Objective To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects(VSD)in offspring.Methods A case-control study was conducted,recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants.A questionnaire survey collected data on maternal exposures,and blood samples were analyzed for genetic polymorphisms.Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD.Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake.Results The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD(P<0.05).The GC and CC genotypes at rs3768139,AG and GG at rs1050993,AT and TT at rs4659743,GG at rs3768142,and GT and TT at rs3820571 were associated with a decreased risk of VSD(P<0.05).The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD(P<0.05).Conclusions Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring.Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period,suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Objective To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease(CHD)in offspring.Methods The parents of children with simple CHD aged 0 to 1 year(n=683)were recruited as the case group,while the parents of healthy children aged 0 to 1 year(n=740)served as the control group.A case-control study was conducted,and a questionnaire was used to collect information on perinatal exposures.After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching,the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined,as well as the cumulative effects of smoking and drinking on CHD risk.Results Maternal active smoking(OR=2.91,95%CI:1.60-5.30),passive smoking(OR=1.94,95%CI:1.56-2.42),and alcohol consumption(OR=2.59,95%CI:1.89-3.54),as well as paternal smoking(OR=1.52;95%CI:1.22-1.90)and drinking(OR=1.48,95%CI:1.19-1.84),were associated with an increased risk of CHD in offspring.There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring(P>0.05).The more parents'smoking and drinking behaviors during the perinatal pregnancy,the higher the risk of CHD in their offspring(OR=1.50,95%CI:1.36-1.65).Conclusions Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring,and there is a cumulative effect on CHD risk,suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

AIM: To analyze the incidence and disease burden of foreign body in eyes in 1990 and 2019 of China.METHODS: Using the global burden of disease database in 2019, the incidence and disability adjusted life years(DALY)of foreign body in eyes in 1990 and 2019 of China were analyzed among the total population and different age groups of China.RESULTS: In 2019, the number of cases of foreign body in eyes in China was 11.2535 million, and the incidence was 79.12/10 000. The number and incidence of foreign body in eyes in 2019 decreased 12.87% and 27.49% respectively compared with those in 1990. In 2019, the DALY of foreign body in eyes in China was 181 200 person-years, and the DALY of foreign body in eyes in 2019 increased by 6.14% compared with 1990. In 2019, the age groups with the highest number of cases, incidence and DALY were all 20-54 years old, which were 8 012 600, 103.97/10 000 and 102 500 person-years, respectively. From 1990 to 2019, the incidence of foreign body in eyes in China showed a decreasing trend, average annual percentage change(AAPC)=-1.2%(95%CI: -1.8～-0.7, P<0.05), and DALY rate also showed a decreasing trend, AAPC=-0.6%(95%CI:-2.1～0, P<0.05). From 1990 to 2019, the incidence and DALY rate of foreign body in eyes in China and the World showed a downward trend. In 2019, the incidence and DALY rate of foreign body in eyes in China were significantly higher than those in the World and regions with different sociodemographic index(SDI).CONCLUSION: Although the incidence and DALY rates of foreign body in eyes in China have been decreasing in recent years, China has a large population base and the burden of foreign body in eyes is still large in the World. Active preventive measures should be taken to reduce the disease burden of foreign body in eyes.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020. RESULTS: After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs. CONCLUSIONS In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.
Adult ; Cytochrome P-450 Enzyme System/genetics* ; Female ; Genotype ; Heart Defects, Congenital/genetics* ; Humans ; Infant, Newborn ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications/drug therapy*

Wuzhi tablet (WZ) is a prescribed herbal medicine extracted from Schisandra sphenanthera, which is widely used to protect the liver injury and drug-induced hepatotoxicity in clinical practices. Previous studies showed that WZ significantly increased the blood concentrations of tacrolimus, cyclosporine A, paclitaxel by inhibiting the cytochrome P450 3A (CYP3A)-mediated metabolism. CYP3A4 and CYP3A5 are the most important isoenzymes among the CYP3A subfamily. However, there are some differences in the catalytic and inhibitory activities between CYP3A4 and CYP3A5, which may lead to different risk of drug-drug and herb-drug interactions, and the risks may be further amplified in vivo. Currently, few reports have compared the herbal medicine inhibitory effects between CYP3A4 and CYP3A5 mediated metabolic reactions. Therefore, detailing the inhibitory effect of WZ on CYP3A4 and CYP3A5 will help understand and predict the potential herb-drug interaction. The results showed that WZ inhibited CYP3A4 and CYP3A5 in a NADPH-, time- and concentration- dependent manner. WZ showed more potent inhibition on CYP3A5 than CYP3A4. Cautions warranted when combining WZ with other therapeutic drugs to avoid the potential herb-drug interaction.

OBJECTIVES: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD. RESULTS: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05). CONCLUSIONS Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.
Aminohydrolases/genetics* ; Case-Control Studies ; Child ; Female ; Genetic Predisposition to Disease ; Heart Defects, Congenital/genetics* ; Humans ; Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics* ; Minor Histocompatibility Antigens/genetics* ; Mothers ; Multifunctional Enzymes/genetics* ; Polymorphism, Single Nucleotide ; Risk Factors

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective To characterize Chinese families in which both parents and at least one child are diagnosed with malignant diseases and provide reference for cancer screening or early detection in people whose both parents are diagnosed with cancer. Methods Medical records of all clients to the center of cancer screening and prevention of the National Cancer Center/Cancer Hospital between January 2008 and February 2018 were screened to select families in which both parents and at least one child were diagnosed with malignant diseases. The cancer profiles of fathers, mothers, sons and daughters, their age distribution at diagnosis, and similarity of cancers between two generations were analyzed. The proportions of each cancer in males and females of the cohort were compared with corresponding data from the National Cancer Center Registry of China (NCCRC) in 2013. Results Totally 135 families were identified from records of 33 200 clients. Proportion of lung cancer in fathers (40/135, 29.6%) and in mothers (38/135, 28.1%) were higher than the national data (23.9% in males and 14.9% in females, respectively). The proportion of breast cancer in daughters (35/109, 32.1%) was higher than that of mothers (14/135, 10.4%) and the national data (17.1%). In 71 father-son pairs of cancer, 46.5% (33/71) were of the same systematic disease, and 16.9% (12/71) were of the same cancer. These two indexes were 31.2% (

OBJECTIVE: To study the association between maternal reduced folate carrier ( METHODS: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that maternal CONCLUSIONS Maternal
Case-Control Studies ; Child ; Female ; Genetic Predisposition to Disease ; Genotype ; Heart Defects, Congenital/genetics* ; Humans ; Infant ; Polymorphism, Single Nucleotide ; Reduced Folate Carrier Protein/genetics* ; Risk Factors