2017年 · 第130卷第09期

Background: Hyperglycemia is associated with adverse pregnancy outcomes. However, the relationships between them remain ambiguous. This study aimed to analyze the effect of different oral glucose tolerance test (OGTT) results on adverse perinatal outcomes. Methods: This retrospective cohort study included data from 15 hospitals in Beijing from June 20, 2013 to November 30, 2013. Women with gestational diabetes mellitus (GDM) were categorized according to the number and distribution of abnormal OGTT values, and the characteristics of adverse pregnancy outcomes were evaluated. Chi-square test and logistic regression analysis were used to determine the associations. Results: In total, 14,741 pregnant women were included in the study population, 2927 (19.86%) of whom had GDM. As the number of hyperglycemic values in the OGTT increased, the risk of cesarean delivery, preterm births, large-for-gestational age (LGA), macrosomia, and neonatal complications significantly increased. Fasting hyperglycemia had clear associations with macrosomia (odds ratios [ORs]:1.84, 95% confidence intervals [CIs]: 1.39–2.42, P < 0.001), LGA (OR: 1.70, 95% CI: 1.29–2.25, P < 0.001), and cesarean delivery (OR: 1.33, 95% CI: 1.15–1.55, P < 0.001). The associations were stronger as fasting glucose increased. GDM diagnosed by hyperglycemia at OGTT-2 h was more likely to lead to preterm birth (OR: 1.50, 95% CI: 1.11–2.03, P < 0.01). Conclusions: Various characteristics of OGTTs are associated with different adverse outcomes. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT characteristics is needed.

Background: Gestational diabetes mellitus (GDM) is associated with both short- and long-term adverse health consequences for both the mother and her offspring. The aim was to study the prevalence and risk factors for GDM in Beijing. Methods: The study population consisted of 15,194 pregnant women attending prenatal care in 15 hospitals in Beijing, who delivered between June 20, 2013, and November 30, 2013, after 28 weeks of gestation. The participants were selected by cluster sampling from the 15 hospitals identified through random systematic sampling based on the number of deliveries in 2012. A questionnaire was designed to collect information. Results: A total of 2987 (19.7%) women were diagnosed with GDM and 208 (1.4%) had diabetes in pregnancy (DIP). Age (OR: 1.053, 95% CI: 1.033–1.074, P < 0.01), family history of diabetes mellitus (OR: 1.481, 95% CI: 1.254–1.748, P < 0.01), prepregnancy body mass index (BMI) (OR: 1.481, 95% CI: 1.254–1.748, P < 0.01), BMI gain before 24 weeks (OR: 1.126, 95% CI: 1.075–1.800, P < 0.01), maternal birth weight (P < 0.01), and fasting plasma glucose at the first prenatal visit (P < 0.01) were identified as risk factors for GDM. In women with birth weight <3000 g, GDM rate was significantly higher. Conclusions: One out of every five pregnant women in Beijing either had GDM or DIP and this constitutes a huge health burden for health services. Prepregnancy BMI and weight gain before 24th week are important modifiable risk factors for GDM. Ensuring birth weight above 3000 g may help reduce risk for future GDM among female offsprings.

Background: Excessive reactive oxygen species (ROS) may lead to a number of reproductive diseases such as polycystic ovary syndrome. This study aimed to establish an animal model of ovarian oxidative stress and to assess the protective effect of curcumin against oxidative injury. Methods: Ovarian oxidative stress was induced in female Kunming mice (n = 40) with intraperitoneal injection of 8 mg/kg sodium arsenite (As) once every other day for 16 days; meanwhile, they were, respectively, treated by intragastric administration of 0, 100, 150, or 200 mg/kg (n = 10/group) curcumin once per day for 21 days. Ten normal mice were used as control. Then, the mice were injected intraperitoneally with BrdU and sacrificed; the right ovaries were collected for hematoxylin and eosin (HE) staining and BrdU immunohistochemistry, and the left ovaries for enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. Results: The ELISA results showed that ROS (11.74 ± 0.65 IU/mg in 8 mg/kg AS + 0 mg/kg curcumin group vs. 10.71 ± 0.91 IU/mg in control group, P = 0.021) and malondialdehyde (MDA) (0.32 ± 0.02 nmol/g in 8 mg/kg AS + 0 mg/kg curcumin group vs. 0.27 ± 0.02 nmol/g in control group, P = 0.048) increased while superoxide dismutase (SOD) (3.96 ± 0.36 U/mg in 8 mg/kg AS + 0 mg/kg curcumin group vs. 4.51 ± 0.70 U/mg in control group, P = 0.012) and glutathione peroxidase (17.36 ± 1.63 U/g in 8 mg/kg AS + 0 mg/kg curcumin group vs. 18.92 ± 1.80 U/g in control group, P = 0.045) decreased in the ovary after injection of As, indicating successful modeling of oxidative stress. Curcumin treatment could considerably increase SOD (4.57 ± 0.68, 4.49 ± 0.27, and 4.56 ± 0.25 U/mg in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, all P < 0.05) while significantly reduce ROS (10.64 ± 1.38, 10.73 ± 0.71, and 10.67 ± 1.38 IU/mg in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, all P < 0.05) and MDA (0.28 ± 0.02, 0.25 ± 0.03, and 0.27 ± 0.04 nmol/g in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively; both P < 0.05) in the ovary. HE staining and BrdU immunohistochemistry of the ovarian tissues indicated the increased amount of atretic follicles (5.67 ± 0.81, 5.84 ± 0.98, and 5.72 ± 0.84 in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, all P < 0.05), and the inhibited proliferation of granular cells under oxidative stress would be reversed by curcumin. Furthermore, the Western blotting of ovarian tissues showed that the p66Shc expression upregulated under oxidative stress would be lowered by curcumin. Conclusion: Curcumin could alleviate arsenic-induced ovarian oxidative injury to a certain extent.

Background: The pathogenesis of some types of preeclampsia is related to fatty acid oxidation disorders. Rapamycin can regulate fatty acid metabolism. This study aimed to investigate the effects of rapamycin on the clinical manifestations and blood lipid parameters in different preeclampsia-like mouse models. Methods: Two preeclampsia-like mouse models and a control group were established: L-NA (injected with Nω-nitro-L-arginine methyl ester), LPS (injected with lipopolysaccharide), and the control group with normal saline (NS). The mouse models were established at preimplantation (PI), early- and late-pregnancy (EP, LP) according to the time of pregnancy. The administration of rapamycin (RA; L-NA+RA, LPS+RA, and NS+RA) or vehicle as controls (C; L-NA+C, LPS+C, NS+C) were followed on the 2nd day after the mouse models’ establishment. Each subgroup consisted of eight pregnant mice. The mean arterial pressure (MAP), 24-h urinary protein, blood lipid, fetus, and placental weight were measured. The histopathological changes and lipid deposition of the liver and placenta were observed. Student’s t-test was used for comparing two groups. Repeated measures analysis of variance was used for blood pressure analysis. Qualitative data were compared by Chi-square test. Results: The MAP and 24-h urinary protein in the PI, EP, and LP subgroups of the L-NA+C and LPS+C groups were significantly higher compared with the respective variables in the NS+C group (P < 0.05). The preeclampsia-like mouse models were established successfully. There was no significant difference in the MAP between the PI, EP, and LP subgroups of the L-NA+RA and L-NA+C groups and the LPS+RA and LPS+C groups. The 24-h urine protein levels in the PI and EP subgroups of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C groups (1037 ± 63 vs. 2127 ± 593 µg; 976 ± 42 vs. 1238 ± 72 μg; both P < 0.05), also this effect appeared similar in the PI and EP subgroups of the LPS+RA and LPS+C groups (1022 ± 246 vs. 2141 ± 432 μg; 951 ± 41 vs. 1308 ± 30 μg; both P < 0.05). The levels of serum-free fatty acid (FFA) in the PI and EP subgroups of the L-NA+RA groups were significantly lower compared with the respective levels in the L-NA+C group (2.49 ± 0.44 vs. 3.30 ± 0.18 mEq/L; 2.23 ± 0.29 vs. 2.84 ± 0.14 mEq/L; both P < 0.05). The levels of triglycerides (TG) and total cholesterol in the PI subgroup of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C (1.51 ± 0.16 vs. 2.41 ± 0.37 mmol/L; 2.11 ± 0.17 vs. 2.47 ± 0.26 mmol/L; both P < 0.05), whereas high-density lipoprotein serum concentration was significantly higher (1.22 ± 0.19 vs. 0.87 ± 0.15 mmol/L; P < 0.05) and low-density lipoprotein serum concentration did not exhibit a significant difference. There were no significant differences in the FFA of the PI, EP, and LP subgroups between the LPS+RA and the LPS+C groups. The levels of TG in the PI subgroup of the LPS+RA group were significantly lower compared with the respective levels in the LPS+C group (0.97 ± 0.05 vs. 1.22 ± 0.08 mmol/L; P < 0.05). Conclusion: Rapamycin can improve clinical manifestations and blood lipid profile in part of the preeclampsia-like mouse models.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MRI) findings. Methods: Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First Hospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microbleeds were evaluated. All patients and controls underwent EDI-OCT to measure subfoveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman’s correlation was used to investigate the correlation between retinal vessel changes and MRI lesions. Results: In CADASIL patients, mean SFCT (268.37 ± 46.50 μm) and mean arterial inner diameter (93.46 ± 9.70 μm) were significantly lower than that in controls (P < 0.001, P = 0.048, respectively). Mean arterial outer diameter (131.74 ± 10.87 μm), venous inner (128.99 ± 13.62 μm) and outer diameter (164.82 ± 14.77 μm), and mean arterial (19.13 ± 1.85 μm) and venous (17.91 ± 2.76 μm) wall thickness were significantly higher than that in controls (P = 0.023, P = 0.004, P < 0.001, P < 0.001, respectively). Arterial inner diameter (rs = −0.39, P = 0.044), AVRin (rs = −0.65, P < 0.001), and AVRout (rs = −0.56, P = 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs = 0.46, P = 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (rs = 0.59, P = 0.002), outer diameter (rs = 0.47, P = 0.017), showed a positive correlation with the number of cerebral microbleeds (CMBs). AVRin (rs = −0.52, P = 0.007) and AVRout (rs = −0.40, P = 0.048) showed a negative correlation with the number of CMBs. Conclusions: Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might be a useful evaluation tool for CADASIL patients.

Background: X-linked Charcot-Marie-Tooth type 1 (CMT1X) disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein (GJB1) gene (also known as connexin 32). This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations. Methods: A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJB1 mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing (NGS). Nucleotide alternations were confirmed with Sanger sequencing. Results: The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years (ranging from 1 year to 42 years). The sudden onset of cerebral symptoms appeared in four patients (18.2%); two were initial symptoms. One case had constant central nervous system (CNS) signs. There were 19 different heterozygous mutations, including 15 known mutations and four novel mutations (c.115G>T, c.380T>A, c.263C>A, and c.818_819insGGGCT). Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 (TM1), 4.5% in TM2, 22.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 (EC1), 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-terminal domain. CMT1X with CNS impairment appeared in five (22.7%) of these patients. Conclusions: This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJB1 gene were hotspot in Chinese CMT1X patients.

Background: Four single nucleotide polymorphisms (SNPs) in the modulator recognition factor 2/AT-rich interaction domain 5B (MRF2/ARID5B) gene located at chromosome 10q21.2 have been shown to be associated with both type 2 diabetes mellitus (T2DM) and coronary artery disease in a Japanese cohort. This study aimed to investigate the relationship between these SNPs (rs2893880, rs10740055, rs7087507, rs10761600) and new-onset T2DM and lipid metabolism in a Northern Chinese population. Methods: This was a case-control study. The rs2893880, rs10740055, rs7087507, and rs10761600 genetic variants were genotyped by SNPscan and analyzed in relation to T2DM susceptibility in 2000 individuals (999 with newly diagnosed T2DM and 1001 controls without diabetes mellitus). Associations between the MRF2/ARID5B genetic models and T2DM were determined by multivariate logistic regression. Results: Regarding the rs10740055 SNP, AA was associated with a higher risk of T2DM compared with codominant-type CC (adjusted by sex, age, and body mass index [BMI], P = 0.041, odds ratio [OR] = 1.421, 95% confidence interval [CI] 1.014–1.991). Meanwhile, AA individuals were at increased risk of presenting with T2DM compared with individuals with CC or a single C (adjusted by sex, age, and BMI, P = 0.034, OR = 1.366, 95% CI 1.023–1.824). With respect to rs10761600, AT contributed to a higher risk of T2DM compared with AA (adjusted by sex, age, and BMI, P = 0.013, OR = 1.585, 95% CI 1.101–2.282), while TT also increased the risk of presenting with T2DM compared with AA or A (adjusted by sex, age, and BMI, P = 0.004, OR = 1.632, 95% CI 1.166–2.284). High-density lipoprotein cholesterol (HDL-C) levels were significantly different among the three genotypes of rs7087507 in the controls (P = 0.048) (GG>GA). Conclusions: The present results identified MRF2/ARID5B as a potential susceptibility gene for new-onset T2DM in a Northern Chinese population, while the rs7087507 SNP was associated with HDL-C levels. Further larger studies are required to validate these findings.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases with high mortality rates. This study was designed to analyze the pathogenic factors, clinical manifestations, complications, treatment, and prognosis of SJS/TEN and to explore the differences between surviving and deceased patients. Methods: SJS/TEN patients admitted to Beijing Friendship Hospital from January 2006 to December 2015 were included in the study. Patients’ data were retrospectively analyzed. Comparative studies were performed on the survival group and the deceased group, and Fisher’s exact probability test was used for statistical analysis. Results: Among the 88 patients included, 40 (45.5%) were male with a mean age of 45 ± 18 years. Forty-eight (54.5%) had SJS, 34 (38.6%) had SJS/TEN, and 6 (6.8%) had TEN. Fifty-three (60.2%) cases were caused by medications, mainly antibiotics (n = 24) followed by traditional Chinese medicines (n = 7). Forty-two cases (47.7%) developed visceral damage. Eighty-two patients improved or recovered and were discharged from hospital, and six patients died. Comparative studies on the survival group and the deceased group showed that the presence of malignant tumor (χ2 = 27.969, P < 0.001), connective tissue diseases (χ2 = 9.187, P = 0.002), previous abnormal liver/kidney functions (χ2 = 6.006, P = 0.014), heart rate >100 times/min (χ2 = 6.347, P = 0.012), detached skin area >20% (χ2 = 5.594, P = 0.018), concurrent mucosal involvement at the mouth, eyes, and external genitals (χ2 = 4.945, P = 0.026), subsequent accompanying liver/kidney damage (χ2 = 11.839, P = 0.001, and χ2 = 36.302, P < 0.001, respectively), and SCORTEN score >2 (χ2 = 37.148, P < 0.001) increased the risk of death. Conclusions: SJS/TEN is mainly caused by medications, and nearly half of patients develop visceral damage. Multiple factors increase the mortality risk.

Background: Congenital heart disease (CHD) is the most common congenital malformations with high mortality and morbidity. The prevalence of CHD reported previously ranged from 4 per 1000 live births to 50 per 1000 live births. In this cross-sectional study, we aimed to document the prevalence of CHD in Langfang district of Hebei Province, China by analyzing data collected by hospitals located in 11 the counties of the district, as supported by a public health campaign. Methods: A total of 67,718 consecutive 3-month-old infants were included from July 19, 2012 to July 18, 2014. Structural abnormalities were diagnosed based on echocardiography findings, including two-dimensional and color Doppler echocardiography results. Results: Of the 67,718 infants, 1554 were found to have cardiac structural abnormalities. The total prevalence of CHD was 22.9 per 1000 live births, a value significantly higher than the previously reported prevalence of 8 cases per 1000 live births. The top five most common cardiac abnormalities were as follows: atrial septal defect (ASD, 605 cases, 8.93‰); ventricular septal defect (550 cases, 8.12‰); patent ductus arteriosus (228 cases, 3.37‰); pulmonary stenosis (66 cases, 0.97‰); and tetralogy of Fallot (32 cases, 0.47‰). The CHD prevalence differed by gender in this study (χ2 = 23.498, P < 0.001), and the majority of ASD cases were females. Regional differences in prevalence were also found (χ2 = 24.602, P < 0.001); a higher prevalence was found in urban areas (32.2 cases per 1000 live births) than in rural areas (21.1 cases per 1000 live births). There was a significant difference in the prevalence of CHD in preterm versus full-term infants (χ2 = 133.443, P < 0.001). Prevalence of CHD in infants of maternal aged 35 years or over was significantly higher (χ2 = 86.917, P < 0.001). Conclusions: The prevalence of CHD in Langfang district was within the range reported using echocardiography. Echocardiography can be used to early diagnose the CHD.

Background: Breast cancer is the most common type of cancer among females. Genetic polymorphisms might have a role in carcinogenesis. The aim of this study was to determine whether C to T base substitution within TaqI Vitamin D receptor (VDR) gene (rs731236) in exon 9 was a risk factor among patients with breast cancer. Methods: Peripheral blood was drawn from 122 Jordanian breast cancer patients and 100 healthy Jordanian volunteers in Al-Basheer Hospital during the summer months (from June to November of 2013, 2014, and 2015). DNA was amplified using polymerase chain reaction (PCR), followed by TaqI restriction enzyme digestion. Quantification of serum 25-hydroxy Vitamin D (25[OH]D) level was determined by competitive immunoassay Elecsys. Results: Genotypic frequencies for TaqI TT, Tt, and tt genotypes were 41%, 46%, and 13% for breast cancer compared to 42%, 50%, and 8% for control, respectively. Vitamin D serum level was significantly lower in the breast cancer patients (8.1 ± 0.3 ng/ml) compared to the control group (21.2 ± 0.6 ng/ml; P = 0.001). This study showed an inverse association between 25(OH)D serum level and breast cancer risk (odds ratio [OR], 22.72, 95% confidence interval [CI], 10.06–51.29). Conclusions: An inverse association was found between 25(OH)D serum level and breast cancer risk. Statistical difference was also found between different VDR TaqI genotypes and circulating levels of 25(OH)D among Jordanian females with breast cancer.

Background: Diagnosis of syphilis is difficult. Follow-up and therapy evaluation of syphilitic patients are poor. Little is known about positron emission tomography (PET) in syphilis. This review was to systematically review usefulness of PET for diagnosis, disease extent evaluation, follow-up, and treatment response assessment in patients with syphilis. Methods: We searched PubMed, EMBASE, SCOPUS, Cochrane Library, Web of Science, ClinicalTrials.gov, and three Chinese databases (SinoMed, Wanfang, and CNKI) for English and Chinese language articles from inception to September 2016. We also collected potentially relevant studies and reviews using a manual search. The search keywords included the combined text and MeSH terms "syphilis" and "positron emission tomography" . We included studies that reporting syphilis with a PET scan before and/or after antibiotic treatment. The diagnosis of syphilis was based on serological criteria or dark field microscopy. Outcomes include pre- and post-treatment PET scan, pre- and post-treatment computed tomography, and pre- and post-treatment magnetic resonance imaging. We excluded the articles not published in English or Chinese or not involving humans. Results: Of 258 identified articles, 34 observational studies were included. Thirty-three studies were single-patient case reports and one study was a small case series. All patients were adults. The mean age of patients was 48.3 ± 12.1 years. In primary syphilis, increased fluorodeoxyglucose (FDG) accumulation could be seen at the site of inoculation or in the regional lymph nodes. In secondary syphilis with lung, bone, gastrointestinal involvement, or generalized lymphadenopathy, increased FDG uptake was the most commonly detected changes. In tertiary syphilis, increased glucose metabolic activity, hypometabolic lesions, or normal glucose uptake might be seen on PET. There were five types of PET scans in neurosyphilis. A repeated PET scan after treatment revealed apparent or complete resolution of the asymmetry of radiotracer uptake. Conclusion: PET is helpful in targeting diagnostic interventions, characterizing disease extent, assessing nodal involvement, and treatment efficacy for syphilis.

Objective: Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima (atherosclerotic calcification) or tunica media (Mönckenberg’s sclerosis). Vascular calcification is also closely related to other pathologies, such as diabetes mellitus, dyslipidemia, and chronic kidney disease. It has been concluded that the degree of vascular calcification may vary from person to person, even if the associated pathologies and environmental factors are the same. Therefore, this suggests an important genetic contribution to the development of vascular calcification. This review aimed to find the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Data Sources: We conducted an exhaustive search in Scopus, EBSCO, and PubMed with the keywords "genetics and vascular calcification" , "molecular pathways, genetic and vascular calcification" and included the main articles from January 1995 up to August 2016. We focused on the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Study Selection: The most valuable published original and review articles related to our objective were selected. Results: Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development. Conclusion: Although several molecular aspects of this mechanism have been elucidated, there is still a need for a better understanding of the factors that predispose to this disease.