Hepatitis B virus RNAs co-opt ELAVL1 for stabilization and CRM1-dependent nuclear export.

Hepatitis B virus (HBV) chronically infects 296 million people worldwide, posing a major global health threat. Export of HBV RNAs from the nucleus to the cytoplasm is indispensable for viral protein translation and genome replication, however the mechanisms regulating this critical process remain largely elusive. Here, we identify a key host factor embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) that binds HBV RNAs and controls their nuclear export. Using an unbiased quantitative proteomics screen, we demonstrate direct binding of ELAVL1 to the HBV pregenomic RNA (pgRNA). ELAVL1 knockdown inhibits HBV RNAs posttranscriptional regulation and suppresses viral replication. Further mechanistic studies reveal ELAVL1 recruits the nuclear export receptor CRM1 through ANP32A and ANP32B to transport HBV RNAs to the cytoplasm via specific AU-rich elements, which can be targeted by a compound CMLD-2. Moreover, ELAVL1 protects HBV RNAs from DIS3+RRP6+ RNA exosome mediated nuclear RNA degradation. Notably, we find HBV core protein is dispensable for HBV RNA-CRM1 interaction and nuclear export. Our results unveil ELAVL1 as a crucial host factor that regulates HBV RNAs stability and trafficking. By orchestrating viral RNA nuclear export, ELAVL1 is indispensable for the HBV life cycle. Our study highlights a virus-host interaction that may be exploited as a new therapeutic target against chronic hepatitis B.

G-quadruplex in hepatitis B virus pregenomic RNA promotes its translation.

Hepatitis B virus (HBV) is a hepatotropic DNA virus that has a very compact genome. Due to this genomic density, several distinct mechanisms are used to facilitate the viral life cycle. Recently, accumulating evidence show that G-quadruplex (G4) in different viruses play essential regulatory roles in key steps of the viral life cycle. Although G4 structures in the HBV genome have been reported, their function in HBV replication remains elusive. In this study, we treated an HBV replication-competent cell line and HBV-infected cells with the G4 structure stabilizer pyridostatin (PDS) and evaluated different HBV replication markers to better understand the role played by the G4. In both models, we found PDS had no effect on viral precore RNA (pcRNA) or pre-genomic RNA (pgRNA), but treatment did increase HBeAg/HBc ELISA reads and intracellular levels of viral core/capsid protein (HBc) in a dose-dependent manner, suggesting post-transcriptional regulation. To further dissect the mechanism of G4 involvement, we used in vitro-synthesized HBV pcRNA and pgRNA. Interestingly, we found PDS treatment only enhanced HBc expression from pgRNA but not HBeAg expression from pcRNA. Our bioinformatic analysis and CD spectroscopy revealed that pgRNA harbors a conserved G4 structure. Finally, we introduced point mutations in pgRNA to disrupt its G4 structure and observed the resulting mutant failed to respond to PDS treatment and decreased HBc level in in vitro translation assay. Taken together, our data demonstrate that HBV pgRNA contains a G4 structure that plays a vital role in the regulation of viral mRNA translation.

Knowledge, skills, and attitudes of medical students to patient safety: a cross-sectional pilot investigation in China.

BACKGROUND: To reduce harm caused by health care is a global priority. Medical students should be able to recognize unsafe conditions, systematically report errors, and near misses, investigate and improve such systems with a thorough understanding of human fallibility, and disclose errors to patients. Therefore, incorporating knowledge about patient safety into medical school curriculums is an urgent necessity. OBJECTIVES: To describe the extent to which Chinese medical students have patient safety in their knowledge, skills, and attitudes so as to provide evidence for implementation of a patient safety curriculum in medical schools, and to assess the quality of this investigative questionnaire. METHODS: Our questionnaire of 31 items was developed based on a 2008 WHO pilot study for a patient safety curriculum guide. Our investigation was conducted in three university medical schools in China. Year 3 and year 4 medical students were asked to complete an anonymous questionnaire in their classroom settings. All items were scored from 1 to 5. Differences in responses among different universities, genders, and levels, as well as the validity and reliability of the questionnaire, were analyzed using SPSS 15.0. RESULTS: A total of 500 questionnaires were distributed, and 143 male and 262 female students completed the survey. An average of 0.96% of survey questions were not answered, of which the most frequently unanswered item was "what will happen when medical error occurs?" The students' attitudes to learning about patient safety were positive, although their knowledge of medical error and how to report error was poor. There were no statistical differences among different medical schools and levels in any item responses. The only gender difference appeared in the response to "I would like to discuss with others when I made a medical error." There was a good coherence of reliability in sections 2, 3, and 4 of the questionnaire (Cronbach's alpha > 0.8), while sections 5 and 6 scored as less reliable. The validity of the questionnaire was good. CONCLUSIONS: Although medical students' understanding of patient safety is very poor in China, the students have a positive attitudes to learning about the knowledge of patient safety in their future careers.

Patient safety education for undergraduate medical students: a systematic review.

BACKGROUND: To reduce harm caused by health care is a global priority. Medical students should be able to recognize unsafe conditions, systematically report errors and near misses, investigate and improve such systems with a thorough understanding of human fallibility, and disclose errors to patients. Incorporating the knowledge of how to do this into the medical student curriculum is an urgent necessity. This paper aims to systematically review the literature about patient safety education for undergraduate medical students in terms of its content, teaching strategies, faculty availability and resources provided so as to identify evidence on how to promote patient safety in the curriculum for medical schools. This paper includes a perspective from the faculty of a medical school, a major hospital and an Evidence Based Medicine Centre in Sichuan Province, China. METHODS: We searched MEDLINE, ERIC, Academic Source Premier(ASP), EMBASE and three Chinese Databases (Chinese Biomedical Literature Database, CBM; China National Knowledge Infrastructure, CNKI; Wangfang Data) from 1980 to Dec. 2009. The pre-specified form of inclusion and exclusion criteria were developed for literature screening. The quality of included studies was assessed using Darcy Reed and Gemma Flores-Mateo criteria. Two reviewers selected the studies, undertook quality assessment, and data extraction independently. Differing opinions were resolved by consensus or with help from the third person. RESULTS: This was a descriptive study of a total of seven studies that met the selection criteria. There were no relevant Chinese studies to be included. Only one study included patient safety education in the medical curriculum and the remaining studies integrated patient safety into clinical rotations or medical clerkships. Seven studies were of a pre and post study design, of which there was only one controlled study. There was considerable variation in relation to contents, teaching strategies, faculty knowledge and background in patient safety, other resources and outcome evaluation in these reports. The outcomes from including patient safety in the curriculum as measured by medical students' knowledge, skills, and attitudes varied between the studies. CONCLUSIONS: There are only a few relevant published studies on the inclusion of patient safety education into the undergraduate curriculum in medical schools either as a selective course, a lecture program, or by being integrated into the existing curriculum even in developed countries with advanced health and education systems. The integration of patient safety education into the existing curriculum in medical schools internationally, provides significant challenges.

Assessment of the quality of reporting in abstracts of randomized controlled trials published in five leading Chinese medical journals.

BACKGROUND: Clear, transparent and sufficiently detailed abstracts of randomized trials (RCTs), published in journal articles are important because readers will often base their initial assessment of a trial on such information. However, little is known about the quality of reporting in abstracts of RCTs published in medical journals in China. METHODS: We identified RCTs abstracts from 5 five leading Chinese medical journals published between 1998 and 2007 and indexed in MEDLINE. We assessed the quality of reporting of these abstracts based on the Consolidated Standards of Reporting Trials (CONSORT) abstract checklist. We also sought to identify whether any differences exist in reporting between the Chinese and English language version of the same abstract. RESULTS: We identified 332 RCT abstracts eligible for examination. Overall, the abstracts we examined reported 0-8 items as designated in the CONSORT checklist. On average, three items were reported per abstract. Details of the interventions (288/332; 87%), the number of participants randomized (216/332; 65%) and study objectives (109/332; 33%) were the top three items reported. Only two RCT abstracts reported details of trial registration, no abstracts reported the method of allocation concealment and only one mentioned specifically who was blinded. In terms of the proportion of RCT abstracts fulfilling a criterion, the absolute difference (percentage points) between the Chinese and English abstracts was 10% (ranging from 0 to 25%) on average, per item. CONCLUSIONS: The quality of reporting in abstracts of RCTs published in Chinese medical journals needs to be improved. We hope that the introduction and endorsement of the CONSORT for Abstracts guidelines by journals reporting RCTs will lead to improvements in the quality of reporting.

[The basic concept of patient safety and its evolution].

Patient safety has become a hot topic and a big challenge for healthcare services globally during the past ten years. Patient safety is not a new concept but has its explicit cultural root. There were some related elaborations early in the collected works of Hippocrates. Reviewing the origin and developmental process of the concept of patient safety can benefit acquiring a deeper recognition of the basic concept of patient safety. "Medical risk is everywhere" has become the consensus of healthcare professions globally. Patient safety is a perpetual task of the medical area as well as the most basic starting point and final destination in healthcare service.

Quality of trials reported as conference abstracts in China: how well are they reported?

OBJECTIVES: Clear, transparent, and sufficiently detailed abstracts of journal articles and conference abstracts are important because readers often base their assessment of a trial on such information. There are concerns over the reliability and quality of trials published only in the proceedings of scientific meetings. This study aims to assess the reporting quality of abstracts of randomized trials published in Chinese medical conference abstracts. METHODS: Conference abstracts reporting randomized trials included in the China National Knowledge Infrastructure (CNKI) in 2007 were identified. A revised checklist (based on the CONSORT extension for reporting randomized controlled trials in journal and conference abstracts) was used to assess the reporting quality of these conference abstracts. RESULTS: A total of 567 conference abstracts of randomized trials were identified. Some aspects were well reported, including 94 percent of authors contact details, 83 percent of trial interventions and 78 percent of control interventions, 62 percent of participant eligibility criteria, and 66 percent the number of participants randomized to each group. Other areas were very poorly reported: only 1 percent identified the study as randomized in the abstract title, 2 percent reported the trial design, and only 7 percent reported on blinding. No details of allocation concealment, trial registration, or funding were reported. CONCLUSION: The information given for trials in conference proceedings in China is very poor, especially in some aspects of methodological quality, trial registration, and funding source. The quality of conference abstracts for trials should be improved to further facilitate understanding of their conduct and validity.

Treatment with lamivudine versus lamivudine and thymosin alpha-1 for e antigen-positive chronic hepatitis B patients: a meta-analysis.

BACKGROUND: Currently, there is no evidence on the combination of lamivudine and thymosin alpha-1 on chronic hepatitis B patients. The aim of this study was to compare the effect of lamivudine monotherapy with that of lamivudine and thymosin alpha-1 combination therapy for the treatment of hepatitis B e antigen (HBeAg)-positive hepatitis B patients. RESULTS: We searched PUBMED (from 1966 onwards), EMBASE (from 1966), CBMdisk (Chinese Biomedical Database, from 1978), CNKI (National Knowledge Infrastructure, from 1980), the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Eight trials (583 patients in total) were identified. The lamivudine and thymosin alpha-1 combination treatment was significantly superior to lamivudine treatment in terms of ALT normalization rate (80.2% vs. 68.8%, P = 0.01), virological response rate (84.7% vs. 74.9%, P = 0.002), and HBeAg seroconversion rate (45.1% vs. 15.2%, P < 0.00001). CONCLUSION: Among HBeAg-positive patients, thymosin alpha-1 and lamivudine combination therapy may be more effective than lamivudine monotherapy, providing superior rates of biochemical response, virological response, and HBeAg seroconversion.