Summary Background Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant ...hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial. Methods Healthy adults aged 16–65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 μg of purified recombinant hepatitis E antigen adsorbed to 0·8 mg aluminium hydroxide suspended in 0·5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov , number NCT01014845. Findings 11 165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56 302) or placebo (n=56 302). 48 693 (86%) participants in the vaccine group and 48 663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100·0% (95% CI 72·1–100·0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted. Interpretation HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16–65 years. Funding Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.
Currently available echocardiographic reference values are derived mainly from North American and European population studies, and no echocardiographic reference values are available for the Chinese ...population. The aim of this study was to establish normal values of echocardiographic measurements of the cardiac chambers and great arteries in a nationwide, population-based cohort of healthy Han Chinese adults.
A total of 1,586 healthy Han Chinese volunteers aged 18 to 79 years were screened at 43 collaborating laboratories throughout China. Standard M-mode and two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries. The impacts of gender and age on all echocardiographic measurements were analyzed.
A total of 1,394 qualified healthy subjects (mean age, 47.3 ± 16.0 years; 678 men) were ultimately enrolled. Except for left ventricular ejection fraction, values of cardiac chamber and great arterial dimensions were significantly higher in men than in women. Most measurements of the atrial and great arterial dimensions, left ventricular wall thickness, and left ventricular mass increased with age in both men and women.
Normal reference values of cardiac dimensional parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Because most of these parameters were found to vary with gender and age, reference values stratified for gender and age should be used in clinical practice.
Low-level carotid baroreflex stimulation (LL-CBS) appears to have a potential antiarrhythmogenic effect.
The purpose of this study was to investigate effects of short-term LL-CBS on an atrial ...fibrillation (AF) canine model.
Group 1 (LL-CBS in the 6 hour-rapid atrial pacing model): Anesthetized dogs underwent 6 hours of rapid atrial pacing (RAP) with concomitant LL-CBS in last 3 hours (LL-CBS group; n = 7) or without (control group; n = 6). Effective refractory period (ERP), ERP dispersion, and window of vulnerability to AF were determined. Left stellate ganglion (LSG) neural activity and heart rate variability were analyzed. Group 2 (LL-CBS on electrically or mechanically induced AF with acetylcholine): In subgroup 1, sustained AF was induced by injecting acetylcholine (Ach; 10 mM) into the anterior right ganglionated plexus at baseline and after 3-hour LL-CBS (n = 7) or sham operation (n = 6). In subgroup 2, Ach was applied onto the right atrial appendage. The time of duration of AF and the average AF cycle length were determined in both subgroups.
Group 1: LL-CBS reversed the RAP-induced ERP shortening and increase in ERP dispersion and window of vulnerability (P < .05). The activation of LSG, decrease in high frequency, and increase in low frequency and low frequency/high frequency ratio induced by RAP were also reversed by LL-CBS (P < .05). After 6-hour RAP, plasma norepinephrine and angiotensin II concentrations were significantly lower in the LL-CBS group than in the control group (P < .05). Group 2: The AF duration was shortened and the average AF cycle length was prolonged markedly in both subgroups (P < .01) by LL-CBS.
LL-CBS can reverse RAP-induced atrial electrical remodeling and suppress electrically or mechanically induced AF with Ach, and the anti-AF effect is attributed to attenuation of autonomic nerve remodeling, including inhibition of the LSG activity.
Abstract Background Clinical observations suggest that the incidence of cough in Chinese patients taking angiotensin-converting enzyme (ACE) inhibitors is much higher than other racial groups. The ...aim of this study was to investigate whether SLCO1B1 genetic polymorphisms, previously reported to be important determinants of the inter-individual pharmacokinetic differences of enalapril, are associated with the enalapril-induced cough. Methods This pharmacogenetics study took place in rural communities in Anhui Province in China between May, 2008 and July, 2009. Eligible participants were of Han Chinese origin, women or men, had systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher, or both, or were taking 10 mg enalapril antihypertensive durgs. DNA samples obtained from patients were genotyped for the functional genetic polymorphisms in SLCO1B1 , 388A→G (Asn130Asp, rs2306283) and 521T→C (Val174Ala, rs4149056), using Sequenom MassArray technology. The primary endpoint was cough, which was recorded when participants were bothered by respiratory symptoms and cough during enalapril treatment without an identifiable cause. The association of SLCO1B1 polymorphisms with enalapril-induced cough was assessed through odds ratios (ORs) and corresponding 95% CIs, estimated by logistic regression model using SPSS v.19.0. A two-sided p value less than 0·05 was considered statistically significant. Ethics approval was granted by the Ethical Committee of Institute of Clinical Pharmacology, Central South University, and informed consent was obtained from each participating patient. This trial is registered with Chinese Clinical Trial Register, number ChiCTR-OCH-12002611. Findings Between May, 2008, and July, 2009, we recruited 450 Han Chinese patients. Enalapril-induced cough was recorded in 144 (32%) patients. Sex was significantly associated with enalapril-induced cough (104 72% participants were women in the cough group vs 108 59% in the no-cough group, p=0·006). The SLCO1B1 *5 (521T→C) variant was associated with a statistically increased risk of cough incidence (50 18% patients had the C allele in the cough group vs 58 10% in the no-cough groups), OR 2·02 1·34–3·04; p=0·0006). Additionally, we found strong evidence for a gene-dose effect (97 28% patients with cough had no copies of the C allele, 40 43% patients with cough had one copy of the C allele, and 5 71% patients with cough had two copies of the C allele; ptrend =0·0007). Haplotype analysis of the two SLCO1B1 polymorphisms revealed that the risk of enalapril-induced cough might be substantially increased in patients carrying SLCO1B1 *15 (388A→G and 521T→C; OR=1·99 1·26–3·14; p=0·003). Interpretation We have identified that the SLCO1B1 common variants and female sex are strongly associated with an increased risk of enalapril-induced cough. Genotyping SLCO1B1 variants might be a useful strategy to achieve the benefits of enalapril treatment more effectively and safely in China. Our current findings are from an independent retrospective study cohort and the clinical application deserves to be confirmed in a prospective trial. Funding National High Technology Research and Development Program of China, “863” Project (No. 2012AA02A517, 2012AA02A518), National Scientific Foundation of China (No. 81522048, 81573511, 81273595, 81302850), Hunan Provincial Innovation Foundation for Postgraduate (No. CX2014B100).
Purpose To describe the pattern of maxillofacial injuries sustained by survivors of the 2008 Wenchuan earthquake in the West China Hospital of Stomatology from May 12 to June 23, 2008. Patients and ...Methods Cross-sectional data were analyzed using hospital-based records of earthquake survivors admitted to the West China Hospital of Stomatology. A self-designed form to record information about variables such as the gender and age of the survivors and type of location of soft and hard tissue injuries was used. Results The age of earthquake survivors of maxillofacial injuries ranged from 4 to 84 years. Fractures and soft tissue injuries were the most common of all injuries in the maxillofacial region, constituting 40.7% and 38.9%, respectively. Thirteen patients (11.5%) had dental injuries and 9 (8.0%) also had other organ injuries. Conclusion During the Wenchuan earthquake, the incidence of maxillofacial injuries in survivors was relatively low compared with injury in other organs. However, because most injuries were maxillofacial fractures and facial soft tissue damage, special attention was paid to maxillofacial injury when planning and providing emergency treatment. The effective management of earthquake injuries and those caused by other types of disaster requires a multidisciplinary approach, and maxillofacial surgeons should form an integral part of this multidisciplinary team.
Abstract Background Most cardiovascular studies have implicated the central transcription factor nuclear factor kappa-B (NF-κB) as contributing to the detrimental effects of cardiac injury. This ...ostensibly negative view of NF-κB competes with its important role in the normal host inflammatory and immune response. Pressure overload, left ventricular hypertrophy (LVH), and heart failure represent a spectrum of disease that has both adaptive and maladaptive components. In contrast to its known effects related to myocardial ischemia–reperfusion, we hypothesized that NF-κB is necessary for the compensatory phase of cardiac remodeling. Methods C57BL6 mice underwent minimally invasive transverse aortic constriction with or without inhibition of the proximal NF-κB kinase, inhibitory kappa-B kinase-β. Isolated cardiomyocytes were cultured. Transthoracic echocardiography was performed on all mice. Results Inhibitory kappa-B kinase-β inhibition successfully decreased cardiomyocyte expression of phosphorylated p65 NF-κB and decreased expression of hypertrophic markers with stimulation in vitro . Three weeks after transverse aortic constriction, the mice treated with inhibitory kappa-B kinase-β inhibition more aggressively developed LVH, as measured by heart weight/body weight ratio, left ventricular mass, and wall thickness. These mice also demonstrated a functional decline, as measured by decreased fractional shortening and ejection fraction. These findings were associated with decreased protein expression of p65 NF-κB. Conclusions Although short-term pressure-overload results in compensatory LVH with normal cardiac function, NF-κB inhibition resulted in increased LVH that was associated with functional deterioration. These observations suggest that NF-κB is an important part of the adaptive phase of LVH, and its inhibition detrimentally affects cardiac remodeling.
Our purpose was to investigate the prognostic role of plasma Epstein-Barr virus (EBV) DNA levels in the middle of intensity modulated radiation therapy (IMRT).
In total, 1881 patients with stage ...III-IVa tumors were included. The overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Receiver operating characteristic curve analysis was performed to analyze the diagnostic value of EBV DNA levels for tumor progression or death. Multivariate analyses using the Cox model were used to evaluate potential prognostic factors.
The positive predict value and negative predict value of plasma EBV DNA > 0 copies/mL in the middle of IMRT in predicting nasopharyngeal carcinoma progression was 37.4% and 85.5%, respectively. In patients with plasma EBV DNA level = 0 copies/mL, no significant differences in OS were observed between patients treated with 200 mg/m² cisplatin and those treated with >200 mg/m² cisplatin (5-year OS, 94.9% vs 94.4%; PFS, 81.5% vs 87.6%). However, those treated with >200 mg/m² cisplatin had higher PFS. In patients with plasma EBV DNA level > 0 copies/mL, patients treated with >200 mg/m² cisplatin displayed a favorable 5-year OS (84.6% vs 73.9%) and PFS (72.3% vs 54.8%) compared with those treated with 200 mg/m² cisplatin. Additionally, higher incidences of grade 3 and 4 adverse events were recorded in patients treated with >200 mg/m² cisplatin than in those treated with 200 mg/m² cisplatin.
Plasma EBV DNA > 0 copies/mL in the middle of IMRT suggests that higher doses of chemotherapy should be used. For concurrent chemoradiation therapy, >200 mg/m² cisplatin is recommended for patients with plasma EBV DNA level > 0 copies/mL in the middle of IMRT but not for patients with plasma EBV DNA level = 0 copies/mL considering the similar OS rates.
Abstract Background Whether calcium channel blockers exert a greater effect on cardiovascular risk reduction in Asian populations than other antihypertensive agents is unclear. We conducted a ...meta-analysis of hypertension trials of dihydropyridine calcium channel blockers in Asian populations to clarify this association. Methods EMBASE, MEDLINE, and Cochrane databases were searched (inception-August 2016) for randomized controlled trials evaluating cardiovascular death, major adverse cardiovascular events, stroke, congestive heart failure and coronary revascularization in Asian persons with hypertension. We identified 9 trials that reported data specific to Asian populations (N=29,643). These trials included 1 placebo-controlled trial and 8 active comparator trials; of these, 5 had angiotensin receptor blockers as the active comparator. Results One placebo-controlled trial (N=9,711) demonstrated significantly reduced cardiovascular mortality, major adverse cardiovascular events, and stroke with calcium channel blockers. Among 8 active comparator trials (N=19,932), there were no significant differences in mortality (RR 1.10, 95% CI 0.72, 1.67, I 2 =0.0% ), major adverse cardiovascular events (RR 1.02, 95% CI 0.90, 1.15, I 2 =0.0% ), stroke (RR 0.97, 95% CI 0.80, 1.17, I 2 = 0.0% ), congestive heart failure (RR 1.01, 95% CI 0.51, 2.00, I 2 =53.7 ), or coronary revascularization rates (RR 0.98, 95% CI 0.76, 1.25, I 2 =0.0% ) in the calcium channel blocker group compared to other antihypertensive agents. When restricting the meta-analysis to angiotensin receptor blocker comparators (N= 10,384), there were no significant differences in cardiovascular outcomes. Conclusion There is no evidence that dihydropyridine calcium channel blockers are superior to other antihypertensive agents in Asian populations for the treatment of hypertension.
Abstract
A consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency (PEI) after pancreatic surgery was developed based on the latest references, combined with China's ...actual situation. More than 20 Chinese excellent experts participated in this work and contributed many thorough discussions. This consensus discusses the definition, epidemiology, diagnosis, treatment, and follow-up of PEI after pancreatic surgery. The authors hope this consensus will promote the standard procedure of diagnosis and treatment of PEI in China.
Objective The aim of this study was to investigate the effect of intra-articular sodium hyaluronate (SH) injections on the main components of plasminogen activator (PA) system in the synovial fluid ...of temporomandibular joint (TMJ) osteoarthritis (OA). Study design Forty patients diagnosed with TMJ OA and 20 healthy control subjects were included in this study. Synovial fluid was collected in the OA group and the healthy group at baseline. The OA patients were randomly divided into 2 groups (20 patients for each group): One group received 5 injections of SH, and the other received 5 injections of physiologic saline solution in the upper joint space at weekly intervals. Synovial fluid was collected before and after treatment. Urokinase-type PA (uPA), soluble uPA receptor (suPAR) and PA inhibitor 1 (PAI-1) levels in synovial fluid were quantified by enzyme-linked immunosorbent assay. Results The OA patients had significantly higher uPA activity and levels of uPA (median 80.01 ng/L), suPAR (median 7.54 ng/L), and PAI-1 (median 54.9 ng/mL) than the healthy control subjects (median 20.47 ng/L uPA, 2.34 ng/L suPAR, and 19.9 ng/mL PAI-1; ( P < .05). The uPA activity and levels of uPA, suPAR, and PAI-1 were significantly decreased after SH injections in TMJs of OA patients ( P < .05), and there was no difference after saline injection. Visual analog pain score reduction correlated with changes in uPA and uPAR levels as well as uPA activity. Conclusion The effects of SH on PA system provide new insight into a possible underlying mechanism by which SH alleviates pain of patients with TMJ OA.
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