Discovery of novel selective phosphodiesterase­1 inhibitors for the treatment of acute myelogenous leukemia.

Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. PDE1 (Phosphodiesterase 1) is a subfamily of the PDE super-enzyme families that can hydrolyze the second messengers cAMP and cGMP simultaneously. Previous research has shown that suppressing the gene expression of PDE1 can trigger apoptosis of human leukemia cells. However, no selective PDE1 inhibitors have been used to explore whether PDE1 is a potential target for treating AML. Based on our previously reported PDE9/PDE1 dual inhibitor 11a, a series of novel pyrazolopyrimidinone derivatives were designed in this study. The lead compound 6c showed an IC50 of 7.5 nM against PDE1, excellent selectivity over other PDEs and good metabolic stability. In AML cells, compound 6c significantly inhibited the proliferation and induced apoptosis. Further experiments indicated that the apoptosis induced by 6c was through a mitochondria-dependent pathway by decreasing the ratio of Bcl-2/Bax and increasing the cleavage of caspase-3, 7, 9, and PARP. All these results suggested that PDE1 might be a novel target for AML.

Analysis on the association between PPARα/γ polymorphisms and lipoprotein(a) in a Chinese Han population.

Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, is recognized as an independent risk factor for atherosclerosis, cardiovascular diseases, and diabetic vascular diseases. Our recent studies revealed that the single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors (PPARα/δ/γ) gene are involved in the regulation of lipid storage and metabolism. In order to investigate the relationships between the SNPs of PPARα/γ gene and plasma levels of Lp(a), 644 participants were randomly selected from Chinese Han population in the present study. As the results shown, Lp(a) was significantly associated with L162V (rs1800206) in PPARα. Compared with those subjects with widetype (LL), significantly higher Lp(a) concentration was determined in the individuals with mutant (LV + VV) (mean difference: 49.07 mg/l, 95% CI 23.32-74.82 mg/l, p = 0.0002). Moreover, with generalized multifactor dimensionality reduction analysis, our present results indicated that there was a significant association between plasma Lp(a) level and gene-gene interaction among the polymorphisms rs1800206, rs135539 in PPARα and rs10865710, rs1805192, and rs4684847 in PPARγ. Therefore, our presented study indicated that PPARα/γ polymorphisms should be involved in the regulation of plasma Lp(a) in independently and/or in an interactive manner, suggesting that PPARα/γ gene may influence the risk of hypertension, cardiovascular diseases, and dyslipidemia by regulating Lp(a) level.

PPAR α and PPAR γ polymorphisms as risk factors for dyslipidemia in a Chinese Han population.

BACKGROUND: The PPAR α and PPAR γ are the key messengers responsible for the translation of nutritional stimuli into changes for the expression of genes, particularly genes involved in lipid metabolism. However, the associations between PPAR α/γ polymorphisms and lipid serum levels in the general population were rarely studied, and the conclusions were conflicting. The objective was to investigate the associations of the PPAR α and PPAR γ polymorphisms with dyslipidemia. METHODS: 820 subjects were randomly selected from the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort populations. The logistic regression model was used to examine the association between these polymorphisms and dyslipidemia. SNPstats was used to explore the haplotype association analyses. RESULTS: In the codominant and log-additive models, rs1800206, rs1805192 and rs3856806 were all associated with dyslipidemia (P < 0.005). When the most common haplotype L-G (established by rs1800206, rs4253778) was treated as the reference group, the V-G haplotype was associated with dyslipidemia (P < 0.001), higher TC and TG levels (P < 0.01). Moreover, when compared to Pro-C haplotype (established by rs1805192, rs3856806), the Pro-T, Ala-C, Ala-T haplotypes were associated with dyslipidemia (p < 0.001). A-T haplotype was associated with higher TC levels, (p < 0.01), and the P-T, A-C, A-T haplotypes were associated with higher TG levels (p < 0.01). CONCLUSIONS: PPAR α and PPAR γ polymorphisms and haplotypes may be the genetic risk factors for dyslipidemia.

The application of visceral adiposity index in identifying type 2 diabetes risks based on a prospective cohort in China.

BACKGROUND: Visceral adiposity index (VAI), a novel sex-specific index for visceral fat measurement, has been proposed recently. We evaluate the efficacy of VAI in identifying diabetes risk in Chinese people, and compare the predictive ability between VAI and other body fatness indices, i.e., waist circumference (WC), body mass index (BMI) and waist- to- height ratio (WHtR). METHODS: Participants (n=3,461) were recruited from an ongoing cohort study in Jiangsu Province, China. Hazard ratio (HR) and corresponding 95% confidence interval (CI) between diabetes risk and different body fatness indices were evaluated by Cox proportional hazard regression model. Receiver operating characteristic (ROC) curve and area under curve (AUC) were applied to compare the ability of identifying diabetes risk between VAI, WC, WHtR and BMI. RESULTS: A total number of 160 new diabetic cases occurred during the follow-up, with an incidence of 4.6%. Significant positive associations were observed for VAI with blood pressure, fasting plasma glucose, triglyceride, WC, BMI and WHtR. Moreover, increased VAI was observed to be associated with higher diabetes risk with a positive dose-response trend (p for trend<0.001). As compared to individuals with the lowest VAI, those who had the highest VAI were at 2.55-fold risk of diabetes (95% CI: 1.58-4.11). The largest AUC was observed for VAI, following by WC, WHtR and BMI. CONCLUSIONS: VAI is positively associated with the risk of diabetes. Compared to other indices for body fatness measurements, VAI is a better and convenience surrogate marker for visceral adipose measurement and could be used in identifying the risk of diabetes in large-scale epidemiologic studies.

[The prospective study of association between C-reactive protein and hypertension in community population].

OBJECTIVE: The aim was to explore the association between high-sensitivity C-reactive protein level at baseline and hypertension in follow-up periods in a Chinese cohort. METHODS: We analyzed data from a cohort established in "Prevention of metabolic syndrome and multi-metabolic disorders in Jiangsu province" in April 2000. A follow-up investigation was carried out for those whose follow up time met 5 years in June 2006. A total of 2035 persons completed investigation and hs-CRP was tested. Subjects with normal baseline blood pressure were classified into four groups(514, 498, 515 and 508 subjects in each group) according to quartiles of hs-CRP level (<1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L). The relationship between the risk of hypertension and baseline level of hs-CRP were analyzed using Cox proportional hazards regression model. RESULTS: The median of follow up time was 6.39 years among the 2035 subjects (926 males and 1109 females). Hypertension incidence was 2378/100 000 person-years, 2942/100 000 person-years, 3693/100 000 person-years and 4390/100 000 person-years in hs-CRP < 1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively. Compared to the group of hs-CRP < 1.3 mg/L, the relative risk (RR) (95%CI) of hypertension in groups of hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L was 1.22 (0.87-1.72), 1.43 (1.03-2.00), 1.70 (1.21-2.41) respectively, adjusted for sex, age, baseline blood pressure, BMI, smoking, alcohol drinking, physical activity and family history of myocardial infarction and diabetes.When stratified by quartiles of baseline blood pressure, the incidence of hypertension in each group increased with level of hs-CRP.In the group whose baseline SBP < 110 mm Hg (1 mm Hg = 0.133 kPa) , compared to the group of hs-CRP < 1.3 mg/L, RR (95%CI) were 2.24 (1.32-4.03), 2.57 (1.57-4.57) and 3.57 (2.54-5.90) in hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively.In the group whose baseline DBP < 65 mm Hg, RR (95%CI) were 1.78 (1.03-3.24), 2.74 (1.63-4.93) and 4.13 (2.35-7.27) respectively. CONCLUSION: Inflammation was an important process in the development of hypertension.

[Genotype and haplotype analysis of peroxisome proliferators activated receptor α gene and the risk of essential hypertension].

OBJECTIVE: PPARα, which is expressed in the liver, heart, skeletal muscle, and kidney, regulates lipid and lipoprotein metabolism. The aim of this study was to investigate the association between the PPARα gene and essential hypertension (EH) using a haplotype-based cohort study in a Chinese-Han population. METHODS: 820 subjects (270 males, 550 females) were genotyped for the three single-nucleotide polymorphisms used as genetic marker for the PPARα gene (rs1800206, rs4253778 and rs135539). Individual polymorphism and haplotype data were available for analyses. RESULTS: In the dominant model, the presence of the G allele of rs1800206 and the C allele of rs135539 were at a decreased risk of EH (OR = 0.48, 95%CI 0.40 - 0.64, P < 0.01; OR = 0.75, 95%CI 0.62 - 0.93, P < 0.01, respectively). A 3.16-fold increase (95%CI 1.86 - 6.94, P = 0.002) in the risk of the development of EH was observed in homozygous genotype (CC) of rs4253778 compared to carriers of GG genotype (co-dominant model). The A-G-V and C-G-V haplotype (established by rs135539, rs4253778, rs1800206) was associated with a statistically significant decreased risk of EH (OR = 0.56, 95%CI 0.33 - 0.83, P = 0.027; OR = 0.53, 95%CI 0.30 - 0.84, P = 0.033, respectively). CONCLUSION: These results may help to clarify the role of PPARα gene in EH and the evaluation of its polymorphisms and haplotypes as being characterized as genetic decreased risk factors for EH.

[Effects of PPARD-87T > C and interactions with single nucleotide polymorphisms in PPARA and PPARG on abdominal obesity].

OBJECTIVE: To examine the main effect of 10 single nucleotide polymorphisms (SNPs) in contribution to abdominal obesity and study whether there is an interaction in the 10 SNPs in the cause of abdominal obesity. METHODS: A total of 820 subjects were randomly selected and no individual was related. Individual polymorphism and interactions were available for analyses. RESULTS: C allele carrier (CC + TC) was significantly higher than that of TT genotype (OR (95%CI) = 0.68 (0.52 - 0.90), P = 0.005). A 5-dimension gene-to-gene interaction model existed among rs135539, rs2016520, rs10865710, rs1805192 and rs709158 on the incidences of abdominal obesity. CONCLUSIONS: The C allele in rs2016520 is significantly associated with a lower rate of abdominal obesity. And there is an interaction among rs2016520, rs135539, rs10865710, rs1805192 and rs709158 on the incidences of abdominal obesity.

[Impact of lifestyle and obesity to the risk of type 2 diabetes: a prospective study in Jiangsu province].

OBJECTIVE: To investigate the relative contribution of lifestyle and obesity to the risk of developing type 2 diabetes. METHODS: All baseline survey data were based on the program Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province (PMMJS) which was conducted during April 1999 to May 2004. In the baseline survey, 8685 participants were selected using multi-stage sampling method. Frem March 2006 to November 2007, 4582 participants who had been in the study for at least 5 years were included in the follow-up survey. A total of 3847 participants were followed and of them 3461 non-diabetic subjects were included in this analysis. High fat diet or not, low fiber diet or not, sedentary or not and occupational physical activity classification were defined as lifestyle variables and the incidence of type 2 diabetes at follow-up survey was defined as outcome variable. It was prospectively examined that the separate and joint association of lifestyle and obesity with the development of type 2 diabetes in subjects recruited from PMMJS, using logistic regression model. RESULTS: A total of 162 incident cases of type 2 diabetes during 6.3 years of follow-up in total 3461 participants were documented. The incidence rate was 4.7%. After adjusted for sex, age, family history of diabetes, blood pressure, lipids and fast plasma glucose, risk of type 2 diabetes increased with lighter occupational physical activity (compared with vigorous group, moderate group aRR = 2.15, 95%CI: 1.26 - 3.68; light group aRR = 2.39, 95%CI: 1.12 - 4.87), sedentary lifestyle (aRR = 2.94, 95%CI: 1.90 - 4.54), low fiber diet (aRR = 1.58, 95%CI: 1.01 - 2.53), overweight (aRR = 1.33, 95%CI: 1.01 - 1.90) and obesity (aRR = 1.59, 95%CI: 1.07 - 3.75). In joint analysis of lifestyle and obesity, the impact of sedentary lifestyle (in BMI < 25 group, aRR = 3.42, 95%CI: 1.99 - 5.86; in BMI ≥ 25 group, aRR = 2.41, 95%CI: 1.13 - 5.12) and low fiber diet (in BMI < 25 group, aRR = 1.42, 95%CI: 0.81 - 2.54; in BMI ≥ 25 group, aRR = 2.63, 95%CI: 1.15 - 6.03) on diabetes were independent of overweight and obesity. When stratified by sedentary lifestyle or low fiber diet, there was no association between overweight/obesity and diabetes risk (sedentary aRR = 2.04, 95%CI 0.87 - 4.71, non sedentary aRR = 1.21, 95%CI: 0.82 - 1.78; non low fiber diet aRR = 1.26, 95%CI: 0.87 - 1.84, low fiber diet aRR = 1.88, 95%CI: 0.80 - 4.80). CONCLUSION: Unhealthy lifestyle, overweight and obesity independently increase the risk of type 2 diabetes. The magnitude of risk contributed by sedentary lifestyle and low fiber diet are much greater than that imparted by overweight and obesity.

[Gene-gene interactions among the peroxisome proliferator-activated receptor polymorphisms for hypertriglyceridemia].

OBJECTIVE: To investigate the association of ten SNP at peroxisome proliferator-activated receptors (PPARα, δ, γ) with hypertriglyceridemia and the gene-gene interaction. METHODS: Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu province of China Study (PMMJS). A total of 820 subjects were selected from the 4083 participants who had received follow-up examination, by using simple random sampling. Participants in baseline and follow-up study surveys were both collected blood samples 11 ml in the morning after at least 8 hours of fasting. Blood samples which collected at the baseline were subjected to PPARα, PPARδ and PPARγ genotype analyses. Blood samples which collected at the follow-up were used to measure serum triglyceride levels. The logistic regression model was used to analyze the association between different SNP and hypertriglyceridemia, and the generalized multifactor dimensionality reduction (GMDR) was applied to explore the gene-gene interaction. RESULTS: The samples included 474 in the non-hypertriglyceridemia group and 346 in the hypertriglyceridemia group. The genotype frequencies of rs1800206 in the hypertriglyceridemia group were 211 (61.0%) for LL, 132 (38.2%) for LV and 3 (0.9%) for VV, and in the non-hypertriglyceridemia group were 411 (86.7%) for LL, 59 (12.4%) for LV and 4(0.8%) for VV (χ(2) = 74.18, P < 0.01). V allele frequencies of rs1800206 in the hypertriglyceridemia group was 138(19.9%), and in the non-hypertriglyceridemia group was 67 (7.1%) (χ(2) = 60.62, P < 0.01). The genotype frequencies of rs2016520 in the hypertriglyceridemia group were 177 (51.2%) for TT, 154 (44.5%) for TC and 15 (4.3%) for CC, and in the non-hypertriglyceridemia group were 211 (44.5%) for TT, 212 (44.7%) for TC and 51 (10.8%) for CC(χ(2) = 15.93, P < 0.01). C allele frequencies of rs2016520 in the hypertriglyceridemia group was 184(26.6%), and in the non-hypertriglyceridemia group was 314 (33.1%) (χ(2) = 8.07, P < 0.01). The genotype frequencies of rs3856806 in the hypertriglyceridemia group were 149 (43.1%) for CC, 156 (45.1%) for CT and 41 (11.8%) for TT, and in the non-hypertriglyceridemia group were 269 (56.8%) for CC, 170 (35.9%) for CT and 35 (7.4%) for TT (χ(2) = 15.93, P < 0.01). T allele frequencies of rs3856806 in the hypertriglyceridemia group was 238(34.4%), and was 240 (25.3%) in the non-hypertriglyceridemia group (χ(2) = 15.96, P < 0.01). The genotype frequencies of rs1805192 in the hypertriglyceridemia group were 145 (41.9%) for PP, 158(45.7%) for PA and 43(12.4%) for AA, and in the non-hypertriglyceridemia group were 314 (66.2%) for PP, 137(28.9%) for PA and 23(4.9%) for AA (χ(2) = 50.92, P < 0.01). A allele frequencies of rs1805192 in the hypertriglyceridemia group was 244(35.2%), and was 183 (19.3%) in the non-hypertriglyceridemia group(χ(2) = 52.89, P < 0.01). After adjusting age, gender, smoking, alcohol consumption, high-fat diet, low -fiber diet and occupational physical activity factors, rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceride, while the OR (95%CI) was 3.88 (2.69 - 5.60), 0.71 (0.52 - 0.96), 1.40 (1.03 - 1.90) and 2.56 (1.88 - 3.49), respectively (P < 0.05). GMDR model analysis showed that the second-order model (rs1800206 and rs1805192) was the best model when quality traits of triglyceride was chosen as outcome (P < 0.01); while third-order model (rs1800206, rs1805192 and rs2016520) was the best model when quantitative traits of triglyceride was chosen as outcome (P < 0.01). CONCLUSION: The rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia. There was a gene-gene interaction between multiple SNP.

[A comparative study of incidence and prevalence of Crohn's disease in mainland China in different periods].

OBJECTIVE: To collect data and analyze the current status and prevalence changes of Crohn's disease (CD) in mainland China in recent decades. METHODS: A computer-based literature search was previously performed by using 50-year (1950 to 2002) of records of CD from the Chinese Database of Biology and Medicine (CBM) (1979 to 2002) and a manual year-by-year search of the literature (1950 to 1978). Using similar method, descriptive epidemiological data from 2003 to 2007 were collected, analyzed and compared with previous research. RESULTS: Four hundred and seventeen relevant papers during 2003 and 2007 were collected and 62 papers were eligible for inclusion. Within 62 papers, a total of 2149 cases with CD from 2003 to 2007 have been reported nationwide, comprising 1288 male and 861 female patients, with a 1.50:1 male predominance, and indicating 1.41 time of increment as compared with our previous result (ie, 1526 cases from 1950 - 2002). There were no obvious changes in incidence age (younger and middle age were main components) and sex ratio (number of male was still larger than that of female). The extrapolated CD incidence and prevalence rates were 1.21/100 000 person·year and 2.29/100 000, respectively, which were higher than that of year 1950 - 2002, 0.28/100 000 person·year and 1.38/100 000, respectively. CONCLUSIONS: The incidence and prevalence rates of CD have been increasing rapidly, but these rates are still lower than those in Western world.

[Impact of dynamic change of waist circumference or body mass index in hypertension incidence].

OBJECTIVE: To study the impact of dynamic change of waist circumference (WC) and body mass index(BMI) in two years on hypertension incidence in cohort populations. METHODS: A perspective cohort study was conducted. The participants (5888 subjects) whose follow-time were 2 years or longer from the program Prevention of multiple metabolic disorders and metabolic syndrome (MS) in Jiangsu province were investigated. Amongst 5888 subjects, 4582 participants received the first follow-up investigation in January 2002. Among 4582 subjects who received first follow-up investigation and whose follow-time met 5 years, total 3847 participants received the second follow-up investigation in March 2006. Total 2778 free hypertension subjects were included in this analysis. Subjects with normal WC or BMI at baseline but abnormal WC or BMI at the first follow-up or subjects with abnormal WC or BMI both at baseline and the first follow-up were defined as non-control group. Subjects with abnormal WC or BMI at baseline but normal WC or BMI at the first follow-up or subjects with normal WC or BMI both at baseline and the first follow-up were defined as control group. The incidence of hypertension at second follow-up investigation was defined as the final variable(hypertension = 1, non-hypertension = 0). The association between dynamic change of WC or BMI and incident hypertension was analyzed by using Cox proportional hazards regression model. The OR, RR value and 95%CI were calculated through WC and BMI risk stratification. RESULTS: Among 2778 participants without hypertension at baseline, 660 subjects developed hypertension. When both BMI difference value (D-value) and WC D-value were included in the regression model, WC D-value was associated with hypertension in both genders (males: OR = 1.04, 95%CI: 1.01 - 1.05; females: OR = 1.04, 95%CI: 1.02 - 1.06), but BMI D-value was not associated with hypertension in both men and women (males: OR = 1.04, 95%CI: 0.97 - 1.11; females: OR = 0.98, 95%CI: 0.93 - 1.03). Hypertension risk of WC non-control group was higher than that in WC control group in baseline normal and abnormal WC groups (normal baseline WC group: RR = 1.41, 95%CI: 1.01 - 2.39, abnormal baseline WC group: RR = 4.41, 95%CI: 1.66 - 9.80). But in baseline abnormal BMI group, there was no significant difference between BMI control and non-control group (RR = 1.33, 95%CI: 0.88 - 2.02). Whether BMI was controlled can not influence hypertension risk if WC was controlled (males: RR = 1.03, 95%CI: 0.36 - 2.96; females: RR = 1.02, 95%CI: 0.70 - 5.85), however, control WC could reduce hypertension risk obviously even though BMI was not controlled (males: RR = 4.03, 95%CI: 1.61 - 10.09; females: RR = 1.55, 95%CI: 1.13 - 3.60). CONCLUSION: Both WC and BMI dynamic change were associated with change of hypertension. But reducing WC can decrease hypertension risk more than reducing BMI.

Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria.

BACKGROUND: The effects of enterolignans, e.g., enterodiol (END) and particularly its oxidation product, enterolactone (ENL), on prevention of hormone-dependent diseases, such as osteoporosis, cardiovascular diseases, hyperlipemia, breast cancer, colon cancer, prostate cancer and menopausal syndrome, have attracted much attention. To date, the main way to obtain END and ENL is chemical synthesis, which is expensive and inevitably leads to environmental pollution. To explore a more economic and eco-friendly production method, we explored biotransformation of enterolignans from precursors contained in defatted flaxseeds by human intestinal bacteria. RESULTS: We cultured fecal specimens from healthy young adults in media containing defatted flaxseeds and detected END from the culture supernatant. Following selection through successive subcultures of the fecal microbiota with defatted flaxseeds as the only carbon source, we obtained a bacterial consortium, designated as END-49, which contained the smallest number of bacterial types still capable of metabolizing defatted flaxseeds to produce END. Based on analysis with pulsed field gel electrophoresis, END-49 was found to consist of five genomically distinct bacterial lineages, designated Group I-V, with Group I strains dominating the culture. None of the individual Group I-V strains produced END, demonstrating that the biotransformation of substrates in defatted flaxseeds into END is a joint work by different members of the END-49 bacterial consortium. Interestingly, Group I strains produced secoisolariciresinol, an important intermediate of END production; 16S rRNA analysis of one Group I strain established its close relatedness with Klebsiella. Genomic analysis is under way to identify all members in END-49 involved in the biotransformation and the actual pathway leading to END-production. CONCLUSION: Biotransformation is a very economic, efficient and environmentally friendly way of mass-producing enterodiol from defatted flaxseeds.

[Relationship between peroxisome proliferator-activated receptor alpha intron 1A/C genetic polymorphism and metabolic syndrome].

OBJECTIVE: To identify the relationship between genetic polymorphisms of peroxisome proliferator-activated receptor alpha (PPARalpha) intron 1A/C and metabolic syndrome (MS) in a Chinese population. METHODS: A population-based case-control study was conducted in Suzhou city, Changshu County and Ganyu County in Jiangsu Province China, on the basis of an ongoing cohort study and 2348 cases were investigated. After the exclusion of the known MS cases, 1847 eligible subjects were successfully followed-up and their waist circumference (WC), body mass index, blood pressure, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fasting plasma glucose were measured. Newly diagnosed MS patients were recruited as cases, controls were individual matched with each case. TaqMan fluorescence probe method was used to detect the genetic polymorphism of PPARalpha intron 1A/C. RESULTS: The current analysis consisted of 389 MS patients and 389 matched controls. The C allele gene frequency of PPARalpha intron 1A/C in the case group was 22.24% (173/778), lower than that in the control group, which was 24.68% (192/778); whereas the difference was not statistically significant (chi(2) = 1.29, P > 0.05). In the genotypes AA + AC and CC, MS patients were accounted for 50.70% (363/716) and 41.94% (26/62) and hyperglycemia accounted for 21.37% (153/716) and 11.29% (7/62). Compared to the genotypes AA + AC, genotype CC was observed to be inversely associated with hyperglycemia (the adjusted OR = 0.39; 95%CI: 0.17 - 0.90) but not related to the occurrence of MS (OR = 0.75; 95%CI: 0.44 - 1.28) and other components of MS e.g., abdominal obesity (the adjusted OR = 0.67; 95%CI: 0.38 - 1.17), hypertriglyceridemia (the adjusted OR = 0.97; 95%CI: 0.53 - 1.76), low HDL-C (the adjusted OR = 0.72; 95%CI: 0.41 - 1.25) and hypertension (the adjusted OR = 0.72; 95%CI: 0.42 - 1.25) all P values > 0.05. CONCLUSION: C allele of PPARalpha intron 1A/C is not found to be associated with MS in the Chinese population. But comparing with the genotypes AA + AC, there is an inverse association between CC genotype and hyperglycemia.

Interaction of tobacco smoking and alcohol consumption with obesity on cardiovascular disease in a Chinese cohort.

OBJECTIVE: We aimed to detect the synergistic effect between alcohol drinking, smoking and obesity on incident cardiovascular disease (CVD) in a Chinese population- based cohort. METHODS: We performed this study based on a prospective cohort based on a Chinese population in Jiangsu, China. Logistic regression was employed to detect the interaction of smoking, drinking with obesity on susceptibility to CVD, and calculate the odds ratio (OR) of CVD and corresponding 95% confidence interval (CI). RESULTS: A total of 3598 subjects (1451 males and 2147 females) were enrolled, including 82 CVD patients (36 males and 46 females) who new developed CVD at the follow-up. We found a significant abdominal obesity-current smoking interaction on CVD risk. Compared to never-smokers with normal waist circumference, OR (95% CI) of CVD were 2.44 (1.56-3.81), 1.58 (0.93-2.69), and 5.37 (3.08-9.34) for smokers with normal waist circumference, abdominal obese nonsmokers and abdominal obese smokers, respectively. Synergy index for this interaction was 2.35 (1.05-4.50). We also found a significant abdominal obesity-alcohol drinking interaction on CVD. Compared to never-drinkers with normal waist circumference, OR (95% CI) of CVD were 1.57 (1.01-2.45), 1.84 (1.08-3.12), and 4.44 (2.55-7.72) for drinkers with normal waist circumference, abdominal obese non- drinkers and abdominal obese drinkers, respectively. Synergy index for this interaction was 2.44 (1.04-5.72). CONCLUSION: We found significant interactions between alcohol drinking and abdominal obesity, smoking and abdominal obesity on CVD risk, suggested that the effect of alcohol drinking or smoking on CVD susceptibility seems to be modified by abdominal obesity.

E. coli diversity: low in colorectal cancer.

BACKGROUND: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. METHODS: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. RESULTS: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. CONCLUSIONS: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.

[A comparison of applicability in three diagnostic criteria of metabolic syndrome in Jiangsu population].

OBJECTIVE: To compare the applicability of the three diagnostic criteria for metabolic syndrome (MS) proposed by the International Diabetes Federation (IDF) in 2005, Adult Treatment Panel III of National Cholesterol Education Program (NCEP-ATP III) in 2005 and Chinese Diabetes Socie (CDS) in 2004. METHODS: Based on the findings of cohort study of multiple metabolic disorders and metabolic syndrome (1971 cases) in Jiangsu province, MS was diagnosed according to these three definitions respectively, and by calculating the sensitivity, specificity, and ROC curve distance, those with lower false positive and false negative rates were identified as to detecting cardio vascular diseases (CVD) and type 2 diabetes mellitus (T2DM). While, through Cox regression analysis, to compare their relative risk (RR) and 95% confidential interval (CI) was wade. RESULTS: Among three diagnostic criteria, the specificity by CDS of MS was higher than the other criteria (83.52%, 76.36%, 89.57%; 85.02%, 78.67%, 92.28%), however the sensitivity of CDS of MS was low (40.82%, 29.47%). When using CDS, over 50 percent of diagnosis might be missed. ATP III definition corresponded to the shortest distance in ROC curve, namely, at the diagnostic criteria, the rates of false positive and false negative for identifying clustering of CVD and T2DM were minimum (0.4369; 0.5777). The incidence of CVD [5.59 (2.62 - 11.92) vs 2.90 (1.41 - 5.93)], T2DM [3.36 (1.92 - 5.79) vs 1.97 (1.16 - 3.34)] was significantly higher in cases of ATP III+/IDF-than ATP III+/IDF+, as compared with ATP III-/IDF-. CONCLUSION: Among three diagnostic criteria, the ATP III definition of the MS should be the most applicable diagnostic criteria for MS in Jiangsu population.

[Association and interaction between the components of metabolic syndrome and cardiovascular disease].

OBJECTIVE: To explore the association and interaction between the components of metabolic syndrome (MS) and cardiovascular disease (CVD). METHOD: In this cohort study, participants (total 3598, male 1451) were recruited and followed up for five years from the program "prevention of multiple metabolic disorders and MS in Jiangsu province". We used modified Asian criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) to define the presence of MS. COX regression was used to analyze the association between the MS and its components with CVD; both the multiplication of blood pressure (BP) and 2, 3, or 4 other components of MS in the logistic regression model and the estimation of the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S) and 95% confidence intervals (95%CI) were used to evaluate the interactions between the components of MS. RESULTS: After adjustment for traditional CVD risks, the adjusted risk ratio (aRR) of CVD was 2.49 (95%CI: 1.59 - 3.90) in the MS group compared with the non-MS group at baseline. The aRRs of MS components to CVD were as follows: 1.44 (95%CI: 0.88 - 2.37) for waist circumference; 2.84 (95%CI: 1.73 - 4.68) for BP; 1.31 (95%CI: 0.83 - 2.07) for low high density lipoprotein; 1.84 (95%CI: 1.19 - 2.85) for triglyceride; 1.55(95%CI: 0.98 - 2.45) for fasting plasma glucose, respectively. BP was the single component significantly related to CVD (aRR = 2.58, 95%CI: 1.55 - 4.29). The risk of CVD was significantly increased (aOR = 4.47, 95%CI: 2.35 - 8.51) when BP was combined with 2, 3 or 4 other components of MS in the participants. CONCLUSIONS: Only BP is an independent CVD risk factor in the components of MS, the risk of CVD was significantly increased when BP was combined with other components of MS in this cohort.

Haplotype Analysis of PPARγ Gene Polymorphisms and the Lipoprotein (a) Level.

BACKGROUND: Lipoprotein (a) [Lp(a)], as an independent risk factor for cardiovascular disease, is more likely to be genetically determined according to the increasing evidence of epidemiologic and clinical studies in recent years. Peroxisome proliferator-activated receptor (PPAR) γ, the ligand-activated transcription factors, was considered as an indispensable role in the process of lipid metabolism. This study was designed to explore the associations of three single-nucleotide polymorphisms (SNPs) and the haplotypes of the peroxisome proliferator-activated receptor (PPAR)γ gene with the level of Lp(a). METHODS: Participants were recruited under the framework of the PMMJS (The Prevention of Metabolic Syndrome (MS) and Multi-metabolic Disorders in Jiangsu Province of China Study) from Apr 1999 to Jun 2004. Overall, 644 subjects were randomly selected and 3 SNPs of PPARγ gene (rs10865710, rs1805192, rs4684847) were genotyped. RESULTS: After adjusting for age, sex, cigarette smoking, alcohol drinking, waist circumference and body mass index, rs4684847 was significantly associated with Lp (a). The presence of the rs4684847 T allele (CT+TT) have a lower level of Lp (a) than the allele (CC) in the dominant model, mean difference was -27.30 (95% CI: -52.88∼-1.73) mg/L, P<0.05. G-P-T and G-A-T haplotype were associated with lower levels of Lp (a) (P=0.0041 and <0.0001), mean difference was 49.79 (95% CI: -97.52∼-2.06) mg/L and 17.75 (95% CI: -25.75∼-9.75) mg/L. CONCLUSION: PPAR gamma polymorphisms (rs10865710, rs1805192, rs4684847) and haplotypes may be the genetic risk factors for Lp (a) level.

Hepatitis B vaccine response in obesity: A meta-analysis.

BACKGROUND: Hepatitis B vaccination is critical in preventing hepatitis B virus (HBV) infection and transmission. However, the impact of obesity on immune response to hepatitis B vaccine remains unclear. METHODS: We performed a meta-analysis of the literature and summarized the results of immune response to hepatitis B vaccine among persons with and without obesity. We used Pubmed, Embase, Web of Science and Cochrane Library to identify all related studies between January 1973 and November 2015. Unadjusted and adjusted pooled OR and 95% CI were calculated by fixed-effect model or random-effect model according to the heterogeneity of the selected studies. RESULTS: Totally, 16 studies contributed to the present meta-analysis. Fifteen of them provided absolute numbers of non-responders in obese group and non-obese group. Overall, we found that the obese population was significantly associated with non-response to hepatitis B vaccination (adjusted OR: 2.46, 95% CI: 1.50-4.03). Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with uniform criteria of obesity and restricted to study in adults. No publication bias was observed in the present analysis. CONCLUSIONS: The present meta-analysis suggested that obesity is significantly associated with the decreased response to hepatitis B vaccines. Future studies should be performed to unravel this relationship in order to prevent HBV infection and transmission.

Crohn's disease in mainland China: a systematic analysis of 50 years of research.

BACKGROUND: Crohn's disease appears to be increasing in frequency in many areas of the world. However, little information with regard to disease incidence, prevalence and temporal trends has been published in China. OBJECTIVE: The aim of this review is to better understand the occurrence of Crohn's disease in mainland China, and to give an overview of the current status of the disease. METHODS: We used a computer-based literature search using 50-years of records from the Chinese Database of Biology and Medicine (CBM, 1979-2002), combined with a manual year-by-year search of the literature from 1950 to 1979. Each article was double-reviewed, and all descriptive epidemiological data were recorded, pooled and statistically analyzed. RESULTS: In total, 1526 cases of Crohn's disease since 1950 have been reported by more than 50 hospitals from 22 provinces and cities in mainland China, comprising 884 male and 642 female patients, with a 1.38:1 male predominance. More than 70% of patients were aged 20 to 50 years old, with a mean age of 37.2 +/- 2.68 (ranging from 1 to 83) years. The extrapolated disease incidence and prevalence rates are 0.28/100,000 person years and 1.38/100,000 persons, respectively. CONCLUSIONS: The incidence and prevalence rates of Crohn's disease are still lower than those in Western and other Asian countries, but these rates have been increasing rapidly, and the disease is no longer uncommon. An underestimation may occur because the patients who were misdiagnosed or did not seek medical advice could not be included in the study. A future population-based survey is warranted.