Association Between Serum 25-Hydroxyvitamin D and Trichomonas vaginalis Infection Among American Adults: NHANES 2013-2016.

BACKGROUND: Previous studies have suggested that vitamin D may possess anti-infection properties, but the relationship between vitamin D and Trichomonas vaginalis infection remains unexplored. METHODS: Using data from the National Health and Nutrition Examination Survey between 2013 and 2016, we conducted multivariate regression analyses and subgroup analyses to investigate the association between 25-hydroxyvitamin D (25[OH]D) levels and T. vaginalis infection, ensuring the robustness of our results. RESULTS: The final sample included data from 4318 individuals aged 20 to 59 years, among which 92 were diagnosed with T. vaginalis infection. For every 10 nmol/L increase in serum 25(OH)D level, there was a 22% reduction in the likelihood of T. vaginalis infection incidence (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69-0.90). Similarly, higher concentration tertiles demonstrated relatively lower infection ratios compared with the tertile with the lowest 25(OH)D concentration (aOR, 0.54 [95% CI, 0.30-0.95; P = 0.030] for T2; aOR, 0.23 [95% CI, 0.09-0.61; P < 0.001] for T3). CONCLUSIONS: Our cross-sectional study indicates a negative association between 25(OH)D levels and the prevalence of T. vaginalis infection. However, further high-quality evidence is needed to establish a causal relationship between 25(OH)D levels and T. vaginalis infection, as well as to evaluate the potential role of vitamin D supplementation in preventing T. vaginalis infection.

Developing Salt-Rejecting Evaporators for Solar Desalination: A Critical Review.

Solar desalination, a green, low-cost, and sustainable technology, offers a promising way to get clean water from seawater without relying on electricity and complex infrastructures. However, the main challenge faced in solar desalination is salt accumulation, either on the surface of or inside the solar evaporator, which can impair solar-to-vapor efficiency and even lead to the failure of the evaporator itself. While many ideas have been tried to address this ″salt accumulation″, scientists have not had a clear system for understanding what works best for the enhancement of salt-rejecting ability. Therein, for the first time, we classified the state-of-the-art salt-rejecting designs into isolation strategy (isolating the solar evaporator from brine), dilution strategy (diluting the concentrated brine), and crystallization strategy (regulating the crystallization site into a tiny area). Through the specific equations presented, we have identified key parameters for each strategy and highlighted the corresponding improvements in the solar desalination performance. This Review provides a semiquantitative perspective on salt-rejecting designs and critical parameters for enhancing the salt-rejecting ability of dilution-based, isolation-based, and crystallization-based solar evaporators. Ultimately, this knowledge can help us create reliable solar desalination solutions to provide clean water from even the saltiest sources.

The potential presence of infection may be indicated through non-invasive prediction of procalcitonin and C-reactive protein levels within the initial three days after cervical cerclage: a retrospective case-control study.

PURPOSE: To identify which non-invasive infection indicators could better predict post-cervical cerclage (CC) infections, and on which days after CC infection indicators should be closely monitored. METHODS: The retrospective, single-center study included 619 single-pregnancy patients from January 2021 to December 2022. Patients were categorized into infected and uninfected groups based on physicians' judgments of post-CC infections. Registered information included patient characteristics, cervical insufficiency history, gestational age at CC, surgical method (McDonald/Shirodkar), purpose of CC, mid-pregnancy miscarriage/preterm birth, infection history or risk factors, and infection indices on days 1, 3, 5, and 7 after CC. Propensity score matching (PSM) was applied to reduce patient characteristic bias. Statistical analysis of C-reactive protein (CRP), white blood cell (WBC), neutrophil count (NEU), percentage of neutrophil count (NEU_P), interleukin-6 (IL-6), and procalcitonin (PCT) in the infected group compared with the uninfected group was performed using chi-square tests and t-tests. Receiver operating characteristic (ROC) curves were used to further assess the diagnostic value of CRP, PCT, and CRP-PCT in combination. RESULTS: Among the 619 included patients, 206 patients were matched using PSM and subsequently assessed. PCT values on day 1 and day 3 after CC exhibited significant differences between the two groups in two statistical ways (P < 0.01, P < 0.05). The CRP levels on day 1 were significantly higher in the infected group compared to the uninfected group in two statistical ways (P < 0.05). On day 3, the mean CRP value was significantly elevated in the infected group compared to the uninfected group (P < 0.05). Analyses of IL-6, WBC, NEU, and NEU_P did not yield clinically significant results. The area under the ROC curves for CRP, PCT, and CRP-PCT on day 1 and day 3 were all below 0.7. In the preventive CC group, the AUC values of CRP and CRP-PCT obtained on d1 were found to be higher than 0.7, indicating moderate diagnostic accuracy. CONCLUSION: For women after CC surgery, especially of preventive aim, increased serum CRP and PCT levels from post-CC day 1 to day 3 may signal a potential postoperative infection, warranting close monitoring.

Abnormal dynamic functional connectivity of hippocampal subregions associated with working memory impairment in melancholic depression.

BACKGROUND: Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions - including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. METHODS: Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. RESULTS: Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. CONCLUSIONS: These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Proteomic study of aqueous humour in diabetic patients with cataracts by TMT combined with HPLC-MS/MS.

BACKGROUND: The purpose of this study is to identify the proteomic differences between the aqueous humour of diabetes patients with cataracts and that of non-diabetic sufferers of cataracts in a clinical setting. METHODS: Patients were divided into the diabetic experimental group and the non-diabetic control group. Aqueous humour specimens were obtained via cataract surgery. Sample proteins were treated with a TMT reagent, separated using a cation chromatography column, and analysed using a C18 desalting column. Proteins were identified using HPLC-MS/MS. The differential proteins were identified using both a p value of < 0.05 and a fold change of > 1.2. GO classification enrichment analysis, KEGG pathway enrichment analysis, protein interaction network analysis, and ingenuity pathway analysis were all carried out. The expression level of four differential proteins were verified by Western blot, and GC and TTR expressions were further examined using an expanded sample pool. RESULTS: The postprandial glucose levels between the experimental group (9.40 ± 1.35 mmol/L) and the control group (6.56 ± 0.81 mmol/L) were significantly different, with a p value of 1.16E-06. It is important to note, however, that the baseline levels of the parameters showed no statistical differences. In total, 397 aqueous humour proteins were identified; of these, 137 showed significant differences, with 63 upregulated ones and 74 down-regulated ones. The differential proteins play important roles in numerous biological processes and pathways, such as complement and coagulation cascades (p = 1.71E-09). Some of these differential proteins are associated with diabetic retinal degeneration and other diabetic complications. Differential proteins, such as HP, GC, and TTR, have high node degree in the protein interaction network. Western blot results further confirmed that GC were down-regulated while TTR was up-regulated in aqueous humour under diabetic condition. CONCLUSION: A list of differential proteins in the human aqueous humour of diabetic patients was established. Proteins with high interaction scores as per protein interaction analysis, such as GC and TTR, were further verified and could potentially be used as early diagnostic markers for diabetic eye complications in clinical practice.

Meta-Analysis of the Risk for Abnormal Liver Function in Pregnancy with High HBV DNA After Antiviral Therapy Withdrawal.

Objective: We aimed to explore the relationship between the withdrawal of antiviral therapy after delivery and the risk for abnormal liver function (ALF) after delivery in pregnant women with high hepatitis B virus (HBV) DNA load by meta-analysis, in order to provide the corresponding theoretical basis for further guiding the clinical use of antiviral drugs in such pregnant women. Methods: We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy from January 1, 2010 to November 1, 2020. Study selection and data extraction were performed by pairs of independent reviewers. The main index was the percentage of ALF higher than the upper limit of normal at 0 to 12 and 12 to 24 weeks after delivery. Meta-analysis was used to compare the risk for ALF after stopping antiviral drugs at different time points following delivery, and subgroup analysis was conducted according to the types of drugs used. Results: We included 10 studies that enrolled 1080 pregnant women. There were 749 pregnant women in the treatment group and 331 pregnant women in the control group (who were not treated with antiviral therapy). The risk ratio (RR) for ALF in the 2 groups at 0 to 12 weeks after delivery: RR = 0.88; 95% CI, 0.71-1.09; at 12-24 weeks: RR = 0.46; 95% CI, 0.29-0.73, were compared. According to the different types of medication, subgroup analysis showed that the lamivudine treatment group compared with the control group at 0-12 weeks: RR = 0.67; 95% CI, 0.26-1.75; at 12-24 weeks, RR = 0.27; 95% CI, 0.11-0.67. The telbivudine treatment group was compared with the control group: at 0-12 weeks: RR = 0.77; 95% CI, 0.43-1.39; at 12-24 weeks: RR = 0.62, 95% CI, 0.23-1.64. The tenofovir treatment group was compared with the control group: at 0-12 weeks RR = 1.02; 95% CI, 0.67-1.55; at 12-24 weeks RR = 0.5; 95% CI, 0.25, 0.99. The lamivudine antiviral treatment group was further analyzed according to different treatment withdrawal time points. Compared with the control group, the immediate withdrawal of lamivudine in labor group at 0-12 weeks RR = 0.29; 95% CI, 0.11-0.77; at 12-24 weeks RR = 0.22; 95% CI, 0.05-0.88; the results were significantly different. There was no significant difference between the 4-week group and the 4-12 week group and the control group. Conclusion: In pregnant women with a high HBV DNA load, immediate withdrawal after antiviral treatment in the second or third trimester of pregnancy did not increase the risk for ALF after delivery.

Mutation of Beclin1 acetylation site at K414 alleviates high glucose-induced podocyte impairment in the early stage of diabetic nephropathy by inhibiting hyperactivated autophagy.

BACKGROUND: Our group recently reported that a mutation of the novel Beclin1 K414R acetylation site impacts the stability of Beclin1 protein, which decreases autophagy in adipocytes and further impedes adipocyte differentiation and lipolysis. This study was to explore whether Beclin1 acetylation plays a role in the early renal injury induced by high glucose and to further investigate the K414R mutation site in podocytes. METHODS: Male Sprague-Dawley rats were randomized to con (control) and diabetic nephropathy (DN) groups. The DN group was induced by a single 55 mg/kg intraperitoneal injection of streptozotocin and fed a high-fat and high-sugar diet (the con group received an equal volume of the vehicle and fed a plain diet), after 3 days of induction, blood glucose levels were measured to confirm the onset of diabetes. Then, at weeks 0 and 4, the biochemical index was assayed and renal cortex tissues were harvested. MPC5 podocytes were cultured in vitro. Beclin1 (K414R)-pLVX-ZsGreen1-N1(wild-type or mutant) lentiviral plasmids were transfected into podocytes. Western blot or immunoprecipitation was used to test proteins or the acetylation levels respectively, and immunohistochemistry was used to analyze morphological changes of podocytes. Immunofluorescence was used to detect the aggregation of LC3 puncta. RESULTS: The acetylation level of Beclin1 was upregulated with podocyte injury exacerbated in high glucose at 24 h and that a mutation at K414R could inhibit hyperactivated autophagy, which ameliorated podocyte impairment. CONCLUSION: These findings suggest that the acetylation site at K414 is a critical molecule and drug target and that further research into this area is warranted.

Low calf circumference can predict nutritional risk and mortality in adults with metabolic syndrome aged over 80 years.

BACKGROUND: Metabolic disorders and malnutrition are a double burden worldwide. The aim was to determine whether low calf circumference (CC) could predict nutritional risk and the cut-off values of CC for predicting nutritional risk in metabolic syndrome (MetS) patients aged over 80 years. We aimed to evaluate the risk factors for predicting mortality in MetS. METHODS: A total of 514 patients aged over 80 years with MetS were enrolled and followed for 2.5 years. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with a Nutritional Risk Screening 2002 (NRS 2002) total score ≥ 3 were considered to have nutritional risk. RESULTS: The CC level was significantly lower in the nutritional risk group than in the non-nutritional risk with MetS group (27.1 ± 4.0 cm vs. 30.8 ± 3.9 cm). Logistic regression analysis of nutritional risk revealed that increasing CC (adjusted OR, 0.81; 95% CI, 0.74-0.88) was an independent protective factor against nutrition risk. The best CC cut-off value for predicting nutritional risk according to the NRS 2002 was 28.8 cm. Cox regression multivariate models showed nutritional risk (HR, 2.48; 95% CI, 1.22-5.04) and decreased CC (HR, 2.78; 95% CI, 1.27-5.98) remained independent risk factors for mortality. CONCLUSION: Decreased CC could predict not only nutritional risk but also mortality in MetS patients aged over 80 years. The elderly who had MetS with nutritional risk should be discovered early, early intervention and early treatment. CC may be a valuable index to screen out this population.

Rab31, a receptor of advanced glycation end products (RAGE) interacting protein, inhibits AGE induced pancreatic ß-cell apoptosis through the pAKT/BCL2 pathway.

Receptor of advanced glycation end products (RAGE) mediates diverse signal transduction following ligand stimulation and plays an important role in diabetes complications and aging associated disease. We have previously verified that advanced glycation end products (AGE) bind to RAGE to cause pancreatic ß-cell apoptosis through the mitochondrial pathway. However, the direct interacting protein(s) of RAGE in ß cells has never been appreciated. In the present study, we utilized GST pull-down assay combined with mass spectrometry to identify the interacting proteins of the RAGE intracellular domain (C-terminal 43 amino acid of RAGE). Overall four RAGE interacting proteins, including Rab31, were identified with scores over 160. Rab31 was detected in three ß-cell lines and confirmed to have interacted with RAGE via co-immunoprecipitation and immunostaining assays. This interaction was further enhanced by glycation-serum (GS) stimulation due to membrane distribution of Rab31 following treatment with GS. We further confirmed that Rab31 promoted RAGE endocytosis and inhibited GS-induced ß-cell apoptosis through the pAKT/BCL2 pathway. These findings reveal a new RAGE interaction protein Rab31 that prevents AGE/RAGE-induced pancreatic ß-cell apoptosis. Rab31 is therefore a promising therapeutic target for preserving functional ß cells under diabetes conditions.

M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3ß/ß-catenin pathway in mice.

AIMS/HYPOTHESIS: Macrophage levels are elevated in pancreatic islets, and the resulting inflammatory response is a major contributor to beta cell failure during obesity and type 2 diabetes mellitus. Previous studies by us and others have reported that exosomes released by macrophages play important roles in mediating cell-to-cell communication, and represent a class of inflammatory factors involved in the inflammatory process associated with type 2 diabetes mellitus. However, to date, no reports have demonstrated the effect of macrophage-derived exosomes on beta cells, and little is known regarding their underlying mechanisms in beta cell injury. Thus, we aimed to study the impact of macrophage-derived exosomes on islet beta cell injury in vitro and in vivo. METHODS: The phenotypic profiles of islet-resident macrophages were analysed in C57BL/6J mice fed a high-fat diet (HFD). Exosomes were collected from the medium of cultured bone marrow-derived macrophages (BMDMs) and from isolated islet-resident macrophages of HFD-fed mice (HFD-Exos). The role of exosomes secreted by inflammatory M1 phenotype BMDMs (M1-Exos) and HFD-Exos on beta cell function was assessed. An miRNA microarray and quantitative real-time PCR (qPCR) were conducted to test the level of M1-Exos-derived miR-212-5p in beta cells. Then, miR-212-5p was overexpressed or inhibited in M1-Exos or beta cells to determine its molecular and functional impact. RESULTS: M1-polarised macrophages were enriched in the islets of obese mice. M1 macrophages and islet-resident macrophages of HFD-fed mice impaired beta cell insulin secretion in an exosome-dependent manner. miR-212-5p was notably upregulated in M1-Exos and HFD-Exos. Enhancing the expression of miR-212-5p impaired beta cell insulin secretion. Blocking miR-212-5p elicited a significant improvement in M1-Exos-mediated beta cell insulin secretion during injury. Mechanistically, M1-Exos mediated an intercellular transfer of the miR-212-5p, targeting the sirtuin 2 gene and regulating the Akt/GSK-3ß/ß-catenin pathway in recipient beta cells to restrict insulin secretion. CONCLUSIONS/INTERPRETATION: A novel exosome-modulated mechanism was delineated for macrophage-beta cell crosstalk that drove beta cell dysfunction and should be explored for its therapeutic utility.

The effects of increased dose of hepatitis B vaccine on mother-to-child transmission and immune response for infants born to mothers with chronic hepatitis B infection: a prospective, multicenter, large-sample cohort study.

BACKGROUND: Appropriate passive-active immunoprophylaxis effectively reduces mother-to-child transmission (MTCT) of hepatitis B virus (HBV), but the immunoprophylaxis failure was still more than 5% under the current strategy. The study objective was to investigate the effects of high dose of HB vaccine on MTCT and immune response for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. METHODS: This was a prospective, multicenter, large-sample cohort study in four sites of China, and 955 pairs of HBsAg-positive mothers and their infants were enrolled in our investigation. The infants were given 10 µg or 20 µg HB vaccine (at age 0, 1, and 6 months) plus HB immunoglobulin (at age 0 and 1 month). Serum HBsAg, antibody to HBsAg (anti-HBs), and/or HBV DNA levels in the infants were determined at age 12 months. The safety of 20 µg HB vaccine was evaluated by adverse events and observing the growth indexes of infants. RESULTS: Thirteen of 955 infants were HBsAg-positive at 12 months. Stratification analysis showed that immunoprophylaxis failure rates in the 20 µg group were not significantly different from the 10 µg group, whatever maternal HBV load was high or not. But the high dose of HB vaccine significantly reduced low-response rate (anti-HBs 10-100 IU/L) (P = 0.002) and middle-response rate (anti-HBs 100-1000 IU/L) (P = 0.022) and improved high-response rate (anti-HBs ≥ 1000 IU/L) (P < 0.0001) in infants born to mothers with HBV DNA < 5 log10 IU/mL. For infants born to mothers with HBV DNA ≥ 5 log10 IU/mL, 20 µg HB vaccine did not present these above response advantages. The 20 µg HB vaccine showed good safety for infants. CONCLUSIONS: The 20 µg HB vaccine did not further reduce immunoprophylaxis failure of infants from HBsAg-positive mothers, but increased the high-response and decreased low-response rates for infants born to mothers with HBV DNA < 5 log10 IU/mL. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-PRC-09000459.

Maternal and fetal outcomes of patients with liver cirrhosis: a case-control study.

BACKGROUND: We aimed to describe the characteristics and outcomes in pregnant women with liver cirrhosis, and identify the predictors of adverse events of mother and fetus. METHODS: Retrospectively collected mothers with liver cirrhosis in our center from 6/2010 to 6/2019. Women without liver cirrhosis were selected as a control in a 1:2 ratio. The primary assessment was the frequency of maternal and fetal adverse events. The secondary assessment was the adverse events in patients continuing pregnancy or not and the factors to predict the severe adverse events. RESULTS: Of 126 pregnancies enrolled, 29 pregnancies were terminated for worrying disease progression and 97 pregnancies continued. One hundred ninety-four pregnancies without liver cirrhosis were selected as control. At baseline, patients with liver cirrhosis have a lower level of platelet, hemoglobin, prothrombin activity, and a higher level of ALT, total Bilirubin, creatinine. Compared to control, patients with liver cirrhosis had a higher frequency of adverse events, including bleeding gums (7.2%vs. 1.0%), TBA elevation (18.6%vs.3.1%), infection (10.3%vs.0.5%), cesarean section (73.6%vs.49.5%), postpartum hemorrhage (13.8% vs 2.1%), blood transfusion (28.9% vs 2.1%), new ascites or aggravating ascites (6.2% vs.0%), MODS (7.2% vs.0.5%) and intensive care unit admissions (24.1% vs 1.1%). The incidence of severe maternal adverse events was also higher (32.0% vs 1.5%). Women who chose to terminated the pregnancy had less severe adverse events (3.4% vs.32.0%). A higher frequency of fetal/infants' complications was observed in liver cirrhosis population than control, including newborn asphyxia (10.2% vs1.1%), low birth weight infant (13.6% vs. 2.6%). In patients who progressed into the third trimester, multivariable regression analysis demonstrated that severe adverse events were associated with a higher CTP score (OR 2.128, 95% CI [1.002, 4.521], p = 0.049). Wilson's disease related liver cirrhosis has a better prognosis (OR = 0.009, 95% CI [0, 0.763], p = 0.038). CONCLUSIONS: The incidence of the adverse events was significantly increased in pregnancies complicated by cirrhosis. The predictor of severe adverse events is higher CTP score. Wilson's disease induced liver cirrhosis have a better prognosis. Timely termination of pregnancy during the first trimester may avoid the incidence of severe adverse events.

A low follicle-stimulating hormone level is a protective factor for non-alcoholic fatty liver disease in older men aged over 80.

PURPOSE: Recent studies have suggested the significant relationship between follicle-stimulating hormone (FSH) and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. However, it is unknown whether FSH impacts the risk of NAFLD in men. This study aimed to investigate the association between serum FSH levels and NAFLD in elderly Chinese men aged 80-98, a particular group with worse outcomes of NAFLD. PATIENTS AND METHODS: A cross-sectional analysis was performed in 444 subjects in a geriatric health center. The highest quartile of serum FSH was used as reference. Hepatic steatosis was defined according to the results of liver ultrasound. Fibrosis-4 (FIB-4) Index > 2.67 was defined as advanced fibrosis. RESULTS: Based on liver ultrasound, 108 (24.3%) subjects had NAFLD. FSH level were negatively correlated with total testosterone, estradiol, nutritional risk, and the prevalence of high education level (all P < 0.01), and positively correlated with age, luteinizing hormone, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The correlation between FSH and body mass index or antihypertensive drug usage was marginally significant (P = 0.057; P = 0.066, respectively). The percentage of subjects with NAFLD had a trend to increase following the quartiles of serum FSH (20.0% in quartile 1, 18.2% in quartile 2, 27.3% in quartile 3, and 31.6% in quartile 4). After adjustment for common pathogenic risk factors, nutritional risk, and other sex hormones, serum FSH were progressively associated with odds ratios for NAFLD. The adjusted odds ratios and 95% CIs for quartile 1, quartile 2, and quartile 3, compared with quartile 4 were 0.132 (0.034-0.516), 0.190 (0.052-0.702), and 0.404 (0.139-1.173), respectively. Obesity was not involved in the potential negative role of circulating FSH on the risk of NAFLD in our population. Furthermore, our results revealed no significant association between FSH and advance fibrosis, the OR (95% CI) for advanced fibrosis was 1.018 (0.983-1.054) (P = 0.316) after adjusting for the potential covariates, although a positive correlation of FSH and FIB-4 score was observed (r = 0.325, P = 0.001). CONCLUSION: Low FSH level may decrease the risk of NAFLD in elderly Chinese men. These findings warrant replication in more extensive studies.

Pregnancy outcomes of patients with acute fatty liver of pregnancy: a case control study.

BACKGROUND: Limited data exists regarding the pregnancy and infant outcomes of Acute Fatty Liver of Pregnancy (AFLP). METHODS: Retrospectively collected mothers with AFLP and mothers without AFLP in our center from 1/2008 to 6/2018. The primary assessment was to analyze and compare the frequency of negative maternal and fetal outcomes. The secondary assessment was to investigate the role of intrauterine balloon tamponade in reducing negative maternal outcomes. RESULTS: Compared to 220 matched mothers, 55 AFLP mothers were younger (P < 0.001), with fewer pregnancies (P = 0.033), complicated with more pregnancy induced hypertension (P < 0.001), twins(P = 0.002), fetal growth restriction (P = 0.044) and male fetus (P < 0.001). 3 (5.5%) of AFLP patients were diagnosed in the postpartum period. Mean gestational week of AFLP diagnosis was 35.25 ± 5.80 weeks. Jaundice (89.1%), nausea or vomiting (58.2%), anorexia (49.1%), fatigue (45.5%) and polydipsia (30.9%) were the main prodromal symptoms. The median duration from diagnosis to delivery was 1.55 ± 4.62 days and 75% (39/52) pregnancy were terminated the pregnancy at the day of diagnosis. 78.8% (41/52) patients received cesarean section, 53.6% (22/41) of which received preventive plasma transfusion before surgery and no one received artificial liver support during the treatment. In comparison, higher frequency of 16 maternal complications, severe negative outcomes (27.3% vs. 0.9%) and newborn asphyxia (24.6% vs.0.9%) were observed in AFLP population. 3 mothers (mortality rates: 5.5%) died of multiple organ system failure and 6 fetus/infants (death rates: 9.8%) died of distress. When compared to those without negative outcomes, patients with negative fetal outcomes were younger (P = 0.042), had more singleton rates (p = 0.041), increased mean value of ALT(P = 0.011) and T-Bilirubin (P = 0.014), decreased prothrombin activity (P = 0.011). Although no statistical significance for the small sample size, there were less refractory postpartum hemorrhage (0% vs.31.3%), hysterectomy (0% vs.12.5%), negative maternal outcomes (16.7% vs.56.3%) in patients underwent intrauterine balloon tamponade when postpartum hemorrhage exceeded 500 ml. CONCLUSIONS: Several symptoms were found to be the main prodromal symptoms of AFLP. Higher frequency of adverse maternal and fetal outcomes was observed in mothers with AFLP than mothers without AFLP. We found five potential risk factors of negative fetal outcomes.

Low calf circumference is associated with frailty in diabetic adults aged over 80 years.

BACKGROUND: Frailty is now seen as a significant factor in older people with diabetes, whose mortality and disability increased. This study aims to investigate the association between calf circumference (CC) with frailty in diabetic adults aged over 80 years. METHODS: A cross-sectional analysis was performed on the data of 426 diabetic adults aged over 80 years. On admission, demographic data and laboratory parameters were recorded. CC was measured on the lower right leg at the point of the maximal circumference. All participants accepted frailty assessments. Frailty was mainly defined using the Fried frailty phenotype criteria. RESULTS: The CC levels were significantly lower in the frail than the non-frail (26.7 ± 4.0 vs. 31.2 ± 4.0, P < 0.001). CC was negatively correlated with the Fried frailty phenotype index (P < 0.001). Logistic regression analysis of frailty revealed that age (Odds Ratio (OR), 1.368; 95% Confidential Interval (CI) 1.002-1.869; P = 0.049), CC (OR, 0.756; 95%CI 0.598-0.956; P = 0.019) were independent impact factors of frailty after adjusting all the potential confounders. Participants with low CC tertile had a significantly higher Fried frailty phenotype index than those with high CC tertiles. The best CC cut-off value for predicting frailty was 29.3 cm, its sensitivity was 75.0%, and the specificity was 78.6%, and areas under the curve (AUC) was 0.786 (P < 0.001). CONCLUSIONS: CC was strongly related to frailty in diabetic adults aged over 80 years, suggesting that CC may be helpful for monitoring physical frailty in older adults in clinical and research settings.

SAD-A, a downstream mediator of GLP-1 signaling, promotes the phosphorylation of Bad S155 to regulate in vitro ß-cell functions.

The incretin hormone GLP-1 reduces ß-cell failure in patients with type 2 diabetes. Previous studies demonstrated that GLP-1 activates SAD-A, a member of the AMPK family, to regulate glucose-stimulated secretion (GSIS), but the underlying mechanisms of SAD-A regulation of ß-cell functions remain poorly understood. Here, we propose that activation of SAD-A by GLP-1 promotes the phosphorylation of Bad S155, which in turn positively affects GSIS and ß-cell survival. Bad therefore appears to be a downstream molecule of a SAD-A pathway that mediates the GLP-1-triggered reduction in ß-cell failure. Knockdown of endogenous SAD-A expression significantly exacerbated in vitro ß-cell dysfunction under lipotoxic conditions and promoted lipotoxicity-induced apoptosis, whereas overexpression of SAD-A inhibited ß-cell apoptosis. SAD-A silencing increased ER stress and inhibited the autophagic flux, which contributed to ß-cell apoptosis. Thus, SAD-A appears to function as a downstream molecule of GLP-1 signaling that results in Bad S155 phosphorylation. This phosphorylation might therefore be involved in the GLP-1-linked protection against ß-cell dysfunction and apoptosis.

Characterization of the bagremycin biosynthetic gene cluster in Streptomyces sp. Tü 4128.

Bagremycin A and bagremycin B isolated from Streptomyces sp. Tü 4128 have activities against Gram-positive bacteria, fungi and also have a weak antitumor activity, which make them have great potential for development of novel antibiotics. Here, we report a draft genome 8,424,112 bp in length of S. sp. Tü 4128 by Illumina Hiseq2000, and identify the bagremycins biosynthetic gene cluster (BGC) by bioinformatics analysis. The putative bagremycins BGC includes 16 open reading frames (ORFs) with the functions of biosynthesis, resistance and regulation. Disruptions of relative genes and HPLC analysis of bagremycins production demonstrated that not all the genes within the BGC are responsible for the biosynthesis of bagremycins. In addition, the biosynthetic pathways of bagremycins are proposed for deeper inquiries into their intriguing biosynthetic mechanism.

Associations between G6PD, OATP1B1 and BLVRA variants and susceptibility to neonatal hyperbilirubinaemia in a Chinese Han population.

AIM: Hyperbilirubinaemia is a common disorder in newborns. The aim of this study was to investigate the associations between G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512 variants and the risk of neonatal hyperbilirubinaemia in a Chinese neonate population. METHODS: A total of 447 Chinese neonates with hyperbilirubinaemia were selected as the study group and 544 healthy subjects were recruited as the control group matched by baseline sex, age, feeding pattern and delivery mode. About 2 mL of peripheral venous blood was taken from all subjects. The single nucleotide polymorphisms (SNPs) of G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512 loci were examined by the polymerase chain reaction and Sanger sequencing technique in the peripheral blood of all subjects. RESULTS: For the G6PD 1388 G>A SNP, individuals carrying the A-allele were associated with a significantly increased risk of neonatal hyperbilirubinaemia (adjusted odds ratio (OR) = 1.49, P < 0.001, 95% confidence interval (CI): 1.31-1.67). This risk increased significantly in the CC genotype carriers at the rs4149056 locus of the SLCO1B1 gene (OR = 2.17, 95% CI: 1.87-2.33), whereas it decreased significantly in individuals carrying the G-allele at the rs699512 locus of the BLVRA gene (adjusted OR = 0.84, P = 0.01, 95% CI: 0.75-0.95). The G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512 SNPs had a significant impact on serum total bilirubin levels. Moreover, individuals carrying the A-allele of G6PD 1388 G>A and BLVRA rs699512 had a significantly increased risk of developing neonatal hyperbilirubinaemia (OR = 5.01, P < 0.001, 95% CI: 3.42-7.85). CONCLUSION: Genetic variants of bilirubin metabolism genes, including G6PD 1388 G>A, SLCO1B1 rs4149056 and BLVRA rs699512, are associated with the risk of neonatal hyperbilirubinaemia, and are potential markers for predicting the disorder.

MicroRNA-218 Negatively Regulates Osteoclastogenic Differentiation by Repressing the Nuclear Factor-κB Signaling Pathway and Targeting Tumor Necrosis Factor Receptor 1.

BACKGROUND/AIMS: Postmenopausal osteoporosis is a common disease associated with estrogen deficiency leading to bone loss and bone tissue changes. The resultant bone fragility and increased risk of fracture has serious adverse effects on health and quality of life of the elderly, making it an important health issue. MicroRNA-218 (miR-218) is closely related to the development of osteoporosis. In this study, we investigated the regulatory mechanisms of miR-218 in osteoclastogenesis. METHODS: We investigated miR-218 levels on differentiation of RAW 264.7 cells into osteoclasts compared with normal cells. Next, RAW 264.7 cells were transfected with miR-218 mimics or inhibitors to study the role of miR-218 in osteoclastogenic differentiation. Tartrate-resistant acid phosphatase (TRAP) staining was performed to determine osteoclastogenic differentiation. Bioinformatics analysis and luciferase reporter assay were used to identify and validate miR-218 target genes. RESULTS: miR-218 was downregulated following RAW 264.7 cell differentiation into osteoclasts. miR-218 overexpression attenuated osteoclast differentiation, whereas low miR-218 expression promoted it as demonstrated by increased expression of osteoclast-specific genes and TRAP staining. Bioinformatics analysis and the luciferase reporter assay showed that tumor necrosis factor receptor 1 (TNFR1), a cell membrane receptor of TNF (TNF is an activator of nuclear factor-κB [NF-κB]), is a direct target of miR-218. CONCLUSIONS: Our findings indicate that miR-218 regulates osteoclastogenic differentiation negatively by repressing NF-κB signaling by targeting TNFR1, suggesting that targeting miR-218 may be a therapeutic approach in postmenopausal osteoporosis.