Associations of serum aminotransferase and the risk of all-cause and cause-specific mortality in Chinese type 2 diabetes: a community-based cohort study.

OBJECTIVE: Investigating the associations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of community-dwelling patients with type 2 diabetes mellitus (T2DM). DESIGN: Community-based prospective cohort study conducted between 2013 and 2014. SETTING: 44 selected townships in Changshu and Huai'an City, Jiangsu province, China. PARTICIPANTS: 20340 participants with T2DM were recruited in Jiangsu province, China. METHODS: We use Cox proportional hazard models to estimate the HR and 95% CIs of associations of serum ALT and AST levels with all-cause and cause-specific mortality. Restricted cubic splines were used to explore the dose-response relationships between ALT and AST levels with mortality. RESULTS: ALT and AST levels were inversely associated with CVD mortality, compared with the lowest quintile (Q1), the multivariable HRs of the highest quintile (Q5) was 0.82 (95% CI: 0.66 to 1.01, p for trend=0.022) and 0.78 (95% CI: 0.63 to 0.96, p for trend=0.022), respectively. Furthermore, the HRs for ALT levels in all-cause mortality were 0.90 (95% CI: 0.79 to 1.01, p for trend=0.018), and the HRs for AST levels in cancer mortality were 1.29 (95% CI: 1.02 to 1.63, p for trend=0.023). Stronger inverse effects of ALT and AST levels on all-cause mortality were observed in the older subgroup and in those with dyslipidaemia (all p for interaction <0.05). Further analysis based on gender showed that the associations between serum aminotransferases and the mortality risk were more significant in women and substantially attenuated in men. CONCLUSION: Our findings suggested patients with T2DM with lower levels of ALT and AST had an increased risk of CVD mortality, which needs confirmation in future clinical trials.

Association of gamma-glutamyl transferase concentrations with all-cause and cause-specific mortality in Chinese adults with type 2 diabetes.

BACKGROUND: Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. METHODS: We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. RESULTS: During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m2 group and those without dyslipidemia. CONCLUSIONS: Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.

Mediating effect of BMI on the relation of dietary patterns and glycemic control inT2DM patients: results from China community-based cross-sectional study.

OBJECTIVE: To analyze the effects of different dietary types on in type 2 diabetes mellitus (T2DM) and determine the mediating effects of Body Mass Index (BMI) on dietary type with Fasting Plasma Glucose (FPG), Glycosylated Hemoglobin (HbA1c) on the associations in T2DM. METHODS: Data of community-based cross-sectional study with 9602 participants including 3623 men and 5979 women were collected from the project 'Comprehensive Research in prevention and Control of Diabetes mellitus (CRPCD)' conducted by Jiangsu Center for Disease Control and Prevention in 2018. The dietary data were collected from a food frequency qualitative questionnaire (FFQ) and dietary patterns were derived through Latent Class Analysis (LCA). Then, Logistics regression analyses were used to evaluate the associations of FPG, HbA1c with different dietary patterns. The BMI (BMI = height/weight2) was used as a moderator to estimate the mediating effect. Mediation analysis was performed using hypothetical variables, the mediation variables, to identify and explain the observed mechanism of association between the independent and dependent variables while the moderation effect was tested with multiple regression analysis with interaction terms. RESULTS: After completing Latent Class Analysis (LCA), the dietary patterns were divided into three categories: TypeI, TypeII, TypeIII. After adjusting for confounding factors such as gender, age, education level, marital status, family income, smoking, drinking, disease course, HDL-C, LDL-C, TC, TG, oral hypoglycemic drugs, insulin therapy, Hypertension, Coronary heart disease, Stroke, Type III were all significantly associated with HbA1c compared to those with Type I (P < 0.05), and the research showed the patients with Type III had High glycemic control rate. Taking type I as the reference level, the 95% Bootstrap confidence intervals of the relative mediating effect of TypeIII on FPG were (-0.039, -0.005), except 0, indicating that the relative mediating effect was significant (αIII = 0.346*, ßIIIFPG = -0.060*). The mediating effect analysis was performed to demonstrate that BMI was used as a moderator to estimate the moderation effect. CONCLUSIONS: Our findings demonstrate that consuming Type III dietary patterns associates with good glycemic control in T2DM and the BMI associations would be playing a two-way effect between diet and FPG in Chinese population with T2DM, indicated that Type III could not only directly affect FPG, but also affect FPG through the mediating effect of BMI.

LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC. METHODS: The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2. RESULTS: RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. CONCLUSIONS: Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.

Association between dietary patterns and stroke in patients with type 2 diabetes mellitus in China: a propensity score-matched analysis.

OBJECTIVE: This study aimed to examine the impact of different dietary patterns on stroke outcomes among type 2 diabetes mellitus (T2DM) patients in China. DESIGN: Participants were enrolled by a stratified random cluster sampling method in the study. After collecting dietary data using a quantified food frequency questionnaire, latent class analysis was used to identify dietary patterns, and propensity score matching was used to reduce confounding effects between different dietary patterns. Binary logistic regression and conditional logistic regression were used to analyze the relationship between dietary patterns and stroke in patients with T2DM. SETTING: A cross-sectional survey available from December 2013 to January 2014. PARTICIPANTS: A total of 13731 Chinese residents aged 18 years or over. RESULTS: Two dietary patterns were identified: 61.2% of T2DM patients were categorized in the High-fat dietary pattern while 38.8% of patients were characterized by the Balanced dietary pattern. Compared to the High-fat dietary pattern, the Balanced dietary pattern was associated with reduced stroke risk (OR=0.63, 95%CI: 0.52-0.76, P<0.001) after adjusting for confounding factors. The protective effect of the balanced model did not differ significantly (interaction P>0.05). CONCLUSION: This study provides sufficient evidence to support the dietary intervention strategies to prevent stroke effectively. Maintaining a Balanced dietary pattern, especially with moderate consumption of foods rich in quality protein and fresh vegetables in T2DM patients, might decrease the risk of stroke in China.

Fresh fruit consumption, physical activity, and five-year risk of mortality among patients with type 2 diabetes: A prospective follow-up study.

BACKGROUND AND AIMS: We explored the associations among fruit consumption, physical activity, and their dose-response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients. METHODS AND RESULTS: We prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21-94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose-response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64-0.88), CVD mortality (HR 0.69, 0.51-0.94) and stroke mortality (HR 0.57, 0.36-0.89), but not with heart disease mortality (HR 0.93, 0.56-1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37-0.53) for all-cause mortality, 0.46 (0.33-0.64) for CVD mortality, 0.46 (0.29-0.74) for stroke mortality and 0.51 (0.29-0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease. CONCLUSIONS: Fruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.

Infection with Human Papillomavirus 18 Promotes Alkylating Agent-Induced Malignant Transformation in a Human Esophageal Cell Line.

The relationship between human papillomavirus (HPV) and esophageal cancer (EC) has been controversial, which may be caused by the difference in geographic regions of sample origin. Thus, we conducted a case-control study to find that HPV increased the risk of esophageal cancer, and the HPV18 detection rate is the highest (24.2%) among patients with EC, suggesting that HPV18 could be the most risk subtype of HPV infected. We then identified high-risk HPV18 and N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) to establish a model on the viral etiology cooperating with environmental carcinogens. Het-1A cells containing HPV18 were continuously exposed to MNNG or not; then the morphological phenotype and function assays were performed in 25th passage cells. MNNG promoted the proliferation and invasion abilities and inhibited apoptosis both in Het-1A-HPV18 and control group. However, the Het-1A-HPV18 had a stronger change in phenotypic features and formed more transformed foci in soft agar. Further, Western blot found p53 and p21 were down-regulated, and expression of c-Myc, MMP-2, and MMP-9 and Bcl-2/Bax ratio were up-regulated. Our results revealed that MNNG was easier to induce malignant transformation of Het-1A cells transfected with HPV18. It is good evidence for the close relationship between HPV and the etiology of EC, providing foundation for further study in molecular mechanism and specific intervention targets.

Factors associated with stroke among patients with type 2 diabetes mellitus in China: a propensity score matched study.

OBJECTIVE: This study aimed to examine the prevalence of stroke and associated factors of stroke in patients with type 2 diabetes(T2DM) in China. METHODS: Participants were 18,013 T2DM patients recruited with stratified random cluster sampling method from December 2013 to January 2014 in China. Propensity score matching was used to eliminate confounding effects between groups and logistic regression analysis was used to examine factors associated with stroke among T2DM patients. RESULTS: Overall, the prevalence of stroke in the subjects with T2DM was 9.5%. After nearest neighbor matching, smoking (OR = 1.60, 95%CI: 1.26-2.03), hypertension (OR = 2.96, 95%CI: 2.55-3.43), dyslipidemia (OR = 2.00, 95%CI: 1.71-2.33), family history of stroke (OR = 2.02, 95%CI: 1.61-2.54), obesity (OR = 1.21, 95%CI: 1.01-1.45) and sleep duration < 6 h/day (OR = 1.44, 95%CI: 1.20-1.73) or > 8 h/day (OR = 1.22, 95%CI: 1.05-1.42) were positively associated with stroke, whereas drinking 1-3 days/week (OR = 0.64, 95%CI: 0.45-0.90) or daily (OR = 0.45, 95%CI: 0.33-0.60), effective exercise (OR = 0.65, 95%CI: 0.57-0.73) and underweight (OR = 0.30, 95%CI: 0.13-0.71) were negatively related to stroke. Besides, the risk of stroke increased substantially with accumulation of above seven modified risk factors. The odds ratio values of stroke in patients having ≥ 5 of the above seven risk factors was 14.39 (95% CI: 8.87-23.26). CONCLUSIONS: The prevalence of stroke was high among T2DM in China. It is of great significance to strengthen comprehensive management of health-related behaviors including smoking cessation, moderate alcohol consumption, effective exercise, 6-8 h of sleep duration, keeping normal weight and the prevention of hypertension and dyslipidemia to have sustained beneficial effects on improvements of stroke risk factors.

COVID-19 outbreak following a single patient exposure at an entertainment site: An epidemiological study.

We investigated an outbreak of COVID-19 infection, which was traced back to a bathing pool at an entertainment venue, to explore the epidemiology of the outbreak, understand the transmissibility of the virus and analyse the influencing factors. Contact investigation and management were conducted to identify potential cases. Epidemiological investigation was carried out to determine the epidemiological and demographic characteristics of the outbreak. We estimated the secondary attack rate (SAR), incubation time and time-dependent reproductive number (Rt ) and explored the predisposing factors for cluster infection. The incubation time was 5.4 days and the serial interval (SI) was 4.4 days, with the rate of negative-valued SIs at 24.5%. The SAR at the bathing pool (3.3%) was relatively low due to its high temperature and humidity. The SAR was higher in the colleagues' cluster (20.5%) than in the family cluster (11.8%). Super-spreaders had a longer isolation delay time (p = .004). The Rt of the cluster decreased from the highest value of 3.88 on January 27, 2020 to 1.22 on February 6. Our findings suggest that the predisposing factors of the outbreak included close contact with an infected person, airtight and crowded spaces, temperature and humidity in the space and untimely isolation of patients and quarantine of contacts at the early stage of transmission. Measures to reduce the risk of infection at these gatherings and subsequent tracking of close contacts were effective.

Synergism of HPV and MNNG repress miR-218 promoting Het-1A cell malignant transformation by targeting GAB2.

Dysregulation of microRNAs (miRNAs) is induced during tumorigenesis. Our previous research suggested that HPV and MNNG led to malignant transformation of esophageal epithelial cells. To investigate the regulation and function of miR-218(miR-218-5p) during the malignant transformation of esophageal epithelial cells, we found miR-218 was inhibited synergistically by HPV and MNNG, suppressing cell proliferation, migration and invasion by up-regulating 3' untranslated region (3'UTR) GAB2 in Het-1A-HPV-MNNG cells (malignant Het-1A cells induced by HPV and MNNG). A negative correlation was found between miR-218 and GAB2 mRNA expression in esophageal cancer patients and control people. GAB2 was up-regulated in Het-1A-HPV-MNNG cells. Further, down-expression of GAB2 reversed HPV&MNNG-mediated activation of migration and invasion and repressed SHP2/ERK and Akt/mTOR pathway signaling. In conclusion, miR-218 partially accounts for the prevention effect during malignant transformation of normal esophageal epithelial cells, which targets GAB2, which supplies the potential treatment in cancer therapy.

Urinary exposure of N-nitrosamines and associated risk of esophageal cancer in a high incidence area in China.

Esophageal cancer (EC) is a deadly malignancy worldwide with a high incidence and exhibits unevenly geographic prevalence, which suggests that environmental factors are deeply involved in the development of EC. Although the carcinogenesis of nitrosamines in the esophagus has been identified by tremendous toxicological data, the role of nitrosamines in the genesis of human EC has so far proved inconclusive largely due to a lack of convincing evidences. In this study, urinary nitrosamines in population controls and cases with esophageal precancerous lesions, including reflux esophagitis (RE) accompanying with basal cell hyperplasia (BCH) and dysplasia (DYS), and esophageal squamous cell carcinoma (ESCC) were detected by a SPE-LC-MS/MS method and the associated risk was evaluated. Higher excretion concentrations of N-nitrosomethylethylamine (NMEA) in the RE/BCH patients, NMEA and N-nitrosodibutylamine (NDBA) in the DYS patients, and NMEA, NDBA, N-nitrosopyrrolidine (NPyr) and N-nitrosomorpholine (NMor) in the ESCC patients were observed compared with the controls (p < .05). And with the progression of esophageal lesion, the exposure complexity increased in terms of the categories of nitrosamines. Furthermore, the observed positive associations between the hazardous exposure of NMEA, NDBA and NPyr and the increased risk of ESCC, and between NMEA and NDBA and RE/BCH were established. These findings provided direct evidence to support the hypothesis that exposure to nitrosamines are involved in the carcinogenesis of esophageal epithelia in this high incidence area from the perspective of endogenous exposure assessment. However, discoveries in this study need to be confirmed by systematic researches in the future. And the dose-response relationships, the reference ranges or cutoff values to predict the risks of nitrosamines exposure also need to be defined.

Physical activity, sedentary time and their associations with clustered metabolic risk among people with type 2 diabetes in Jiangsu province: a cross-sectional study.

OBJECTIVE: Investigating the association between total physical activity, physical activity in different domains and sedentary time with clustered metabolic risk in patients with type 2 diabetes from Jiangsu province, China. DESIGN: Interview-based cross-sectional study conducted between December 2013 and January 2014. SETTING: 44 selected townships across two cities, Changshu and Huai'an, in Jiangsu province. PARTICIPANTS: 20 340 participants selected using stratified cluster-randomised sampling and an interviewer-managed questionnaire. METHODS: We constructed clustered metabolic risk by summing sex-specific standardised values of waist circumference, fasting triacylglycerol, fasting plasma glucose, systolic blood pressure and the inverse of blood high-density lipoprotein cholesterol (HDL-cholesterol). Self-reported total physical activity included occupation, commuting and leisure-time physical activity. The un-standardised regression coefficient [B] and its 95% CI were calculated using multivariate linear regression analyses. RESULTS: This study included 17 750 type 2 diabetes patients (aged 21-94 years, 60.3% female). The total (B=-0.080; 95% CI: -0.114 to -0.046), occupational (B=-0.066; 95% CI: -0.101 to- 0.031) and leisure-time physical activity (B=-0.041; 95% CI: -0.075 to -0.007), and sedentary time (B=0.117; 95% CI: 0.083 to 0.151) were associated with clustered metabolic risk. Total physical activity, occupational physical activity and sedentary time were associated with waist circumference, triacylglycerol and HDL-cholesterol, but not with systolic blood pressure. Commuting physical activity and sedentary time were significantly associated with triacylglycerol (B=-0.012; 95% CI: -0.019 to -0.005) and fasting plasma glucose (B=0.008; 95% CI: 0.003 to 0.01), respectively. Leisure-time physical activity was only significantly associated with systolic blood pressure (B=-0.239; 95% CI: -0.542 to- 0.045). CONCLUSIONS: Total, occupational and leisure-time physical activity were inversely associated with clustered metabolic risk, whereas sedentary time increased metabolic risk. Commuting physical activity was inversely associated with triacylglycerol. These findings suggest that increased physical activity in different domains and decreased sedentary time may have protective effects against metabolic risk in type 2 diabetes patients.

ACTB Variants Confer the Genetic Susceptibility to Diabetic Kidney Disease in a Han Chinese Population.

Beta-actin (ACTB) loss-of-function mutations result in a pleiotropic developmental disorder of kidney. The present study aims to explore whether the common variants at the ACTB gene contribute to diabetic kidney disease (DKD) susceptibility in patients with type 2 diabetes mellitus (T2DM). From the baseline population of 20,340 diabetic patients, 1,510 DKD cases and 1,510 age-matched T2DM controls were selected. All subjects were Han Chinese. Three tagging single nucleotide polymorphisms (SNPs), rs852423, rs852426, and rs2966449, at the ACTB gene were genotyped. Logistic regression was performed to estimate the association with DKD. SNPs, rs852426 and rs2966449, were significantly associated with DKD [additive model; odds ratio (OR), 1.217 and 1.151; P = 0.001 and 0.018, respectively]. The association of rs852426 with DKD still remained statistically significant after Bonferroni correction and particularly significant in the population older than 70 years rather than the 70 years or younger (P = 0.047 for heterogeneity test). Furthermore, the association of rs852426 with DKD was observed in populations of male and females without smoking, drinking, and with duration for T2DM 10-20 years. The association of rs2966449 with DKD was also found in the populations older than 70 years, male, not smoking, not drinking, and with duration for T2DM over 20 years. The estimated glomerular filtration rate (eGFR) levels of the individuals with TT or CC genotypes of rs2966449 were significantly lower than that of TC genotype in DKD cases (P = 0.021). The present study provides evidence that the ACTB variants, i.e., rs852426 and rs2966449, may confer the genetic susceptibility to DKD in a Han Chinese population.

Distribution of N-nitrosamines in drinking water and human urinary excretions in high incidence area of esophageal cancer in Huai'an, China.

The Huai'an area in Jiangsu Province of East China is an endemic region of esophageal cancer (EC). The regional heterogeneity of EC suggests that the levels of potential carcinogens might vary throughout the environment. It has been suggested that the most likely carcinogens related to EC are a group known as the N-nitrosamines. In this study, we measured the concentrations of nine nitrosamines in drinking water and human urine in two areas in China, one with a high incidence of EC (Huai'an) and one with a low incidence (Nanjing). Among the nine target analytes, N-nitrosodi-n-propylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosopyrrolidine (NPyr), N-nitrosodiethylamine (NDEA) and N-nitrosomorpholine (NMor) occurred at higher concentrations in drinking water in the high incidence area. Inhabitants from the high incidence area also had urinary excretions with significantly higher concentrations of NDEA, NDBA, N-nitrosopiperidine (NPip) and N-nitrosodiphenylamine (NDPhA). These findings indicated that people in the high EC incidence area were exposed to higher levels of nitrosamines. However, the association between the incidence of EC and nitrosamines exposure will need to be evaluated in more detail.

Age at menarche and age at natural menopause as predictors of glycemic control in type 2 diabetic patients.

OBJECTIVE: To investigate the influence of age at menarche (AM) and age at natural menopause (ANM) on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was undertaken in Jiangsu, China. Logistic regression was used to evaluate the association between AM/ANM and glycemic control. RESULTS: 1195 (14.3%) premenopausal and 7149 (85.7%) postmenopausal women were included in this study. With the increase of AM per 1 year, patients had a low risk of uncontrolled FPG (≥7 mmol/L) and uncontrolled HbA1c (≥7%), as well as poor glycemic control (FPG ≥7 mmol/L and HbA1c ≥7%) after adjusting for age and BMI (model I, P < 0.05) with odds ratio (OR) 0.965, 0.978 and 0.962 respectively. Whereas after adjusting for age, BMI, education, duration of diabetes, smoking, drinking and antidiabetic treatment (model II) as well as further plus diabetic familial history and physical activity (model III), the association between AM and glycemic control was not significant (P > 0.05). Compared with premenopausal women, postmenopausal women had a low risk of uncontrolled FPG and uncontrolled HbA1c after adjusting for confounders in model II (P < 0.05). Furthermore, both patients with early ANM (<45 years) and late ANM (>55 years) had a high risk of uncontrolled HbA1c as well as poor glycemic control even adjusted for full confounders in model III (P < 0.05 for all). CONCLUSION: Early AM, early and late ANM were significantly associated with worse glycemic control. Ascertaining the AM and ANM in women with T2DM may help to identify the risk predisposed to worse glycemic control.

Familial History of Diabetes is Associated with Poor Glycaemic Control in Type 2 Diabetics: A Cross-sectional Study.

To investigate the association of familial history (FH) of diabetes with the glycaemic control status of patients with type 2 diabetes (T2D), a cross-sectional study using stratified cluster sampling was conducted with 20,340 diabetic patients in Jiangsu, China. In total, 21.3% of the subjects reported a FH of diabetes. Patients with a FH of diabetes showed a higher risk of poor glycaemic control (59.7%) than those without a diabetic FH (49.8%), with an odds ratio (OR) of 1.366 (P < 0.001). Glycaemic control status did not significantly differ between the T2D patients with parental FH and those with sibling FH. Compared with patients with paternal FH, patients with maternal FH had a higher risk of poor glycaemic control (OR = 1.611, P = 0.013). Stratified analyses showed that a FH of diabetes was significantly associated with poor glycaemic control among T2D patients with a low education level (P < 0.05). In the <60 years old, overweight, and low level of physical activity groups, patients with a maternal history of diabetes showed a higher risk of poor glycaemic control than those without a FH (P < 0.05). In conclusion, FH of diabetes, especially a maternal history, had an independently adverse effect on the glycaemic control of T2D patients.

Relationship between serum uric acid and ischemic stroke in a large type 2 diabetes population in China: A cross-sectional study.

OBJECTIVE: To investigate the relationship of serum UA and ischemic stroke in type 2 diabetes patients in China. METHOD: We examined the above relationship using the data of the project "Comprehensive Research on the Prevention and Control of the Diabetes" (CRPCD) study. A total of 19,442 participants were enrolled in the cross-sectional study. The enrolled participants were divided into quintiles of the serum UA levels with cut off values for two age groups (<60 versus ≥60years). Binary logistic regression analyses were used to evaluate whether the levels of serum UA were independently associated with ischemic stroke in type 2 diabetes. RESULTS: The serum UA levels were significantly higher in the participants with age≥60years than those with age<60years (P=0.000). In the age group of <60years, the odds ratio for ischemic stroke with type 2 diabetes in quintile 5 over quintile 1 was 2.420 (95% CI, 1.566-3.470) in the unadjusted model and 1.765 (95% CI, 1.097-2.840) after controlling potential confounders. However, the reverse results were observed in the age group of ≥60years. The odds ratio in quintile 4 over quintile 1 in model 3 and model 4 were 0.767 (95% CI, 0.630-0.934) and 0.782 (95% CI, 0.640-0.957). CONCLUSION: Our results indicated that serum UA levels were independently positively associated with ischemic stroke in patients aged <60years, but the association was U-shaped in patients aged ≥60years.

Possible tumor suppressive role of the miR-144/451 cluster in esophageal carcinoma as determined by principal component regression analysis.

MicroRNA (miRNA) clusters are expressed universally across different types of organisms, and an accumulating number of studies have demonstrated that miRNA clusters function more efficiently compared with single miRNAs during the development of certain cancer types. miRNA clusters may have increased stability and reliability over individual miRNAs as diagnostic or therapeutic biomarkers. In the present study, the expression levels of mature miRNAs within the miR-144/451 cluster were examined using stem­loop reverse transcription­quantitative polymerase chain reaction in 102 patients pathologically diagnosed with esophageal carcinoma. Bioinformatics tools were used to identify a possible miRNA­mediated network of the miR­144/451 cluster. The expression levels of hsa­miR­451a, hsa­miR­144­3p and hsa­miR­144­5p in tumor tissues were significantly lower compared with those in adjacent non­tumor tissues (P<0.05). Pearson correlation analysis demonstrated that the expression levels of individual miR­144/451 cluster members were correlated with each other, except for the pair of hsa­miR­144­3p and hsa­miR­4732­3p. In particular, hsa­miR­144­5p expression was highly associated with hsa-miR-4732­5p and hsa-miR-451a expression levels, with correlation coefficients of 0.729 and 0.608, respectively. Furthermore, the low expression levels of hsa­miR­144­3p [odds ratio (OR), 0.85; P<0.05] and hsa-miR-144-5p (OR, 0.84; P<0.05) were determined to be risk factors for esophageal carcinoma development. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that miRNAs forming the miR­144/451 cluster may cooperate to regulate the cell cycle. Therefore, the miR­144/451 cluster may serve an important role in the progression of esophageal carcinoma and may be considered as a biomarker for the detection of esophageal carcinoma at an early stage.

Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1.

miR-218, consisting of miR-218-1 at 4p15.31 and miR-218-2 at 5q35.1, was significantly decreased in esophageal squamous cell carcinoma (ESCC) in our previous study. The aim of this study was to determine whether aberrant methylation is associated with miR-218 repression. Bisulfite sequencing analysis (BSP), methylation specific PCR (MSP), and 5-aza-2'-deoxycytidine treatment assay were applied to determine the methyaltion status of miR-218 in cells and clinical samples. In vitro assays were performed to explore the role of miR-218. Results showed that miR-218-1 was significantly CpG hypermethylated in tumor tissues (81%, 34/42) compared with paired non-tumor tissues (33%, 14/42) (p < 0.05). However, no statistical difference was found in miR-218-2. Accordingly, expression of miR-218 was negatively correlated with miR-218-1 methylation status (p < 0.05). After demethylation treatment by 5-aza-2'-deoxycytidine, there was a 2.53- and 2.40-fold increase of miR-218 expression in EC109 and EC9706, respectively. miR-218 suppressed cell proliferation and arrested cells at G1 phase by targeting 3' untranslated region (3'UTR) of roundabout guidance receptor 1 (ROBO1). A negative correlation was found between miR-218 and ROBO1 mRNA expression in clinical samples. In conclusion, our results support that aberrant CpG hypermethylation at least partly accounts for miR-218 silencing in ESCC, which impairs its tumor-suppressive function.

Study on the relationship between manganese concentrations in rural drinking water and incidence and mortality caused by cancer in Huai'an city.

BACKGROUND: Cancer is a significant disease burden in the world. Many studies showed that heavy metals or their compounds had connection with cancer. But the data conflicting about the relationship of manganese (Mn) to cancer are not enough. In this paper, the relationship was discussed between Mn concentrations in drinking water for rural residents and incidence and mortality caused by malignant tumors in Huai'an city. METHODS: A total of 158 water samples from 28 villages of 14 towns were, respectively, collected during periods of high flow and low flow in 3 counties of Huai'an city, along Chinese Huai'he River. The samples of deep groundwater, shallow groundwater, and surface water were simultaneously collected in all selected villages. Mn concentrations in all water samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS 7500a). The correlation analysis was used to study the relationship between the Mn concentration and cancer incidence and mortality. RESULTS: Mn concentrations detectable rate was 100% in all water samples. The mean concentration was 452.32 µg/L ± 507.76 µg/L. There was significant difference between the high flow period and low flow period (t = -5.23, P < 0.05) and also among deep groundwater, shallow groundwater, and surface water (F = 5.02, P < 0.05). The ratio of superscale of Mn was 75.32%. There was significant difference of Mn level between samples in the high flow period and low flow period (χ(2) = 45.62, P < 0.05) and also among deep groundwater, shallow groundwater, and surface water (χ(2) = 10.66, P < 0.05). And also we found that, during the low flow period, Mn concentration has positive correlation with cancer incidence and mortality; for a 1 µg/L increase in Mn concentration, there was a corresponding increase of 0.45/100000 new cancer cases and 0.35/100000 cancer deaths (P < 0.05). CONCLUSIONS: In Huai'an city, the mean concentration of Mn in drinking water was very high. Mn concentration correlated with cancer incidence and mortality.