Xiubin Sun

ERG Rearrangement Is Associated with Prostate Cancer-Related Death in Chinese Prostate Cancer Patients

Recently, ETS-related gene (ERG) gene rearrangements, phosphatase tensin homologue (PTEN) deletions and EGFR family aberrations were characterized as potential biomarkers for prostate cancer (PCa) patient management. Although ERG gene rearrangement has been identified in approximately 50% of localized prostate cancers in western countries, the prognostic significance of this critical molecular event remains unknown in Chinese patients. Using fluorescence in situ hybridization (FISH) and immunohistochemistry, we evaluated ERG, PTEN and EGFR family aberrations in a cohort of 224 Chinese prostate cancer patients diagnosed in transurethral resection of the prostate (TUR-P). Overall, ERG rearrangement was detected in 23.2% (44/190) cases, of which 54.5% (24/44) showed deletion of the 5′end of ERG. PTEN deletion was identified in 10.8% (19/176) cases. Amplification of EGFR and HER2 genes was present in 1.1% (2/178) and 5.8% (10/173) of cases, respectively. Significant correlation between ERG rearrangement and PTEN deletion was identified in this cohort. EGFR and HER2 aberrations occurred more frequently in PCas without ERG rearrangement than in those with ERG rearrangement, although this did not reach statistical significance. Overall, ERG rearrangement was associated with pre-operative PSA values (P = 0.038) and cancer-related death (P = 0.02), but not with the age, clinical T stage, Gleason score, or Ki-67 labeling index (LI). Notably, multivariate analysis including known prognostic markers revealed ERG rearrangement was an independent prognostic factor (P = 0.022). Additionally, ERG rearrangement status was helpful to identify patients with poor prognosis from PCa group with low Ki-67 LI. In summary, we reported that ERG rearrangement was associated with cancer-related death in Chinese PCa patients. Determination of ERG rearrangement status allows stratification of PCa patients into different survival categories.

Characterization of EGFR family gene aberrations in cholangiocarcinoma

Cholangiocarcinoma (CCA) is a highly lethal malignancy of the biliary tract with very few treatment options. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER2) have been considered as potential therapeutic targets in CCA. In the present study, we attempted to clarify the clinicopathological significance of all EGFR family members, EGFR, HER2, HER3 and HER4, across the full spectrum of CCAs. Immunohistochemistry and FISH were performed to validate expressions and genetic aberrations of these molecules retrospectively in 175 CCA patients. EGFR, HER3 and HER4 were overexpressed in 20 (30.8%), 8 (12.3%) and 41 (63.1%) of the 65 intrahepatic cholangiocarcinomas (IHCCs), and in 23 (20.9%), 13 (11.8%) and 62 (56.4%) of the 110 extrahepatic cholangiocarcinomas (EHCCs), respectively. Overexpression of HER2 was exclusively identified in EHCCs, among which the rate was 4.5% (5/110). A significant association was identified between EGFR amplification and EGFR overexpression (P=0.002). Similarly, HER2 amplification was strongly associated with HER2 overexpression (P<0.001). Multivariate analysis suggested that EGFR overexpression is an independent prognostic factor in IHCC, but not in EHCC cases [HR (95% CI): 3.689 (1.253-10.587), P=0.018]. Notably, for the first time, we demonstrated HER4 expression is a prognostic factor in EGFR-negative IHCC patients. In vitro data further suggested a tumor-suppressor role of HER4 in CCA. siRNA knockdown of HER4 significantly increased RBE cell migration and invasion. By contrast, HER4 overexpression decreased proliferation of HuCCT-1 cells and their migratory and invasive capacity. In summary, our results revealed expression of the EGFR family members in CCA development and progression. CCAs differentially express HER2 protein based on tumor location. HER4 expression status allows stratification of CCA patients into different survival categories.

Worldwide spatial genetic structure of angiotensin-converting enzyme gene: a new evolutionary ecological evidence for the thrifty genotype hypothesis

As JV Neel put forward the ‘thrifty genotype’ hypothesis, many researches tend to support this hypothesis involved in the regulation of energy balance. However, the phrase could equally well encapsulate broader traits and the forms of thrift should be multiple. In particular, genes involved in the regulation of water and sodium balance may also be excellent candidates as thrifty genes. In the present study, we selected the ancestral D allele of angiotensin-converting enzyme (ACE) gene, a key gene involved in water and sodium balance regulation, as a candidate to confirm the ‘thrifty genotype’ hypothesis in the framework of evolutionary ecology. On the basis of our compiled worldwide spatial genetics database of I/D frequency of ACE gene and spatial climate database, using techniques of spatial statistics, we found (1) an obvious decreasing geographic genetic cline following the route of out-of-Africa expansion from East Africa, (2) a positive association between D allele and synthetic temperature factor, (3) and a negative relationship between D allele and synthetic humidity factor that covered most regions of the world, and obvious spatial dependence between D allele and these two climate factors followed the route of out-of-Africa expansion from Africa. This suggested that D allele of ACE gene is not only plastic in response to its environmental circumstance but also presents a striking geographic distribution showing the evidence of ‘signatures of selection’ by climate factors. Thus, it can be identified as a thrifty allele and could provide a new evolutionary ecological evidence for the ‘thrifty genotype’ hypothesis.

Association between white blood cell count and non-alcoholic fatty liver disease in urban Han Chinese: a prospective cohort study.

Objectives The white blood cell (WBC) count is a simple and convenient marker of inflammation for use in medical practice; however, its association with non-alcoholic fatty liver disease (NAFLD) has not been determined. We examined the relationship between WBC and NAFLD to provide a convenient and useful marker for the prediction of NAFLD. Setting A longitudinal cohort participating in a large health check-up programme for the Chinese population was selected and followed up from 2005 to 2011. Participants A total of 21 307 male and female participants without NAFLD who underwent health check-ups at least twice between 2005 and 2011 were included in this study. 15 201 participants (7286 men and 7915 women) were eligible for inclusion. Results The baseline distribution of age, WBC, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum total protein (TP), albumin (ALB) and globin (GLO) and the prevalence of males, hypertension, hyperglycaemia, smoking and regular exercise were significantly different between the incident NAFLD and non-NAFLD groups (p<0.05). Cox proportional hazards regression analysis was performed to estimate the HRs and 95% CIs of WBC, which predicted the occurrence of NAFLD. Compared with the lowest WBC quartile (Q1), the HRs and 95% CIs of the other WBC quartiles (Q2, Q3 and Q4) for incident NAFLD were 1.090 (0.978 to 1.215), 1.174 (1.055 to 1.305) and 1.152 (1.035 to 1.281), respectively, after adjusting for age, gender, smoking, regular exercise, BMI, hypertension, hyperglycaemia, TC, TG, HDL-C, LDL-C, ALB and GLO. Conclusions Our study clearly showed that WBC count was a significant factor associated with incident NAFLD in Han Chinese.

A genetic epidemiological survey of idiopathic epilepsy in the Chinese Han population

BACKGROUND Idiopathic epilepsy (IE) is a syndrome that comprises epilepsy only, with no underlying structural brain lesion or other neurological signs or symptoms. Numerous studies have shown that genetic factors play an important role in IE. IE is a common disease in the Chinese Han population. However, the genetic epidemiological characteristics of IE in the Chinese population, such as its heritability and genetic models remain unclear. PURPOSE To study the clinical and epidemiological profile of IE, to estimate the heritability and determine the possible genetic models for IE in the Chinese Han population. METHODS A case-control family-based study was carried out in a rural Chinese county. We collected data from eligible IE patients, controls, and their relatives by a uniform structured questionnaire, and then established an epidemiologic database of epilepsy using Access2010. General statistical and genetic epidemiological analyses (Falconers-method-based heritability, simple segregation ratio and complex segregation analysis) were performed using SAS9.1 and the SAGE-SEGREG program. RESULTS (1) The prevalence of IE among the relatives of probands with IE (2.75‰) was higher than that among the relatives of the control group (0.61‰). The prevalence of IE among the first-, second-, and third-degree relatives of the probands with IE was 11.45‰, 2.64‰ and 0.98‰, respectively, which were all higher than the corresponding prevalences in the relatives of controls. Trend-chi-squared tests indicated that the prevalence of epilepsy increased among the relatives of probands with decreasing kinship distance (χ(2)=97.16, P=0.00). (2) The heritability of IE among first-, second-, and third-degree relatives was 55.06%, 50.72% and 16.98%, respectively. The weighted mean heritability was 46.07%. (3) The simple segregation ratio of IE was 0.03, significantly lower than the Mendelian recessive segregation ratio of 0.25. Complex segregation analysis showed that the population we studied accepted a Mendelian genetic model (dominant, recessive, additive, and a major gene model) and excluded the general model, non-transmitted model, and environment-only model. A Mendelian additive inheritance model was ultimately the best-fit because it had the lowest Akaike Information Criteria score. CONCLUSION In the Chinese Han population, IE follows a pattern of polygenic Mendelian additive inheritance rather than single-gene inheritance. Nearly half of the total variance can be explained by genetic factors.

Association between Multidrug-Resistant Tuberculosis and Risk Factors in China: Applying Partial Least Squares Path Modeling

Background Multidrug-resistant tuberculosis (MDR-TB) resulting from various factors has raised serious public health concerns worldwide. Identifying the ecological risk factors associated with MDR-TB is critical to its prevention and control. This study aimed to explore the association between the development of MDR-TB and the risk factors at the group-level (ecological risk factors) in China. Methods Data on MDR-TB in 120 counties were obtained from the National Tuberculosis Information Management System, and data on risk-factor variables were extracted from the Health Statistical Yearbook, provincial databases, and the meteorological bureau of each province (municipality). Partial Least Square Path Modeling was used to detect the associations. Results The median proportion of MDR-TB in new TB cases was 3.96% (range, 0–39.39%). Six latent factors were extracted from the ecological risk factors, which explained 27.60% of the total variance overall in the prevalence of MDR-TB. Based on the results of PLS-PM, TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors were all associated with the risk of MDR-TB, but socioeconomic factors were not significant. Conclusions The development of MDR-TB was influenced by TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors. Such information may help us to establish appropriate public health intervention strategies to prevent and control MDR-TB and yield benefits to the entire public health system in China.

Incidence and Simple Prediction Model of Hyperuricemia for Urban Han Chinese Adults: A Prospective Cohort Study

Background: Hyperuricemia (HUA) contributes to gout and many other diseases. Many hyperuricemia-related risk factors have been discovered, which provided the possibility for building the hyperuricemia prediction model. In this study we aimed to explore the incidence of hyperuricemia and develop hyperuricemia prediction models based on the routine biomarkers for both males and females in urban Han Chinese adults. Methods: A cohort of 58,542 members of the urban population (34,980 males and 23,562 females) aged 20–80 years old, free of hyperuricemia at baseline examination, was followed up for a median 2.5 years. The Cox proportional hazards regression model was used to develop gender-specific prediction models. Harrell’s C-statistics was used to evaluate the discrimination ability of the models, and the 10-fold cross-validation was used to validate the models. Results: In 7139 subjects (5585 males and 1554 females), hyperuricemia occurred during a median of 2.5 years of follow-up, leading to a total incidence density of 49.63/1000 person years (64.62/1000 person years for males and 27.12/1000 person years for females). The predictors of hyperuricemia were age, body mass index (BMI) systolic blood pressure, serum uric acid for males, and BMI, systolic blood pressure, serum uric acid, triglycerides for females. The models’ C statistics were 0.783 (95% confidence interval (CI), 0.779–0.786) for males and 0.784 (95% CI, 0.778–0.789) for females. After 10-fold cross-validation, the C statistics were still steady, with 0.782 for males and 0.783 for females. Conclusions: In this study, gender-specific prediction models for hyperuricemia for urban Han Chinese adults were developed and performed well.

Evaluation and screening ultrasonic signs in the diagnosis of fetal biliary cystic malformation

Abstract Objective: To evaluate and screen for fetal biliary cystic malformation (BCM) associated-ultrasonic key signs or sign-combinations. Methods: Thirty cases of fetal abdominal cysts were investigated, followed up and divided into BCM and non-BCM groups. Expression rates of seven fetal BCM-associated ultrasonic signs in the two groups (A: the cyst was located in the right upper quadrant of the abdomen, B: located beneath the porta hepatis, C: having no septum, D: not the gallbladder, E: connected to the gallbladder, F: connected to the hepatic ducts, G: its inferior portion ended in the epigastric region, anterior to the spinal column) were compared. The diagnostic efficacy of single signs and sign-combinations was evaluated by diagnostic test. Results: The expressions of Sign A and Sign D had no statistically significant differences between the two groups. Single sign of B, F and G had diagnostic efficacy. The diagnostic index of B reached 1.8571. The diagnostic index of the sign-combinations B and D, F or G, and E or F or G reached 2.0000. Conclusion: When the fetal cyst was located beneath the porta hepatis and was not the gallbladder, BCM could be diagnosed. Sign G might be another significant ultrasonic sign in BCM prenatal diagnosis.

A Multicity Analysis of the Short-Term Effects of Air Pollution on the Chronic Obstructive Pulmonary Disease Hospital Admissions in Shandong, China

Although there is growing evidence linking chronic obstructive pulmonary disease (COPD) hospital admissions to the exposure to ambient air pollution, the effect can vary depending on the local geography, pollution type, and pollution level. The number of large-scale multicity studies remains limited in China. This study aims to assess the short-term effects of ambient air pollution (PM2.5, PM10, SO2, NO2) on chronic obstructive pulmonary disease hospital admissions from 2015 to 2016, with a total of 216,159 records collected from 207 hospitals in 17 cities all over the Shandong province, east China. Generalized additive models and penalized splines were applied to study the data whilst controlling for confounding meteorological factors and long-term trends. The air pollution was analyzed with 0–6 day lag effects and the percentage change of hospital admissions was assessed for a 10-μg/m3 increase in the air pollution levels. We also examined the percentage changes for different age groups and gender, respectively. The results showed that air pollution was significantly associated with adverse health outcomes and stronger effects were observed for females. The air pollution health effects were also impacted by geographical factors such that the air pollution had weaker health effects in coastal cities.

The long-term spatial-temporal trends and burden of esophageal cancer in one high-risk area: A population-registered study in Feicheng, China

Background Feicheng County is a high-risk area for esophageal cancer in Shandong province, China. It is important to determine the long-term spatio-temporal trends in epidemiological characteristics and the burden of esophageal cancer, especially since the implementation of the national esophageal cancer screening program for early detection and treatment in 2005. Methods The data collected in Feicheng County from 2001 to 2012 was extracted from the whole-population cancer registry system. The incidence, mortality, disability-adjusted life years (DALY) and changing trends in esophageal cancer according to age and sex were calculated and described. Results The incidence rate of esophageal cancer in Feicheng was consistently high, and increased significantly for male, but not for female from 2001 to 2012, according to the joinpoint regression analysis. The highest and lowest yearly crude incidence rates were 160.78 and 95.97 per 100000 for males, and 81.36 and 52.17 per 100000 for females. The highest and lowest crude yearly mortality rates were 122.26 and 94.40 per 100000 for males, and 60.75 and 49.35 per 100000for females. Esophageal squamous cell carcinoma was the main pathology type and the tumor location changed significantly from 2001 to 2012. Overall, the DALY remained roughly stable and was estimated as 11.50 for males and 4.90 for females per 1000 people. The burden was mainly caused by premature death. There is an obvious spatial pattern in the distribution of incidence density and burden. Conclusion Esophageal cancer remains a public health issue in Feicheng County with a high incidence, mortality and disease burden. The incidence and burden have obvious spatial heterogeneity, and further studies should be conducted to identify geographical risk factors for precise local prevention and control measures.