[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.

[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.

Scrotal elephantiasis associated with follicular occlusion triad: A case report and literature review.

RATIONALE: Follicular occlusion triad (FOT) is an autosomal recessive inherited disease and no more than 3 variants of the triad have been reported. We give a report in which scrotal elephantiasis is a variant of FOT and further perform a literature review. PATIENT CONCERNS: A 41-year-old man came to us because of a large scrotal cyst and generalized skin lesions that had occurred over the past 10 years. The generalized skin lesions consisted of hidradenitis suppurativa on the perineum and back, acne conglobata in the armpit, and dissecting cellulitis of the scalp. He took antibiotics for a long time but achieved poor effect. Furthermore, he told his father and elder brother also manifested such skin lesions. DIAGNOSES: Magnetic resonance showed a mass in the left scrotum with clear boundaries. A routine blood test showed a high leukocyte level of 12 × 10/L and a hemoglobin content of 78 g/L. C-reactive-protein increased. Series of autoimmune antibody tests were negative. The postoperative pathologic findings showed that the mass was an epidermoid cyst, and hematoxylin and eosin staining showed hyperkeratosis of the skin as well as inflammatory and edematous changes. A diagnosis of a variant of FOT was made. INTERVENTIONS: We removed skin abscesses and lesioned the inner part with hydrogen peroxide. Then we performed an excision of the scrotal lesion. OUTCOME: The patient recovered well and had no evidence of recurrence at a 16-month follow-up. LESSONS: We reported a case in which scrotal elephantiasis was a variant of FOT and surgical intervention played an important role in secondary urologic diseases.

Synthesis and anti-hepatocellular carcinoma activity of novel O2-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid.

Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.

[Growth inhibition of human hepatocellular carcinoma xenograft in nude mice by combined treatment with human cytokine-induced killer cells and chemotherapy].

OBJECTIVE: To compare the inhibitory effects of cytokine-induced killer (CIK) cells alone, chemotherapeutic drug alone, and CIK cells combined with chemotherapeutic drug on the growth of hepatocellular carcinoma (HCC) cells transplanted in nude mice. METHODS: Peripheral blood mononuclear cells (PBMC) collected from five healthy donors by blood cell separator were incubated in vitro to induce CIK cells in the presence of interferon-gamma (IFN-gamma), IL-2 and anti-CD3 monoclonal antibody (mAb). The phenotype of CIK cells was characterized by flow cytometric analysis. BEL-7402 HCC cells were inoculated subcutaneously to nude mice. On day 5, at the inoculation site were injected normal saline (group 1), CIK cells (3 x 10(7) and 6 x 10(7), group 2 and 3), mitomycin-C (MMC 80 microg in 0.2 ml, group 4), and CIK cells combined with MMC (group 5), respectively. RESULTS: The percentage of CD3(+), CD3(+)CD8(+), CD3(+)CD56(+), CD25(+) cells increased from 64.0%, 28.0%, 7.8%, and 9.1% to 94.7%, 67.7%, 61.3%, and 84.0% respectively after cytokine induction. The percentage of CD3(+) and CD3(+)CD8(+) cells remained at high levels during incubation period, but that of CD25(+) and CD3(+)CD56(+) cells peaked respectively on day 7 and 13 and then declined. During the 90-day observation, the tumor formation rates were 100%, 70.0%, 80.0%, 70.0% and 66.7%; and the mouse survival rates were 10.0%, 60.0%, 40.0%, 50.0% and 75.0%, respectively from group 1 to group 5. Compared to the other groups, in the combined therapy group of mice, not only the tumor grew slowly and but also showed more marked tissue necrosis. CONCLUSION: The growth inhibitory effect on human HCC transplanted in nude mice of combined CIK cells and MMC treatment is more potent than that of CIK cells or MMC alone.

[Characterization of peripheral dendritic cell subsets and its implication in patients infected with severe acute respiratory syndrome].

OBJECTIVE: To investigate the dynamic changes of dendritic cell subsets in peripheral blood of patients infected with severe acute respiratory syndrome (SARS) and evaluate their roles in the immunopathogenesis of SARS. METHODS: Flow cytometry was applied to study the dynamic alteration of the number and frequencies in circulating DC cell subsets in 30 SARS patients including critical SARS (n = 11) and general SARS (n = 19). The reasons and clinic significances of the peripheral blood DC subsets changes in SARS patients were also analyzed in our study. RESULTS: The patients in critical status had a 9-week course of disease, longer than the 6-week course observed in subjects in general status. The frequency of peripheral DC cell subsets significantly dropped beginning from the onset of symptom in SARS patients and was maintained at significant low levels during the following 4 - 5 weeks, 1.7 +/- 1.8, 5.3 +/- 5.0/ micro l for DC1, 0.57 +/- 1.02, 0.98 +/- 1.11/ micro l for DC2 for cases in critical and general statuses, respectively, compared with healthy subjects; more importantly, the pDC2 even disappeared in the patients who died from SARS diseases. The possible reasons responsible for the alteration of DC subsets in peripheral blood is likely to be the direct attack of SARS-CoVin circulation and be partially involved the application of large dose of steroid. The frequency in DC cell subsets returned to normal level in convalescent stage. CONCLUSION: Our results showed SARS patients had a significant decrease of circulating DC cell subset frequency, which maybe lead to the host immunodeficiency response to SARS-associated coronavirus (SARS-CoV).

[Identification of phenotype and Interferon-alpha-producing capability of circulating type II dendritic cells and its clinical implication in HBV-infected patients].

OBJECTIVE: To investigate the number, phenotype, and interferon-alpha (INF-alpha) of type II dendritic cells (DC2) in persons with hepatitis B and evaluate the role of DC2 subset in the immunopathogenesis of chronic HBV infection. METHODS: Peripheral blood was extracted from 103 hepatitis B (HB) virus-infected persons, including 11 cases of HB virus (HBV)-infected persons, 11 cases of acute HB, 81 cases of chronic HB, and 11 cases of asymptomatic HBV infection, and 25 healthy blood donors used as controls. Flow cytometry was used to calculate the number and the phenotype of circulating DC2. Ultraviolet-inactivated herpes simplex virus (HSV)-1 was added into the suspension of peripheral blood mononuclear cells (PBMCs) and then co-cultured for 24 hours to stimulate the production of INF-alpha by DC2 that was examined by ELISA assay. RESULTS: The number of DC2 in patients with chronic HB was 3.3 +/- 1.0 10(6)/L, significantly lower than that in the healthy controls (7.2 +/- 2.4 10(6)/L, P < 0.01). However, the number of DC2 was not significantly different between any other groups. The proportion of GS2 to PBMCs in the patients with chronic HB was 1.12 +/- 1.13 approximately 0.22 +/- 0.10, all significantly lower than that in the healthy controls (0.32% +/- 0.13%, P < 0.01). However, the proportion of GS2 to PBMCs was not significantly different between any other groups. The decrease of number of DC2 and that of proportion of DC2 to PBMCs in patients with chronic HB were related with the progress of disease. The INF-alpha concentration in the suspensions of PBMCs of different groups without stimulation by HSV-1 were low and there was no significant difference in INF-alpha concentration between different groups. The INF-alpha concentration in the suspension of PBMCs of healthy controls was 789 +/- 82 pg/ml, significantly higher than those of the patients with acute HB (161 +/- 36 pg/ml) and the patients with chronic HB (183 +/- 113 pg/ml, 147 +/- 39 pg/ml, and 156 +/- 39 pg/ml, all P < 0.05). However, there was no significant difference between the patient groups (all P > 0.05). CONCLUSION: The number and INF-alpha producing function of DC2, and the numbers of NK cells and CD8+ T cells in peripheral blood of patients with chronic HB decrease significantly, which results the deficiency of HBV-specific immune response.

[Frequency and function decrease of circulating type 2 pre-dendritic cells (pDC2) and its clinical significance in liver cirrhotic patients with chronic HBV infection].

OBJECTIVE: To identify the frequency and interferon (IFN)-alpha-producing ability of circulating type 2 pre-dendritic cells (pDC2) and evaluate its role in liver cirrhotic patients with chronic HBV infection. METHODS: 27 liver cirrhotic patients were included in our study and 25 patients with chronic hepatitis B and 25 healthy individuals were enrolled as controls. The numbers of circulating pDC2 and lymphocytes including CD4+ T cells, CD8+ T cells, NK cells as well as B cells were analyzed by flow cytometry. The IFN-alpha-producing function of peripheral blood mononuclear cells (PBMCs) representing the circulating pDC2 was determined by ELISA assay after stimulated by ultraviolet-inactivated herpes simplex virus-1 (UV-HSV-1). RESULTS: The number of pDC2 were (7.21+/-2.38)*10(6)/L, (4.49+/-3.08) *10(6)/L and (2.89+/-1.17) *10(6)/L for healthy control, chronic hepatitis B and cirrhotic patients respectively. Both the number and IFN-alpha-producing function of circulating pDC2 in liver cirrhotic patients significantly lower than that in healthy subjects. There was a correlated simultaneous decrease numbers of circulating CD8+ T cells, NK cells in HBV-infected cirrhotic patients. Furthermore, cirrhotic patients with opportunistic infections have lower numbers of pDC2, CD8+ T cells and NK cells compared to those without opportunistic infections. CONCLUSIONS: Liver cirrhotic patients with chronic HBV infection have a significant decrease of circulating pDC2 level and IFN-alpha-producing function. The decreased number and function of pDC2, together with the lower number of CD8+ T cells and NK cells may result in the decline of host immune response, which may partially contribute to the disease progression of HBV infection and opportunistic infections.

[Interaction of both hypertriglyceridemic waist and impaired fasting glucose on the incidence of diabetes mellitus].

OBJECTIVE: To study the use of hypertriglyceridemic waist (HTGW) to predict the occurrence of diabetes. Also to independently study whether there was an interaction between HTGW and impaired fasting glucose impaired fasting glucose (IFG) on the cause of diabetes. METHODS: We undertook a cohort study based on data from the "Prevention of Multiple Metabolic Disorders and Metabolic Syndrome (MS) Study in Jiangsu Province, China". We used the logistic regression model to analyze the relations between both HTGW, IFG and diabetes mellitus and to evaluate the multiplied interaction between HTGW and IFG to include product terms method. Counting additive interaction was carried out under the Excel Calculation Sheet, compiled by Anderson and his colleagues. RESULTS: After adjusted for general risk factors and baseline fasting plasma glucose (FPG), results showed that subjects with HTGW had a 2.10 (95% CI: 1.36 - 3.25) adjusted relative risk (HR) of developing a diabetes when compared with those individuals without HTGW at the baseline study. When IFG was stratified, participants with HTGW were significantly associated with diabetes, regardless of IFG. The multi-adjusted HRs of diabetes were 3.09 (1.70 - 5.61) and 2.09 (1.08 - 4.02), respectively. Compared to the participants with non-HTGW and their FPG level below the threshold, those having HTGW and their FPG level was above the threshold, had the highest adjusted HR values [12.05 (95% CI: 6.89 - 21.07)]. Data from the additive interaction analysis showed that RERI as 7.00 (95% CI: 0.49 - 13.51), AP as 0.57 (95% CI: 0.32 - 0.82) and SI as 2.66 (95% CI: 1.36 - 5.21). CONCLUSION: HTGW could predict the occurrence of diabetes, independent from IFG while the presence of HTGW with IFG could have an additive interaction on the cause of diabetes.

[A prospective study on the association between dynamic change of waist circumference and incident hypertension].

OBJECTIVE: To study the impact on dynamic change of waist circumference (WC) through follow-up data on the incidence of hypertension in several cohort groups. METHODS: In this prospective study, 2778 free-hypertension subjects were recruited from a program "Prevention of Multiple Metabolic disorders and metabolic syndrome (MS) in Jiangsu province" (PMMJS) to evaluate the risk of hypertension in relation to WC dynamic change on normal WC or abnormal obesity group. Dynamic change of WC was measured by WC D-value, which was expressed by data on the difference of WC between baseline and the first follow up. Study outcome was defined as incident hypertension during the first to the second follow up period in this study. The association between dynamic change of WC and incident hypertension was analyzed by using Cox proportional hazards regression model. RESULTS: There were 2778 participants, 660 subjects developed hypertension during the follow-up, regardless of the normality of the baseline WC, the risk of hypertension increased across the tertiles of WC, while the incidence of hypertension was higher in non-control group than that in control group. In populations with abdominal obesity and normal WC at baseline, RRs (95%CI) of hypertension were 1.95 (1.19 - 3.19) and 2.38 (1.89 - 2.99) in subjects with abdominal obesity seen at the first follow up period, compared to subjects with normal WC in the same period. After adjustment for gender, age and other hypertension related risk factors, in populations with abdominal obesity and normal WC at baseline survey, RRs (95%CI) of hypertension were 4.36 (1.69 - 9.74) and 1.44 (1.03 - 2.35) respectively, for the non-control group. CONCLUSION: WC dynamic change was associated with hypertension, WC control while WC reduction was important for early prevention on hypertension.

[Association of both peroxisome proliferator-activated receptor, gene-gene interactions and the body mass index].

OBJECTIVE: To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor (α, δ, γ) with obesity and the additional role of a gene-gene interaction among 10 SNPs. METHODS: Participants were recruited within the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province)-cohort-population-survey in the urban community of Jiangsu province, China. 820 subjects (513 non obese subjects, 307 obese subjects) were randomly selected and no individuals were related to each other. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, rs4684847) were selected from the HapMap database, which covered PPARα, PPARδ and PPARγ. Logistic regression model was used to examine the association between ten SNPs in the PPARs and obesity. Odds ratios (OR) and 95% confident interval (95%CI) were calculated. Interactions were explored by using the Generalized Multifactor Dimensionality Reduction (GMDR). RESULTS: A group of 820 participants (mean age was 50.05± 9.41) was involved. The frequency of the mutant alleles of rs2016520 in obese populations was less than that in non-obese populations (26% vs. 33%, P < 0.01). The frequency of the mutant alleles of rs10865710 in obese populations was more than that in non-obese populations (37% vs. 31%, P = 0.01). C allele carriers had a significantly lower obesity occurrence than TT homozygotes [OR (95%CI) = 0.63 (0.47 - 0.84)] for rs2016520 but no significant association was observed between other SNP and incident obesity. GMDR analysis showed a significant gene-gene interaction among rs2016520, rs9794 and rs10865170 for the three-dimension models (P = 0.0010), in which prediction accuracy was 0.5834 and cross-validation consistency was 9/10. It also showed a significant gene-gene interactions between rs2016520 and rs10865170 in all the two-dimensional models (P = 0.0010), in which predictive accuracy was 0.5746 and cross-validation consistency was 9/10. CONCLUSION: Our data showed that rs2016520 was associated with lower obesity risk, as well as interactions among rs2016520, rs9794 and rs10865170 on incident obesity.

Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2).

BACKGROUND AND AIM: To investigate the frequencies, numbers and function of circulating dendritic cell (DC) subsets in patients with hepatitis B virus (HBV) infection, we assayed the circulating precursor DC subsets (including pDC1 and pDC2) and their ability in patients at various stages of HBV infection in vitro. METHODS: Circulating pDC1 and pDC2 frequencies in peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometric analysis. Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction (AMLR) of DC1, cultured from PBMC in vitro, were detected in patients with chronic hepatitis B (CHB). On behalf of pDC2, interferon (IFN)-alpha production of PBMC was determined by the ELISA method in HBV-infected patients. RESULTS: The number of circulating pDC1 decreased only in patients with liver cirrhosis (LC) compared with that in normal controls. However, pDC2 numbers decreased in both CHB and LC patients. DC1 from CHB patients showed lower expression of costimulatory molecules CD80, CD86 and impaired allostimulatory mixed lymphocyte reaction (AMLR) compared with those in normal controls. The ability of PBMC to secrete IFN-alpha also decreased significantly in patients with chronic HBV infection. CONCLUSIONS: Our results suggest that patients with chronic HBV infection have a significantly lower expression of costimulatory molecules and impaired AMLR of pDC1, as well as decreased number and impaired function of circulating pDC2, which may be partially related to HBV disease progression in these patients.