Association between rheumatoid arthritis and autoimmune thyroid disease: evidence from complementary genetic methods.

OBJECTIVES: To assess the causal association of Rheumatoid Arthritis (RA) with Autoimmune thyroid disease (AITD). METHOD: Complementary genetic approaches, including genetic correlation, Mendelian randomization (MR) and colocalization analysis, were conducted to assess the potential causal association between RA and AITD using summary statistics from large-scale genome-wide association studies (GWASs). Various sensitivity analyses had been conducted to assess the robustness and the consistency of the findings. RESULTS: The linkage disequilibrium score regression revealed a shared genetic structure between RA and AITD, with the significant genetic correlation between RA and autoimmune hyperthyroidism and autoimmune hypothyroidism estimated to be 0.3945 (P = 2.83 × 10-6) and 0.2771 (P = 1.04 × 10-6) respectively. The results of MR analysis showed that RA had a positive causal relationship with autoimmune hypothyroidism and autoimmune hyperthyroidism. The odds ratio (OR) were 1.29 (95% CI, 1.17-1.42; P = 1.08 × 10-7) and 1.47 (95% CI, 1.25-1.72; P = 1.85 × 10-6), respectively. In reverse MR analysis, autoimmune hypothyroidism had a positive causal relationship with RA, OR was 1.51 (95% CI, 1.37-1.66; P = 1.10 × 10-16); autoimmune hyperthyroidism had no causal relationship with RA relationship (P = 0.22). Similar results were found using different MR methods. In addition, colocalization analysis suggested that shared causal variants existed between RA and AITD. CONCLUSIONS: Our study suggested a potentially causal effect of genetically predicted RA on autoimmune hyperthyroidism and a bidirectional causal relationship between RA and autoimmune hypothyroidism was also observed with complementary genetic approaches, which supports the importance and necessity of thyroid function screening and monitoring in RA patient management in clinical practice.

Protein-centric omics integration analysis identifies candidate plasma proteins for multiple autoimmune diseases.

It remains challenging to translate the findings from genome-wide association studies (GWAS) of autoimmune diseases (AIDs) into interventional targets, presumably due to the lack of knowledge on how the GWAS risk variants contribute to AIDs. In addition, current immunomodulatory drugs for AIDs are broad in action rather than disease-specific. We performed a comprehensive protein-centric omics integration analysis to identify AIDs-associated plasma proteins through integrating protein quantitative trait loci datasets of plasma protein (1348 proteins and 7213 individuals) and totally ten large-scale GWAS summary statistics of AIDs under a cutting-edge systematic analytic framework. Specifically, we initially screened out the protein-AID associations using proteome-wide association study (PWAS), followed by enrichment analysis to reveal the underlying biological processes and pathways. Then, we performed both Mendelian randomization (MR) and colocalization analyses to further identify protein-AID pairs with putatively causal relationships. We finally prioritized the potential drug targets for AIDs. A total of 174 protein-AID associations were identified by PWAS. AIDs-associated plasma proteins were significantly enriched in immune-related biological process and pathways, such as inflammatory response (P = 3.96 × 10-10). MR analysis further identified 97 protein-AID pairs with potential causal relationships, among which 21 pairs were highly supported by colocalization analysis (PP.H4 > 0.75), 10 of 21 were the newly discovered pairs and not reported in previous GWAS analyses. Further explorations showed that four proteins (TLR3, FCGR2A, IL23R, TCN1) have corresponding drugs, and 17 proteins have druggability. These findings will help us to further understand the biological mechanism of AIDs and highlight the potential of these proteins to develop as therapeutic targets for AIDs.

CoNet: Efficient Network Regression for Survival Analysis in Transcriptome-Wide Association Studies-With Applications to Studies of Breast Cancer.

Transcriptome-wide association studies (TWASs) aim to detect associations between genetically predicted gene expression and complex diseases or traits through integrating genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) mapping studies. Most current TWAS methods analyze one gene at a time, ignoring the correlations between multiple genes. Few of the existing TWAS methods focus on survival outcomes. Here, we propose a novel method, namely a COx proportional hazards model for NEtwork regression in TWAS (CoNet), that is applicable for identifying the association between one given network and the survival time. CoNet considers the general relationship among the predicted gene expression as edges of the network and quantifies it through pointwise mutual information (PMI), which is under a two-stage TWAS. Extensive simulation studies illustrate that CoNet can not only achieve type I error calibration control in testing both the node effect and edge effect, but it can also gain more power compared with currently available methods. In addition, it demonstrates superior performance in real data application, namely utilizing the breast cancer survival data of UK Biobank. CoNet effectively accounts for network structure and can simultaneously identify the potential effecting nodes and edges that are related to survival outcomes in TWAS.

Role of the Gut-Brain Axis in the Shared Genetic Etiology Between Gastrointestinal Tract Diseases and Psychiatric Disorders: A Genome-Wide Pleiotropic Analysis.

Importance: Comorbidities and genetic correlations between gastrointestinal tract diseases and psychiatric disorders have been widely reported, with the gut-brain axis (GBA) hypothesized as a potential biological basis. However, the degree to which the shared genetic determinants are involved in these associations underlying the GBA is unclear. Objective: To investigate the shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders and to identify shared genomic loci, genes, and pathways. Design, Setting, and Participants: This genome-wide pleiotropic association study using genome-wide association summary statistics from publicly available data sources was performed with various statistical genetic approaches to sequentially investigate the pleiotropic associations from genome-wide single-nucleotide variation (SNV; formerly single-nucleotide polymorphism [SNP]), and gene levels and biological pathways to disentangle the underlying shared genetic etiology between 4 gastrointestinal tract diseases (inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, and gastroesophageal reflux disease) and 6 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and anorexia nervosa). Data were collected from March 10, 2021, to August 25, 2021, and analysis was performed from January 8 through May 30, 2022. Main Outcomes and Measures: The primary outcomes consisted of a list of genetic loci, genes, and pathways shared between gastrointestinal tract diseases and psychiatric disorders. Results: Extensive genetic correlations and genetic overlaps were found among 22 of 24 trait pairs. Pleiotropic analysis under a composite null hypothesis identified 2910 significant potential pleiotropic SNVs in 19 trait pairs, with 83 pleiotropic loci and 24 colocalized loci detected. Gene-based analysis found 158 unique candidate pleiotropic genes, which were highly enriched in certain GBA-related phenotypes and tissues, whereas pathway enrichment analysis further highlighted biological pathways primarily involving cell adhesion, synaptic structure and function, and immune cell differentiation. Several identified pleiotropic loci also shared causal variants with gut microbiomes. Mendelian randomization analysis further illustrated vertical pleiotropy across 8 pairwise traits. Notably, many pleiotropic loci were identified for multiple pairwise traits, such as 1q32.1 (INAVA), 19q13.33 (FUT2), 11q23.2 (NCAM1), and 1p32.3 (LRP8). Conclusions and Relevance: These findings suggest that the pleiotropic genetic determinants between gastrointestinal tract diseases and psychiatric disorders are extensively distributed across the genome. These findings not only support the shared genetic basis underlying the GBA but also have important implications for intervention and treatment targets of these diseases simultaneously.

Integrative Analysis of Transcriptome-Wide Association Study and Gene-Based Association Analysis Identifies In Silico Candidate Genes Associated with Juvenile Idiopathic Arthritis.

Genome-wide association study (GWAS) of Juvenile idiopathic arthritis (JIA) suffers from low power due to limited sample size and the interpretation challenge due to most signals located in non-coding regions. Gene-level analysis could alleviate these issues. Using GWAS summary statistics, we performed two typical gene-level analysis of JIA, transcriptome-wide association studies (TWAS) using FUnctional Summary-based ImputatiON (FUSION) and gene-based analysis using eQTL Multi-marker Analysis of GenoMic Annotation (eMAGMA), followed by comprehensive enrichment analysis. Among 33 overlapped significant genes from these two methods, 11 were previously reported, including TYK2 (PFUSION = 5.12 × 10-6, PeMAGMA = 1.94 × 10-7 for whole blood), IL-6R (PFUSION = 8.63 × 10-7, PeMAGMA = 2.74 × 10-6 for cells EBV-transformed lymphocytes), and Fas (PFUSION = 5.21 × 10-5, PeMAGMA = 1.08 × 10-6 for muscle skeletal). Some newly plausible JIA-associated genes are also reported, including IL-27 (PFUSION = 2.10 × 10-7, PeMAGMA = 3.93 × 10-8 for Liver), LAT (PFUSION = 1.53 × 10-4, PeMAGMA = 4.62 × 10-7 for Artery Aorta), and MAGI3 (PFUSION = 1.30 × 10-5, PeMAGMA = 1.73 × 10-7 for Muscle Skeletal). Enrichment analysis further highlighted 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 10 Gene Ontology (GO) terms. Our findings can benefit the understanding of genetic determinants and potential therapeutic targets for JIA.

A Mendelian Randomization Study of the Effect of Tea Intake on Type 2 Diabetes.

Background: The association reported between tea intake and type 2 diabetes (T2D) is inconsistent in previous studies and remains controversial. We aimed to explore the causal relationship between tea intake, T2D, and glycemic traits including hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model of insulin resistance (HOMA-IR) levels. Methods: A 2-sample Mendelian randomization (MR) was performed using summary statistics from large-scale genome-wide association studies of tea intake from the UK Biobank, T2D from the DIAGRAM consortium, and glycemic traits from the Magic consortium. The findings were verified through sensitivity analyses using various MR methods with different model assumptions and by comprehensively evaluating the influence of pleiotropy effects and outliers. Results: With the use of a two-sample MR with inverse variance-weighted method, the odds ratio per unit SD change of tea intake (SD: 2.85 cups/day) for T2D, HbA1c, FPG, FSI, and HOMA-IR levels was 0.949 (95% CI 0.844-1.067, p = 0.383), 0.994 (95% CI 0.975-1.013, p = 0.554), 0.996 (95% CI 0.978-1.015, p = 0.703), 0.968 (95% CI 0.948-0.986, p = 0.001), and 0.953 (95% CI 0.900-1.009, p = 0.102), respectively. The results were consistent with those of the other six methods that we used with different model assumptions, suggesting that the findings were robust and convincing. We also performed various sensitivity analyses for outlier removal, pleiotropy detection, and leave-one-out analysis. Conclusion: Our MR results did not support the causal effect of tea intake on T2D and crucial glycemic traits. These findings suggest that previous observational studies may have been confounded.

Regular Physical Activities and Related Factors among Middle-Aged and Older Adults in Jinan, China: A Cross-Sectional Study.

The objective of this study was to investigate the prevalence of regular physical activity (RPA) among middle-aged and older adults in urban communities in Jinan, China, and to identify the factors related to RPA. A cross-sectional survey was conducted among middle-aged and elderly urban residents. A total of 1406 participants were included in the final data analysis. The results of the four models consistently showed that the relevant factors of RPA were educational level, previously diagnosed hypertension (PDH) and depression. In terms of educational level, compared with illiteracy, from the first model to the fourth model, the odds ratios (ORs) and 95% confidence intervals (CIs) of senior middle school were 2.072 (1.418, 3.026), 2.072 (1.418, 3.026), 1.905 (1.289, 2.816) and 1.926 (1.302, 2.848), respectively, and the ORs and 95% CIs of college or above were 2.364 (1.462, 3.823), 2.364 (1.462, 3.823), 2.001 (1.208, 3.312) and 2.054 (1.239, 3.405). In terms of PDH, compared with those with PDH, from the first model to the fourth model, ORs and 95% CIs of non-PDH were 1.259 (1.003, 1.580), 1.259 (1.003, 1.580), 1.263 (1.006, 1.585) and 1.261 (1.004, 1.584), respectively. For depression, compared with those without depression, also from the first model to the fourth model, ORs and 95% CIs of depression were 0.702 (0.517, 0.951), 0.702 (0.517, 0.951), 0.722 (0.532, 0.981) and 0.719 (0.529, 0.977), respectively. In conclusion, the results of this study showed that participation in RPA among middle-aged and older adults in Jinan urban communities was significantly associated with education level, PDH and depression.

Relationship between Lipid Profiles and Glycemic Control Among Patients with Type 2 Diabetes in Qingdao, China.

Glycosylated hemoglobin (HbA1c) was the best indicator of glycemic control, which did not show the dynamic relationship between glycemic control and lipid profiles. In order to guide the health management of Type 2 diabetes (T2D), we assessed the levels of lipid profiles and fasting plasma glucose (FPG) and displayed the relationship between FPG control and lipid profiles. We conducted a cross-sectional study that included 5822 participants. Descriptive statistics were conducted according to gender and glycemic status respectively. Comparisons for the control of lipid profiles were conducted according to glycemic control. Four logistic regression models were generated to analyze the relationship between lipid profiles and glycemic control according to different confounding factors. The metabolic control percentage of FPG, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) was 27.50%, 73.10%, 28.10%, 64.20% and 44.80% respectively. In the fourth model with the most confounding factors, the odds ratios (ORs) and 95% confidence intervals (CIs) of TG, TC, LDL-C and HDL-C were 0.989 (0.935, 1.046), 0.862 (0.823, 0.903), 0.987 (0.920, 1.060) and 2.173 (1.761, 2.683). TC and HDL-C were statistically significant, and TG and LDL-C were not statistically significant with adjustment for different confounding factors. In conclusion, FPG was significantly associated with HDL and TC and was not associated with LDL and TG. Our findings suggested that TC and HDL should be focused on in the process of T2D health management.

Trajectories of Haemoglobin and incident stroke risk: a longitudinal cohort study.

BACKGROUND: Studies have demonstrated that high or low haemoglobin increases the risk of stroke. Previous studies, however, performed only a limited number of haemoglobin measurements, while there are dynamic haemoglobin changes over the course of a lifetime. This longitudinal cohort study aimed to classify the long-term trajectory of haemoglobin and examine its association with stroke incidence. METHODS: The cohort consisted of 11,431 participants (6549 men) aged 20 to 50 years whose haemoglobin was repeatedly measured 3-9 times during 2004-2015. A latent class growth mixture model (LCGMM) was used to classify the long-term trajectory of haemoglobin concentrations, and hazard ratios (HRs) and 95% confidence intervals (95% CI) according to the Cox proportional hazard model were used to investigate the association of haemoglobin trajectory types with the risk of stroke. RESULTS: Three distinct trajectory types, high-stable (n = 5395), normal-stable (n = 5310), and decreasing (n = 726), were identified, with stroke incidence rates of 2.7, 1.9 and 3.2 per 1000 person-years, respectively. Compared to the normal-stable group, after adjusting for the baseline covariates, the decreasing group had a 2.94-fold (95% CI 1.22 to 7.06) increased risk of developing stroke. Strong evidence was observed in men, with an HR (95% CI) of 4.12 (1.50, 11.28), but not in women (HR = 1.66, 95% CI 0.34, 8.19). Individuals in the high-stable group had increased values of baseline covariates, but the adjusted HR (95% CI), at 1.23 (0.77, 1.97), was not significant for the study cohort or for men and women separately. CONCLUSIONS: This study revealed that a decreasing haemoglobin trajectory was associated with an increased risk of stroke in men. These findings suggest that long-term decreasing haemoglobin levels might increase the risk of stroke.

A Cross Sectional Examination of the Relation Between Depression and Frequency of Leisure Time Physical Exercise among the Elderly in Jinan, China.

Depression has become a major global public health problem. Many studies have shown the positive effects of physical exercise on depression. However, few studies have examined the relationship between frequency of leisure time physical exercise and depression without considering the time and intensity of exercise among middle-aged and elderly people of urban communities in northern China. We conducted a cross-sectional survey that included 1604 participants among urban residents aged 50 years or older in China to evaluate how the frequency of physical exercise was related to depression. Our study showed that the prevalence of depression in the urban community of Jinan is 16.52%. For physical exercise, the odds ratios (ORs) and 95% confidence intervals (CIs) for 1~2 times per week, 3~4 times per week and ≥5 times per week were 1.137 (0.661, 1.953), 0.516 (0.304, 0.875) and 0.548 (0.392, 0.768) respectively, with adjustment for age, gender, marital status, BMI, hypertension, previously diagnosed type 2 diabetes, triglyceride, total cholesterol, soy food intake, milk food intake, vegetable and fruit intake and meat intake. We concluded that physically exercising three times a week is associated with a low prevalence of depression.

Genetic polymorphisms of IL-18 rs1946518 and IL-1ß rs16944 are associated with prognosis and survival of acute myeloid leukemia.

BACKGROUND: Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS: We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1ß (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1ß (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival. CONCLUSION: IL-1ß (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.

Association between obesity indices and type 2 diabetes mellitus among middle-aged and elderly people in Jinan, China: a cross-sectional study.

BACKGROUND: The relationship between obesity and type 2 diabetes mellitus (T2DM) varies with geographical area and race. OBJECTIVES: To investigate the prevalence of T2DM and the proportion of subjects with undiagnosed T2DM. In addition, to compare the associations between different obesity indices and T2DM for middle-aged and elderly people from six communities in Jinan, China. SETTING: A cross-sectional study was designed and the study subjects were chosen from blocks which were randomly selected in the 6 communities of Jinan, China in 2011-2012. PARTICIPANTS: A total of 3277 residents aged ≥50 years were eligible for this study, but 1563 people were excluded because they did not provide anthropometric data such as height, weight, waist circumference (WC), hip circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglyceride (TG), total cholesterol (TC) or information about their current medication use. Hence, 1714 participants were included in the final data analysis. RESULTS: The prevalence of T2DM among people aged ≥50 years was 16.6% (19.3% for men and 15.3% for women) and the proportion of patients with undiagnosed T2DM was 32.7%. Compared with the lowest levels of body mass index (BMI), WC, waist-to-hip ratio or waist-to-stature ratio (WSR), the ORs and 95% CIs of the highest levels for men, after adjusting for age, smoking, alcohol drinking, regular exercise, hypertension, TG and TC, were 1.607 (0.804 to 3.210), 2.189 (1.118 to 4.285), 1.873 (0.968 to 3.623) and 2.572 (1.301 to 5.083), respectively, and for women, 2.764 (1.622 to 4.712), 2.407 (1.455 to 3.985), 2.500 (1.484 to 4.211) and 2.452 (1.447 to 4.155), respectively. CONCLUSIONS: Among adults aged ≥50 years in Jinan, China, the best indicator of the relationship between obesity and T2DM is WSR for men and BMI for women, respectively.

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.

Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma.

Although cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC), the association between cholecystectomy and prognosis of HCC patients underwent curative resection has never been examined. Through retrospective analysis of the data of 3933 patients underwent curative resection for HCC, we found that cholecystectomy was an independent prognostic factor for recurrence-free survival (RFS) of patients at early stage (BCLC stage 0/A) (p = 0.020, HR: 1.29, 95% CI: 1.04-1.59), and the 1-, 3-, 5-year RFS rates for patients at early stage were significantly worse in cholecystectomy group than in non-cholecystectomy group (80.5%, 61.8%, 52.0% vs 88.2%, 68.8%, 56.8%, p = 0.033). The early recurrence rate of cholecystectomy group was significantly higher than that of non-cholecystectomy group for patients at early stage (59/47 vs 236/333, p = 0.007), but not for patients at advanced stage (BCLC stage C) (p = 0.194). Multivariate analyses showed that cholecystectomy was an independent risk factor for early recurrence (p = 0.005, HR: 1.52, 95% CI: 1.13-2.03) of early stage HCC, but not for late recurrence (p = 0.959). In conclusion, cholecystectomy is an independent predictor for early recurrence and is associated with poorer RFS of early stage HCC. Removal of normal gallbladder during HCC resection may be avoided for early stage patients.

Positive HBcAb is associated with higher risk of early recurrence and poorer survival after curative resection of HBV-related HCC.

BACKGROUND & AIMS: Previous studies predicted the prognosis of hepatocellular carcinoma (HCC) mainly based on tumour-related factors, whereas the impacts of hepatitis B virus (HBV)-related factors are usually ignored. The objective of this exploratory study was to investigate the prognostic role of hepatitis B core antibody (HBcAb) on post-operative survival and recurrence of HCC. METHODS: A retrospective analysis of 3388 HBsAg positive (HBV-related) HCC patients treated by curative resection was performed. Multivariate analysis of independent prognostic factors was performed by Cox proportional hazards regression model. RESULTS: HBcAb positivity was an independent prognostic factor for recurrence-free survival (RFS) of HBV-related patients (P < 0.001, HR: 1.723, 95% CI: 1.278-2.324), and the 1-, 3-, 5-year RFS rates for HBcAb-negative patients were significantly better than those of HBcAb-positive patients (92.5%, 72.1% and 65.9% vs 77.9%, 58.6% and 46.9%, P < 0.001). HBcAb-positive HCC was much bigger (P = 0.006), more often involved with vascular invasion (P = 0.001), elevated AFP (P = 0.001) and ALT (P = 0.046) levels, but less often involved with capsule formation (P = 0.034). Besides vascular invasion, tumour size, interferon-α treatment, AFP and GGT level, HBcAb positivity was an independent prognostic factor for early intrahepatic recurrence of HBV-related patients (P = 0.025, HR: 1.766, 95% CI: 1.073-2.907) and the majority of HBcAb-positive recurrence were early recurrence while most of HBcAb-negative recurrence were late recurrence (P = 0.004). CONCLUSION: Positive HBcAb may represent a more invasive phenotype of HBV-related HCC, and is associated with a higher risk of early intrahepatic recurrence and poorer RFS of HBV-related patients after curative resection.

A novel quantitative body shape score for detecting association between obesity and hypertension in China.

BACKGROUND: Obesity is a major independent risk factor for chronic diseases such as hypertension and coronary diseases, it might not be only related to the amount of body fat but its distribution. The single body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) or waist to stature ratio (WSR) provides limited information on fat distribution, and the debate about which one is the best remained. On the other hand, the current classification of body shape is qualitative rather than quantitative, and only crudely measure fat distribution. Therefore, a synthetical index is highly desirable to quantify body shape. METHODS: Based on the China Health and Nutrition Survey (CHNS) data, using Lohmäller PLSPM algorithm, six Partial Least Squares Path Models (PLSPMs) between the different obesity measurements and hypertension as well as two synthetical body shape scores (BSS1 by BMI/WC/Hip circumference, BSS2 by BMI/WC/WHR/WSR) were created. Simulation and real data analysis were conducted to assess their performance. RESULTS: Statistical simulation showed the proposed model was stable and powerful. Totally 15,172 (6,939 male and 8,233 female) participants aged from 18 to 87 years old were included. It indicated that age, height, weight, WC, WHR, WSR, SBP, DBP, the prevalence of hypertension and obesity were significantly sex-different. BMI, WC, WHR, WSR, Hip, BSS1 and BSS2 between hypertension and normotensive group are significantly different (p < 0.05). PLSPM method illustrated the biggest path coefficients (95% confidence interval, CI) were 0.220(0.196, 0.244) for male and 0.205(0.182, 0.228) for female in model of BSS1. The area under receiver-operating characteristic curve (AUC(95% CI)) of BSS1(0.839(0.831,0.847)) was significantly larger than that of BSS2(0.834(0.825,0.842)) as well as the four single indices for female, and similar trend can be found for male. CONCLUSIONS: BSS1 was an excellent measurement for quantifying body shape and detecting the association between body shape and hypertension.

Obesity and its relationship with hypertension among adults 50 years and older in Jinan, China.

BACKGROUND: The relationship between obesity and hypertension varies with geographical area, race and definitions of obesity. Our study aimed to investigate the prevalence of obesity using standard Chinese criteria based on the body mass index (BMI) and the waist circumference (WC) and to examine the association between obesity and hypertension among middle-aged and elderly people in Jinan city. METHODS: This cross-sectional study examined 1,870 subjects from the blocks randomly selected from among the 6 communities of Jinan, China in 2011-2012. The Student's t-test was used to compare numerical data, and the χ2 test was used to compare categorical data. Multivariate logistic regression analyses were performed to assess the effects of general and central obesity on hypertension after adjusting for age or for education level, smoking, alcohol consumption, and continuous age. RESULTS: The prevalence of general obesity among people age 50 years and older was 21.1% (17.0% for males and 23.1% for females), and the prevalence of central obesity was 77.8% for men and 78.7% for women. For men, compared with a normal BMI, the ORs and 95% CIs for overweight and general obesity were 1.853 (1.252, 2.744) and 3.422 (1.894, 6.182), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.334 (1.573, 3.465) and 2.318 (1.544, 3.479), respectively, for men. For women, compared with a normal BMI, the ORs and 95% CIs were 1.942 (1.473, 2.599) and 4.011 (2.817, 5.712), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.488 (1.865, 3.319) and 2.379 (1.773, 3.192), respectively, for women. CONCLUSIONS: The relationship between hypertension and general obesity was stronger than the relationship between hypertension and either overweight or central obesity in both genders.

Chronic diseases knowledge and related factors among the elderly in Jinan, China.

BACKGROUND: It has been reported that the prevalence of chronic diseases is high among old people and they have poor chronic diseases knowledge. This study was therefore designed to evaluate the awareness rate of chronic diseases knowledge among people aged over 60 years, to explore its related factors and to provide evidence for future health education. METHODS: A cross-sectional study was conducted from April to August in 2011. People aged 60 years and above from 3 communities in Jinan were selected by cluster sampling. Nine hundred and twenty five participants were interviewed face-to-face using a structured questionnaire. RESULTS: The awareness rates of chronic diseases knowledge varied from 29.5% to 90.2%. Four healthy lifestyles including quitting smoking and less drinking, keeping broad-minded, maintaining balanced diet and moderate physical activity were best known (from 86.3% to 90.2%). The least known knowledge were 2 complications of hypertension: nephropathy (29.5%) and retinopathy (37.2%). Participants with the following characteristics or behaviors were more likely to have higher chronic diseases knowledge: younger age, female, Han Chinese, higher level of education, having health insurance, participating in societies, having family history of chronic diseases, frequently gathering with friends/relatives, usually going to provincial hospitals/hospitals affiliated with medical universities, usually going to municipal hospitals and usually going to community health center/station. CONCLUSIONS: Old people in Jinan had incomplete chronic diseases knowledge and the overall awareness rate was not high. The older people's chronic diseases knowledge should be improved and health education programs should target males, older people with lower educational level, having no health insurance, having no family history of chronic diseases, participating in no societies, and less frequently gathering with friends/relatives. Also, lower level medical facilities should improve their skills of health education.

[Chromosomal aberrations in chronic lymphocytic leukemia by interphase fluorescence in situ hybridization and their association with clinical features].

This study was aimed to investigate the common chromosomal aberrations in chronic lymphocytic leukemia (CLL) and to explore the relationship between these chromosomal aberrations and clinical features of CLL. Sequence-specific DNA probes (D13S25, RB1, p53, ATM) and one centromeric probe CSP12 were applied to detect del(13q14), del(17p13), del(11q22-q23) and trisomy 12 by using interphase fluorescence in situ hybridization (I-FISH). 9 CLL patients with negative conventional cytogenetics or without mitotic figure were enrolled in this study. The threshold was established using 10 controls without hematopoietic malignancies. The results indicated that compared with the established threshold, all of the 9 CLL patients showed cytogenetic abnormalities. The detection using p53 and D13S25 showed positive in 7 cases, positive was observed in 5 cases by using ATM and in 4 cases by using both RB1 and CSP12. There was significant correlation between the ATM and the hemoglobin level of the patients. In addition, the elevated probability of gaining bulky lymphadenopathy was found in ATM positive patients. It is concluded that the I-FISH is a more rapid and sensitive technique for analysis of chromosome aberrations in CLL. A large series study with long-term follow-up is needed to reveal the role of cytogenetic abnormalities in the determination of CLL prognosis.

Seroprevalence and risk factors of human cytomegalovirus infection in the eastern Chinese population.

Epidemiology and clinical outcomes of human cytomegalovirus (HCMV) infection are known to vary between countries and are associated with socio-economic background. So far, few data are available from developing countries, where the overall burden of infectious diseases is frequently higher. Therefore, we analyzed the seroprevalence in a population of 3,740 individuals selected randomly from eastern China, aiming to determine the seroprevalence of and risk factors for HCMV infection. The overall seroprevalence was 48.07%, higher in the socioeconomically developing inland districts than in the developed forelands. The seroprevalence in females (54.60%) was significantly higher than that in males (41.58%) (P < 0.001). As for profession, peasants (61.54%) and doctors (68.48%) had a higher seropositive rate than members of other professions (P < 0.0001). A significant association between seroprevalence and increasing age was identified (P < 0.05). Our study might help to identify appropriate populations on which to focus for future HCMV vaccination.