Xie Dx

Genetic variations in the TGFβ signaling pathway, smoking, and risk of colorectal cancer in a Chinese population

Recent genome-wide association studies (GWAS) have reported multiple risk loci associated with risk of colorectal cancer (CRC), some of which are involved in the transforming growth factor beta (TGFβ) signaling pathway. We systematically examined associations of common genetic variations in the TGFβ signaling pathway and environmental factors with CRC risk using a two-staged case-control study in a Chinese population. A set of 77 single-nucleotide polymorphisms (SNPs) in 10 candidate genes involved in the TGFβ signaling pathway and several environmental factors including sex, age, smoking and drinking were examined by random forest (RF) to capture the potential gene-gene and gene-environment interactions in stage 1 of the study with 443 CRC patients and 480 controls. Three promising SNPs (SMAD7 rs11874392, TGFBR1 rs10988706 and rs6478972) selected by the RF method were genotyped in stage 2 comprising 351 cases and 360 controls for validation. SMAD7 rs11874392 presented consistently significant associations with a risk of CRC at both stages, with odds ratio = 1.41 (95% confidence interval = 1.21-1.63) using additive modes in combined analyses. Moreover, the potential interactions between SMAD7 rs11874392, TGFBR1 rs10988706 and rs6478972 were indicated consistently in both stages of the study by using pair-wise interaction and multilocus genotype pattern analysis. Additionally, gene-smoking interactions for rs11874392, rs10988706 and rs6478972 were also found to enhance the risk of CRC at both stages, with P for multiplicative interaction equal to 1.162×10(-6), 8.574×10(-8) and 9.410×10(-8) in combined analyses, respectively. This study emphasized the substantial role of the TGFβ signaling pathway in CRC, especially in interaction with smoking.

Interactions between Genetic Variants in the Adiponectin, Adiponectin Receptor 1 and Environmental Factors on the Risk of Colorectal Cancer

Background Metabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis. Methodology/Principal Findings To investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48–2.54) for CC genotype compared with TT genotype. In two-factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78–7.34), 3.18 (95%CI: 1.73–5.82) and 1.97 (95%CI: 1.27–3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18–fold (95%CI:0.89–fold to 1.58–fold), 1.87–fold (95%CI: 1.38–fold to2.54–fold) and 4.39–fold (95%CI: 2.75–fold to 7.01–fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P trend <0.0001). Conclusions/Significance Our results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI.

Point prevalence surveys of healthcare-associated infection in 13 hospitals in Hubei Province, China, 2007-2008

Successive point prevalence surveys were conducted in November 2007 and 2008 to monitor the prevalence of healthcare-associated infection (HCAI) in 13 grade III, 1st class hospitals in Hubei Province of China, using the case definition criteria established by the Ministry of Health in the Peoples Republic of China. In total, of 20 350 patients surveyed, 833 (4.09%) HCAIs were observed in 790 (3.88%) patients. There was no significant difference between the overall prevalence of HCAI in 2007 (4.14%) and 2008 (3.72%). Respiratory tract infection was the most common HCAI (63.15%), followed by surgical site infection (9.60%) and urinary tract infection (8.64%). Only 35.29% (294/833) of HCAI patients had positive microbiology results. Gram-negative bacteria were isolated most frequently and the most frequent organism was Pseudomonas aeruginosa, followed by Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Antibiotic use was documented for 10,344 (50.83%) patients, and cephalosporins, penicillins, and quinolones were the most commonly used agents for treatment or prophylaxis.

Ventilator-associated pneumonia in intensive care units in Hubei Province, China: a multicentre prospective cohort survey.

A multicentre prospective cohort study was performed in 17 intensive care units (ICUs) in tertiary care hospitals in Hubei Province, China. Ventilator-associated pneumonia (VAP) was defined according to modified criteria from the published literature. Among 4155 ventilated patients, the crude incidence and incidence rate of VAP were 20.9% and 28.9 cases per 1000 ventilator-days. Multivariate analysis using logistic regression revealed risk factors including male sex [risk ratio (RR): 1.5; P<0.001], coma (RR: 2.1; P<0.001), chronic obstructive pulmonary disease (RR: 1.4; P<0.001), infections at other sites (RR: 1.6; P=0.001), serious disease predating the onset of VAP (RR: 1.6; P<0.001) and interventions including antacid treatment (RR: 1.4; P<0.001), antimicrobial treatment (RR: 5.1; P<0.001), bronchoscopy (RR: 1.5; P=0.041) and tracheostomy (RR: 1.4; P=0.014). The most frequently isolated causative pathogens were Pseudomonas aeruginosa and Acinetobacter baumannii. Of all Staphylococcus aureus isolates, 45.7% were meticillin resistant. Rates, risk factors and causal pathogens of VAP in ICUs in Hubei differ from those reported from developed countries. These data show the need for more effective infection control interventions in Hubei, China.

The positive effect of an intervention program on the hypertension knowledge and lifestyles of rural residents over the age of 35 years in an area of China

Hypertension (HTN) is a leading cause of cardiovascular and cerebrovascular diseases. Lifestyle modification may be the preferential approach to prevent and control HTN. The purpose of this study was to evaluate the effects of a community intervention program, which focused on improving the HTN knowledge, diets and lifestyles in a rural Chinese area. The study was carried out in a rural area of the Hubei Province from May 2003 to April 2006. A total of 1632 participants were recruited. Of the participants, 826 from the town of Xiaoxita and 806 from the town of Fenxiang were assigned to the intervention group (group I) and to the control group (group C), respectively. Group I participants underwent an intervention that included HTN education and dietary and lifestyle guidance. Group C participants were not subjected to an intervention. The outcome measures included HTN knowledge, dietary and lifestyle behaviors, and prevalence, awareness, treatment and control rates of HTN. Along with the changes in HTN education (P<0.05), the participants in group I exhibited a significantly greater improvement in dietary habits and lifestyle behaviors, including reducing salty food intake (13.6%), fat intake (22.9%) and alcohol consumption (9.6%), after 3 years in comparison with those in group C (21.7, 31.9 and 18%, respectively). The prevalence of HTN was significantly lower in group I (22.5%) than in group C (36%) after the intervention strategies. The study showed that the implementation of a community intervention program involving HTN education and lifestyle modifications for rural residents is a powerful approach to reduce HTN prevalence and improve long-term health outcomes.

The Leptin Gene Family and Colorectal Cancer: Interaction with Smoking Behavior and Family History of Cancer

Background Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin. Methodology/Principal Findings A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13–1.76) and 1.74 (95%CI 1.08–2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82×10−10). Conclusions/Significance Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.

Predicting the incidence risk of ischemic stroke in a hospital population of southern China: A classification tree analysis

OBJECTIVE To determine the major risk factors and their interactions of ischemic stroke (IS) and to develop a classification tree model to predict the incidence risk of IS for a Chinese population. METHODS Exhaustive Chi-squared Automatic Interaction Detection (Exhaustive CHAID) algorithm of classification tree method was applied to build a prediction model for the incidence risk of IS under the design of 1:1 matched case-control study. The statistics of misclassification risk was used to evaluate the fitness of the model. RESULTS In the prediction model, six variables of physical exercise, history of hypertension, tea drinking, HDL-c level, smoking status and educational level were in turn selected as the predictors of IS incidence risk. In the subgroup of lacking of physical exercise, individuals who had history of hypertension would have a significantly higher IS risk (92%) than that of the ones who had no history of hypertension (64%). The misclassification risk estimate of the prediction model was 0.21 with the standard error of 0.02, indicating that 79% of the cases could be classified correctly based on current prediction model. CONCLUSIONS Lacking of physical exercise and history of hypertension are identified to be the prominent predicting variables of IS risk for a hospital population of southern China. Although CHAID analysis could provide detailed information and insight about interactions among risk factors of IS, we still need to validate our model and improve the vascular risk prediction for Chinese subjects in further studies.

Surveys of catheter-associated urinary tract infection in a university hospital intensive care unit in China

PhD; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Hubei, China MD; Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Hubei, China MSc; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Are progenitor cells pre‐programmed for sequential cell cycles not requiring cyclins D and E and activation of Cdk2?

Abstract.  Objectives: Based on studies of unicellular organisms or cultured mammalian cells, the generally accepted model of cell‐cycle regulation has been developed in which sequential (scheduled) expression of cyclins D, E, A and B and activation of Cdk2 and Cdk1 takes place. It is assumed that the same model is applicable both in vivo and in vitro. Materials and methods: In the present study, we compared proliferating marrow cells freshly isolated from healthy individuals with proliferating lymphocytes in cultures. Results: We demonstrate that during progression of freshly collected human bone marrow cells through G1, S and G2/M, only Cdk1 combined with cyclins A and B1 was distinctly present and active, and its activity gradually increased. In contrast, in vitro growing mitogen‐stimulated lymphocytes had perfectly scheduled sequential expression of all four cyclins and Cdk1 and Cdk2 activities. Conclusion: Our findings demonstrate that the pattern of cyclin expression and Cdk activity in bone marrow in vivo is distinctly different from the one observed for normal cells in vitro. Because proliferating bone marrow cells are predominantly expanding populations of committed progenitors, it is likely that during the expansion phase their cell‐cycle progression is pre‐programmed, being driven solely by Cdk1 combined either with cyclin A or with cyclin B1. Expansion of progenitor cells thus may not require the early steps of cell‐cycle regulation, associated with triggering progression by availability of growth factors and mitogens.

Detection of carcinoembryonic antigen in peritoneal fluid of patients undergoing laparoscopic distal gastrectomy with complete mesogastric excision: Carcinoembryonic antigen in peritoneal fluid of patients with gastric cancer

Surgery for gastric cancer may result in free intraperitoneal cancer cells. This study aimed to determine whether laparoscopic gastrectomy with complete mesogastric excision (D2 + CME) reduces the number of free intraperitoneal cancer cells.