Genetic variants reducing MTR gene expression increase the risk of congenital heart disease in Han Chinese populations.

AIMS: Elevated homocysteine levels are known to be a risk factor for congenital heart disease (CHD), but the mechanism underlying this effect is unknown. During early embryonic development, homocysteine removal is dictated exclusively by the MTR activity. To examine the role of MTR in CHD risk, we identified genetic variants in MTR and investigated the mechanisms that affect its expression levels and that increase the risk of CHD in Chinese populations. METHODS AND RESULTS: The association between regulatory variants of the MTR gene and CHD was examined in three independent case-control studies in a total of 2340 patients with CHD and 2270 controls. The functional consequences of these variants were demonstrated using dual-luciferase assays, real-time polymerase chain reaction (PCR), electrophoretic mobility shift assays, surface plasma resonance, chromatin immunoprecipitation, and bisulfite sequencing, as well as by a group of predicted microRNAs using a gene reporter system. Two regulatory variants of MTR, -186T>G and +905G>A, were associated with an increased risk of CHD in both the separate and combined case-control studies (-186GG P = 1.32 × 10(-9); +905AA P = 6.35 × 10(-14)). Compared with the major allele, the -186G allele exhibited significantly lower promoter activity, decreased hnRNA and mRNA levels, reduced transcription factor binding affinity, and a more highly methylated promoter. The +905A allele exhibited a statistically stronger binding affinity to functional microRNAs that down regulate MTR expression at the translational level. Both of the minor alleles were correlated with elevated plasma homocysteine concentrations, indicating a genetic component for hyperhomocysteinaemia. CONCLUSIONS: Regulatory variants of the MTR gene increase CHD risk by reducing MTR expression and inducing the homocysteine accumulation and elevation.

Functional variant in methionine synthase reductase intron-1 significantly increases the risk of congenital heart disease in the Han Chinese population.

BACKGROUND: Homocysteine is known to be an independent risk factor for congenital heart disease (CHD). Methionine synthase reductase (MTRR) is essential for the adequate remethylation of homocysteine, which is the dominant pathway for homocysteine removal during early embryonic development. METHODS AND RESULTS: Here, we report that the c.56+781 A>C (rs326119) variant of intron-1 of MTRR significantly increases the risk of CHD in the Han Chinese population. In 3 independent case-control studies involving a total of 2340 CHD patients and 2270 healthy control participants from different geographic areas, we observed that patients carrying the heterozygous AC and homozygous CC genotype had a 1.40-fold (odds ratio=1.40; P=2.32×10(-7)) and 1.84-fold (odds ratio=1.84; P=2.3×10(-11)) increased risk, respectively, of developing CHD than those carrying the wild-type AA genotype. Both in vivo quantitative real-time polymerase chain reaction analysis of MTRR mRNA in cardiac tissue samples from CHD patients and in vitro luciferase assays in transfected cells demonstrated that the c.56+781 C allele profoundly decreased MTRR transcription. Further analysis demonstrated that the c.56+781 C allele manifested reduced CCAAT/enhancer binding protein-α binding affinity. In addition, healthy individuals with the homozygous CC genotype had significantly elevated levels of plasma homocysteine compared with the wild-type AA carriers. CONCLUSIONS: We have demonstrated that the MTRR c.56+781 A>C variant is an important genetic marker for increased CHD risk because this variant results in functionally reduced MTRR expression at the transcriptional level. Our results accentuate the significance of functional single-nucleotide polymorphisms in noncoding regions of the homocysteine/folate metabolism pathway core genes for their potential contributions to the origin of CHD.

[Association of polymorphisms of potassium voltage-gated channel, KQT-like subfamily, member 1 and type 2 diabetes in Jiangsu province, China].

OBJECTIVE: To study the association of polymorphisms in the potassium voltage-gated channel, KQT-like subfamily,member 1(KCNQ1) gene with type 2 diabetes in Chinese population from Jiangsu province. METHODS: Subjects consisting of 2925 cases and 3281 controls were enrolled from a community based cohort study of type 2 diabetes in Wuxi in 2007 and a community based cross-sectional survey on chronic non-communicable disease in Nantong in 2009. Epidemiological questionnaire survey and physical examinations were conducted and 10 h overnight fasting blood samples of 5 ml were drawn for all subjects.Genotypes were determined by TaqMan OpenArray Genotyping System and i-PLEX Sequenom MassARRAY platform. The relationship between KCNQ1 gene polymorphism and risk of type 2 diabetes after adjustment for age,sex and body mass index (BMI) was analyzed. RESULTS: The C allele of rs2237897, rs2237892 and rs2237895 at KCNQ1 increased the risk of type 2 diabetes with adjusted OR (95%CI) value being 1.41(1.30-1.54), 1.35(1.24-1.47), 1.22(1.12-1.33) respectively (all P value < 0.05) under the additive genetic model after adjusted by age,sex and BMI. Stratification analyses in additive genetic model showed that the C allele of rs2237897 increased the risk of type 2 diabetes in subgroups stratified by age ( ≤ 56 years and > 56 years), sex (females and males), BMI (< 24 kg/m(2) and ≥ 24 kg/m(2)) with OR (95%CI) value being 1.39(1.22-1.59), 1.43(1.28-1.60), 1.40(1.26-1.55), 1.44(1.26-1.66), 1.48(1.33-1.66), 1.34(1.17-1.53) respectively (all P value< 0.05). CONCLUSION: Polymorphisms of rs2237897, rs2237892 and rs2237895 in the KCNQ1 gene were associated with occurrence of type 2 diabetes among Jiangsu province population.

Safety, immunogenicity and protection of heterologous boost with an aerosolised Ad5-nCoV after two-dose inactivated COVID-19 vaccines in adults: a multicentre, open-label phase 3 trial.

BACKGROUND: Aerosolised Ad5-nCoV is one of the first licensed mucosal respiratory vaccine against SARS-CoV-2 in the world; however, the safety profile of this vaccine has not been reported in a large population yet. METHODS: This multicentre, open-label phase 3 trial, done in 15 centres in six provinces (Jiangsu, Hunan, Anhui, Chongqing, Yunnan, Shandong) in China, aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV in healthy adults (members of the general population with no acute febrile disorders, infectious disease, serious cardiovascular diseases, serious chronic diseases or progressive diseases that cannot be controlled) at least 18 years old, who had received two doses of inactivated COVID-19 vaccine as their primary regimen. This study contained a non-randomly assigned safety cohort and a centrally randomly assigned (1:1) immunogenicity subcohort. The patients in the immunogenicity subcohort received aerosolised Ad5-nCov (aerosolised Ad5-nCoV group) or inactivated vaccine (inactivated COVID-19 group) The primary endpoints were the incidence of adverse reactions within 28 days following the booster vaccination with aerosolised Ad5-nCoV in the safety population (collected through a daily record of any solicited or unsolicited adverse events filled by each participant) and the geometric mean titre of neutralising antibodies at day 28 after the booster dose in the immunogenicity subcohort (measured with a pseudovirus neutralisation test). This study was registered with ClinicalTrials.gov, NCT05204589. FINDINGS: Between Jan 22, 2022, and March 12, 2022, we recruited 11 410 participants who were screened for eligibility, of whom 10 267 (99·8%) participants (5738 [55·9%] men, 4529 [44·1%] women; median age 53 years [18-92]) received the study drugs: 9847 (95·9%) participants in the open-label cohort to receive aerosolised Ad5-nCoV, and 420 (4·1%) in the immunogenicity subcohort (212 in the aerosolised Ad5-nCoV group and 208 in the inactivated vaccine group). Adverse reactions were reported by 1299 (13%) of 10 059 participants within 28 days after receiving the booster vaccination with aerosolised Ad5-nCoV, but most of the adverse reactions reported were mild to moderate in severity. Participants in the aerosolised Ad5-nCoV group had a significantly higher level of the neutralising antibodies against omicron BA.4/5 (GMT 107·7 [95% CI 88·8-130·7]) than did those in the inactivated vaccine group (17·2 [16·3-18·2]) at day 28. INTERPRETATION: The heterologous booster regimen with aerosolised Ad5-nCoV is safe and highly immunogenic, boosting both systemic and mucosal immunity against omicron subvariants. FUNDING: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

[Single nucleotide polymorphism in flanking region of miR-30c influences the maturing process of miR-30c in lung carcinoma].

OBJECTIVE: To investigate the effect of a common polymorphism rs928508(A/G) in flanking region of miR-30c on the expression of pri, pre and mature miR-30c, and discuss the effect of this polymorphism on the maturing process of miR-30c in lung carcinoma. METHODS: The pGL3-promoter-miR-30c-A and pGL3-promoter-miR-30c-G luciferase plasmids were created containing A or G allele of miR-30c flanking region. Taqman assay was used to genotype rs928508 polymorphism in 50 lung cancer tissues. RT-PCR was performed to determine the expression of pri-miR-30c, pre-miR-30c, mature miR-30c and miR-30c host gene NFYC in the 50 lung cancer tissues. RESULTS: The luciferase expression level of the pGL3-promoter-miR-30c-A construct group was not significantly different compared with that in the the pGL3-promoter-miR-30c-G construct group (A549 cells, P = 0.758; 293A cells, P = 0.554; CHO cells, P = 0.175). The results demonstrated that rs928508(A/G) variant had no effect on the transcriptional regulation of pri-miR-30c. In the genotype-phenotype collection analysis of the 50 lung cancer tissues, the expression of pre-miR-30c and mature miR-30c for rs928508 AG/GG genotypes showed significantly lower levels compared with those in the AA genotype (P = 0.009, P = 0.011). However, the expression of pri-miR-30c showed no significant difference between AG/GG genotypes and AA genotype. Similarly, the expression of host NFYC gene was correlated with pri-miR-30c, showed no significant difference between AG/GG genotypes and AA genotype. CONCLUSION: The rs928508(A/G) polymorphism in flanking region of miR-30c could influence the processing from pri-miR-30c to mature miR-30c, but does not influence the transcription of pri-miR-30c.

Epidemiologic differences in esophageal cancer between Asian and Western populations.

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.

[The relationship between gene polymorphism of telomerase reverse transcriptase and susceptibility to hepatocellular carcinoma].

OBJECTIVE: To explore the correlation between single-nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase (TERT) rs2736098 and rs2736100 and the susceptibility to hepatocellular carcinoma (HCC). METHODS: This case-control study design included 1300 diagnosed HCC patients with HBsAg positive and 1344 HBsAg positive people as control-group.rs2736098 and rs2736100 on TERT were selected as research sites, whose polymorphisms were detected by TaqMan allelic discrimination assay. The OR values (95%CI) were calculated by logistic regression to compare the correlation between different genotype and susceptibility to HCC. RESULTS: The distribution frequencies of three genotypes as GG, AG and AA on rs2736098 were separately 39.3% (500/1273), 44.2% (563/1273) and 16.5% (210/1273) in case group; while respectively 39.6% (526/1328), 45.5% (604/1328) and 14.9% (198/1328) in control group. The distribution frequencies of three genotypes as AA, AC and CC on rs2736100 were separately 33.7% (428/1269), 49.9% (633/1269) and 16.4% (208/1269) in case group; while respectively 34.0% (449/1322), 49.2% (651/1322) and 16.8% (222/1322) in control group. The multi-variates logistic regression analysis showed that there was no significant difference between rs2736098 mutated A carriers and genotype GG carriers in the susceptibility to HCC after adjusting by age, sex, smoking and drinking factors (rs2736098, AA + AG vs GG: adjusted OR = 1.00 (95%CI: 0.86 - 1.18)); and there was no significant different between rs2736100 mutated C carriers and genotype AA carriers in the susceptibility to HCC either (AC + CC vs AA: adjusted OR = 1.03 (95%CI: 0.87 - 1.22)). CONCLUSION: The polymorphisms of rs2736098 and rs2736100 on TERT may not play a landmark role in susceptibility to HCC among Chinese population.

[Relationship between genetic polymorphism in microRNAs precursor and genetic predisposition of hepatocellular carcinoma].

OBJECTIVE: To investigate the relationship between genetic polymorphism in microRNAs (miRNAs) precursor and genetic predisposition of hepatocellular carcinoma (HCC) in Chinese population. METHODS: A case-control study including 963 HCC cases and 829 HBsAg positive controls and 852 HBsAg negative controls was conducted. hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C were selected, where the genotypes were determined by the primer introduced restriction analysis-PCR (PIRA-PCR) assay. Odd ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression analysis to investigate the relationship between onset risk of HCC and different genotypes. RESULTS: The genotype frequencies of CC, CG and GG at rs2910164 gene locus were separately 34.5% (319/925), 48.6% (450/925) and 16.9% (156/925) in cases; 36.4% (274/753), 45.0% (339/753) and 18.6% (140/753) in HBsAg positive controls; and 36.1% (303/840), 46.0% (386/840) and 18.0% (151/840) in HBsAg negative controls. The genotype frequencies of TT, CT and CC at rs11614913 were respectively 29.7% (277/934), 48.1% (449/934) and 22.3% (208/934) in cases; 30.3% (238/785), 51.0% (400/785) and 18.7% (147/785) in HBsAg positive controls; and 28.6% (239/837), 49.8% (417/837) and 21.6% (181/837) in HBsAg negative controls. No significant relationships were observed between these two single nucleotide polymorphisms (SNPs) and onset risk of HCC after adjusting the factors as age, gender, smoking and drinking status in comparison with HBsAg positive controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.10, 95%CI: 0.90 - 1.36; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 1.01, 95%CI: 0.81 - 1.25; as well as in comparison with HBsAg negative controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.06, 95%CI: 0.87 - 1.29; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 0.94, 95%CI: 0.76 - 1.16. As well, no significant relationships were observed between these two SNPs and onset risk of HCC in the subgroups stratified by age, gender, smoking and drinking status. CONCLUSION: hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C may not play an important role in the HCC predisposition among Chinese populations.

[The application of time series analysis in predicting the influenza incidence and early warning].

OBJECTIVE: This research aimed to explore the application of ARIMA model of time series analysis in predicting influenza incidence and early warning in Jiangsu province and to provide scientific evidence for the prevention and control of influenza epidemic. METHODS: The database was created based on the data collected from monitoring sites in Jiangsu province from October 2005 to February 2010. The ARIMA model was constructed based on the number of weekly influenza-like illness (ILI) cases. Then the achieved ARIMA model was used to predict the number of influenza-like illness cases of March and April in 2010. RESULTS: The ARIMA model of the influenza-like illness cases was (1 + 0.785B(2))(1-B) ln X(t) = (1 + 0.622B(2))ε(t). Here B stands for back shift operator, t stands for time, X(t) stands for the number of weekly ILI cases and ε(t) stands for random error. The residual error with 16 lags was white noise and the Ljung-Box test statistic for the model was 5.087, giving a P-value of 0.995. The model fitted the data well. True values of influenza-like illness cases from March 2010 to April 2010 were within 95%CI of predicted values obtained from present model. CONCLUSION: The ARIMA model fits the trend of influenza-like illness in Jiangsu province.

Plasma Vitamin D Levels And Vitamin D Receptor Polymorphisms Are Associated with Survival of Non-small Cell Lung Cancer.

OBJECTIVE: Vitamin D and its receptor (VDR) involve in multiple cellular processes and play an important role in the initiation and progression of malignancy. Thus we hypothesized that plasma vitamin D levels and single nucleotide polymorphisms (SNPs) in VDR may be of prognostic significance in non-small cell lung cancer (NSCLC). METHODS: We examined plasma 25-hydroxyvitamin D [25(OH)D] levels in 87 patients diagnosed with NSCLC using enzyme-linked immunosorbent assay (ELISA) and genotyped seven potentially functional SNPs in VDR in 568 NSCLC patients on Illumina Golden Gate platform. RESULTS: Patients with higher plasma 25(OH)D levels had worse survival than patients with lower ones (P for trend = 0.048). The SNPs of rs1544410 and rs739837 were independently associated with NSCLC survival (adjusted HR = 1.61, 95% CIs = 1.06-2.45 for rs739837 AA vs AC/CC and adjusted HR = 1.51, 95% CIs = 1.06-2.16 for rs1544410 AG/AA vs GG). A joint effect was observed between rs1544410 and rs739837 and the risk of death elevated as the number of unfavourable genotypes patients carried increased (P for trend = 0.003). There were no significant associations between VDR polymorphisms and plasma 25(OH)D levels. CONCLUSION: Our findings indicate that plasma 25(OH)D levels and genetic variants of VDR may serve as prognostic markers for NSCLC in this Chinese population.

[Relationship between polymorphisms of X-ray repair cross-complementing group 1 gene Arg194Trp, Arg399Gln and susceptibility of breast cancer].

OBJECTIVE: To study the relationship between two polymorphisms, Arg194Trp and Arg399Glu, of DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) and the susceptibility of breast cancer in Chinese women. METHODS: A case-control study with 698 histologically-confirmed female breast cancer cases and 813 cancer-free controls frequency-matched by age and residential area was conducted, and the genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Logistic regression analysis was used to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) of XRCC1 Arg194Trp and Arg399Glu with susceptibility of breast cancer. A Meta-analysis was used to evaluate the association of Arg399Glu with breast cancer in Chinese women. RESULTS: The genotype frequencies of Arg/Arg, Arg/Trp, Trp/Trp, Arg/Trp + Trp/Trp of XRCC1 gene 194 locus were 48.81% (327/670), 39.85% (267/670), 11.34% (76/670), 51.19% (343/670) in cases and 48.80% (387/793), 41.99% (333/793), 9.21% (73/793), 51.20% (406/793) in controls. Compared to Arg/Arg, the adjusted ORs (95%CIs) were 0.98 (0.75 - 1.28), 1.17 (0.76 - 1.80), 1.09 (0.86 - 1.40). The frequencies of Arg/Arg, Arg/Trp, Trp/Trp, Arg/Gln + Gln/Gln of XRCC1 399 locus were 52.40% (349/666), 38.29% (255/666), 9.31%(62/666), 47.60% (317/666) in cases and 52.22% (412/789), 38.53% (304/789), 9.25% (73/789), 47.78%(377/789) in controls. Compared to Arg/Arg, the adjusted ORs (95%CIs) were 0.93(0.63 - 1.08), 0.96 (0.42 - 1.09), 0.91 (0.62 - 1.05). No significant associations were found between these two polymorphisms and breast cancer risk, also in subgroups stratified by menopause status, history of breast-feed, reproduction and taking oral contraceptives. The overall ORs (95%CIs) of 399 Arg/Trp + Trp/Trp vs Arg/Arg from Meta analysis was 0.97 (0.85 - 1.10). CONCLUSION: The XRCC1 Arg194Trp and Arg399Gln may not play an important role in the susceptibility of breast cancer in Chinese women.

Basic reproduction number and predicted trends of coronavirus disease 2019 epidemic in the mainland of China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a serious epidemic around the world, but it has been effectively controlled in the mainland of China. The Chinese government limited the migration of people almost from all walks of life. Medical workers have rushed into Hubei province to fight against the epidemic. Any activity that can increase infection is prohibited. The aim of this study was to confirm that timely lockdown, large-scale case-screening and other control measures proposed by the Chinese government were effective to contain the spread of the virus in the mainland of China. METHODS: Based on disease transmission-related parameters, this study was designed to predict the trend of COVID-19 epidemic in the mainland of China and provide theoretical basis for current prevention and control. An SEIQR epidemiological model incorporating asymptomatic transmission, short term immunity and imperfect isolation was constructed to evaluate the transmission dynamics of COVID-19 inside and outside of Hubei province. With COVID-19 cases confirmed by the National Health Commission (NHC), the optimal parameters of the model were set by calculating the minimum Chi-square value. RESULTS: Before the migration to and from Wuhan was cut off, the basic reproduction number in China was 5.6015. From 23 January to 26 January 2020, the basic reproduction number in China was 6.6037. From 27 January to 11 February 2020, the basic reproduction number outside Hubei province dropped below 1, but that in Hubei province remained 3.7732. Because of stricter controlling measures, especially after the initiation of the large-scale case-screening, the epidemic rampancy in Hubei has also been contained. The average basic reproduction number in Hubei province was 3.4094 as of 25 February 2020. We estimated the cumulative number of confirmed cases nationwide was 82 186, and 69 230 in Hubei province on 9 April 2020. CONCLUSIONS: The lockdown of Hubei province significantly reduced the basic reproduction number. The large-scale case-screening also showed the effectiveness in the epidemic control. This study provided experiences that could be replicated in other countries suffering from the epidemic. Although the epidemic is subsiding in China, the controlling efforts should not be terminated before May.

Dexmedetomidine attenuates inflammation and pancreatic injury in a rat model of experimental severe acute pancreatitis via cholinergic anti-inflammatory pathway.

BACKGROUND: Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism. METHODS: SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria. RESULTS: Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ±â€Š30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ±â€Š46.8 vs. 421.7 ±â€Š48.3 pg/ml; amylase: 2102.3 ±â€Š165.3 vs. 3186.4 ±â€Š245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ±â€Š50.3 vs. 332.4 ±â€Š25.1 Hz; discharge amplitude: 33.4 ±â€Š5.3 vs. 20.5 ±â€Š2.9 µV). CONCLUSIONS: Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus- and α7nAChR-dependent mechanisms.

Promoter polymorphisms of IL2, IL4, and risk of gastric cancer in a high-risk Chinese population.

Interleukin 2 (IL2) is a typical Th1 cytokine, and interleukin 4 (IL4) is an inducible Th2 cytokine. These cytokines are critical mediators of the Th1/Th2 balance and apoptosis potential and involved in the process of inflammation-mediated carcinogenesis in human organs, including the gastrointestinal tract. Therefore, we tested the hypothesis that functional variants in IL2 and IL4 were associated with risk of gastric cancer by genotyping two promoter polymorphisms in IL2 G-330T (rs2069762) and IL4 T-168C (rs2070874) in a case-control study of 1045 patients with incident gastric cancer and 1100 cancer-free controls in a high-risk Han Chinese population. We found that, compared with the IL4 -168TT genotype, heterozygous -168TC and combined -168TC/CC genotypes were associated with a significantly decreased gastric cancer risk [adjusted odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.67-0.98 for -168TC; OR = 0.83, 95% CI = 0.69-1.00 for -168TC/CC, respectively]. Furthermore, this significant protective effect was more evident for gastric cardia cancer patients (adjusted OR = 0.73, 95% CI = 0.56-0.95 for -168TC/CC vs. -168TT). For IL2 G-330T, subjects carrying GT/TT genotypes also had a significantly reduced risk of gastric cardia cancer (adjusted OR = 0.68, 95% CI = 0.46-0.99), compared with those carrying the GG genotype. Our results indicate that IL4 T-168C and IL2 G-330T promoter polymorphisms may contribute to the etiology of gastric cardia cancer in Chinese populations.

Combining previously published studies with current data in Bayesian logistic regression model: an example for identifying susceptibility genes related to lung cancer in humans.

A general analysis method is proposed that utilizes meta-analysis to incorporate similar studies in addition to our current investigation in order to obtain informative prior effect parameters in a logistic regression model. It is common in epidemiological studies that data from similar previous studies are available. The case of gene susceptibility association with increased lung cancer frequency was used to demonstrate this methodology. Results of Markov chain Monte Carlo (MCMC) iterations provided a more precise estimation of the regression coefficient in a logistic model with informative prior distribution compared to the noninformative prior distribution model. In situations where similar historical data are available, it is proposed to include as much relevant information as previously published results in the analysis of current data.

Potentially functional polymorphisms of the vascular endothelial growth factor gene and risk of gastric cancer.

Vascular endothelial growth factor (VEGF), the key mediator of angiogenesis, plays an important role in the development of different kind of tumors, including gastric cancer (GC). The aim of this study is to test the hypothesis that genetic variants of VEGF are associated with risk of GC. We genotyped four potentially functional polymorphisms (-2578C > A, -1498T > C, -634G > C, and +936C > T) of the VEGF gene in a population-based case-control study of 540 GC cases and 561 frequency-matched cancer-free controls in a high risk Chinese population. We found that none of the four polymorphisms or their haplotypes achieved significant difference in their distributions between GC cases and controls. Multiple logistic regression analyses revealed that GC risk was not significantly associated with the variant genotypes of the four VEGF polymorphisms as compared with their wild-type genotypes. In conclusion, our data did not support a significant association between VEGF SNPs and the risk of GC.

Diet habits, alcohol drinking, tobacco smoking, green tea drinking, and the risk of esophageal squamous cell carcinoma in the Chinese population.

OBJECTIVE: This study aims to investigate the risk of esophageal squamous cell carcinoma in relation to exogenous factors in a rural area of China with a high incidence of esophageal squamous cell carcinoma. METHODS: A population-based case-control study was conducted in Yangzhong County, Jiangsu Province, China, with 355 histologically confirmed esophageal squamous cell carcinoma cases recruited between 1 January 2004 and 28 February 2006 and 408 controls matched by sex and age, randomly selected from the local population. RESULTS: Stratified logistic regression analysis by sex revealed that hot-temperature food items, pork braised in brown sauce and old stocked rice intake could increase the risk of esophageal squamous cell carcinoma with odds ratio of 2.127 (95% confidence interval: 1.394-3.245), 2.059 (95% confidence interval: 1.417-2.993) and 9.059 (95% confidence interval: 5.930-13.840), respectively, in men and 3.048 (95% confidence interval: 1.733-5.364), 1.914 (95% confidence interval: 1.159-3.162) and 14.532 (95% confidence interval: 7.816-27.019), respectively, in women, whereas diet high in salt and chili, tobacco smoking and alcohol drinking only showed possible risk effects in men with odds ratio 2.338 (95% confidence interval: 1.568-3.485), 3.378 (95% confidence interval: 2.117-5.389), 1.976 (95% confidence interval: 1.337-2.921) and 2.197 (95% confidence interval: 1.510-3.195), respectively. Green tea drinking showed a protective effect in women (odds ratio=0.257; 95% confidence interval: 0.070-0.941). CONCLUSIONS: Findings from this study provided evidence that dietary habits, tobacco-smoking and alcohol drinking contribute to the etiology of esophageal squamous cell carcinoma. A healthy dietary habit, with smoking cessation and alcohol controlling is of a great importance in the prevention of esophageal cancer.

Association between delta-aminolevulinic acid dehydratase (ALAD) polymorphism and blood lead levels: a meta-regression analysis.

A meta-regression analysis was undertaken to evaluate the association between delta-aminolevulinic acid dehydratase (ALAD) genotypes and blood lead levels obtained from data published in various journals. In total, 15 studies were included in the final analysis. Both fixed effects and random effects models were used to undertake the pooled analysis. Using a fixed effects model, pooled estimates of mean differences of various ALAD genotypes was significant at 0.61 microg/dl. Using a random effects model, the pooled estimate was also significant at 1.51 microg/dl. Data indicated that certain ALAD genotypes may affect the susceptibility of humans to lead.

Identification and functional characterization of JWA polymorphisms and their association with risk of gastric cancer and esophageal squamous cell carcinoma in a Chinese population.

Recently, a novel single nucleotide polymorphism (SNP) in the promoter of the JWA gene (-76G --> C) was identified that may alter the transcription activity and thus play a role in increased risk of bladder cancer. In this study, a screen for more novel variants in the JWA exons was undertaken by using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by a PCR-restriction fragment length polymorphism (PCR-RFLP) method and evaluating the functions of newl identified JWA -76G --> C using the reporter gene assay. In addition to the -76G --> C polymorphism, another novel SNP (723T --> G) in exon 3 of JWA was identified. In a case-control study of these two SNPs in 413 gastric cancer and 250 esophageal squamous-cell carcinoma (ESCC) patients and 814 cancer-free controls in a Chinese population, data showed that both SNPs were associated with enhanced risk of these cancers. The reporter gene assay showed that the -76C variant allele lost its response to benzo[a]pyrene (BaP) exposure, compared to the -76G allele. In addition, the JWA -76C allele was found to be associated with increased gastric and esophageal cancer risks in this study population. Further studies are needed to substantiate the biological significance and related mechanisms underlying the associations.