Functional status of pediatric patients with trauma and risk factors for mortality from a single center in China.

Introduction: The influence of reduced functional status has become increasingly relevant because of the gradual decline in mortality rate over the recent years. Nonetheless, only a few studies investigating the functional status of patients with trauma at hospital discharge have been conducted. This study aimed to identify the risk factors influencing the mortality rate in pediatric trauma survivors at a pediatric intensive care unit and analyze their functional status using the Functional Status Scale (FSS). Methods: A retrospective analysis was conducted at Shengjing Hospital of China Medical University. Children admitted to the pediatric intensive care unit between January 2015 and January 2020 who met the trauma diagnostic criteria were included. The FSS score and the Injury Severity Score (ISS) were recorded upon admission and discharge, respectively. Clinical data were compared between the survival and non-survival groups to identify the risk factors for poor prognosis. The risk factors for mortality were identified using multivariate and univariate analyses. Results: A total of 246 children {59.8%, male; median [interquartile range (IQR)] age: 3 [1-7] years} were diagnosed with trauma (including head trauma, chest trauma, abdominal trauma, and extremity trauma). Of these patients, 207 were discharged, 11 dropped out mid-treatment, and 39 died (hospital mortality rate, 15.9%). Upon admission, the median FSS and trauma scores were 14 (IQR, 11-18) and 22 (IQR, 14-33) points, respectively. At discharge, the FSS score was 8 (IQR, 6-10) points. The patient clinical status improved with a ΔFSS score of -4 (IQR, -7, 0) points. At hospital discharge, 119 (48.3%), 47 (19.1%), 27 (11.0%), 12 (4.8%), and 2 (0.9%) survivors had good, mildly abnormal, moderately abnormal, severely abnormal, and very severely abnormal function, respectively. Reduced functional status in patients was categorized as follows: motor, 46.4%; feeding, 26.1%; sensory, 23.2%; mental, 18.4%; and communication, 17.9%. In the univariate analysis, ISS >25 points, shock, respiratory failure, and coma were independently associated with the mortality rate. Multivariate analysis revealed that the ISS was an independent risk factor for mortality. Conclusion: The mortality rate of patients with trauma was high. ISS was an independent risk factor for mortality. Mildly reduced functional status remained at discharge and was reported in nearly half of the discharged patients. Motor and feeding functions were the most severely impacted domains.

Kcnma1 is involved in mitochondrial homeostasis in diabetes-related skeletal muscle atrophy.

Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.

Integrated Transcriptome and Metabolome Analysis Reveals the Regulatory Mechanisms of FASN in Geese Granulosa Cells.

FASN plays a critical role in lipid metabolism, which is involved in regulating ovarian follicular development. However, the molecular mechanisms of how FASN regulate the function of ovarian follicular cells still remain elusive. In this study, by overexpression or interference of FASN in pre-hierarchical follicle granulosa cells (phGCs) and hierarchical follicle granulosa cells (hGCs), we analyzed their effects on the granulosa cell transcriptome and metabolome profiles using RNA-Seq and LC-MS/MS, respectively. The results showed that overexpression of FASN promoted proinflammatory factors expression by activating TLR3/IRF7 and TLR3/NF-κB pathways in phGCs, but only by activating TLR3/IRF7 pathways in hGCs. Then, necroptosis and apoptosis were triggered through the JAK/STAT1 pathway (induced by inflammatory factors) and BAK/caspase-7 pathway, respectively. The combined analysis of the metabolome and transcriptome revealed that FASN affected the demand of GCs for 5-hydroxytryptamine (5-HT) by activating the neuroactive ligand-receptor interaction pathway in two categorized GCs and only altering the metabolic pathway of tryptophan in phGCs, and ultimately participated in regulating the physiological function of geese GCs. Taken together, this study showed that the mechanisms of FASN regulating the physiological function of geese phGCs and hGCs were similar, but they also had some different characteristics.

Evaluation of SI, MSI and DSI for very early (3-day) mortality in patients with septic shock.

BACKGROUND: Septic shock is associated with increased mortality. Predicting mortality, including early prediction for septic shock patients in intensive care units (ICUs), remains an important challenge. METHOD: We searched the Medical Information Mart for Intensive Care IV database. Odds ratios (ORs) with 95% confidence intervals (CIs) of the relationships between shock index (SI), modified SI (MSI), and diastolic SI (DSI) of patients with septic shock requiring vasopressors and 3-day/in-hospital mortality were calculated using logistic regression models. The time-course changes of these parameters were compared between survivors and non-survivors. The performance of the different parameters was described by the area under the receiver operating characteristic (ROC) curve (AUC) and compared with DeLong analysis. RESULTS: A total of 1266 patients with septic shock requiring vasopressors were identified. The 3-day mortality rate and in-hospital mortality rate were 8.7% and 23.5%, respectively. Multivariable logistic regression analysis showed significant associations between pre-vasopressor SI/MSI/DSI and 3-day mortality in patients with septic shock requiring vasopressors in fully adjusted models (Ps for trend < 0.01). The AUCs of pre-vasopressor SI, MSI, and DSI were 0.746, 0.710, and 0.732 for 3-day mortality, respectively. There were significant differences in the time-course of SI, MSI, and DSI between survivors and non-survivors at 3-day/in-hospital mortality among patients with septic shock requiring vasopressors (repeated-measures ANOVA, inter-subjects difference P < 0.001). CONCLUSION: Pre-vasopressor SI, MSI, and DSI values identified patients with septic shock requiring vasopressors who are at increased risk of early death. Of these easy-to-acquire values, SI and MSI show a comparatively better performance.

Maternal Consumption of Milk or Dairy Products During Pregnancy and Birth Outcomes: A Systematic Review and Dose-Response Meta-Analysis.

Purpose: This study aimed to systematically review current evidence and quantitatively evaluate the associations between milk or dairy consumption during pregnancy and birth outcomes. Methods: This systematic review had been reported in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A supplementary literature search in PubMed, Web of Science, Cochrane Library, and Embase was conducted on 30 March 2021. Studies that assessed the association of maternal consumption of milk or dairy with birth-related outcomes were identified. The dose-response meta-analyses of continuous data and categorical data were applied. One-stage approach and two-stage approach were used where appropriate. Results: In total, 42 studies were eligible for the present systematic review, and 18 of them were included in the outcome-specific meta-analyses. The dose-response meta-analysis [Number of studies (N) = 9] predicted a maximum mean change in birthweight of 63.38 g [95% Confidence Interval (CI) = 0.08, 126.67] at 5.00 servings per day. Intake of dairy products had the greatest protective effect on small for gestational age at a maximum of 7.2 servings per day [Relative risk (RR) = 0.69, 95% CI = 0.56, 0.85] (N = 7). The risk of large for gestational age was predicted to be maximum at 7.20 servings per day of dairy consumption, with the RR and 95% CI of 1.30 (1.15, 1.46; N = 4). In addition, the relationship between dairy consumption and low birth weight (RR = 0.70, 95% CI = 0.33, 1.50; N = 5) and pre-mature birth (RR = 1.13, 95% CI = 0.87, 1.47; N = 5) was not significant, respectively. Conclusions: Maternal consumption of dairy during pregnancy has a potential effect on fetal growth. Further well-designed studies are warranted to clarify the specific roles of individual dairy products. Systematic Review Registration: identifier: PROSPERO 2020 CRD42020150608.

Association Between Clinical Competencies and Mental Health Symptoms Among Frontline Medical Staff During the COVID-19 Outbreak: A Cross-Sectional Study.

Background: In China, mental health of frontline medical staff might be influenced by clinicians' ability to handle the outbreak of coronavirus disease 2019 (COVID-19). Few studies to-date have addressed the association between clinicians' competencies and mental health in this context. This cross-sectional study was to examine the prevalence of mental health symptoms among frontline medical staff that fought against the COVID-19 outbreak, and explore the associations between their competencies, and separate and concurrent depressive and anxiety symptoms. Methods: A total of 623 frontline medical staff was included in this study. Competencies, depressive symptoms, and anxiety symptoms were assessed using a self-reported short form of the Chinese clinical physicians' competency model, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 questionnaire, respectively. Logistic regression models were used to evaluate the associations between one SD increase in competency scores and the prevalence of mental health problems. Results: The prevalence of depressive, anxiety, and comorbid depressive and anxiety symptoms was 40.93, 31.78, and 26.00%, respectively. Among the medical staff with higher total competency scores, the prevalence of depressive [odds ratios (ORs) = 0.67, 95% confidence intervals (CIs): 0.55-0.81], anxiety (OR = 0.68, 95% CI: 0.56-0.83), and comorbid anxiety and depressive symptoms (OR = 0.69, 95% CI: 0.55-0.83) was lower than among their lower-scoring counterparts. Subgroup analyses stratified by core competency scores revealed similar associations as the main analyses. Conclusion: The present findings highlight the association between high core competency scores and lower prevalence of depressive, anxiety, and comorbid anxiety and depressive symptoms.

Risks of specific congenital anomalies in offspring of women with diabetes: A systematic review and meta-analysis of population-based studies including over 80 million births.

BACKGROUND: Pre-gestational diabetes mellitus (PGDM) has been known to be a risk factor for congenital heart defects (CHDs) for decades. However, the associations between maternal PGDM and gestational diabetes mellitus (GDM) and the risk of specific types of CHDs and congenital anomalies (CAs) in other systems remain under debate. We aimed to investigate type-specific CAs in offspring of women with diabetes and to examine the extent to which types of maternal diabetes are associated with increased risk of CAs in offspring. METHODS AND FINDINGS: We searched PubMed and Embase from database inception to 15 October 2021 for population-based studies reporting on type-specific CAs in offspring born to women with PGDM (combined type 1 and 2) or GDM, with no limitation on language. Reviewers extracted data for relevant outcomes and performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. Risk of bias appraisal was performed using the Cochrane Risk of Bias Tool. This study was registered in PROSPERO (CRD42021229217). Primary outcomes were overall CAs and CHDs. Secondary outcomes were type-specific CAs. Overall, 59 population-based studies published from 1990 to 2021 with 80,437,056 participants met the inclusion criteria. Of the participants, 2,407,862 (3.0%) women had PGDM and 2,353,205 (2.9%) women had GDM. The meta-analyses showed increased risks of overall CAs/CHDs in offspring born to women with PGDM (for overall CAs, relative risk [RR] = 1.99, 95% CI 1.82 to 2.17, P < 0.001; for CHDs, RR = 3.46, 95% CI 2.77 to 4.32, P < 0.001) or GDM (for overall CAs, RR = 1.18, 95% CI 1.13 to 1.23, P < 0.001; for CHDs, RR = 1.50, 95% CI 1.38 to 1.64, P < 0.001). The results of the meta-regression analyses showed significant differences in RRs of CAs/CHDs in PGDM versus GDM (all P < 0.001). Of the 23 CA categories, excluding CHD-related categories, in offspring, maternal PGDM was associated with a significantly increased risk of CAs in 21 categories; the corresponding RRs ranged from 1.57 (for hypospadias, 95% CI 1.22 to 2.02) to 18.18 (for holoprosencephaly, 95% CI 4.03 to 82.06). Maternal GDM was associated with a small but significant increase in the risk of CAs in 9 categories; the corresponding RRs ranged from 1.14 (for limb reduction, 95% CI 1.06 to 1.23) to 5.70 (for heterotaxia, 95% CI 1.09 to 29.92). The main limitation of our analysis is that some high significant heterogeneity still persisted in both subgroup and sensitivity analyses. CONCLUSIONS: In this study, we observed an increased rate of CAs in offspring of women with diabetes and noted the differences for PGDM versus GDM. The RRs of overall CAs and CHDs in offspring of women with PGDM were higher than those in offspring of women with GDM. Screening for diabetes in pregnant women may enable better glycemic control, and may enable identification of offspring at risk for CAs.

Non-Coding RNAs and Extracellular Vehicles: Their Role in the Pathogenesis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition in the second or third trimester of pregnancy. GDM has a considerable impact on health outcomes of the mother and offspring during pregnancy, delivery, and beyond. Although the exact mechanism regarding GDM remains unclear, numerous studies have suggested that non-coding RNAs, including long non-coding (lnc)RNAs, microRNAs, and circular RNAs, were involved in the pathogenesis of GDM in which they played vital regulatory roles. Additionally, several studies have revealed that extracellular vehicles also participated in the pathogenesis of GDM, highlighting their important role in this disease. Considering the lack of effective biomarkers for the early identification of and specific treatment for GDM, non-coding RNAs and extracellular vehicles may be promising biomarkers and even targets for GDM therapies. This review provides an update on our understanding of the role of non-coding RNAs and extracellular vehicles in GDM. As our understanding of the function of lncRNAs and extracellular vehicles improves, the future appears promising for their use as potential biomarkers and treatment targets for GDM in clinical practice.

Reference Values for Five-Repetition Chair Stand Test Among Middle-Aged and Elderly Community-Dwelling Chinese Adults.

Background: Previous studies on the five-repetition chair stand test (CS-5) are limited by the representativeness of the sample or the lack of reference equations for CS-5. Defined reference values for CS-5 in a large population are not available for middle-aged and elderly Chinese adults. Objective: We established age- and sex-stratified reference values for CS-5 times in a large population in China, and to investigate the associations between demographic and anthropometric factors and CS-5 times. Methods: Analysis of data from the national baseline survey of the China Health and Retirement Longitudinal Study, a nationally representative longitudinal survey that includes 450 urban communities and rural villages within 28 provinces, municipalities, and autonomous regions of China. Results: Twelve thousand six hundred five of seventeen thousand seven hundred eight participants were included for the reference value analyses. Twelve thousand three hundred out of seventeen thousand seven hundred eight participants were included for the risk factor analyses. Of 12,605 participants, the mean CS-5 time was 10.13 s (SD, 3.32) in men and 11.03 s (SD, 3.54) in women aged 40+ year. The CS-5 times were shorter in men than women of all age categories (P < 0.001). The cut-off points ranged from 5.36 to 9.98 s and from 6.48 to 10.29 s in men and women, respectively. Mean velocity was higher in men than in women (P < 0.001). Age, waist circumference, living in a rural village, and having chronic diseases were positively associated with CS-5 time, whereas male, handgrip strength, currently married, income, and current or ex-drinker were negatively associated with CS-5 time in this population (all P < 0.001). Conclusions: The comprehensive normative values for CS-5 are essential for enabling clinicians to better evaluate functional performance, determine the appropriate interventional strategy, and promote healthy aging of older adults.

Association between maternal antenatal depression and neonatal Apgar score: A systematic review and meta-analysis of prospective cohort studies.

INTRODUCTION: Antenatal depression is common, but most women with the condition choose to remain untreated. The Apgar score, an important indicator of newborn health, has been reported to be influenced by antenatal depression; thus, maternal antenatal depression, as reflected by a poor Apgar score, may harm children's health. AIM: To conduct a systematic review and meta-analysis to explore whether maternal antenatal depression is associated with the neonatal Apgar score. METHODS: We registered the protocol for this study with PROSPERO (CRD42019137585). We searched PubMed, Embase, Web of Science, and the Cochrane Library for published papers that reported the association between depression and Apgar score from inception to December 4, 2019. Two reviewers independently screened and selected the studies according to the inclusion and exclusion criteria, and extracted data according to the predesigned table. Stata version 12.0 software was used to analyze data. RESULTS: We finally identified 13 studies for inclusion, including a total of 12017 women. We did not find an association between antenatal depression and the 1 min Apgar score of neonates (mean difference= -0.03, 95% CI= -0.15-0.09) or the risk of a low Apgar score (OR=1.82, 95% CI=0.51 to 3.13). We found that antenatal depression increased the risk of a low Apgar score at 5 min (OR= 1.91, 95% CI= 1.23-2.59), but the association between the 5 min Apgar score and antenatal depression was not significant (mean difference= -0.001, 95% CI= -0.07-0.07). The results of the subgroup analyses also indicated that there was no association between the 5 min Apgar score and antenatal depression. CONCLUSIONS: Antenatal depression increased the risk of a low 5 min Apgar score; however, we did not find a difference in the mean and distribution of neonatal Apgar scores of mothers with depression and mothers without depression.

Co-culture model reveals the characteristics of theca cells and the effect of granulosa cells on theca cells at different stages of follicular development.

Theca cells (TCs) play an important role in follicular development, which cannot be separated from granulosa cells (GCs). However, compared with mammals, the TCs and the effects of GCs on TCs at different follicular development stages (FDSs) have specific characteristics in avian species, but none of them have been clearly defined. In this study, we established an in vitro co-culture (with GC at the corresponding stage) model of goose TCs at different FDSs (pre-hierarchical, hierarchical and F1) by using a transwell system. The properties of TCs in co-culture at the three FDSs, including cell morphology, activity and intracellular lipid content, as well as the expression of key genes involved in de novo lipogenesis, steroidogenesis, proliferation and apoptosis, were examined and defined. We further compared the mono-culture and co-culture groups. After co-culture, the activity of TCs showed significant (p < .01) increases in all stages; moreover, in pre-hierarchical TCs, the expression levels of FAS, SREBP, 3ß-HSD and CCND1 were promoted, and PPARγ, CYP19, BCL2 and CAS3 were inhibited (p < .05); in the hierarchical TCs, the expression levels of PPARγ, FAS, CYP19, CCND1 and BCL2 were promoted, and SREBP, STAR, 3ß-HSD and CAS3 were inhibited (p < .05), whereas in the F1 TCs, the expression levels of PPARγ, FAS, 3ß-HSD, CYP19 and CCND1 were promoted, and STAR and CAS3 were inhibited (p < .05). These results suggested that GCs at the three FDSs have dynamic and complex influences on the physiological characteristics of TCs, and the influences on TCs at the three FDSs were varied.

Exploration of the effects of goose TCs on GCs at different follicular stages using a co-culture model.

Granulosa cells (GCs) play a critical role in follicular development, which cannot be separated from the assistance of theca cells (TCs). In the present study, we used a transwell system to develop three stages of goose GCs in vitro mono-culture and co-culture models, and we analyzed the morphology, activity, intracellular lipid content and the expression of core genes involved in de novo lipogenesis (DNL), steroidogenesis, proliferation and apoptosis of the GCs. In the co-culture group, the activity of all three stages of GCs showed significant (P<0.01) changes, and they had a strong (P<0.01) correlation with culture time; further, the intracellular lipid deposition of hierarchical GCs was significantly different (P<0.01) between the two methods. Moreover, after co-culture, in pre-hierarchical GCs, the expression of SREBP, CYP11 and 3ßHSD was promoted (P<0.01). In hierarchical GCs, the expression of ACC, SREBP, STAR, CYP11, 3ßHSD and CCND1 was promoted at 48 h, but they were inhibited (P<0.05) at 96 h. In F1 GCs, the expression of ACC, FAS, SREBP, CYP11, BCL2 and CAS3 was inhibited (P<0.01). The results indicate that goose TCs had complex and time-dependent effects on the biological function of GCs at each corresponding stage, and the effects were distinct in the different stages. In addition, DNL, steroidogenesis, proliferation and apoptosis in hierarchical and F1 GCs might have some synergistic relationships in the effects of TCs on GCs. Furthermore, we speculated that TCs might play an important role in the differentiation and maturation of GCs during follicular development.

FASN-Mediated Lipid Metabolism Regulates Goose Granulosa Cells Apoptosis and Steroidogenesis.

Lipid metabolism participates in regulating the functions of granulosa cells (GCs), which is important for follicular development. In this experiment, goose GCs from pre-hierarchical follicles and hierarchical follicles were selected to be the model for studying the putative regulatory role of lipid metabolism in apoptosis and steroidogenesis, through overexpression and interference with fatty acid synthase (FASN). When FASN was overexpressed, the lipid accumulation was increased in hierarchical GCs (hGCs) and it was increased in the two categorized GCs when FASN was interfered. In addition, the apoptosis of the two categorized GCs was increased when FASN was overexpressed, and their progesterone production was decreased when FASN was interfered. The results of qRT-PCR showed that, when FASN was overexpressed, the expression level of CYP11A1 was decreased in pre-hierarchical GCs (phGCs), while the expression levels of SCD1, DGAT2, APOB, and StAR were increased in hGCs. When FASN was interfered, the expression levels of CPT-1, DGAT2, and StAR were decreased whereas the expression level of CYP11A1 was increased in phGCs, and the expression levels of CPT-1, SCD1, and StAR were decreased in hGCs. These results not only identify the different effects of manipulated FASN expression on lipid metabolism of goose phGCs and hGCs but also demonstrate that FASN-mediated lipid metabolism plays an important role in regulating apoptosis and steroidogenesis of in vitro cultured goose GCs.

Differential actions of diacylglycerol acyltransferase (DGAT) 1 and 2 in regulating lipid metabolism and progesterone secretion of goose granulosa cells.

Accumulating evidence shows that granulosa cells within both mammalian and avian ovaries have the ability to synthesize fatty acids through de novo lipogenesis and to accumulate triglycerides essential for oocyte and ovarian development. However, very little is known about the exact roles of key genes involved in the lipid metabolic pathway in granulosa cells. The goal of this study was to investigate the differential actions of diacylglycerol acyltransferase (DGAT) 1 and 2, which are recognized as the rate-limiting enzymes catalyzing the last step of triglyceride biosynthesis, in regulating lipid metabolism and steroidogenesis in granulosa cells of goose follicles at different developmental stages. It was observed that the mRNAs encoding DGAT1 and DGAT2 were ubiquitous in all examined granulosa cell layers but exhibited distinct expression profiles during follicle development. Notably, the mRNA levels of DGAT1, DGAT2, FSHR, LHR, STAR, CYP11A1, and 3ßHSD remained almost constant in all except for 1-2 follicles within the 8-10 mm cohort, followed by an acute increase/decrease in the F5 follicles. At the cellular level, siRNA-mediated downregulation of DGAT1 or DGAT2 did not change the amount of lipids accumulated in both undifferentiated- and differentiated granulosa cells, while overexpression of DGAT2 promoted lipid accumulation and expression of lipogenic-related genes in these cells. Meanwhile, we found that interfering DGAT2 had no effect but interfering DGAT1 or overexpressing DGAT2 stimulated progesterone secretion in undifferentiated granulosa cells; in contrast, interference or overexpression of DGAT1/2 failed to change progesterone levels in differentiated granulosa cells but differently modulated expression of steroidogenic-related genes. Therefore, it could be concluded that DGAT1 is less efficient than DGAT2 in promoting lipid accumulation in both undifferentiated- and differentiated granulosa cells and that DGAT1 negatively while DGAT2 positively regulates progesterone production in undifferentiated granulosa cells.

Relationship between Maternal Central Obesity and the Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Cohort Studies.

OBJECTIVE: Nowadays, body mass index (BMI) is used to evaluate the risk stratification of obesity-related pregnancy complications in clinics. However, BMI cannot reflect fat distribution or the proportion of adipose to nonadipose tissue. The objective of this study is to evaluate the association of maternal first or second trimester central obesity with the risk of GDM. Research Design and Methods. We searched in PubMed, Embase, and Web of Science for English-language medical literature published up to 12 May 2019. Cohort studies were only included in the search. Abdominal subcutaneous fat thickness, waist circumference, waist-hip ratio or body fat distribution were elected as measures of maternal central obesity, and all diagnostic criteria for GDM were accepted. The random effect meta-analysis was performed to evaluate the relationship between central obesity and the risk of GDM. RESULTS: A total of 11 cohort studies with an overall sample size of 27,675 women and 2,226 patients with GDM were included in the analysis. The summary estimate of GDM risk in the central obesity pregnant women was 2.76 (95% confidence interval [CI]: 2.35-3.26) using the adjusted odds ratio (OR). The degree of heterogeneity among the studies was low (I 2 = 14.4, P = 0.307). The subgroup analyses showed that heterogeneity was affected by selected study characteristics (methods of exposure and trimesters). After adjusting for potential confounds, the OR of adjusted BMI was significant (OR = 3.07, 95% CI: 2.35-4.00). CONCLUSIONS: Our findings indicate that the risk of GDM was positively associated with maternal central obesity.

Association between the ferritin level and risk of gestational diabetes mellitus: A meta-analysis of observational studies.

AIMS/INTRODUCTION: The relationship between ferritin and the risk of gestational diabetes mellitus (GDM) has not been established. Thus, we carried out a meta-analysis based on the current literature. MATERIALS AND METHODS: We searched relevant databases on Embase, PubMed, Cochrane Library and Web of Science before 10 May 2019 to determine the relationship between ferritin and the risk of GDM. The relative risks and 95% confidence intervals of GDM risk were summarized using a random effects model. Studies using categories of ferritin as exposure were combined by dose-response analysis. We carried out both linear and non-linear trends. We also carried out subgroup analysis, whether or not the studies adjusted for potential confounders, and meta-regression analysis to explore the source of heterogeneity. Sensitivity analysis was carried out to explore the robustness of the meta-analysis results. RESULTS: A total of 10 studies involving 4,690 participants were identified. The summary relative risk comparing persons with the highest concentration categories of ferritin with the lowest concentration categories of ferritin was 1.87 (95% confidence interval 1.50-2.34; I2  = 20.1%). Linear dose-response showed that an increase in ferritin of 10 µg/L increased the risk of GDM by 8% (1.08, 95% confidence interval 1.05-1.13, I2  = 55.1%; n = 4). A non-linear dose-response relationship also showed a consistently increasing risk of GDM with increased ferritin. No evidence of publication bias was detected. CONCLUSIONS: The findings from this meta-analysis suggest that increased ferritin levels are associated with an increased risk of GDM; however, we require further prospective cohort studies to confirm the results, especially the dose-response relationship between ferritin and GDM.

Dynamic characteristics of lipid metabolism in cultured granulosa cells from geese follicles at different developmental stages.

Previous studies have shown that lipid metabolism in granulosa cells (GCs) plays a vital role during mammalian ovarian follicular development. However, little research has been done on lipid metabolism in avian follicular GCs. The goal of the present study was to investigate the dynamic characteristics of lipid metabolism in GCs from geese pre-hierarchical (6-10 mm) and hierarchical (F4-F2 and F1) follicles during a 6-day period of in vitro culture. Oil red O staining showed that with the increasing incubation time, the amount of lipids accumulated in three cohorts of GCs increased gradually, reached the maxima after 96 h of culture, and then decreased. Moreover, the lipid content varied among these three cohorts, with the highest in F1 GCs. The qPCR results showed genes related to lipid synthesis and oxidation were highest expressed in pre-hierarchical GCs, while those related to lipid transport and deposition were highest expressed in hierarchical GCs. These results suggested that the amount of intracellular lipids in GCs increases with both the follicular diameter and culture time, which is accompanied by significant changes in expression of genes related to lipid metabolism. Therefore, it is postulated that the lipid accumulation capacity of geese GCs depends on the stage of follicle development and is finely regulated by the differential expression of genes related to lipid metabolism.

Evidence for the existence of de novo lipogenesis in goose granulosa cells.

De novo lipogenesis (DNL) is an important physiological mechanism, but it is poorly understood in avian follicles. The protein distribution patterns of three key genes related to DNL (i.e., FAS, ACC, and PPARγ) were firstly determined in geese developing follicles using immunohistochemistry, and our results showed that all three proteins were present in both prehierarchical and hierarchical follicles. Furthermore, it was revealed by qPCR that transcripts of these three genes were widely expressed in theca and granulosa layers of all staged follicles; however, the expression of DNL-related genes in granulosa cell changed significantly (P < 0.05) after follicle selection (FAS and PPARγ) and before ovulation (FAS). It is suggested that the DNL mechanism may be closely related to the follicular selection, while FAS may be closely associated with ovulation and steroidogenesis. These results suggested that DNL exists throughout follicle development and it potentially have an important role in the process of follicular selection, development, steroidogenesis, and ovulation, especially in their granulosa layers. To further demonstrate this point, granulosa cells isolated from hierarchical follicles were cultured in vitro. By analyzing the mRNA and protein expression patterns of these three genes, the fatty acid synthase enzyme activity, the contents of extracellular triglyceride, and intracellular lipids, as well as the cell activity at different time points of in vitro culture (0, 6, 12, and 18 h). These findings not only ensured the existence of DNL in the granulosa cells of goose follicles, but also suggested the complex process of lipid metabolism that associated with DNL, may play an important role in cell proliferation and physiological functions. Taken together, we first confirmed the existence of lipid metabolism, especially the DNL in goose follicles, and further suggested its role in the follicles, especially in the granulosa cells.

Bmp4 inhibits goose granulosa cell apoptosis via PI3K/AKT/Caspase-9 signaling pathway.

Bone morphogenetic protein 4 (BMP4) has an important role in regulating cellular proliferation, differentiation and apoptosis. It, however, is still unclear as to the mechanisms by which BMP4 regulates the apoptosis of granulosa cells (GCs) in geese. In the present study, there was cloning of the full-length coding sequence of goose BMP4 gene, which consisted of 1212 nucleotides encoding 403 amino acids. Its deduced amino acid sequence comprised one signal peptide, one TGFß pro-peptide and one mature peptide domain. Results from conducting the quantitative real-time PCR (qPCR) indicated the relative abundances of BMP4 mRNA in geese GCs increased gradually from the relative abundances in pre-hierarchical follicles that were 4 to 6 mm in diameter to that in the fifth largest (F5) follicle and then relative abundances of BMP4 mRNA decreased with further development as the largest (F1) follicle. Results from use of the TUNEL assay indicated that overexpression of the goose BMP4 gene suppressed GC apoptosis and this was confirmed when relative abundances of the CAD, Caspase-9 and Caspase-3 proteins were determined using western blotting. In addition, overexpression of the BMP4 gene induced phosphorylation of AKT, which was inhibited with use of the PI3K inhibitor, LY294002. Co-transfection of BMP4 and LY294002 resulted in increased relative abundances of Caspase-9 and CAD proteins but had no effect on that of Caspase-3. Taken together, these results suggested that expression of the BMP4 gene resulted in a reduction in Caspase-9 protein leading to inhibition of GC apoptosis via the PI3K/AKT signaling pathway in geese.