Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

Continuous glucose monitoring-derived glycemic metrics and adverse pregnancy outcomes among women with gestational diabetes: a prospective cohort study.

Background: Continuous glucose monitoring (CGM) has shown potential in improving maternal and neonatal outcomes in individuals with type 1/2 diabetes, but data in gestational diabetes mellitus (GDM) is limited. We aimed to explore the relationship between CGM-derived metrics during pregnancy and pregnancy outcomes among women with GDM. Methods: We recruited 1302 pregnant women with GDM at a mean gestational age of 26.0 weeks and followed them until delivery. Participants underwent a 14-day CGM measurement upon recruitment. The primary outcome was any adverse pregnancy outcome, defined as having at least one of the outcomes: preterm birth, large-for-gestational-age (LGA) birth, fetal distress, premature rupture of membranes, and neonatal intensive care unit (NICU) admission. The individual outcomes included in the primary outcome were considered as secondary outcomes. We conducted multivariable logistic regression to evaluate the association of CGM-derived metrics with these outcomes. Findings: Per 1-SD difference in time above range (TAR), glucose area under the curve (AUC), nighttime mean blood glucose (MBG), daytime MBG, and daily MBG was associated with higher risk of any adverse pregnancy outcome, with odds ratio: 1.22 (95% CI 1.08-1.36), 1.22 (95% CI 1.09-1.37), 1.18 (95% CI 1.05-1.32), 1.21 (95% CI 1.07-1.35), and 1.22 (95% CI 1.09-1.37), respectively. Time in range, TAR, AUC, nighttime MBG, daytime MBG, daily MBG, and mean amplitude of glucose excursions were positively associated, while time blow range was inversely associated with the risk of LGA. Additionally, higher value for TAR was associated with higher risk of NICU admission. We further summarized the potential thresholds of TAR (2.5%) and daily MBG (4.8 mmol/L) to distinguish individuals with and without any adverse pregnancy outcome. Interpretation: The CGM-derived metrics may help identify individuals at higher risk of adverse pregnancy outcomes. These CGM biomarkers could serve as potential new intervention targets to maintain a healthy pregnancy status among women with GDM. Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Westlake Laboratory of Life Sciences and Biomedicine.

[Aerosol Optical Characteristics with Ground-based Measurements via Sun Photometer and Its Relationship with PM Particle Concentration in Chang'an].

The simultaneous quantitative investigation of aerosol ground observation data and particle concentration data is important for a better understanding of the vertical distribution characteristics of air pollution and formulating reasonable air pollution control measures in Chang'an, Xi'an. CE-318 measurements from October 2018 to April 2021 were systematically analyzed to reveal the seasonal and yearly variations in atmospheric aerosols in Chang'an. Then, the relationship between AOD and particle concentration in different seasons and different pollution degrees was explored. The obtained results were as follows:① the seasonal variation in AOD in Chang'an was determined, whereby autumn (1.02)>winter (1.00)>summer (0.63)>spring (0.47). Distinct monthly and inter-annual differences in AOD were observed, showing that the annual average of AOD in 2019 was higher than that in 2020. ② Obvious seasonal and monthly differences in aerosol main control modes were observed; the dominant mode of aerosols gradually changed from coarse mode to fine mode from spring to winter. The seasonal variation in the main control mode of aerosols in 2019 was similar to that in the whole observation period. The seasonal aerosol Angstrom wavelength index (Angstrom) was evenly distributed in 2020, and aerosol particles existed in coarse mode form. Generally speaking, the aerosol type in Chang'an was mostly mixed aerosol throughout the whole observation period. ③ Significant seasonal variations in the relationship between AOD and Angstrom was shown, in which the air pollution in spring was dominated by coarse mode aerosol particles. The local pollution in summer was caused by coarse and fine mode aerosol particles, and the fine mode particles were dominant when the pollution was obvious. The characteristic distribution of Angstrom in autumn and winter was similar; in case of local pollution, the coarse mode aerosol particles were dominant, and in case of obvious pollution, the fine mode aerosol particles were dominant. ④ The monthly concentration variation trend of PM2.5 and PM10 in Chang'an consistent with the maximum and minimum values appeared in January and summer, respectively. Seasonal variation in the concentration of PM2.5 and PM10 was apparent, with the highest values in winter. ⑤ A positive correlation between AOD and particulate matter concentration in different seasons and pollution levels was obtained during the observation periods, but the correlation coefficient differed. The specific characteristics were as follows:the correlation between AOD and PM2.5 concentration was greater than that with PM10 concentration; the correlation between AOD and particle concentration in autumn and winter was greater than that in spring and summer; and the correlation between AOD and particulate matter concentration was greater in polluted weather. Particle concentration was the most important determinant of AOD change, followed by relative humidity, which was the meteorological factor with the highest interpretation rate of AOD change in Chang'an. This indicates that a higher correlation between AOD and particle concentration would benefit from a reasonable humidity correction of AOD.

Associations of imbalance of intestinal flora with severity of disease, inflammatory factors, adiponectin, and vascular endothelial function of hypertension patients.

To explore the relationship between the severity of hypertension and the imbalanced intestinal flora, inflammatory factors, adiponectin (ADPN) and vascular endothelial function in primary hypertension patients. According to the grading criteria for hypertension, in total of 60 patients with primary hypertension in our hospital from April to July, 2020 were divided into Grade 1 group (n = 20), Grade 2 group (n = 20), and Grade 3 group (n = 20). The feces of the research subjects were collected to extract the deoxyribonucleic acid (DNA) and detect its composition of intestinal flora. Subsequently, the peripheral blood was collected to determine the changes in inflammatory factors interleukin-2 (IL-2), IL-4, tumor necrosis factor-α (TNF-α) and IL-1ß, serum immunoglobulin G (IgG) and IgM, ADPN and vascular endothelial function-related endothelin-1 (ET-1), nitric oxide (NO), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule-1 (ICAM-1). There were no significant differences in the gender, age, and body mass index (BMI), the proportion of smokers, diet habit, probiotics and antihypertensive medication use, and number of diabetic cases among groups (p > 0.05). We found an inverse association between blood pressure measures and microbial diversity, in particular microbial richness (p < 0.05). Among the four major kinds of intestinal flora, the composition of firmicutes (p < 0.05) and bacteroidetes (p < 0.05) showed obvious differences among the three groups, and they had consistent trends with the changes in the abundance of firmicutes and bacteroidetes. Intestinal flora imbalance is closely related to the severity of hypertension, inflammatory factors, ADPN, and vascular endothelial function.

The effects of selenium supplementation on antibody titres in patients with Hashimoto's thyroiditis.

INTRODUCTION: The objective of this study was to evaluate the effect of selenium supplementation on autoantibody titres, thyroid ultrasonography, and thyroid function in patients with Hashimoto's thyroiditis (autoimmune thyroiditis) and normal thyroid reference range. MATERIAL AND METHODS: A total of 100 patients were given 200 ug/d selenium yeast orally, their thyroid function, levels of serum selenium, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and urine iodine were measured, and thyroid ultrasonography was performed before administration and three and six months afterwards, and the data were statistically analysed. RESULTS: The subjects exhibited a selenium deficiency before the administration of selenium, and the serum levels increased to moderate levels three and six months after the selenium supplementation (p < 0.05). The titres of TGAb decreased significantly in patients after six months of selenium supplementation (p < 0.05). In the high antibody group, TgAb decreased after 6 months compared with baseline (p = p < 0.05), and TPOAb decreased after 3 and 6 months of selenium supplementation compared with baseline (p < 0.05). CONCLUSION: In patients with autoimmune thyroiditis and normal thyroid reference range, there was a general selenium deficiency, but after six months of treatment it was shown that selenium supplementation may be effective in reducing the titres of TGAb and TPOAb.

[Spatiotemporal Distribution of Aerosol Optical Depth Based on Landsat Data in the Hinterland of the Guanzhong Basin and Its Relationship with Urbanization].

Aerosol optical depth (AOD) is one of the most fundamental optical properties of aerosols that characterizes the attenuation of light by aerosols and is an indicator of regional air pollution. Based on the blue band surface reflectance database from the MOD09A1 products for the period 2000-2019 and the ASTER spectral database, AOD was estimated from Landsat TM/OLI data using the deep blue algorithm (DB). Multi-year average/annual average and seasonal AOD values for the period 2000-2019 were then calculated to analyze the spatial characteristics and temporal variations of AOD using the empirical orthogonal function method (EOF). Furthermore, the impacts of urbanization on the spatio-temporal distribution of AOD were analyzed. The obtained results are summarized as follows:① The multi-year average AOD spatial distribution in the hinterland of the Guanzhong Basin was significantly affected by topography and human activities, with higher AOD values and variationsin areas of low altitude and high-intensity human activities compared to the surrounding mountains. Thus, changes in AOD in the study area are mainly affected by anthropogenic factors. AOD also showed significant seasonal variations, whereby spring (0.34) > summer (0.33) > autumn (0.23) > winter (0.12), and the largest regional differences occurred in summer; ② The annual average AOD (from 2000-2019) showed the trend of "increase-decrease-increase", and reached a maximum in 2005, with the high AOD area gradually moving to the south. The distribution of AOD values in spring and summer was relatively discrete, while it is in a low-value agglomeration state in winter; ③ Three main AOD spatial distribution modes were identified based on the EOF, which had cumulative contribution rate of 83.0%. The spatial distribution trend of AOD showed regional consistency, with feature vectors consistent with the altitude, thus reflecting the difference of AOD at different altitudes. Taking the Qinling Mountains as the dividing line, the AOD presented the "north-south" pattern, AOD showed a "north-south" pattern, reflecting the uniqueness of the regional development in the Guanzhong Basin compared to the southern Qinling Mountains. The "southeast-northwest" distribution pattern indicated that the AOD presented a reverse change trend between urban and non-urban; and ④ The results of correlation analysis between the AOD and urbanization revealed a positive correlation with permanent population density (R2=0.707, P<0.05), impervious surface density (R2=0.377, P<0.05), and industrial POI density (R2=0.727, P<0.5). These results are significant for improving the monitoring of air quality in the Guanzhong Basin and for the construction of an urban ecological environment.

Mediating Effects of Maternal Blood Triglycerides on the Relationship between Prepregnancy Body Mass Index and Fetal Macrosomia.

OBJECTIVE: To examine whether the association of prepregnancy body mass index (BMI) with fetal macrosomia is mediated through maternal circulating lipid concentrations during pregnancy. STUDY DESIGN: In this prospective cohort, 3011 eligible pregnant women were enrolled. Information on demographic characteristics were collected using questionnaires, and anthropometrics and laboratory tests were performed at 24 weeks of gestation and before delivery. Macrosomia was defined as birth weight ≥4000 g. Logistic regression and multivariable linear regression, adjusted for age, fetal sex, education, gestational weight gain, fasting blood glucose, gestational diabetes, gestational hypertension, gestational age at delivery, delivery mode, and parity, were used to assess the mediation path between prepregnancy BMI, maternal serum lipids, and fetal macrosomia. RESULTS: A total of 2454 participants with completed records were included in the final analyses. Among the maternal circulating lipid biomarkers, only triglyceride was significantly associated with both prepregnancy BMI and fetal macrosomia risk, adjusting for potential confounders. Mediation analyses demonstrated that the direct effect of prepregnancy BMI on fetal macrosomia was 0.0085 (95% CI, 0.0003-0.018; P < .05), the indirect effect mediated through maternal serum triglycerides was 0.0016 (95% CI, 0.0007-0.0029; P < .001), and the estimated proportion of mediated effect was 15.7% (P < .05). CONCLUSIONS: Maternal circulating triglycerides mediate the association of prepregnancy BMI with the risk of fetal macrosomia.

Identifying the insulin resistance index in nondiabetic Chinese subjects.

In the present study, the performance of anthropometric parameters, lipid and glucose indexes, and the combination of anthropometric parameters with the TyG (triglycerides × fasting plasma glucose) metabolic index, was compared in detecting insulin resistance (IR) to evaluate the optimal cut-off points in nondiabetic Chinese individuals. A total of 1067 nondiabetics underwent oral glucose tolerance test, blood lipid, and fasting insulin measurements. The clinical usefulness of various parameters- body mass index (BMI), waist circumference (WC), TyG, triglycerides/ high density lipoprotein cholesterol ratio, and TyG with adiposity status (TyG-BMI [TyG × BMI] and TyG-WC)-was analyzed to identify IR. Spearman correlation and receiver-operating characteristic curve analyses were used to compare the predictive efficacy of different indicators. All indicators showed a positive correlation with IR in both normal glucose and all subjects. However, the correlation between BMI and homeostasis model assessment of IR index was higher than other indicators as assessed by Spearman correlation test (P < .05). Furthermore, BMI and TyG-BMI were better indicators than others as determined by comparing the area under the receiver-operating characteristics curves (P < .05) in detecting IR. BMI is a simple and accurate measure for detecting IR in Chinese subjects. The 27 kg/m threshold was the optimal BMI cut-off point for detecting IR in both normal glucose and all glucose categories subjects.

Reanalysis and External Validation of a Decision Tree Model for Detecting Unrecognized Diabetes in Rural Chinese Individuals.

We reanalyzed previous data to develop a more simplified decision tree model as a screening tool for unrecognized diabetes, using basic information in Beijing community health records. Then, the model was validated in another rural town. Only three non-laboratory-based risk factors (age, BMI, and presence of hypertension) with fewer branches were used in the new model. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC) for detecting diabetes were calculated. The AUC values in internal and external validation groups were 0.708 and 0.629, respectively. Subjects with high risk of diabetes had significantly higher HOMA-IR, but no significant difference in HOMA-B was observed. This simple tool will help general practitioners and residents assess the risk of diabetes quickly and easily. This study also validates the strong associations of insulin resistance and early stage of diabetes, suggesting that more attention should be paid to the current model in rural Chinese adult populations.

Angiopoietin-Like Protein 4 Is a High-Density Lipoprotein (HDL) Component for HDL Metabolism and Function in Nondiabetic Participants and Type-2 Diabetic Patients.

BACKGROUND: ANGPTL4 (angiopoietin-like protein 4) is a LPL (lipoprotein lipase) inhibitor and is present in high-density lipoprotein (HDL). However, it is not defined whether ANGPTL4 in HDLs could affect HDL metabolism and function in type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: ANGPTL4 levels in the circulation and HDLs were quantified in nondiabetic participants (n=201, 68.7% females) and T2DM patients (n=185, 66.5% females). HDLs were isolated from nondiabetic controls and T2DM patients to assess cholesterol efflux or subjected to endothelial lipase (EL)-overexpressed HEK293 cells for EL hydrolysis in vitro. The association between ANGPTL4 in HDLs and HDL components and function was analyzed in nondiabetic participants or diabetic patients, respectively. Plasma or HDLs of ANGPTL4+/+ and ANGPTL4-/- mice was subjected for cholesterol efflux or EL hydrolysis, respectively. ANGPTL4 levels in the plasma and HDLs were 1.7- and 2.0-fold higher in T2DM patients than nondiabetic controls, respectively (P<0.0001). Multivariable analysis demonstrated that per 1 doubling increase of ANGPTL4 levels in HDLs, the changes amounted to +0.27% cholesterol efflux (P=0.03), +0.06 µg/mL apolipoprotein A-I (P=0.09) and -9.41 µg/L serum amyloid A (P=0.02) in nondiabetic controls. In T2DM patients, the corresponding estimates were -0.06% cholesterol efflux (P=0.10), -0.06 µg/mL apolipoprotein A-I (P=0.38), and +3.64 µg/L serum amyloid A (P=0.72). HDLs isolated from ANGPTL4-/- mice showed accelerated hydrolysis by EL and reduced cholesterol efflux compared with ANGPTL4+/+ littermates. CONCLUSIONS: Physically, ANGPTL4 in HDLs protected HDLs from hydrolysis. Resulting from increased circulating ANGPTL4 levels in T2DM, ANGPTL4 levels in HDLs were elevated but with compromised inhibitory effect on EL, leading to increased HDL hydrolysis and dysfunction.

Different relationship between ANGPTL3 and HDL components in female non-diabetic subjects and type-2 diabetic patients.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is a major lipoprotein regulator and shows positive correlation with high-density lipoprotein-cholesterol (HDL-c) in population studies and ANGPTL3 mutated subjects. However, no study has looked its correlation with HDL components nor with HDL function in patients with type 2 diabetes mellitus (T2DM). METHODS: We studied 298 non-diabetic subjects and 300 T2DM patients who were randomly recruited in the tertiary referral centre. Plasma levels of ANGPTL3 were quantified by ELISA. Plasma samples were fractionated to obtain HDLs. HDL components including apolipoprotein A-I (apoA-I), triglyceride, serum amyloid A (SAA), phospholipid and Sphingosine-1-phosphate were measured. HDLs were isolated from female controls and T2DM patients by ultracentrifugation to assess cholesterol efflux against HDLs. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, body mass index and lipid lowering drugs were performed in male or female non-diabetic participants or diabetic patients, respectively. RESULTS: We demonstrated that plasma level of ANGPTL3 was lower in female T2DM patients than female controls although no difference of ANGPTL3 levels was detected between male controls and T2DM patients. After adjusting for confounding factors, one SD increase of ANGPTL3 (164.6 ng/ml) associated with increase of 2.57 mg/dL cholesterol and 1.14 µg/mL apoA-I but decrease of 47.07 µg/L of SAA in HDL particles of non-diabetic females (p < 0.05 for cholesterol and SAA; p < 0.0001 for apoA-I). By contrast, 1-SD increase of ANGPTL3 (159.9 ng/ml) associated with increase of 1.69 mg/dl cholesterol and 1.25 µg/mL apoA-I but decrease of 11.70 µg/L of SAA in HDL particles of female diabetic patients (p < 0.05 for cholesterol; p < 0.0001 for apoA-I; p = 0.676 for SAA). Moreover, one SD increase of ANGPTL3 associated with increase of 2.11 % cholesterol efflux against HDLs in non-diabetic females (p = 0.071) but decrease of 1.46 % in female T2DM patients (p = 0.13) after adjusting for confounding factors. CONCLUSIONS: ANGPTL3 is specifically correlated with HDL-c, apoA-I, SAA and HDL function in female non-diabetic participants. The decrease of ANGPTL3 level in female T2DM patients might contribute to its weak association to HDL components and function. ANGPTL3 could be considered as a novel therapeutic target for HDL metabolism for treating diabetes.

Microwave ablation versus laser ablation in occluding lateral veins in goats.

Increasing number of endovenous techniques are available for the treatment of saphenous vein reflux and endovenous laser ablation (EVLA) is a frequently used method. A newly developed alternative, based on thermal therapy, is endovenous microwave ablation (EMA). This study evaluated the effect of the two procedures, in terms of coagulation and histological changes, in occluding lateral veins in goats. Twelve animals were randomized into two group, with 6 treated with EMA (EMA group), and the rest 6 with EVLA (EVLA group). Results of coagulation, including coagulation, fibrinolysis and platelet activation, were assessed at three or four different time points: before, immediately after, 24 h (and 48 h) after ablation. The diameter change, a measure of efficacy, was ultrasonographically measured before and 1 month after the ablation. Histological changes were grossly and microscopically evaluated immediately, 1 and 3 month(s) after the ablation. The length of the ablated vein and preoperative average diameter were comparable between the two groups. In both EMA and EVLA groups, several coagulation parameters, fibrinolysis and platelet activation parameters only underwent slight changes. Ultrasound imaging displayed that the diameter reduction of the veins treated by EMA was significantly larger than by EVLA, in consistent with the results of macroscopic examination. Microscopic examination revealed necrosis and thickening of the vein wall, and occlusion of the lumen within 3 months after ablation in both EMA and EVLA groups. It is concluded that EMA is a minimally invasive therapy, which appears to be safe and effective for treatment of lateral veins in goats.

Targeted knockdown of IQGAP1 inhibits the progression of esophageal squamous cell carcinoma in vitro and in vivo.

IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thoroughly investigated. In the present study, we showed that IQGAP1 was overexpressed in ESCC tumor tissues, and its overexpression was correlated with the invasion depth of ESCC. Importantly, by using RNA interference (RNAi) technology we successfully silenced IQGAP1 gene in two ESCC cell lines, EC9706 and KYSE150, and for the first time found that suppressing IQGAP1 expression not only obviously reduced the tumor cell growth, migration and invasion in vitro but also markedly inhibited the tumor growth, invasion, lymph node and lung metastasis in xenograft mice. Furthermore, Knockdown of IQGAP1 expression in ESCC cell lines led to a reversion of epithelial to mesenchymal transition (EMT) progress. These results suggest that IQGAP1 plays crucial roles in regulating ESCC occurrence and progression. IQGAP1 silencing may therefore develop into a promising novel anticancer therapy.

[Study on the risk factors related to severe acute respiratory syndrome among close contactors in Beijing].

OBJECTIVE: To understand the risk factors on severe acute respiratory syndrome (SARS) among their contacts and to develop effective strategy for its control. METHODS: Available epidemiological data of SARS cases and close contacts were reviewed and analyzed by SPSS. RESULTS: Out of the 2195 close contacts, 138 (6.3%) were diagnosed as SARS. Among colleagues and classmates of SARS patients, the infection rate was 0.36% versus 31.71% in contacts among families and hospitals, 0.77% in schools. No one was infected among 459 close contacts to SARS in the working unit. CONCLUSIONS: Among close contacts, factors that facilitating transmission would include: time, extent, frequency and place of contact to the patients, as well as factors related to close contacts as way, time of isolation and age. One of the epidemiological characteristics was that SARS were as clustered in the family among those close contacts. It is important to control the spread of SARS through supervision on the close contacts to patients.