OBJECTIVETo investigate the role of a potential diabetes-related mitochondrial region, which includes two previously reported mutations, 3243A-->G and 3316G-->A, in Chinese patients with adult-onset type 2 diabetes.

METHODSA total of 277 patients and 241 normal subjects were recruited for the study. Mitochondrial nt 3116 - 3353, which spans the 16S rRNA, tRNA(leu(UUR)) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR), direct DNA sequencing, PCR-restriction fragment length polymorphism and allele-specific PCR. Variants were analyzed by two-tailed Fisher exact test. The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3.

RESULTSFour homoplasmic nucleotide substitutions were observed, 3200T-->C, 3206C-->T, 3290T-->C and 3316G-->A. Only the 3200T-->C mutation is present in the diabetic population and absent in the control population. No statistically significant associations were found between the other three variants and type 2 diabetes. The 3200T-->C and 3206C-->T nucleotide substitutions located in 16S rRNA are novel variants. The 3200T-->C caused a great alteration in the minimal free energy secondary structure model while the 3206C-->T altered normal 16S rRNA structure little.

CONCLUSIONSThe results suggest that the 3200T-->C mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral. In contrast to the Japanese studies, the 3316G-->A does not appear to be related to type 2 diabetes.

Age of Onset ; Aged ; Alleles ; Base Sequence ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Humans ; Middle Aged ; Models, Molecular ; Nucleic Acid Conformation ; Point Mutation ; Polymerase Chain Reaction ; methods ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S ; chemistry ; genetics

OBJECTIVETo investigate the role of lipoprotein lipase (LPL) gene on Chinese patients with hypertriglyceridemic type 2 diabetes.

METHODSThree subject groups, including hypertriglyceridemic group, normalipidemic type 2 diabetes group and healthy controls, were recruited and screened for sequence changes in LPL gene with PCR, SSCP, restriction analysis and direct DNA sequencing. LPL mass and activity in post-heparin plasma and in in vitro expression were investigated. Comparative modeling was performed via Swiss-PDB Viewer to provide the potential 2-D structures of wildtype and mutant proteins.

RESULTSFour missense mutations, Ala71Thr, Val18Ile, Gly188Glu and Glu242Lys, were identified in patients with hypertriglyceridemic type 2 diabetes, and not in both normalipidemic diabetes and the control subjects. The four missense mutations were located in the highly conserved amino acid sites, which are involved in highly conserved exon 3, 5, or 6 regions. They led to reduced LPL mass and enzyme activities in both post-heparin plasma and in vitro expression. The modeled structures displayed the differences to a great extent between the mutant and wide-type molecules.

CONCLUSIONThese results indicated that the 4 missense mutations lead to LPL deficiency and subsequent hypertriglyceridemia. The LPL deficiency predispose a progressive diabetic pathway to those affected individuals. LPL gene is one of susceptibility gene for hypertriglyceridemic type 2 diabetes.

Asian Continental Ancestry Group ; Diabetes Mellitus, Type 2 ; complications ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Hypertriglyceridemia ; complications ; enzymology ; genetics ; Lipoprotein Lipase ; genetics ; Male ; Middle Aged ; Mutation, Missense ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational

Objective: To study the dose-response relationship between maternal thyroid hormone levels in the first twenty weeks of pregnancy and the infant physical and neuropsychological development. Methods: In this prospective cohort study, a total of 945 women and their children were included. Maternal serum samples during first half of the pregnancy were collected and analyzed for levels of thyroid hormones by using the electro-chemiluminescence immunoassay. Maternal social demographic information was collected by using the a self-administered questionnaire. Physical measurements of newborns and neuropsychological evaluation of infants were performed by doctors of maternal and child health care. Results: The differences in newborns' birth length and head circumference were significant among the newborns of mothers with different percentiles of maternal serum (thyroid-stimulating hormone, TSH) levels (P<0.05). Newborns with maternal TSH level ≥P(95) or <P(5) had significantly lower birth length and birth head circumference, compared with the newborns with maternal TSH level between P(25)-P(75) (P<0.05). Newborns' birth head circumferences showed an inverted U-shaped association with maternal serum TSH level (Y=33.940+0.003X-0.109X(2), F=4.685, P=0.009). The difference in mental development index (MDI) of the infants at 18-30 months were significant among the infants of mothers with different percentiles of maternal serum TSH level (P<0.05). Infants with maternal TSH level ≥P(90) showed lower MDI (6.39, 95%CI: 2.29-10.49, P=0.002) compared with the infants with maternal TSH level between P(25)-P(75). Infant's MDI at 18- 30 months also showed an inverted U-shaped association with maternal serum TSH level (Y=103.249-1.524X-0.939X(2), F=6.616, P=0.001). Conclusions: Maternal TSH level was associated with newborn's birth length, birth head circumference and infant's MDI at 18-30 months. Newborn's birth head circumference and infant's MDI at 18-30 months showed an inverted U-shaped association with maternal serum TSH-Z score.
Birth Weight/physiology* ; Child ; Child Development/physiology* ; China ; Female ; Fetal Blood/metabolism* ; Humans ; Infant ; Infant, Newborn/blood* ; Pregnancy ; Prenatal Exposure Delayed Effects/blood* ; Prospective Studies ; Thyroid Gland/physiology* ; Thyroid Hormones/metabolism* ; Thyrotropin/blood*

Objective: To evaluate the frailty status and understand the relationship between the incidence of fall and frailty status in the elderly in Beijing. Methods: A cross-sectional study was conducted in old people aged ≥60 years in Longtan community of Dongcheng district in Beijing from November 2015 to January 2016. The information about any fall during the past year and frailty status of the elderly were collected with a standardized structured questionnaire in face-to-face interviews. The frailty status of elderly people was assessed with frailty index (FI) method. Logistic regression analysis was used to explore the relationship between fall and frailty status among the elderly. Results: Among 1 557 old people surveyed, the incidence of fall was 17.8% (277/1 557) during the past year. The incidence of fall in women (21.0%, 192/277) was statistically higher than that in men (13.3%, 85/277) (χ(2)=15.288, P=0.000). The median (quartile) value of FI of the elderly surveyed was 0.09 (0.08); and women had a higher FI median value than men [0.10 (0.08) versus 0.08 (0.07)](Z=5.376, P=0.000). The median FI value (quartile range) of 277 old people with history of fall in previous year was 0.12 (0.11), which was higher than the median FI value of 0.08 (0.07) of 1 280 old people without fall history (Z=7.501, P=0.000). Logistic regression analysis showed that higher FI value was associated with more risks for fall; and FI value showed the greatest impact on the incidence and frequency of fall (OR=1.093, 2.234) compared with other related factors of fall, such as age and gender. Conclusion: Frailty status has a greater impact on both incidence and frequency of fall compared with other factors in elderly people in Beijing; more attention should be paid to weak and old adults in the prevention of fall.
Accidental Falls/statistics & numerical data* ; Adult ; Aged ; Beijing ; Cross-Sectional Studies ; Female ; Frail Elderly ; Frailty ; Geriatric Assessment ; Humans ; Incidence ; Male ; Urban Population

Objective: To explore the long-term effects of maternal pregnancy bisphenol A (BPA) exposure on emotional and behavioral problems appeared in their preschool children. Methods: The study sample was a subset of the China-Anhui Birth Cohort Study (C-ABCS). A unified questionnaire was used to collect basic information on both pregnant women and their children. Free BPA concentration in maternal serum was determined by high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS). The parent-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to estimate the emotional and behavioral problems in preschool children. A total of 1 713 pairs of mothers and children were included in this study. Association between BPA exposure during pregnancy and the emotional and behavioral problems in preschool children was evaluated with multinomial logistic regression model. Results: Prevalence rates in 1 713 preschool children appeared as: 6.48% of emotional problems, 8.11% for conduct problems, 8.35% for hyperactivity/inattention, 2.86% for peer problems, 11.38% for prosocial behaviors and 7.94% for total difficulties. Subjects were divided according to the degrees of exposure and the results showed as: low exposure group (≤0.120 ng/ml), medium exposure group (0.120OR=1.876, 95% CI: 1.161-3.029), more obvious in boys (OR=2.291, 95%CI: 1.126-4.661). Conclusion: Maternal exposure to high level of BPA during pregnancy might increase the detrimental effects of abnormal conducts in their preschool children, more obviously seen in boys.
Benzhydryl Compounds/toxicity* ; Child Behavior Disorders/etiology* ; Child, Preschool ; China/epidemiology* ; Cohort Studies ; Emotions/physiology* ; Environmental Exposure ; Environmental Pollutants ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Male ; Maternal Exposure ; Mothers ; Phenols/toxicity* ; Pregnancy ; Prenatal Exposure Delayed Effects ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Tandem Mass Spectrometry

Objective: To investigate the second or third trimester pregnancy-related anxiety on small-for-gestational-age infants. Methods: This study was based on Ma'anshan Birth Cohort Study (MABC), with 3 040 maternal-singleton pairs finally selected for data analysis, from May 2013 to September 2014. The psychological state of pregnancy was evaluated according to a self-developed 'anxiety scale for gestation'. Small-for-gestational-age was defined as 'having birth weight below the 10(th) percentile at a particular gestational week', while large-for-gestational-age infants was defined as 'having birth weight above the 90(th) percentile'. Birth weight between the 10(th) and 90(th) percentile was classified as appropriate-for-gestational age infants. χ(2) test was used to compare the distribution of characteristics in pregnancy among three groups with different birth weights. Multivariate logistic regression models were conducted to evaluate the associations between third trimester pregnancy- related anxiety and birth weight. Results: The incidence rates of small- and large-gestational-age infants were 9.6% and 16.6%, respectively. Difference between women with only one of the second or third trimester pregnancy-related anxiety syndromes and small-for-gestational-age infants showed no statistical significance. Women with both second and third trimester pregnancy-related anxieties might increase the risk of small-for-gestational-age infants (OR=1.39, 95%CI: 1.04-1.87). However, there was no significant difference between pregnancy-related anxiety and large-for- gestational-age infants (OR=1.05, 95%CI: 0.81-1.35) noticed. Conclusion: Women with second and third trimester pregnancy-related anxiety appeared a risk factor for small-for-gestational-age infants.
Anxiety/psychology* ; Birth Weight ; China/epidemiology* ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Small for Gestational Age ; Pregnancy ; Pregnancy Complications/psychology* ; Pregnancy Trimester, Third/psychology*

Objective: To investigate the relationship of thallium exposure and outcomes of births. Methods: A total of 3 236 mothers who had visited in Ma'anshan Maternal and Child Health-Care Hospital between May 2013 and September 2014 were included in this study and their thallium concentrations measured from samples of maternal and umbilical cord blood by inductively coupled plasma mass spectrometry. The results were correlated and evaluated with birth outcomes of the infants, using the multiple linear regression method. Results: The median (P(25)-P(75)) of thallium levels in first trimester, second trimester and umbilical cord blood were 61.7 (50.8-77.0), 60.3 (50.8-75.2) and 38.5 (33.6-44.1) ng/L, respectively. After adjustment for potential confounders, the thallium levels showed an inversely significant association with birth head circumference (unstandardized β coefficient=-0.41, 95%CI: -0.76- -0.06) in the first trimester blood, and associated with reduced birth length (unstandardized β coefficient=-0.65, 95%CI: -1.25- -0.05) in umbilical cord blood. However, there appeared no significantly associations with birth weight, length and head circumference (P>0.05) in second trimester. On stratification by sex, in girls but not in boys, the thallium levels were adversely associated with birth head circumference (unstandardized β coefficient=-0.53, 95%CI: -1.05--0.01) in the first trimester and were associated with decreased birth weight (unstandardized β coefficient=-277.08, 95%CI: -485.13- -69.03) and length (unstandardized β coefficient=-1.39, 95%CI: -2.26- -0.53) in umbilical cord blood thallium. Conclusions: Thallium exposure appeared a gender difference in newborn birth outcomes. In the first trimester, it was negatively associated with the birth head circumference, in the umbilical cord blood, and reduced birth weight and length in girls.
Adult ; Birth Weight ; Environmental Pollutants/blood* ; Female ; Fetal Blood/metabolism* ; Fetus/metabolism* ; Humans ; Infant, Newborn ; Male ; Maternal Exposure ; Parturition ; Pregnancy ; Pregnancy Outcome/epidemiology* ; Thallium/blood*

Objective: To analyze the epidemiological characteristics, dynamic trend of development and related influencing factors of hepatitis C in Shandong, China, 2007-2016, also to provide epidemiological evidence for prevention and control of HCV. Methods: National surveillance data of hepatitis C from 2007 to 2016 in Shandong was used, with distribution and clustering map of hepatitis C drawn at the county level. Panel Poisson regression was used to explore the influencing factors of hepatitis C at the city level. Results: The incidence of hepatitis C in Shandong increased from 1.49/100 000 in 2007 to 4.72/100 000 in 2016, with the high incidence mainly clustered in the urban regions in Jinan, Zibo, Weihai et al. and surrounding vicinities. Majority of the cases were young adults, with 53.16% (14 711/27 671) of them being farmers. Results from the Multiple panel Poisson regression analysis indicated that factors as: population density (aIRR=1.07, 95%CI: 1.05-1.10), number of hospital per hundred thousand people shared (aIRR=1.16, 95%CI: 1.08-1.24), expenditure of medical fee in rural (aIRR=1.21, 95%CI: 1.08-1.37) and the proportion of the tertiary industry (aIRR=1.08, 95%CI: 1.07-1.09) were all correlated to the incidence of hepatitis C. Conclusions: The incidence of hepatitis C had been increasing rapidly in recent years, in Shandong. Prevention and control of HCV should focus on high risk population. In addition, rural, especially in areas with lower economics provision should be under more attentions, so as to find more concealed cases for early treatment.
Adult ; China/epidemiology* ; Cities ; Hepacivirus ; Hepatitis C/prevention & control* ; Humans ; Incidence ; Population Surveillance ; Young Adult

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.
Male ; Female ; Humans ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Adult ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors ; Gastrectomy/methods* ; Esophagogastric Junction/pathology* ; Laparoscopy ; Immunotherapy ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the relationship of pregnancy-related anxiety of pregnant women in second/third trimesters and autism-like behaviors in their offspring at 18 months of age. Methods: Based on a prospective cohort study design, we evaluated the situation of pregnancy-related anxiety of women during second and third trimesters through a Pregnancy-Related Anxiety Questionnaire. Subjects under study were classified into three groups, 1) those with pregnancy- related anxiety during both trimesters, 2) those with pregnancy-related anxiety at one trimester and 3) those without pregnancy-related anxiety in either trimester. When their children were 18 months, autism-like behaviors (ALB) were evaluated, using the part A of Checklist for Autism in Toddlers-23, and then classified into three groups as non-ALB group, minor ALB group and major ALB group. Multi-nominal logistic Regression was used to analyze the relationship of pregnancy-related anxiety with autism-like behaviors. Results: Compared with non-ALB group, children whose mother with pregnancy-related anxiety during both trimesters presented significant higher risk on ALB than children whose mother without pregnancy-related anxiety in these two periods (relative risk, RR=2.43, 95% CI: 1.21-4.86, P=0.012), major factors as pregnant women's IQ and gestational diabetes mellitus, premature delivery and education levels of fosterers on these pregnant women were under control. Our results from the stratified analysis showed: when in the subgroup that mother was the main fosterer of the child, there was an significant increase of risk in children whose mothers with pregnancy-related anxiety during both trimesters (RR=4.22, 95%CI: 1.73-10.32, P=0.002). Conclusion: The association between pregnancy-related anxiety and autism-like behavior was not strong but influenced by the fosterer of the child.
Anxiety/psychology* ; Autistic Disorder/epidemiology* ; China/epidemiology* ; Female ; Humans ; Logistic Models ; Mothers/psychology* ; Pregnancy ; Pregnancy Complications/psychology* ; Pregnancy Trimester, Third ; Pregnancy Trimesters/psychology* ; Pregnant Women/psychology* ; Prospective Studies ; Surveys and Questionnaires