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Purpose: To investigate the prevalence and clinical characteristics of myelinated retinal nerve fibre (MRNF) in a large teleophthalmology system.Methods: All records between January 2015 and Decemb...

BackgroundGrowing evidence suggests that compromised lung health may be linked to cardiovascular disease. However, little is known about its association with sudden cardiac death (SCD).ObjectivesWe aimed to assess the link between impaired lung function, airflow obstruction and risk of SCD by race and gender in four US communities.MethodsA total of 14 708 Atherosclerosis Risk in Communities (ARIC) study participants who underwent spirometry and were asked about lung health (1987–1989) were followed. The main outcome was physician-adjudicated SCD. Fine-Gray proportional subdistribution hazard models with Firth’s penalised partial likelihood correction were used to estimate the HRs.ResultsOver a median follow-up of 25.4 years, 706 (4.8%) subjects experienced SCD. The incidence of SCD was inversely associated with FEV1 in each of the four race and gender groups and across all smoking status categories. After adjusting for multiple measured confounders, HRs of SCD comparing the lowest with the highest quintile of FEV1 were 2.62 (95% CI 1.62 to 4.26) for white males, 1.80 (95% CI 1.03 to 3.15) for white females, 2.07 (95% CI 1.05 to 4.11) for black males and 2.62 (95% CI 1.21 to 5.65) for black females. The above associations were consistently observed among the never smokers. Moderate to very severe airflow obstruction was associated with increased risk of SCD. Addition of FEV1 significantly improved the predictive power for SCD.ConclusionsImpaired lung function and airflow obstruction were associated with increased risk of SCD in general population. Additional research to elucidate the underlying mechanisms is warranted.

Background Abnormal cardiac ion channels current, including transient outward potassium current (Ito), is associated with early repolarization syndrome (ERS). Previous studies showed that mutations in SCN1Bβ both to increase the Ito current and to decrease the sodium current. Yet its role in ERS remains unknown. Objective To determine the role of mutations in the SCN1Bβ subunits in ERS. Methods We screened for mutations in the SCN1B genes from four families with ERS. Wild‐type and mutant SCN1Bβ genes were co‐expressed with wild‐type KCND3 in human embryonic kidney cells (HEK293). Whole‐cell patch‐clamp technique and co‐immunoprecipitation were used to study the electrophysiological properties and explore the underlying mechanisms. Results S248R and R250T mutations in SCN1Bβ were detected in 4 families’ probands. Neither S248R nor R250T mutation had significant influence on the sodium channel current density (IN a) when co‐expressed with SCN5A/WT. Co‐expression of KCND3/WT and SCN1Bβ/S248R or SCN1Bβ/R250T increased the transient outward potassium current Ito by 27.44% and 199.89%, respectively (P

Summary Background Transmission of infection through international travel is a growing health issue, and the frequency of imported infection is increasing in China. We aimed to quantify the total number of infections imported into mainland China by arriving travellers. Methods We actively surveyed arriving travellers at all 272 international entry–exit ports in mainland China. Suspected cases were detected through fever screening, medical inspection, self-declaration, and reporting by on-board staff. Participants completed a standardised questionnaire with questions about demographics, their travel itinerary (including detailed information about all countries or regions visited), and clinical manifestations. Nasopharyngeal swabs, sputum samples, faecal samples, vomitus, blood, and serum were collected as appropriate for diagnoses. Diagnosis was made by specific laboratory tests according to the national technical guidelines. Infections were classified as respiratory, gastrointestinal, vector-borne, blood-transmitted and sex-transmitted, or mucocutaneous. We divided arriving travellers into two groups: travellers coming from countries other than China, and travellers coming from Hong Kong, Macau, and Taiwan. We integrated surveillance data for 2014–16, calculated incidences of travel-related infections, and compared the frequency of infections among subgroups. Findings Between Jan 1, 2014, and Dec 31, 2016, 22 797 cases were identified among 805 993 392 arriving travellers—an overall incidence of 28·3 per million. 45 pathogens were detected in participants: 18 respiratory (19 662 cases), ten gastrointestinal (189 cases), seven vector-borne (831 cases), seven blood-transmitted and sex-transmitted (1531 cases), and three mucocutaneous (584 cases). Both the overall number and incidence of infection were more than five times higher in 2016 than in 2014. Case numbers and incidences also varied substantially by province, autonomous region, and municipality. Overall, 17 643 (77%) infections were detected by fever screening, but 753 (49%) blood-transmitted and sex-transmitted infections were identified through medical inspection. 14 305 (73%) cases of respiratory infection and 96 (51%) of gastrointestinal infections were in tourists. Tuberculosis, hepatitis A virus, vector-borne, and blood-transmitted and sex-transmitted infections were common among Chinese labourers who worked abroad. Dengue and malaria were most commonly diagnosed in travellers arriving from Africa. 12 126 (93%) of the 12 985 cases arriving from Hong Kong, Macau, or Taiwan were respiratory infections. Hand, foot, and mouth disease accounted for 2·90% of infections in travellers from Hong Kong, Macau, or Taiwan and 0·31% of infections in international travellers. Interpretation This report is the first to characterise the profile of travel-related infections among arriving travellers in mainland China. Our findings should increase public awareness of the potential risk of imported infections, and help health-care providers to make evidence-based health recommendations to travellers. Funding The Natural Science Foundation of China.

PURPOSE To assess changes in the optic disc-fovea distance (DFD) with progressing myopia in school children. METHODS The school-based, prospective, longitudinal study included grade-1 children in 2011 who were yearly re-examined until 2016. We measured DFD, optic disc diameters and width of parapapillary gamma zone (parapapillary region without Bruch's membrane (BM)) on fundus photographs. RESULTS Of 382 grade-1 children examined in 2011, 294 (77.0%) children (mean age in 2011: 6.4 ± 0.5 years) returned to be examined in 2016. In relative terms, the increase in DFD (1.15 ± 0.33 mm) was more due to an increase in gamma zone width (+300% or 0.29 ± 0.30 mm) than an increase in macular BM length (+18% or 0.74 ± 0.21 mm). In multivariate regression analysis, longer increase in DFD was correlated (regression coefficient r2 = 0.79) with longer axial elongation during the study period (p

Background/Aims: Early repolarization syndrome (ERS) has been recently recognized as early repolarization pattern with idiopathic ventricular fibrillation. However, the genetic background of ERS has not been fully understood. Methods: A Chinese family with sudden cardiac death associated with ERS was investigated. Direct sequencing of ERS susceptibility genes was performed on the proband and family members. Whole-cell patch-clamp methods were used to characterize the mutant channel expressed in HEK 293 cells. Results: One missense mutation (p. K801T) was found in the hERG (KCNH2 gene) by the direct sequencing of candidate genes. Whole cell voltage clamp studies of the K801T mutation in HEK 293 cells demonstrated a 1.5-fold increase in maximum steady state current (37.2±7.3 vs 20.3±4.4 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -59.5±1.4 vs K801T -44.3±1.2 mV). Kinetic analysis revealed slower inactivation rates of K801T, but faster rates of activation and deactivation. The hERG channel blockers tested inhibited K801T-hERG channel in concentration response, and the potencies of these drugs can be rank-ordered as follows: quinidine> disopyramide> sotalol> flecainide. Conclusion: Our study indicated that the K801T mutation caused the gain of function of hERG channels that may account for the clinical phenotype of ERS. Quinidine and disopyramide could improve the function of K801T-hERG mutant channel, and may be therapeutic options for patients with the K801T hERG mutation.

Background: Recent studies show that microRNA-145 (miRNA-145) might be an attractive tumor biomarker of considerable prognostic value, but little is known about their relationship with acute myocardial infarction (AMI). This study investigated the correlation between the level of miR-145 and AMI. Methods: One-hundred patients were divided into three groups: no coronary artery disease (CAD) group, non-ST segment elevation myocardial infarction group, and ST segment elevation myocardial infarction group. The plasma levels of miR-145 were quantified using real-time quantitative polymerase chain reaction. Logarithmic transformation of miRNA-145 levels (Ln_miRNA-145) was used for statistical analysis due to the skewed data distribution. Results: Plasma levels of miR-145 were significantly lower in patients with AMI compared to patients in the non-CAD group (−6.38 ± 0.11 vs. −4.47 ± 0.17, P < 0.0001). Compared to those without heart failure, the levels of miR-145 were significantly lower in patients with heart failure (−6.91 ± 0.20 vs. −5.35 ± 0.13, P < 0.0001). We also found that the lower plasma levels of miRNA-145 significantly correlated with increased serum levels of B-type natriuretic peptide (Spearman ρ = −0.60, P < 0.0001), troponin T (Spearman ρ = −0.62, P < 0.0001), and decreased ejection fraction (Spearman ρ = 0.65, P < 0.0001). In a multivariable linear regression analysis, AMI and heart failure were independently associated with lower Ln_miRNA-145 (estimate −0.99, standard error [SE] 0.28; P = 0.001 and estimate −0.62, SE 0.21; P = 0.004). Conclusions: Our results suggest that decreased plasma levels of miR-145 are associated with AMI. Circulating miR-145 may be useful in prognosticating cardiac function and the risk of developing heart failure. Key words: Acute Myocardial Infarction; Heart Failure; MicroRNA; MicroRNA-145

Background Recent evidence has linked early repolarisation pattern (ERP) to sudden cardiac death (SCD) in patients without structural heart disease. However, no studies have clarified the prognostic value of ERP in people at high risk for atherosclerotic heart disease. Methods We prospectively assessed the prognostic significance of ERP on ECGs in a community-based population of 18 231 subjects with atherosclerotic risk factors (49.3% men, mean age 64.0 years). Mean follow-up was 7.6 years. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. Results Compared with those without ERP, subjects with ERP had a significantly increased risk of developing SCD (HR 1.91, 95% CI 1.30 to 2.82), death from coronary heart disease (CHD) (HR 1.80, 95% CI 1.45 to 2.22) and death from any cause (HR 1.35, 95% CI 1.22 to 1.50). ERP was not associated with an increased risk of non-sudden CHD death and non-CHD death. ERP with J wave pattern in inferior leads, high amplitude of J wave pattern, notching configuration and horizontal or descending ST segment indicated a higher risk for SCD. ERP was associated with an absolute risk increase of 52.3 additional SCDs per 100 000 person-years in the population at high risk for atherosclerotic heart disease. Conclusions ERP is associated with a significantly increased risk for SCD, CHD death and death from any cause in people with atherosclerotic risk factors. The observed association between ERP and all-cause mortality appears to be driven by an association with CHD death, in particular SCD.

Purpose To study the retinal oxygen saturation in normal eyes of Chinese adolescents. Methods Performing retinal oximetry with the Oxymap T1 Retinal Oximeter in healthy children and adolescents (aged 5–18 years old), we measured the arterial (SaO2) and venular (SvO2) oxygen saturation and the arteriovenous difference in oxygen saturation (Sa-vO2). Results The study included 122 individuals with a mean age of 13.0 ± 2.9 years (range: 5–18 years) and a mean refractive error of −3.25 ± 2.49 dioptres (range:−8.88 to +3.13 dioptres). Mean SaO2, SvO2 and Sa-vO2 was 85.5 ± 7.1%, 48.2 ± 5.5% and 37.3 ± 6.5%, respectively. Mean SaO2 was significantly (p 0.05) between the fundus quadrants. In multiple linear regression analysis, SaO2 increased (regression coefficient r2 = 0.28) with older age (standardized regression coefficient β: 0.23; p = 0.01) and more myopic refractive error (β: −0.39; p

Recent reports show that an early repolarization pattern (ERP) is associated with a higher incidence of sudden cardiac death in patients with obstructive coronary artery disease (CAD). Sporadic case studies have pointed out that ERP might be related to obstructive CAD.In consecutive patients who had undergone coronary angiography, we investigated the relationship between ERP and obstructive CAD by evaluating its association with coronary artery stenosis.The study population consisted of 3785 patients (59.9% men; mean age 63.1 years) with or without obstructive CAD. Adjusting for major cardiovascular risk factors, ERP was significantly associated with obstructive CAD (adjusted odds ratio (OR): 2.24 [95% CI 1.70-2.95]) with an incremental predictive value (ROC AUC 0.76 versus 0.71, P = 0.02; NRI 55.3%, P < 0.001; IDI = 0.05, P = 0.008), specifically in subjects with low risk and intermediate risk. ERP also significantly improved the predictive value for multi-vessel disease (AUC: 0.77 versus 0.72, P = 0.02 for two-vessel disease; 0.79 versus 0.73, P = 0.04 for three-vessel disease). ERP was consistently associated with stenoses of 3 main coronary arteries.ERP is associated with significant increased risk for obstructive CAD.Further studies are warranted to confirm our results and to elucidate the specific pathogenic mechanisms.

Accumulating evidence indicates that the zinc-finger transcription factor ZEB1 is predominantly expressed in the stroma of several tumours. However, the role of stromal ZEB1 in tumour progression remains unexplored. In this study, while interrogating human databases, we uncover a remarkable decrease in relapse-free survival of breast cancer patients expressing high ZEB1 levels in the stroma. Using a mouse model of breast cancer, we show that ZEB1 inactivation in stromal fibroblasts suppresses tumour initiation, progression and metastasis. We associate this with reduced extracellular matrix remodeling, immune cell infiltration and decreased angiogenesis. ZEB1 deletion in stromal fibroblasts increases acetylation, expression and recruitment of p53 to FGF2/7, VEGF and IL6 promoters, thereby reducing their production and secretion into the surrounding stroma. Importantly, p53 ablation in ZEB1 stroma-deleted mammary tumours sufficiently recovers the impaired cancer growth and progression. Our findings identify the ZEB1/p53 axis as a stroma-specific signaling pathway that promotes mammary epithelial tumours., In epithelial cells Zeb1 is involved in the epithelial to mesenchymal transition. In this study, the authors show in a mouse model of breast cancer, that Zeb1 expression in stromal cells is required for tumour formation and metastasis.

Purpose To assess the development and enlargement of the parapapillary gamma zone in school children. Methods This school-based prospective longitudinal study included Chinese children attending grade 1 in 2011 and returning for yearly follow-up examinations until 2016. These examinations consisted of a comprehensive ocular examination with biometry and color fundus photographs. The parents underwent a standardized interview. The parapapillary gamma zone was defined as the area with visible sclera at the temporal optic disc margin, and the optic disc itself was measured on fundus photographs. Results The study included 294 children (mean age in 2016, 11.4 ± 0.5 years [range, 10-13 years]; mean axial length, 24.1 ± 1.1 mm [range, 21.13-27.29 mm]). In multivariate analysis, larger increases in the gamma zone area during the study period were correlated (coefficient of determination for bivariate analysis [r2], r2 = 0.69) with larger increases in the vertical-to-horizontal disc diameter ratios (P < 0.001; standardized regression coefficient beta [beta], 0.53; nonstandardized regression coefficient B [B], 4.05; 95% confidence intervals [CI], 3.37-4.73), larger axial elongation (P < 0.001; beta, 0.32; B, 0.37; 95% CI, 0.26-0.47), a larger vertical disc diameter at baseline (P < 0.001; beta, 0.22; B, 0.98; 95% CI, 0.62-1.33), a larger gamma zone area at baseline (P < 0.001; beta, 0.14; B, 0.41; 95% CI, 0.17-0.64), and more time spent indoors studying (P = 0.015; beta, 0.10; B, 0.09; 95% CI, 0.02-0.17). Conclusions The development and enlargement of the gamma zone in the temporal parapapillary region were associated with an optic disc rotation around the vertical disc axis as indicated by an increasing vertical-to-horizontal disc diameter ratio. These morphologic findings fit with the notion of a backward pull of the temporal peripapillary sclera through the optic nerve dura mater in axially elongated eyes.

Objective. The aim of this study was to investigate the association between COPD and major adverse cardiovascular and cerebral events (MACCE) in patients undergoing percutaneous coronary intervention (PCI).Methods. 2,362 patients who underwent PCI were included in this study. Subjects were divided into 2 groups: with COPD (n=233) and without COPD (n= 2,129). Cox proportional hazards models were analyzed to determine the effect of COPD on the incidence of MACCE.Results. The patients with COPD were older (P<0.0001) and were more likely to be current smokers (P=0.02) and have had hypertension (P=0.02) and diabetes mellitus (P=0.01). Prevalence of serious cardiovascular comorbidity was higher in the patients with COPD, including a history of MI (P=0.02) and HF (P<0.0001). Compared with non-COPD group, the COPD group showed a higher risk of all-cause death (hazard ratio (HR): 2.45,P<0.0001), cardiac death (HR: 2.53,P=0.0002), MI (HR: 1.387,P=0.027), and HF (HR: 2.25,P<0.0001).Conclusions. Patients with CAD and concomitant COPD are associated with a higher incidence of MACCE (all-cause death, cardiac death, MI, and HF) compared to patients without COPD. The patients with a history of COPD have higher in-hospital and long-term mortality rates than those without COPD after PCI.

Background Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. Objectives This study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause. Methods We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses. Conclusions Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.

Background Recent studies have revealed that mutation in KCNE1, β-subunits of cardiac potassium channel, involved in ventricular fibrillation. Whereas its role in early repolarization syndrome (ERS) is less well understood. Objective To study whether mutant in KCNE1 is associated with ERS and explore the possible underlying molecular mechanisms. Methods Whole genome from four unrelated families with ERS was amplified and sequenced. Wild-type (WT) KCNE1 and/or KCNE1-S38G (S38G) were expressed in HEK293 cells with KCNQ1. Functional studies included whole-cell patch-clamp, western blot and immunofluorescence were performed to reveal the possible underlying mechanisms. Results The co-expression of KCNE1-S38G and KCNQ1 decreased tail current density of IKs but had little effect in modulation channel kinetics of IKs. Compared with KCNE1-WT, the expression and membrane location of KCNE1-S38G decreased. Co-expression of KCNE1-WT and KCNE1-S38G partially rescued the function of IKs channel. Conclusions The S38G mutation induced a loss-of-function of IKs due to decreasing of KCNE1 protein expression and defecting in KCNE1 protein membrane trafficking. Our findings suggested that KCNE1 may be one of the possible modulatory genes associated to ERS.

A slower heart rate can exaggerate J-point elevation in a 12-lead ECG. This study examined the role of Holter monitoring in the diagnosis of early repolarisation pattern (ERP).We examined 24-hour Holter recordings of 4000 consecutive patients seen at an outpatient clinic, and found 500 patients (12.5%) with ERP (based on J-point elevation magnitude maximum value≥0.1mV on the Holter recording). The highest magnitude of J-point elevation, R wave amplitude, the ratio between J-point elevation magnitude and R-wave amplitude on the same ECG lead (J/R ratio), QRS interval, and QT/QTc interval were measured on the Holter recording and on a surface 12-lead ECG of the 500 patients with ERP. The magnitude of J-point elevation, J/R ratio, and QT/QTc interval were compared between three groups: nighttime Holter recording, daytime Holter recording, and daytime surface 12-lead ECG.The magnitude of J-point elevation of the nighttime Holter (0.20±0.10mV) was higher than that of the daytime in Holter (0.12±0.07mV, p0.001) and the 12-lead ECG (0.12±0.06mV, p0.001). There was no statistical difference in magnitude of J-point elevation between daytime Holter and surface 12-lead ECG. While all 500 patients were diagnosed with ERP based on J-point elevation maximum value J-point on Holter monitoring, only 425 (85%) patients could be diagnosed with ERP based on the surface 12-lead ECG. The J-point elevation maximum value on the nighttime Holter was negatively correlated with heart rate (r=-0.15, p=0.0007) and QTc (r=-0.13, p=0.0043), and positively correlated with R wave amplitude (r=0.46, p0.0001), J/R ratio (r=0.69, p0.0001), and QRS interval (r=0.29, p0.0001).The J-point elevation on nighttime Holter recording was higher than that on daytime Holter and daytime surface 12-lead ECG, and there was misdiagnosis of ERP based on daytime surface 12-lead ECG. Holter monitoring has a complementary role in the diagnosis of ERP, especially in patients with a suspected diagnosis of ERP based on daytime surface 12-lead ECG.

CKAP4, one kind of type II trans-membrane protein, plays an important role to maintain endoplasmic reticulum structure and inhibits the proliferation of bladder cancer cells by combining its ligand anti-proliferative factor (APF). However, the biological function of CKAP4 in the progression of liver cancer has not been clearly demonstrated. In the present study, we knocked down or overexpressed CKAP4 in hepatocellular carcinoma (HCC) cells and cell proliferation, invasion, and migration capacities were investigated by CCK-8 and transwell assays. In vivo tumor model in mice was used to evaluate the role of CKAP4 on growth and metastasis of HCC. The data documented that HCC cells with high CKAP4 levels were featured by low proliferation capability as well as low invasion potential. Interestingly, we found that CKAP4 suppressed the activation of epithelial growth factor receptor (EGFR) signaling, which may partly explain the role of CKAP4 in cell biological behavior of HCC. Further study revealed that CKAP4 could associate with EGFR at basal status and the complex was reduced upon EGF stimulation, leading to release EGFR into cytoplasm. Thus, we demonstrate the novel mechanism, for the first time, expression of CKAP4 regulates progression and metastasis of HCC and it may provide therapeutic values in this tumor.

To determine prevalence and associations of visual impairment and frequency of spectacle use among grade 1 and grade 4 students in Beijing.This school-based, cross-sectional study included 382 grade 1 children (age 6.3 ± 0.5 years) and 299 grade 4 children (age 9.4 ± 0.7 years) who underwent a comprehensive eye examination including visual acuity, noncycloplegic refractometry, and ocular biometry.Presenting visual acuity (mean 0.04 ± 0.17 logMAR) was associated with younger age (p = 0.002), hyperopic refractive error (p0.001), and male sex (p = 0.03). Presenting visual impairment (presenting visual acuity ≤20/40 in the better eye) was found in 44 children (prevalence 6.64 ± 1.0% [95% confidence interval (CI) 4.74, 8.54]). Mean best-corrected visual acuity (right eyes -0.02 ± 0.04 logMAR) was associated with more hyperopic refractive error (p = 0.03) and rural region of habitation (p0.001). The prevalence of best-corrected visual impairment (best-corrected visual acuity ≤20/40 in the better eye) was 2/652 (0.30 ± 0.21% [95% CI 0.00, 0.72]). Undercorrection of refractive error was present in 53 children (7.99 ± 1.05%) and was associated with older age (p = 0.003; B 0.53; OR 1.71 [95% CI 1.20, 2.42]), myopic refractive error (p = 0.001; B -0.72; OR 0.49 [95% CI 0.35, 0.68]), and longer axial length (p = 0.002; B 0.74; OR 2.10 [95% CI 1.32, 3.32]). Spectacle use was reported for 54 children (8.14 ± 1.06%). Mean refractive error of the worse eyes of these children was -2.09 ± 2.88 D (range -7.38 to +7.25 D).Factors associated with presenting visual impairment were older age, myopic refractive error, and higher maternal education level. Despite a prevalence of myopia of 33% in young schoolchildren in Greater Beijing, prevalence of best-corrected visual impairment (0.30% ± 0.21%), presenting visual impairment (6.64% ± 1.0%), and undercorrection of refractive error (7.99% ± 1.05%) were relatively low.

Purpose To determine the prevalence of myopia in school children in Greater Beijing. Methods The Beijing Childhood Eye Study was a school-based cross-sectional study. One school of each level (primary, junior high, senior high) was randomly selected from nine randomly selected districts of Greater Beijing. The children underwent non-cycloplegic refractometry and their parents an interview. Results Of 16 771 eligible students, 15 066 (89.8%) children with a mean age of 13.2 ± 3.4 years (range: 7–18 years) participated. Prevalence of myopia defined as refractive error of ≤−0.50 diopters (D), ≤−1.00 D, ≤−6.00 D and ≤−8.00 D in the right eye was 64.9 ± 0.4%, 53.0 ± 0.4%, 4.3 ± 0.2% and 1.0 ± 0.1% respectively. In multivariate analysis, prevalence of myopia was significantly (p

Myxovirus resistance A (MxA) is an antiviral protein induced by type I interferons α and β (IFN-α and IFN-β) that can inhibit virus replication. We examined whether the MxA polymorphisms were related to the risk and severity of enterovirus 71 (EV71) infection in Chinese populations. The MxA C-123A and G-88T polymorphisms were genotyped in two independent case–control populations in China by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CIs). MxA messenger RNA was quantified by real-time quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 45 healthy children and 19 patients with EV71 infection. Significantly decreased susceptibility to EV71 infection was observed for the -123A allele and -88T allele carriers, with ORs (95 % CIs) estimated as 0.56 (0.39–0.81) and 0.64 (0.47–0.88), respectively, in the northern population. This association was confirmed in the southern population, with ORs (95 % CIs) estimated as 0.58 (0.38–0.89) and 0.67(0.47–0.95), respectively. The A- 123T- 88 haplotype was also significantly associated with lower risk of EV71 infection in both the northern (OR = 0.62; 95 % CI = 0.44–0.85) and the southern population (OR = 0.63; 95 % CI = 0.43–0.92). Furthermore, we observed higher MxA messenger RNA levels in IFNβ1a-stimulated PBMCs from the -123A or -88T allele carriers compared with that from nocarriers. Our findings suggest that polymorphisms in the MxA promoter may play a role in mediating the susceptibility to EV71 infection in Chinese population.

To assess associations among outdoor activity, ocular biometric parameters, and myopia among grade 1 and grade 4 primary students in Beijing.School-based, cross-sectional study.A total of 382 grade 1 and 299 grade 4 children participated in the study.The children underwent a comprehensive eye examination, including ocular biometry by optical low-coherence reflectometry and noncycloplegic refractometry. Parents and children participated in a detailed interview, including questions on time spent indoors and outdoors.Factors associated with myopia.The study included 681 children, with 382 (56.1%) students from grade 1 (mean age, 6.3 ± 0.5 years; range, 5-8 years) and 299 students from grade 4 (mean age, 9.4 ± 0.7 years; range, 8-13 years); 370 students (54.3%) lived in the urban region. The mean daily time spent outdoors was 1.6 ± 0.8 hours (range, 0.5-5.1 hours). In multivariate analysis, axial length was significantly associated with older age (P0.001; standardized β coefficient, 0.28), taller body height (P = 0.001; β, 0.18), maternal myopia (P = 0.03; β, 0.09), and urban region of habitation (P0.001; β, -0.21), or alternatively to the region of habitation, with less time spent outdoors (P = 0.001; β, -0.16) and more time spent indoors studying (P = 0.02; β, 0.10). The axial length-to-corneal curvature radius ratio was associated with older age, urban region of habitation, maternal and paternal myopia, and paternal level of education. Presence of myopia (defined as refractive error ≤-1 diopters in the right eye) was associated with older age (P0.001; odds ratio [OR], 1.45; 95% confidence interval [CI], 1.24-1.69), maternal myopia (P0.001; OR, 2.99; 95% CI, 1.94-5.35), and urban region of habitation (P0.001; OR, 0.17; 95% CI, 0.11-0.26), or alternatively to the region of habitation, with less time spent outdoors (P0.001; OR, 0.32; 95% CI, 0.21-0.48) and more time spent indoors studying (P0.001; OR, 1.38; 95% CI, 1.09-1.75).Less outdoor activity, more indoor studying, older age, maternal myopia, and urban region of habitation were associated with longer ocular axial length and myopia in grade 1 and grade 4 primary school children in Greater Beijing. Remaining outdoors more (e.g., during school) may reduce the high prevalence of myopia in the young generation in Beijing.

Purpose To investigate factors associated with ocular axial elongation and myopia progression during a 4-year follow-up in primary school children in Beijing. Methods This school-based study included 382 grade-1 children at baseline in 2011 (age:6.3±0.4 years) with 305 (79.8%) returning for the follow-up examination in 2015. At baseline and in yearly follow-up examinations, the children underwent a comprehensive eye examination including auto-refractometry, ocular biometry with measurement of axial length, and fundus photography. The parents underwent a standardized interview. Results During the study period, the mean axial length elongated by 1.15±0.56mm in boys and 1.10±0.63mm in girls. At baseline and at the end of follow-up, axial length was significantly (P

Aplastic anemia (AA) is an autoimmune disease and interleukin-27 (IL-27) is an important cytokine involved in the pathogenesis of autoimmune diseases. To date there have been no reports concerning the intrinsic association among IL-27 and Thelper (Th) 1 and Th17 cells in AA. Enzyme-linked immunosorbent assay (ELISA) to assay IL-27, interferon gamma (IFN-γ) and IL-17 levels, flow cytometry to measure the percentages of Th1 and Th17 cells among peripheral blood mononuclear cells (PBMCs), real-time reverse transcriptase polymerase chain reaction (PCR) for the mRNA levels of IL-27, IFN-γ, T-bet and IL-17 and retinoid related orphan receptor gamma (RORγt) in PBMCs were performed. In addition, the effect of exogenous rhIL-27 on the differentiation of T cells into Th1 and Th17 cells was investigated in vitro. Plasma and mRNA levels of IL-27 in PBMCs from AA patients were significantly higher than those in healthy controls. A positive correlation was found between plasma levels of IL27 and IFN-γ. The proportions of Th1 and Th17 cells accompanied by the mRNA expression of RORγt and T-bet were significantly higher in AA patients than in healthy controls. Plasma levels of IL-27 correlated positively with frequencies of Th1 cells in AA patients. Exogenous rhIL-27 could significantly upregulate the frequency of Th1 cells and the mRNA levels of T-bet and IFN-γ and the application of rhIL-27 in vitro could inhibit the expression of RORγt mRNA. The upregulation of IL-27 might cause Th1 differentiation and immune disorders in AA patients. Blocking the expression of IL-27 could therefore be a reasonable therapeutic strategy for AA.

Background. We followed a cohort of 773 individuals who received a monovalent vaccine against 2009 pandemic influenza A (H1N1). Approximately 6 weeks after vaccination, 12 persons developed the disease. Methods. Three groups of subjects were studied (12 patients who had or had not received previous monovalent vaccine and 1 group of 49 control subjects who had previously been immunized with the same vaccine ). For all patients, clinical features were characterized and the causative viruses sequenced for possible mutations. Nasopharyngeal swabs, serum specimens, and peripheral blood monocyte cells (PBMCs) were collected at different time points up to 11 weeks after symptom onset to measure the virus load and humoral and cellular immune responses. Serum samples and PBMCs were also collected from 49 and 16 vaccinated control subjects, respectively. Results. Both patient groups had similar clinical manifestations. No substantial viral mutations were detected. Compared with unvaccinated patients, viral loads in vaccinated patients were initially higher, but the levels decreased faster to undetectable levels. However, the virus became detectable again for 6 of them. Two weeks after infection, vaccinated and unvaccinated patients had similar neutralizing antibody levels as the vaccinated control subjects. Thereafter, the neutralizing antibody levels decreased markedly in vaccinated patients. During the acute phase, memory T cell counts and tumor necrosis factor‐a levels were significantly higher in vaccinated than in unvaccinated patients. Conclusions. Although the clinical consequences of infection are comparable between vaccinated and unvaccinated patients, humoral and cellular immune responses in vaccinated patients are boosted for some weeks, indicating an additional benefit of vaccination against 2009 pandemic influenza A (H1N1) virus. Early 2009, human infections caused by a novel influenza virus, later designated as 2009 pandemic influenza A (H1N1) virus, were identified in Mexico and spread rapidly to other regions of the world [1, 2]. The first imported case was reported in China on 9 May, fol

To elucidate the importance of the norovirus and other enteric viruses, and the difference of the genetic relatedness on norovirus between the outbreak and sporadic cases, a total of 557 stool samples, consisting of 503 sporadic cases and 54 samples of 4 outbreaks were collected and tested for norovirus and other enteric viruses in Beijing, China, July 2007–June 2008. The data showed norovirus, rotavirus, astrovirus, and sapovirus, were detected in 26.6%, 6.1%, 1.8%, and 0.5%, respectively. Norovirus was detected almost throughout the surveillance period, norovirus co-infecting with rotavirus, astrovirus, and sapovirus, respectively, were identified both in outbreak and the sporadic cases. GII.4/2006 was identified as the predominant strain circulating both in outbreak and sporadic cases. The results showed that norovirus was rather the important agent than other enteric viruses affected adults with acute gastroenteritis; no significant genetic relatedness of the dominant strains was found between the outbreak and sporadic cases.

Background. In early September 2009, an outbreak of influenza occurred at a college campus in Beijing, China, in which both pandemic H1N1 and seasonal H3N2 viruses were detected. Methods. Outbreak investigation was performed in the campus. Epidemiologic, clinical data were collected by interviewing patients and retrieving medical records. Individual contact tracing was performed for detailed contact information. Viruses were identified by reverse-transcription polymerase chain reaction assays followed by sequence analysis. The hemagglutination inhibition test was used to detect antibodies to both viruses for paired serum samples. Results. Forty of 45 people with influenza-like illness had laboratory-confirmed influenza A infection; 22 of these 40 people were infected with pandemic H1N1 virus, 12 were infected with seasonal H3N2 virus, and 6 were coinfected with both viruses. In the subsequent generation of cases with mixed infection, we detected pandemic H1N1 virus infection more often than seasonal H3N2 virus infection. The clinical patterns were essentially similar for patients with different virus infections. No substantial differences in sequences were observed in either pandemic H1N1 or seasonal H3N2 virus between patients with mixed and single infection. Sequence analyses revealed that all of the detected viruses were susceptible to oseltamivir but resistant to adamantane. Hemagglutination inhibition tests of paired serum samples confirmed mixed infection in the outbreak. Conclusions. Cocirculation of pandemic H1N1 virus and seasonal H3N2 virus led to a mixed infection in patients. Pandemic H1N1 virus, however, took prevalence over seasonal influenza virus in the course of transmission. Therefore, competitive circulation of seasonal influenza A virus with the pandemic H1N1 virus seems less likely.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Bupropion, an antidepressant and smoking cessation drug, is metabolized to its active metabolite hydroxybupropion almost exclusively by CYP2B6. • Ginkgo biloba is among the most commonly used herbal extract in the general population, and is likely to be used by depressed patients receiving bupropion. • Studies have reported that G. biloba administration to rats markedly increased the CYP content and CYP2B mRNA in the liver, and intake of G. biloba also induced various hepatic CYP enzymes, especially CYP2B-type enzymes. • There may be drug interactions between G. biloba extract and bupropion (CYP2B6 substrate). WHAT THIS STUDY ADDS • Fourteen-day oral administration of G. biloba extract had no statistically significant effect on the pharmacokinetics of bupropion or its active metabolite hydroxybupropion, as measured by AUC, which suggests G. biloba does not significantly affect the metabolism of bupropion following a single oral dose in healthy Chinese men. AIMS To assess the effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. METHODS Fourteen healthy male volunteers (age range 19–25 years) received orally administered bupropion (150 mg) alone and during treatment with G. biloba 240 mg day−1 (two 60-mg capsules taken twice daily) for 14 days. Serial blood samples were obtained over 72 h after each bupropion dose, and used to derive pharmacokinetic parameters of bupropion and its CYP2B6-catalysed metabolite, hydroxybupropion. RESULTS Ginkgo biloba extract administration resulted in no significant effects on the AUC0–∞ of bupropion and hydroxybupropion. Bupropion mean AUC0–∞ value was 1.4 µg·h ml−1[95% confidence interval (CI) 1.2, 1.6] prior to G. biloba treatment and 1.2 µg·h ml−1 (95% CI 1.1, 1.4) after 14 days of treatment. Hydroxybupropion mean AUC0–∞ value was 8.2 µg·h ml−1 (95% CI 6.5, 10.4) before G. biloba administration and 8.7 µg·h ml−1 (95% CI 7.1, 10.6) after treatment. The Cmax of hydroxybupropion increased from 221.8 ng ml−1 (95% CI 176.6, 278.6) to 272.7 ng ml−1 (95% CI 215.0, 345.8) (P = 0.038) and the t1/2 of hydroxybupropion fell from 25.0 h (95% CI 22.7, 27.5) to 21.9 h (95% CI 19.9, 24.1) (P = 0.000). CONCLUSIONS Ginkgo biloba extract administration for 14 days does not significantly alter the basic pharmacokinetic parameters of bupropion in healthy volunteers. Although G. biloba extract treatment appears to reduce significantly the t1/2 and increase the Cmax of hydroxybupropion, no bupropion dose adjustments appear warranted when the drug is administered orally with G. biloba extract, due to the lack of significant change observed in AUC for either bupropion or hydroxybupropion.

Background Associations between pathogens and hypertension (HT) has been reported, but few studies have focused on the relationship between aggregate pathogens and HT. The present study explored whether the risk of HT is associated with each pathogen (defined as Chlamydia pneumoniae (C. pneumoniaee), Mycoplasma pneumoniae (M. pneumoniae), Helicobacter pylori (H. pylori) and Coxsackie virus) or with aggregate pathogens in Chinese Mongolians. Methods and Results One thousand and thirty Chinese Mongolians aged 30 years or more were recruited, including 488 hypertensive and 942 normotensive subjects. Enzyme-linked immunosorbent assay was used to detect IgG antibodies for C. pneumoniaee, M. pneumoniae, H. pylori and Coxsackie virus. The seroprevalence of Coxsackie virus was significantly associated with HT (odds ratio (OR) 3.7 after adjustment for risk factors), but no significant association was found for C. pneumoniae, M. pneumoniae and H. pylori (OR 1.32, 0.75 and 1.19, respectively). The results also showed that the risk of HT was associated with the aggregate pathogens: it increased with the increasing number of pathogens, and the ORs were 1.629, 2.653, 2.129, and 5.146 for 1, 2, 3 and 4 pathogens, respectively, after controlling for risk factors. Conclusion The risk of HT is associated with Coxsackie virus and aggregate pathogen load. The mechanism(s) underlying the associations remain to be elucidated further. (Circ J 2007; 71: 1761 - 1764)

Objectives To study the role of the Rho/ROCK pathway in Ang II and TGF-β1-induced atrial remodeling. Methods and Results A canine atrial fibrillation (AF) model was established by rapid atrial pacing (RAP) of the left atrium. The roles of TGF-β1, the RhoA/ROCK signaling pathway and connective tissue growth factor (CTGF) in atrial remodeling were studied via both in vitro and in vivo experiments. Each of the dogs that received RAP developed persistent AF within 4 weeks. The mRNA expression levels of TGF-β1 (1.32±0.38), Collagen-I(1.33±0.91), CTGF(5.83±3.71), RhoA(1.23±0.57) and ROCK-1 (1.02±0.27) in the left atrium were significantly increased following 4 weeks of RAP. Angiotensin II (Ang II) induced the proliferation of atrial fibroblasts and up-regulated the expression of both CTGF and ROCK-1 in a dose-dependent manner. Simvastatin and Y27632 reversed Ang II-induced CFs proliferation, as well as ROCK-1(0.89±0.05 and 1.27±0.03, respectively) and CTGF (0.87±0.04 and 0.91±0.02, respectively) expression. The expression mRNA of ROCK-1(1.74±0.13) and CTGF (2.28±0.11) can upregulated by TGF-β1, and down-regulated by Simvastatin (1.22±0.03 vs 2.27±0.11), Y27632 (1.01±0.04 vs 1.64±0.03), Los (1.04±0.11 vs 1.26±0.05), respectively. Losartan and Simvastatin attenuated the effects of TGF-β1, inhibited RhoA activity as opposed to RhoA protein expression. Y27632 had no effect on either the expression or the activity of RhoA. Conclusions The increased expression of profibrotic factors (CTGF, ROCK1 and Smad2/3) played an important role in our RAP-induced AF model. Increased atrial profibrotic factors involve the activation of either the TGF-β1/RhoA/ROCK-1 or the TGF-β1/Smad2/3 signaling pathway.

PURPOSE The purpose of this study was to assess the ovality of the optic disc and its associations with myopia-related factors in primary school children in Beijing. METHODS This longitudinal school-based study included 382 grade 1 children and 299 grade 4 children who were followed for 2 years. Study participants underwent a comprehensive eye examination including autorefractometry, ocular biometry, and fundus photography. RESULTS Fundus photographs were available for 562 children (82.5%). The mean optic disc ovality (maximal-to-minimal disc diameter) was 1.17 ± 0.29 (range, 1.00-1.50). Oval discs defined by an ovality of ≥ 1.33 were detected in 37 children (prevalence: 6.6%; 95% confidence interval: 4.5-8.6). In multivariate linear regression analysis, higher optic disc ovality index was significantly associated with older age (P = 0.001), female sex (P = 0.005), larger parapapillary beta zone (P < 0.001), and shorter time spent indoors with studying (P = 0.003) and was marginally significant (P = 0.057), with greater increase in myopic refractive error from 2011 to 2013. From 2011 to 2013, myopic refractive error increased in the oval optic disc group by 1.03 ± 0.99 diopters compared to 0.67 ± 1.31 diopters in the nonoval disc group. CONCLUSIONS The prevalence of oval optic discs in Beijing school children was markedly higher than in the elderly Beijing Eye Study population (6.6% vs. 0.36%), paralleling the higher prevalence of myopia in school children. The association between oval optic discs and less time spent indoors with studying after adjusting for longitudinal change in myopic refractive error, age, sex and parapapillary beta zone may warrant further exploration of external factors associated with oval optic discs.

PurposeTo evaluate prevalence and associated factors for myopia in high school students in Beijing.MethodsGrade 10 and 11 high school students were randomly selected from nine randomly selected districts of Beijing. The students underwent non-cylcoplegic auto-refractometry and an interview.ResultsOut of 4798 eligible students, 4677 (93.4%) students (mean age:16.9±0.7years;range:16-18 years) participated. Mean refractive error of right eyes and left eyes was -2.78±2.29 diopters and -2.59±2.50 diopters, respectively. Prevalence of myopia (defined as ≤ -1.00 diopters in the worse eye) was 80.7% (95% Confidence Interval (CI): 79.6-81.8%). Out of 3773 students with myopia, 1525 (40.4%) wore glasses daily. In multiple logistic regression analysis, a higher prevalence of myopia was associated with female sex (odds ratio (OR) = 1.31;95%CI:1.11-1.55), Han ethnicity (OR = 1.64;95%CI:1.28-2.11), attending key schools (OR = 1.48;95%CI:1.24,1.77), higher family income (OR = 1.37;95%CI:1.09-1.71), longer time spent for near work (OR = 1.43;95%CI:1.06-1.93), shorter near work distance (OR = 1.87;95%CI:1.55-2.26), lower frequency of active rest during studying (OR = 1.40;95%CI:1.16-1.70), and parental myopia (OR = 2.28;95%CI:1.80-2.87). The interaction between distance from near work and time spent for near work was statistically (P = 0.03) significant. In multiple logistic regression analysis, higher prevalence of high myopia (≤-6.0 diopters) was associated with studying in key schools (OR = 1.38;95%CI:1.05,1.81), lower frequency of active rest during studying (OR = 1.40;95%CI:1.09,1.79), and a higher number of myopic parents (OR = 2.66;95%CI:2.08,3.40).ConclusionsA prevalence of about 80% for myopia and a prevalence of about 10% for high myopia in students aged 16 to 18 years and attending classes of grade 10 and 11 in a Chinese metropolitan region is another example of the high prevalence of moderate and high myopia in metropolitan areas of China. With this young myopic generation getting older, myopia as cause for visual impairment and blindness may further increase in importance. Future studies may address whether active rests during studying with looking into the distance are preventive against myopia development or progression.

Prophylaxis and treatment with oseltamivir effectively controlled a community outbreak of pandemic influenza A (H1N1) in China. The genetic makeup of strains of different generations seemed to be stable. Travel in confined settings might accelerate the transmission of pandemic influenza in a community outbreak.

To investigate the effects and mechanisms of Nardostachys chinensis (NC) on spontaneous ventricular arrhythmias in rats with hyper-acute myocardial infarction (AMI).Seventy-two rats were randomly divided into the control group (n = 24), metoprolol group (n = 24), and the NC group (n = 24). Premature ventricular contractions (PVCs), ventricular tachycardias (VTs), ventricular fibrillations (VFs), and blood pressure were monitored for 4 hours after coronary artery ligation. The connexin 43 (Cx43) expression in ventricular myocardium was measured by immunohistochemistry, Western blot, and real-time RT-PCR.Compared with the control, metoprolol and NC decreased the VF incidence (50% vs. 4.2%, P0.001, and 50% vs. 12.5%, P = 0.005, respectively). There was a steady decrease in the cumulative number of PVCs and VTs within 4 hours from ligating in 3 groups. Compared with the control, metoprolol and NC reduced the cumulative number of VTs and PVCs. Compared with control, metoprolol and NC decreased the infarct size of the left ventricular tissue (55.98% ± 6.20% vs. 39.13% ± 4.53%, P0.001, and 55.98% ± 6.20% vs. 42.39% ± 3.44%, P0.001, respectively). The results from immunohistochemistry, Western blot, and real-time RT-PCR showed that the protein expression of Cx43 in the control group was significantly lower than that in the metoprolol and NC groups in the infarcted zone.NC decreased the incidence of spontaneous ventricular arrhythmias (especially VF), reduced Cx43 degradation, and improved Cx43 redistribution in myocardial infarcted zone in rats with hyper-AMI. The data of the present study indicated that NC may be a promising drug in the future to prevent patients with AMI from lethal ventricular arrhythmias in prehospital setting.

Summary Objectives To evaluate the correlation between IL-10 gene polymorphisms and hepatitis B infection. Methods Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between IL-10 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. Results This study found that rs3024490 G/T allele, located in the intron 1 region and highly prevalent in Chinese populations, was significantly different between the chronic HBV infection cases and the acute infection controls in single allele analysis, genetic models analysis, and haplotypes analysis. Conclusions This suggested that the rs3024490 within IL-10 was associated with susceptibility to chronic hepatitis B in a Chinese Han population.

The functions of cytoskeleton-associated membrane protein 4 (CKAP4), one kind of type II transmembrane protein, are associated with the palmitoyl acyltransferase DHHC2. The objective of the current study was to investigate CKAP4/DHHC2 expression and its prognostic significance in patients with hepatocellular carcinoma (HCC).Two independent cohorts of 416 patients with HCC were enrolled. All the patients included had defined clinicopathologic and follow-up data. Using real-time polymerase chain reaction and immunohistochemical assay, CKAP4 and DHHC2 expression were evaluated. The association between CKAP4/DHHC2 expression and HCC-specific disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses.The data documented that CKAP4 expression was much higher in HCC tumor tissues compared with adjacent normal tissues and its expression was significantly correlated with tumor size, intrahepatic metastases, portal venous invasion, and Barcelona Clinic Liver Cancer stage of disease in 2 cohorts of patients. On survival analysis, patients with high CKAP4 expression appeared to have a favorable overall survival and a longer disease-free survival compared with those with low expression. DHHC2 expression was also examined in tissue microarray analysis by immunohistochemistry and the results demonstrated that 87.6% of the cases had low expression of DHHC2. Kaplan-Meier analysis indicated that a high level of DHHC2 expression predicted favorable overall survival and disease-free survival rates in both the training cohort and validation set. Furthermore, the combination of CKAP4 and DHHC2 was found to have a more powerful efficiency in prognosis prediction than either one alone.To the best of our knowledge, the current study is the first to demonstrate that the expression of CKAP4 and its palmitoyl acyltransferase DHHC2 correlates with disease progression and metastasis in patients with HCC and may provide prognostic and therapeutic value.

Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), which are responsible for tumor relapse and metastases. Portal vein tumor thrombus (PVTT) is raised from HCC and strongly correlated to a poor prognosis. However, the mechanism underling the formation of PVTT is largely unknown. Herein, we provide evidence that RNA polymerase II subunit 5 (RPB5)-mediating protein (RMP) was progressively upregulated in PVTT and overexpressed RMP appeared to increase T-ICs self-renewal. Moreover, RMP promoted metastases of PVTT cells and HCC cells in vitro and in vivo. Knockdown of RMP attenuated T-ICs self-renewal and reversed epithelial-mesenchymal transition (EMT) in HCC and PVTT cells. The neutralizing assays suggested that interleukin-6 (IL-6) had an indispensable role in RMP regulating metastases and self-renewal of HCC cells. Furthermore, the transcription of IL-6 was verified to be modulated by RMP via interaction with p65 and RPB5, through which expanding the T-IC/cancer stem cell populations, as well as inducing EMT was promoted. These results suggested that RMP may promote PVTT formation by promoting IL-6 transcription. Thus, RMP serves as a potent factor contributed to develop PVTT and a promising therapeutic target for HCC patients.

To investigate the correlation between auto-immune antibodies and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS), thus providing clinical evidence for further researches on molecular biological mechanisms of RA patients of SDS.Totally 451 RA patients were assigned to the SDS group and the non-SDS group. Their general conditions (including gender, age, duration, and age of onset), C reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet (PLT), disease activities (DAS28), auto-antibodies [rheumatoid factor (RF), anti-CCP antibodies, anti-nuclear antibody (ANA)] were compared between the two groups.(1) The scores for EST, PLT, and DAS28 were obviously higher in the SDS group than in the non-SDS group (P0.05, P0. 01). (2) The level of average RF was (697.32 +/-1 061.38 IU/mL) in the SDS group, higher than that in the non-SDS group (439.91 +/- 672.24 IU/mL, P0.01). There was no statistical difference in anti-CCP antibody between the two groups (P0.05).(3) The ANA positive rate of RA patients was 29. 63% (120/405). It was 37.19% (74/199) in RA patients of SDS and 22. 33% (46/206) in RA patients of non-SDS, showing statistical difference between the two groups (P0.01). (4) The odds ratio for high level RF positive and ANA positive was 1. 574 and 2. 059 folds in RA patients of SDS as high as that in RA patients of non-SDS.RA patients of SDS would have higher risk of having auto-immune antibodies, fastened development, more worsen joint damage, and more poor prognosis. Its mechanisms might be closely associated with autoimmune tolerance.

BACKGROUND: The prognostic importance of B-type natriuretic peptide (BNP) or N-terminal pro BNP (NT-proBNP) in patients with end-stage renal disease (ESRD) remains controversial. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an unrestricted search from the MEDLINE and EMBASE in all languages that were published between 1966 and Augest2013. Twenty-seven long-term prospective studies met our inclusion criterias. From the pooled analysis, elevated BNP/NT-proBNP was significantly associated with increased all cause mortality [odds ratio (OR), 3.85; 95% CI, 3.11 to 4.75], cardiovascular mortality (OR, 4.05; 95% CI, 2.53 to 6.84), and cardiovascular events (OR, 7.02; 95% CI, 2.21 to 22.33). The funnel plot showed no evidence of publication bias. The corresponding pooled positive and negative likelihood ratio for prediction of all cause mortality were 1.86 (95% CI, 1.66 to 2.08) and 0.48 (95% CI, 0.42 to 0.55), respectively. CONCLUSIONS/SIGNIFICANCE: BNP/NT-proBNP is a promising prognostic tool to risk-stratify the patients with ESRD. Further investigations are warranted to elucidate the specific pathogenic mechanisms and the impact of other potential prognostic factors.

To investigate the expression of anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in different types of immune-mediated optic neuritis (IM-ON).Case-control and cross section study. The serum of 129 consecutive cases of immune-mediated optic neuritis (IM-ON group) seen in Neuro-ophthalmology clinic in Department of Neurology, Beijing Tongren Hospital during May 2010 and February 2011 were collected. All IM-ON cases were further classified into five different types as: 20 cases of multiple sclerosis related ON (MS-ON), 13 cases of neuromyelitis optical related ON (NMO-ON), 33 cases of autoimmune optic neuritis (AON), 43 cases of relapsing isolated optic neuritis (RION) and 20 cases of solitary isolated optic neuritis (SION). MOG-Ab was tested by ELISA. The positivity rate and titer of MOG-Ab among these groups were compared using chi-square test and ANOVA, t test by SPSS17.0 software.MOG-Ab was positive in 12 of all 129 tested IM-ON patients (9.3%), in which there were 5 of 20 MS-ON, none of 13 NMO-ON, 4 of 33 AON, 2 of 43 RION, and 1 of 20 SION patients. There were no statistical significant difference among five groups (Fisher's exact test, χ(2) = 7.051, P = 0.088), but MS-ON group showed statistically higher MOG-Ab positivity and titer than the "NMO spectrum optic neuritis" group which was merged from the other 4 IM-ON groups.MOG-Ab could be detected in different types of immune-mediated optic neuritis except NMO-ON and the expression of MOG-Ab was statistically higher in MS-ON group than the 'NMO spectrum optic neuritis' group.

Background: Asparagine synthetase (ASNS) is associated with drug resistance in leukaemia, and the function of this enzyme in the context of hepatocellular carcinoma (HCC) is not clear. In this study, the relationship between ASNS expression and clinical outcomes after surgical resection was investigated, and the therapeutic value of ASNS was also evaluated. Methods: The expression of ASNS was evaluated in HCC samples by real-time PCR and immunohistochemistry assays. The correlation between ASNS expression and clinicopathological features was investigated. Potential clinicopathological prognostic factors were examined by univariate and multivariate survival analysis. Asparagine synthetase was overexpressed and knocked down in HCC cell lines to assess the influence of the enzyme on cell proliferation, migration and tumourigenicity. L-asparaginase was used to treat HCC cells with high or low levels of ASNS in vitro and in vivo to examine the therapeutic efficacy. Results: The expression of ASNS was higher in HCC tumour tissues and was closely correlated with the serum AFP level, tumour size, microscopic vascular invasion, tumour encapsulation, TNM stage and BCLC stage. Patients with low ASNS expression levels had a poor prognosis with respect to overall survival (OS). The multivariate survival analysis indicated that ASNS is an independent prognostic factor for OS. Furthermore, functional studies demonstrated that ASNS significantly inhibits the proliferation, migration and tumourigenicity of HCC cells. The knockdown of ASNS markedly increased sensitivity to L-asparaginase, indicating that cells with different ASNS protein levels have different sensitivities to L-asparaginase. Conclusion: The expression of ASNS is an independent factor affecting the survival of HCC patients, and low ASNS expression in HCC was correlated with worse surgical outcomes. The ASNS may be a promising therapeutic target for the treatment of HCC.

Myocardial ischemia and reperfusion (MI/R) injury is associated with activation of the complement system. Complement activation generates a series of bioactive substances, including early (C3a, C3b) and terminal (C5a, C5b-9) components. The terminal complement components are key mediators of MI/R injury. This study investigated whether C5 shRNA preconditioning has protective effects following MI/R injury and its potential mechanism. Rats were injected with C5 shRNA 2 days before induction of ischemia. The effects of C5 shRNA were evaluated by the assessment of heart function, infarct size, histopathology, inflammatory cytokine levels, and the plasma level of troponin T. Akt phosphorylation was assessed by immunoblotting. C5 shRNA efficiently inhibited C5 expression both in vitro and in vivo, and attenuated MI/R injury. C5 shRNA preconditioning significantly decreased the level of troponin T and the production of pro-inflammatory cytokine. The infarct size was decreased by 40% in C5 shRNA treated rats. Akt phosphorylation increased after C5 shRNA preconditioning. These results suggest that C5 shRNA preconditioning in rats has protective effects following MI/R injury; this may be partly effected by mediating the activation of the PI3K pathway and by phosphorylation of Akt.

To observe the difference of EMG features between junior athletes and general students of knee flexor and extensor in performing various jumps.30 junior athletes and 30 middle school students took part in the test. EMG signal from knee flexor and extensor were measured, when subjects performed squatting jump, counter-movement jump and drop jump.The results indicated that the agonists EMG activity related to sex. With the load of leg increasing, there were no significant changes in iEMG and Fmean for male. There was some increasing in iEMG but no change in Fmean for female. The antagonists EMG activity maybe related to training. With the load of leg increasing, the EMG activity of antagonists changed slightly for the junior athletes, however, increased obviously for the common students.To improve the performance of jump, male athletes should mostly improve efficiency, however female athletes can increase the recruiting of muscle fiber. Moreover the ability of antagonists coordinating for athlete in the course of jumping is higher than that of general students.

This study was aimed to investigate the transfection efficacy of recombinant adeno-associated virus 2/1 (rAAV2/1) on bone marrow mesenchymal stem cells (BMMSCs) at different multiplicities of infection (MOI) and time, and effect of transfection on growth of rat BMMSCs. The rat BMMSCs cultured in vitro were transfected by using rAAV2/1 with enhanced green fluorescent protein (rAAV2/1-EGFP) at MOI of 1 x 10(4), 1 x 10(5) and 1 x 10(6); the EGFP expression was observed by fluorescent microscopy at 3, 7 and 14 days. The viability, proliferation multiple, differentiation ability of daughter cells were detected for evaluating the effect of rAAV2/1 on survival, proliferation and differentiation of BMMSCs and the fluorescence index (FI) were determined by flow cytometry. The results indicated that after transfection with rAAV2/1 for 24 hours the green fluorescence in BMMSCs were observed, but also the fluorescence gradually was enhanced along with prolonging of time, and reached to steady level after 7 days; the viability, proliferation multiple, differentiation ability of BMMSCs transfected by rAAV2/1-EGFP at different MOI showed no significant changes at 3,7 and 14 days (p0.05), meanwhile at same MOI the proliferation multiple obviously increased in comparison between 7 day vs 3 day and 14 days vs 7 days (p0.01). The flow cytometric detection showed that the transfection efficacy of rAAV2/1-EGFP on BMMSCs and FI increased significantly as the multiplicity of infection and culture time increased (p0.05). It is concluded that rAAV2/1-EGFP is able to transfect into BMMSCs effectively, but the transfection efficiency and fluorescence index increase significantly along with increase of multiplicity of infection and culture time. rAAV2/1-EGFP do not affect viability, proliferation multiple and differentiation ability of BMMSCs. rAAV2/1 is a kind of active vector for gene transfer to reform BMMSCs.

The determination of skeletal maturity has an important role in pediatric clinical practice, especially in relation to endocrinological problems and growth disorders, and it is frequently useful in diagnosis and monitoring treatment. It has been suggested that the difference between radius, ulna and short bonse (RUS) and carpal may be of differential diagnostic significance. However, no data on comparison among bone ages of Chinese children are available. The differences between TW3-Chinese RUS (TW3-C RUS) and TW3-Chinese Carpal (TW3-C Carpal) bone age of Chinese children were observed in this study to provide references for skeletal development estimation.Totally 9408 Han healthy children (5066 boys, 4302 girls) aged 1.5 - 13.5 years from 5 cities of China were enrolled in this study. The bone ages of the children were estimated by TW3-C RUS and TW3-C Carpal. The Z score curves of the differences between them were fitted by BCPE distribution and the goodness-of-fit of Box-Cox power exponential distribution (BCPE) models were assessed by Q-test and percents of cases of sample below the fitted percentile curves.The means of the differences between TW3-C RUS and TW3-C Carpal were -0.19 - 0.17 over the age 2.0 - 13.5 years in boys and -0.12 - 0.13 from age 1.5 - 11.5 years in girls. The standard deviations were respectively 0.47 - 1.01 years for boys and 0.49 - 0.82 years for girls. The degrees of freedom, with respect to the parameter curves from BCPE distribution, were selected and the percentile curves were fitted by BCPE. The differences between percents of cases below the fitted percentile curves and expected values were all under 0.66%, exception of difference for 90th percentile in girls.The differences between TW3-C RUS and TW3-C Carpal varied with age, the standard deviations increased gradually before 4.5 years of age in boys and 4 years of age in girls, and afterwards the variations decreased steadily until the TW3-C Carpal has reached full maturity. However, there was sex diversity in the extent of the variations. The differences between TW3-C RUS and TW3-C Carpal for boys were evidently greater than that for girls. The sex difference decreased progressively after 10 years. The proposed Z scores curves charts should provide reference for clinical practice.

To investigate the relationship of certain skeletal maturity indicators of hand and wrist with adolescent growth spurt.14 757 normal urban children, 7373 boys and 7384 girls, aged 7 - 20, all of Han nationality, from Shanghai, Guangzhou, Wenzhou, Dalian, and Shijiazhuang underwent measurement of height and weight, and left wrist anterior-posterior radiography. The incremental curve was fitted graphically according to the differences between the means for height at series ages. The ages of attainment of eleven skeletal indicators were defined by regression analysis for middle phalange 3, radius, and adductor sesamoid of the first finger.The accelerative phase of adolescent growth spurt was accompanied by becoming square of middle phalange 3 and the appearance of adductor sesamoid of the first finger. Peak growth velocity (PGV) was reached at about the time of epiphysis capping in middle phalange 3 and ossification of the adductor sesamoid of first finger. Decelerated phase of growth was indicated by the beginning of epiphysis fusion in radius and full maturity in adductor sesamoid of first finger. When the epiphysis of middle phalange 3 and the half of epiphysis of radius were respectively fused with their diaphyses, the growth spurt was ended.Certain skeletal maturity indicators of hand and wrist can be used to indicate the period of adolescent growth that a child has reached.

This study included 17 401 normal Han urban children aged 1-20 years from five cities in China in 2005. The skeletal maturity scores were assessed by the Tanner-Whitehouse 3 (TW3) method, and the smoothed centiles curves of scores (TW3-Chinese RUS and TW3-Chinese Carpal) were calculated using the LMS method. The skeletal maturity of the Chinese is approximately the same as Europeans in childhood, but the extent of TW3-RUS skeletal maturity advance in puberty and the ages of complete maturity of TW-Carpals are evidently more advanced in the Chinese.

To estimate the life satisfaction and its predictors between the empty-nest and not-empty-nest elderly. A semi-structured questionnaire including socio-demographic characteristics, physical health, and the Life Satisfaction Index (LSI), UCLA Loneliness Scale (UCLA-LS), and Geriatric Depression Scale (GDS) was administered to 275 empty-nest and 315 not-empty-nest rural elderly in a Chinese county. Linear regression analysis was used to examine the predictors of LSI score. The empty-nest elderly had lower life satisfaction, lower income, poorer relationships with children, less social support, higher prevalence of chronic diseases, and more feelings of depression and loneliness compared to the not-empty-nest elderly. “Empty-nest status” was negatively related with life satisfaction. Depression was the strongest predictor of life satisfaction in both groups. The second strongest predictor was loneliness among the empty-nest group, while it was chronic diseases among the not-empty-nest group. Marital status and income were correlated with life satisfaction only among the empty-nest elderly. The empty-nest elderly were likely to have mental health problems and to feel unsatisfied with their life. These findings also emphasize the importance of mental health as the determinant of life satisfaction among the empty-nest elderly.

To investigate the new surgical method and effect of treatment of Duane's retraction syndrome by recession of medial and lateral rectus muscles combined with Y-splitting procedure.Eight patients with Duane retraction syndrome underwent surgery. Among seven cases of normal direction Duane's retraction syndrome, Six patients were performed recession of medial and lateral rectus muscles with Y-splitting of lateral rectus muscle, one patient was performed recession and Y-splitting of lateral rectus muscle. One patient with inverse Duane's retraction syndrome was performed bilateral recession of medial and lateral rectus muscles combined with Y-splitting of both medial rectus muscles. All patients were followed up 1 to 12 months. Ocular alignment, ocular motility and change of compensatory head posture were evaluated.The compensatory head posture, upshoot or downshoot were eliminated. Globe retraction and narrowing of palpebral fissure got improved. Postoperative ocular alignment of 6 cases achieved orthophoria, with 2 cases of residual strabismus.Recession of medial and lateral rectus muscles combined with Y-splitting procedure is an effective method for treatment of Duane's retraction syndrome, aiming at correction of ocular deviation and head posture and elimination of globe retraction.