include body composition, cardiopulmonary exercise test, respiratory muscle function, locomotor skills, echocardiogram, New York Heart Association classification, heart rate recovery time and laboratory examination. Other measures also include Seattle Angina Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 and Berg Balance Scale. All adverse events will be recorded and analysed. ETHICS AND DISSEMINATION: This study conforms to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of Chinese People's Libration Army General Hospital (approval number: S2019-060-02). Findings from this study will be published and presented at conferences for widespread dissemination of the results. TRIAL REGISTRATION NUMBER: NCT03936504.

[A survey on knowledge of recommended heart failure guidelines among Chinese physicians].

OBJECTIVE: To obtain the knowledge status on recommended heart failure (HF) guidelines among Chinese physicians. METHODS: Questionnaire on heart failure including 20 multiple choice questions and 10 fill in the blank questions was designed based on the Chinese guidelines for the diagnosis and treatment of chronic heart failure in 2007 and the Chinese guidelines for the diagnosis and treatment of acute heart failure in 2010. The rate of correct answer for each item was calculated and compared among physicians specialized for cardiovascular diseases and not. RESULTS: The Questionnaire was completed in 400 physicians, including 208 physician specialized for cardiovascular disease and 192 physicians not specialized in cardiovascular disease. The rate of correct answer for 20 multiple choice questions was lower than 60% in 8 questions, 60%-80% in 8 questions, higher than 80% in 4 questions. The rate of correct answers for 10 fill in the blank questions focusing on the aimed dosage of 10 ACEI/ARB/ß-blockers was 49%. The 8 multiple choice questions with correct answer rate <60% are detailed items of myocardial remodeling, symptoms suggestive of HF, diagnosis tools for patients with suspected HF, the AHA stages of heart failure, the Forrester's hemodynamic classes of acute heart failure, the goals of ACEI/ARBs treatment in patients with HF, names of heart diseases which might benefit from ACEI/ARBs treatment defined by evidenced based medicine, and detailed application methods of ACEI/ARBs and ß-blockers for HF patients. In general, the rate of correct answer was significantly higher in physicians specialized for cardiovascular disease compared physicians not specialized for cardiovascular disease. CONCLUSION: There is a considerable knowledge gap on the Chinese guidelines for the diagnosis and treatment of chronic heart failure and the Chinese guidelines for the diagnosis and treatment of acute heart failure among Chinese physicians. Efforts must be made to educate physicians to improve their knowledge and improve HF patient care.

Lamivudine prophylaxis of liver allograft HBV reinfection in HBV related cirrhotic patients after liver transplantation.

BACKGROUND: Liver allograft hepatitis B virus (HBV) reinfection and hepatitis B (HB) recurrence jeopardize the long-term survival of recipient and liver allograft. Lamivudine has been referred as a novel antiviral agent against HBV in HBV cirrhotic patients even in liver transplantation setting. We assessed the prophylatic effect of lamivudine on liver allograft HBV reinfection and clarified the dynamic changes of HBV markers in HBV related decompensated liver cirrhosis after liver transplantation. METHODS: Twenty-five recipients were divided into three groups: HBV active replication group (15 recipients), HBV inactive replication group (7), and control group (3). 100 mg/d lamivudine was administered preoperatively except in the control group. The HBV markers of serial sera and liver biopsy samples of the 25 recipients were evaluated regularly with enzyme-linked radioimmunoassay, HBV DNA fluorescent quantitative assay, immunohistochemical staining, labelled streptavidin biotin (LSAB) and digoxin labelled HBV DNA hybridization in situ. The dynamic alternation of HBV markers under lamivudine prophylaxis was observed. RESULTS: In the HBV active replication group who had received lamivudine 2 weeks before liver transplantation, serum HBV DNA positive converted to negative by 80%. HBsAg of all recipients disappeared after liver transplantation, but corresponding antibodies of HBV appeared within one week after the operation. HBsAb 9/15, HBcAb 13/15 and HBeAb 11/15 appeared and subsided gradually within 24 weeks. HBV DNA in sera was kept negative; HBsAg, HBcAg and HBV DNA hybridization in situ of liver biopsy samples remained negative after use of lamivudine. Ten of the 15 recipients showed clearance of HBV, and per se HBV markers were undetectable both in serum and liver biopsy samples between 12 to 44 weeks (24 weeks on average). The 1-, 2-year survival rates were 83% in this group. Two of the 15 recipients developed HBV allograft reinfection or recurrence of hepatitis 2 years after lamivudine monoprophylaxis (2/15, 13.3%). In the HBV inactive replication group, the outcome was similar to that of the HBV active group. The HBV antibody frequency was HBsAb 4/7, HBcAb 6/7, and HBeAb 2/7. Three of 7 recipients showed HBV clearance both in sera and liver biopsy samples, whereas in the control group all 3 recipients developed HBV allograft reinfection and recurrent hepatitis 8, 10, 12 months postoperatively; one of them died of fibrosing cholestatic hepatitis, and the remaining 2 recovered after additional lamivudine therapy. The overall allograft reinfection rate was 9.1% (2/22) and the overall 1-, 2-year survival rates were 87% in the lamivudine prophylaxis group. CONCLUSIONS: Lamivudine prophylaxis can prevent effectively liver allograft from HBV reinfection in patients with HBV-related decompensated liver cirrhosis even in HBV active replication recipient after liver transplantation. Its long-term outcome remains to be studied.

Dynamic alteration of HBV markers on active HBV replicative recipients after liver transplantation: a preliminary report.

OBJECTIVE: To investigate the dynamic alternations of HBV markers of active HBV replication recipients receiving lamivudine prophylaxis after liver transplantation. METHODS: Serial liver biopsy samples and sera were obtained from 15 recipients and examined with enzyme-linked radioimmunoassay for HBsAg, HBeAg, HBsAb, HBcAb and HBeAb, and fluorescent quantitative assay for quantitation of HBV DNA in serum. Immunohistochemical staining of HBsAg, HBcAg and HBV DNA hybridization in situ were used to detect HBV markers in liver biopsy samples. RESULTS: 100 mg lamivudine taken orally every day for 2 weeks before transplantation enabled 12 (80%) of 15 active viral replication recipients (HBV DNA positive) to converse to HBV DNA negative. HBsAb, HBcAb and HBeAb in serum emerged in 1-2 weeks after liver transplantation, and disappeared gradually within 6 months; HBV DNA fluorescent quantitative assay showed constant negativity in serum. Immunohistochemical staining of HBsAg, HBcAg and HBV DNA hybridization in situ in liver biopsy samples showed negative results synchorously. Eight of the 15 HBV active replication recipients lost HBV markers thoroughly both in serology and tissue staining as well as HBV DNA hybridization in situ of serial liver biopsy samples from 12 to 44 weeks after liver transplantation. Should any of HBsAg, HBeAg in serology and HBsAg, HBcAg in immunohistochemical staining was positive, or HBV DNA detectable in serum, or HBV DNA hybridization in situ in liver tissue positive, allograft HBV reinfection or De novo liver allograft infection could be diagnosed. Furthermore, if associated with elevation of ALT and bilirubin, the diagnosis of HBV hepatitis recurrence could be established. CONCLUSION: Allograft HBV reinfection or De novo liver allograft infection in active viral replication recipients could be prevented with lamivudine regimen, and further clearance of HBV may be possible if proper measures are taken.