Prevalence of Gestational Diabetes Mellitus and Its Risk Factors in Chinese Pregnant Women: A Prospective Population-Based Study in Tianjin,China

Objective

We compared the increases in the prevalence of gestational diabetes mellitus (GDM) based on the 1999 World Health Organization (WHO) criteria and its risk factors in Tianjin, China, over a 12-year period. We also examined the changes in the prevalence using the criteria of International Association of Diabetes and Pregnancy Study Group (IADPSG).

Methods

In 2010-2012, 18589 women who registered within 12 weeks of gestation underwent a glucose challenge test (GCT) at 24-28 gestational weeks. Amongst them, 2953 women with 1-hour plasma glucose ≥7.8 mmol/L underwent a 75-gram 2-hour oral glucose tolerance test (OGTT) and 781 women had a positive GCT but absented from the standard OGTT. An adjusted prevalence of GDM was calculated for the whole cohort of women by including an estimate of the proportion of women with positive GCTs who did not have OGTTs but would have been expected to have GDM. Logistic regression was used to obtain odds ratios and 95% confidence intervals using the IADPSG criteria. The prevalence of GDM risk factors was compared to the 1999 survey.

Results

The adjusted prevalence of GDM by the 1999 WHO criteria was 8.1%, a 3.5-fold increase as in 1999. Using the IADPSG criteria increased the adjusted prevalence further to 9.3%. Advanced age, higher pre-pregnancy body mass index, Han-nationality, higher systolic blood pressure (BP), a family history of diabetes, weight gain during pregnancy and habitual smoking were risk factors for GDM. Compared to the 1999 survey, the prevalence of overweight plus obesity had increased by 1.8 folds, age≥30 years by 2.3 folds, systolic BP by 2.3 mmHg over the 12-year period.

Conclusions

Increasing prevalence of overweight/obesity and older age at pregnancy were accompanied by increasing prevalence of GDM, further increased by change in diagnostic criteria.     

The Role of Toll-Like Receptor 9 in Chronic Stress-Induced Apoptosis in Macrophage

Emerging evidence implied that chronic stress has been exerting detrimental impact on immune system functions in both humans and animals. Toll-like receptors (TLRs) have been shown to play an essential role in modulating immune responses and cell survival. We have recently shown that TLR9 deficiency protects against lymphocyte apoptosis induced by chronic stress. However, the exact role of TLR9 in stress-mediated change of macrophage function remains unclear. The results of the current study showed that when BALB/c mice were treated with restraint stress (12 h daily for 2 days), the number of macrophages recruited to the peritoneal cavity was obviously increased. Results also demonstrated that the sustained effects of stress elevated cytokine IL-1β, TNF-α and IL-10 production yet diminished IFN-γ production from macrophage, which led to apoptotic cell death. However, TLR9 deficiency prevented the chronic stress-mediated accumulation of macrophages. In addition, knocking out TLR9 significantly abolished the chronic stress-induced imbalance of cytokine levels and apoptosis in macrophage. TLR9 deficiency was also found to reverse elevation of plasma IL-1β, IL-10 and IL-17 levels and decrease of plasma IFN-γ level under the condition of chronic stress. These results indicated that TLR9-mediated macrophage responses were required for chronic stress-induced immunosuppression. Further exploration showed that TLR9 deficiency prevented the increment of p38 MAPK phosphorylation and reduction of Akt/Gsk-3β phosphorylation; TLR9 deficiency also attenuated the release of mitochondrial cytochrome c into cytoplasm, caused upregulation of Bcl-2/Bax protein ratio, downregulation of cleavage of caspase-3 and PARP, as well as decreased TUNEL-positive cells in macrophage of stressed mice. Collectively, our studies demonstrated that deficiency of TLR9 maintained macrophage function by modulating macrophage accumulation and attenuating macrophage apoptosis, thus preventing immunosuppression in restraint-stressed mice.     

Adding Vitamin E-TPGS to the Formulation of Genexol-PM: Specially Mixed Micelles Improve Drug-Loading Ability and Cytotoxicity against Multidrug-Resistant Tumors Significantly

Genexol-PM, produced by Samyang Company (Korea) is an excellent preparation of paclitaxel (PTX) for clinical cancer treatment. However, it cannot resolve the issue of multidrug resistance (MDR)—a significant problem in the administration of PTX to cancer patients. To increase the efficacy of Genexol-PM against MDR tumors, a mixed micelle capable of serving as a vehicle for PTX was developed, and two substances were chosen as carrier materials: 1) Polyethylene glycol–polylactic acid (PEG-PLA), the original vehicle of Genexol-PM. 2) Vitamin E-TPGS, an inhibitor of P-glycoprotein (P-gp). P-gp has been proven to be the main cause of MDR. In vitro evaluation indicated that the mixed micelle was an ideal PTX delivery system for the treatment of MDR tumors; the mixed micelle also showed a significantly better drug-loading coefficient than Genexol-PM.     

Goat Uterine DBA+ Leukocytes Differentiation and Cytokines Expression Respond Differently to Cloned versus Fertilized Embryos

High rate of fetal mortality in ruminant somatic cell nuclear transfer (SCNT) pregnancies is due, at least in part, to immune-mediated abortion of fetuses. In the present study, goat uterine leukocytes were isolated by Dolichos biflorus agglutinin (DBA) coated magnetic beads, and with majority being were CD56⁺CD16^- in phenotype with low levels of perforin and Granzyme B expression. The responses of the isolated cells to SCNT and in vitro fertilization (IVF) embryos conditioned mediums containing hormone steroids were compared by measuring their phenotype and cytokines expression. The results showed there was a 2-fold increase in the numbers of isolated uterine leukocytes after incubation with different conditioned mediums for 120 h. However, significantly lower percentage and absolute numbers of uterine CD56⁺CD16^- leukocytes incubated with SCNT conditioned mediums were detected as compared with those incubated with IVF conditioned mediums (P < 0.05). The group treated with progesterone (P₄) or the combination of P₄ and 17β-estradiol (E₂) were associated with significantly higher percentage and absolute numbers of CD56⁺CD16^- cells as compared with those treated with E₂ alone (P < 0.05). Furthermore, in the presence of steroids, the isolated leukocytes incubated with SCNT conditioned mediums associated with greater levels of IFN-γ secretion and expression, as well as lesser levels of VEGF, as compared with those treated with IVF conditioned mediums (P < 0.05). In conclusion, this study demonstrates that SCNT embryos have a profound effect on the phenotype expression of goat uterine DBA⁺ leukocytes, as well as the secretion and expression of IFN-γ and VEGF by these cells in vitro.     

The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis

Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP) method that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration unit and can accelerate the digestion process with the assistance of a microwave. Additionally, two parameters (P- and D-scores) based on the exponentially modified protein abundance index were developed to define the existence of amyloid deposits and those causative proteins with the greatest abundance. Using our protocol, twenty cases of systemic amyloidosis that were well-typed according to clinical diagnostic standards (training group) and another twenty-four cases without subtype diagnoses (validation group) were analyzed. Using this approach, sample preparation could be completed within four hours. We successfully subtyped 100% of the cases in the training group, and the diagnostic success rate in the validation group was 91.7%. This maFASP-aided proteomic protocol represents an efficient approach for amyloid diagnosis and subtyping, particularly for serum-contaminated samples.     

RAD18 Activates the G2/M Checkpoint through DNA Damage Signaling to Maintain Genome Integrity after Ionizing Radiation Exposure

The ubiquitin ligase RAD18 is involved in post replication repair pathways via its recruitment to stalled replication forks, and its role in the ubiquitylation of proliferating cell nuclear antigen (PCNA). Recently, it has been reported that RAD18 is also recruited to DNA double strand break (DSB) sites, where it plays novel functions in the DNA damage response induced by ionizing radiation (IR). This new role is independent of PCNA ubiquitylation, but little is known about how RAD18 functions after IR exposure. Here, we describe a role for RAD18 in the IR-induced DNA damage signaling pathway at G2/M phase in the cell cycle. Depleting cells of RAD18 reduced the recruitment of the DNA damage signaling factors ATM, γH2AX, and 53BP1 to foci in cells at the G2/M phase after IR exposure, and attenuated activation of the G2/M checkpoint. Furthermore, depletion of RAD18 increased micronuclei formation and cell death following IR exposure, both in vitro and in vivo. Our data suggest that RAD18 can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after IR exposure.     

Increased Sensitivity of DNA Damage Response-Deficient Cells to Stimulated Microgravity-Induced DNA Lesions

Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG). In this study we used mouse embryonic stem (MES) and mouse embryonic fibroblast (MEF) cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs) in Rad9 ^-/- MES and Mdc1 ^-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9 ^-/- MES. As the exposure to SMG was prolonged, Rad9 ^-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9 ^-/- MES were due to SMG-induced reactive oxygen species (ROS). Interestingly, Mdc1 ^-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1 ^-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR) defects.     

Effects of Choline on Meat Quality and Intramuscular Fat in Intrauterine Growth Retardation Pigs

The aim of this study was to investigate the effects of choline supplementation on intramuscular fat (IMF) and lipid oxidation in IUGR pigs. Twelve normal body weight (NBW) and twelve intrauterine growth retardation (IUGR) newborn piglets were collected and distributed into 4 treatments (Normal: N, Normal+Choline: N+C, IUGR: I, and IUGR+Choline: I+C) with 6 piglets in each treatment. At 23 d of age, NBW and IUGR pigs were fed basal or choline supplemented diets. The results showed that the IUGR pigs had significantly lower (P<0.05) BW as compared with the NBW pigs at 23 d, 73 d, and 120 d of age, however, there was a slight decreased (P>0.05) in BW of IUGR pigs than the NBW pigs at 200 d. Compared with the NBW pigs, pH of meat longissimus dorsi muscle was significantly lower (P<0.05), and the meat color was improved in IUGR pigs. The malondialdehyde (MDA) levels were significantly decreased (P<0.05), while triglyceride (TG) and IMF contents were significantly higher (P<0.05) in the IUGR pigs than the NBW pigs. IUGR up-regulated the mRNA gene expression of fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC). Dietary choline significantly increased (P<0.05) the BW at 120d of age, however, significantly decreased (P<0.05) the TG and IMF contents in both IUGR and NBW pigs. FAS and sterol regulatory element-binding proteins 1 (SREBP1) mRNA gene expressions were increased (P<0.05) while the muscle-carnitine palmityl transferase (M-CPT) and peroxisome proliferators-activated receptorγ (PPARγ) mRNA (P<0.05) gene expressions were decreased in the muscles of the IUGR pigs by choline supplementation. Furthermore, choline supplementation significantly increased (P<0.05) the MDA content as well as the O₂•¯ scavenging activity in meat of IUGR pigs. The results suggested that IUGR pigs showed a permanent stunting effect on the growth performance, increased fat deposition and oxidative stress in muscles. However, dietary supplementation of choline improved the fat deposition via enhancing the lipogenesis and reducing the lipolysis.