Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

OBJECTIVES: Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling. METHODS: A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene. RESULTS: Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1). CONCLUSIONS Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.
Case-Control Studies ; Dietary Supplements ; Female ; Folate Receptor 1/genetics* ; Folate Receptor 2/genetics* ; Folic Acid/administration & dosage* ; Heart Defects, Congenital/genetics* ; Hospitals ; Humans ; Infant ; Polymorphism, Single Nucleotide ; Prospective Studies ; Risk Factors

To evaluate whether the in vitro fertilization-embryo transfer (IVF-ET) procedures could increases the risks of adverse pregnancy outcomes (APOs) in offspring.
 Methods: A hospital-based prospective cohort design was conducted, which contained a control group of singleton pregnancies with indicators of subfertility who were still conceived naturally after using simple medical treatment (e.g. minimal medical intervention or ovulation induction), and an exposure group consisted of singleton pregnancies who had a history of infertility and IVF-ET treatment. All factors different between two groups in the univariate analysis were included in the multivariable logistic regression to evaluate the independent effect of IVF-ET procedures themselves on APOs.
 Results: After controlling for confounding factors by using multivariate logistic regression analysis, our results showed that pregnancies after IVF-ET experienced a higher risk of preterm birth (OR=1.28, 95% CI 1.05 to 1.56), low birth weight (OR=1.69, 95% CI 1.27 to 2.31), perinatal mortality (OR=5.33, 95% CI 2.44 to 11.81), and congenital malformations (OR=1.83, 95% CI 1.12 to 2.94).
 Conclusion: The IVF-ET operational factors may increase the risk of APOs.
Cohort Studies ; Embryo Transfer ; statistics & numerical data ; Female ; Fertilization in Vitro ; statistics & numerical data ; Humans ; Infant, Newborn ; Logistic Models ; Pregnancy ; Pregnancy Outcome ; Prospective Studies

Objective:To investigate the effect of nimodipine liposomes for injection(NOLI)on focal cerebral ischemia/reperfusion(I/R)injury in rats.Methods:Seventy SD rats were divided into NDLI 1.00 mg/kg,NDLI 0.50 mg/kg,NDLI 0.25 mg/kg,nimodipine 1.00mg/kg,solvent 10 mL/kg,sham-operation and ischemic model groups.The model of middle cerelral artery occlusion in rat was replicated.The behavioral scores in rats were assessed in all groups.The infarct volume,brain water content,biochemical indices of brain homogenate and histology were detected.Results:1he NDLI 1.00mg/kg,0.50 mg/kg and 0.25 mg/kg groups could significantly improve the behavior scores in focal cerebral ischemic rats,reduce the volume of cerebral infarction,decrease the brain water content,improve the activities of Na+,K+-ATPase,Ca2+-ATPase,glutathione(GSH)and superoxide dismutazse(SOD)in brain tissues,reduce conteras of malondialdehyde(MDA),lactic acid(LA)and nitric oxide(NO),and improve histo logical injury.Conclusions:NDLI has the protective effect on focal cerebral ischemia/reperfusion injury in rats.

AIM: To study the protective effects of nimodipine liposomes for injection (NDLI) on injuries of total cerebral ischemia/reperfusion(I/R) in rats and anoxia in mice. METHODS: Acute anoxia in mice was produced by hypoxia under normal pressure and decapitation. In these two models the survival time and persistent time of gasping were observed. Ameliorated pulsinelli four-vessel occlusion method was used to make global brain ischemia model. The EEG, the time of righting reflex recovery and Evans blue content in the homogenate of the brain tissues were recorded. RESULTS: NDLI obviously prolonged the survival time and persistent time of gasping in mice subjected to acute anoxia, remarkably shortened the time of EEG recovery and righting reflex recovery, and reduced Evens blue content in the homogenate. CONCLUSION: NDLI has significantly protective effects on injuries of total cerebral I/R and anoxia.

Objective To observe the clinical efficacy and safety of5%imiquimod cream in the top-ical treatment of condyloma acuminatum(CA).Methods A randomized,double-blind,parallel placebo-controlled clinical study was conducted.The test drug was topically used in CA patients,three times a week for8weeks.Patients whose warts cleared completely were followed up for one month to determine recurrence rates.Results Two hundred fifty-eight patients with anogenital warts were enrolled into this trial.One hun-dred twenty-nine patients were randomly selected to receive5%imiquimod cream;129patients were ran-domly chosen to receive placebo cream.Results showed that the cure rates were12.30%,32.79%,50%,60.66%respectively in study group for2,4,6,8weeks and were4.88%,14.63%,19.51%,26.02%respec-tively in control group for2,4,6,8weeks(P

Objective To investigate the gene sequence and mutations of human papillomavirus(HPV)type16E6E7in patients with HPV infection in Beijing.Methods Sample DNA was extracted from lesions in patients with HPV infection.HPV types were identified by polymerase chain reaction(PCR).E6E7gene,isolated from samples infected with HPV16only,was cloned into plasmid pGEM-3zf and sequenced.Results The recombinant plasmid pGEM/16E6E7was constructed successfully.The whole HPV E6E7gene was776bp in length which was equal to that of the standard strain.Three nucleotides exchanges,i.e.,p60PROE6,p96GLUE6,p565SERE7,were found in E6E7gene.Conclusion The data suggest that there are nucleotide differences of HPV E6E7gene between HPV obtained from Beijing and that of standard sequence.

Objective To investigate the significance of cyclin E and p27 in genital epidermal benign and malignant tumors. Methods HPV DNA was examined and typed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in 99 biopsy specimens taken from skin lesions of condyloma acuminatum, external genital carcinoma in situ and invasive squamous cell carcinoma. The expression of cyclin E and p27 in the lesions was examined by immunohistochemistry technique. Results (1) The cyclin E expression in epidermis was notably higher in the lesions than that in normal skin. In HPV-positive samples, the cyclin E expression was higher than that in HPV-negative ones. The cyclin E expression was strongest in invasive squamous cell carcinoma lesions and lowest in condyloma acuminatum lesions. (2) The p27 expression in condyloma acuminatum was slightly higher than that in normal epidermis. But it was notably lower in the lesions of carcinoma in situ and invasive squamous cell carcinoma than that in the normal skin. The expression was also lower in HPV-positive lesions than that in HPV-negative ones. Comparing the three kinds of HPV positive lesions, the intensity of expression was highest in condyloma acuminatum and lowest in invasive squamous cell carcinoma. (3) The study also showed that cyclin E expression was correlated with p27 expression in the lesions. Conclusions The expression of cyclin E and p27 is associated with HPV infection in the lesions. HPV infection might induce epidermal proliferation and malignant transformation by influencing the expression and interaction of cyclin E and p27.

Objective To observe the clinical efficacy and safety of topical interferon alfa-1b cream in the treatment of herpes zoster. Methods A randomized, double-blind, parallel placebo-controlled clinical study was conducted. The test drug was topically used in herpes zoster patients, three times a day for 2 weeks. Patients whose skin lesions cleared completely were followed for 29 days to observe postherpetic neuralgia. Results One hundred and twenty-eight patients with herpes zoster were enrolled into this trial. Sixty-five patients were randomly selected to receive interferon alfa-1b cream and sixty-three patients received vehicle cream. After following up for 11, 14, 22, 29 days the cure rates were 69.2%, 81.5%, 90.8%, 95.4% respectively in the study group and were 57.1%, 71.4%, 84.1% and 84.1% respectively in the control group(P