Enterococcus faecalis provides protection during scavenging in carrion crow ( Corvus corone).

The gut microbiota significantly influences host physiology and provides essential ecosystem services. While diet can affect the composition of the gut microbiota, the gut microbiota can also help the host adapt to specific dietary habits. The carrion crow ( Corvus corone), an urban facultative scavenger bird, hosts an abundance of pathogens due to its scavenging behavior. Despite this, carrion crows infrequently exhibit illness, a phenomenon related to their unique physiological adaptability. At present, however, the role of the gut microbiota remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria (75.51%) and Firmicutes (22.37%). Significant differences were observed in the relative abundance of Enterococcus faecalis among groups, highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows. Subsequently, E. faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection. Results showed that E. faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), prevented S. enterica colonization, and regulated the composition of gut microbiota in mice, thereby modulating the host's immune regulatory capacity. Therefore, E. faecalis exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior, offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

Relationship of microvascular complications and healthy lifestyle with all-cause and cardiovascular mortality in women compared with men with type 2 diabetes.

BACKGROUND: Sex differences exist in the prevalence of microvascular disease (MVD) and healthy-lifestyle adherence. Whether MVD and healthy lifestyles are associated with mortality risk similarly for women and men who have type 2 diabetes mellitus (T2DM) remains unknown. METHODS: The present study included 9992 women and 15,860 men with T2DM from the UK Biobank. MVDs included retinopathy, peripheral neuropathy, and chronic kidney disease. Healthy lifestyle factors consisted of ideal BMI, nonsmoking, healthy diet, regular exercise, and appropriate sleep duration. Sex-specific hazard ratios (HRs) of mortality associated with the MVDs or healthy lifestyles were calculated and women-to-men ratio of HRs (RHR) were further estimated, after multivariable adjustment for potential confounders. RESULTS: During a median of 12.7 years of follow-up, 4346 (1202 in women) all-cause and 1207 (254 in women) CVD deaths were recorded. The adjusted HRs (95% CI) of all-cause mortality for 1 additional increment of the MVDs were 1.71 (1.55, 1.88) for women and 1.48 (1.39, 1.57) for men, with an RHR of 1.16 (1.03, 1.30). The corresponding RHR was 1.36 (1.09, 1.69) for cardiovascular mortality. Adhering to a healthy lifestyle (≥4 vs. ≤1 lifestyle factor) was associated with an approximately 60%-70% lower risk of all-cause and cardiovascular mortality without sex differences (P-interaction >0.70). Furthermore, as compared with having no MVD and an unfavorable lifestyle, having ≥2 MVDs but a favorable lifestyle was not associated with a higher risk of all-cause mortality either in women (HR = 0.88; 95% CI: 0.49, 1.60) or in men (HR = 0.95; 95% CI: 0.64, 1.40), similarly when considering cardiovascular mortality. CONCLUSIONS: In T2DM, while MVDs are more strongly associated with mortality risk in women than in men, adhering to a favorable lifestyle is associated with a substantially lower risk of mortality and may eliminate the detrimental impact of MVDs in both sexes.

Correlation between serum markers and transjugular intrahepatic portosystemic shunt prognosis in patients with cirrhotic ascites.

BACKGROUND: Individuals with refractory ascites in the context of liver cirrhosis typically face an adverse prognosis. The transjugular intrahepatic portosystemic shunt (TIPS) is an efficacious intervention, but there is a lack of reliable tools for postoperative prognosis assessment. Previously utilized clinical biochemical markers, such as the serum albumin concentration (Alb), sodium (Na+) concentration, and serum creatinine (Scr), have limited predictive value. Therefore, the quest for novel, specific biomarkers to evaluate the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites holds significant practical importance. AIM: To investigate the associations between the Child-Pugh score, model for end-stage liver disease (MELD) score, and serum cystatin C (Cys C) level and post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. METHODS: A retrospective analysis was conducted on 75 patients with liver cirrhosis and refractory ascites who underwent TIPS at our institution from August 2019 to August 2021. These patients were followed up regularly for two years, and the death toll was meticulously documented. The patients were allocated into a survival group (n = 45 patients) or a deceased group (n = 30 patients) based on their prognosis status. The clinical data of the two groups were collected, and Child-Pugh scores and MELD scores were calculated for analysis. Spearman correlation analysis was carried out to evaluate the correlation of prognosis with Child-Pugh grade, MELD score, and Cys C level. Additionally, a multiple-factor analysis utilizing the Cox proportional hazard model was used to identify independent risk factors affecting the post-TIPS prognosis of patients with liver cirrhosis and refractory ascites. The receiver operating characteristic curve (ROC) ascertained the predictive value of the Cys C concentration, Child-Pugh grade, and MELD score for the prognosis of liver cirrhosis with refractory ascites in post-TIPS patients. RESULTS: During a 2-year follow-up period, among 75 patients with liver cirrhosis and refractory ascites who underwent TIPS treatment, 30 patients (40.00%) passed away. The deceased cohort exhibited heightened aspartate aminotransferase, alanine aminotransferase, total bilirubin, Scr, prothrombin time, Cys C, international normalized ratio, Child-Pugh, and MELD scores compared to those of the survival cohort, while Alb and Na+ levels were attenuated in the deceased group (P < 0.05). Spearman analysis revealed moderate to high positive correlations between prognosis and Child-Pugh score, MELD score, and Cys C level (r = 0.709, 0.749, 0.671, P < 0.05). Multivariate analysis using the Cox proportional hazard model demonstrated that the independent risk factors for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites were Cys C (HR = 3.802; 95%CI: 1.313-11.015), Child-Pugh (HR = 3.030; 95%CI: 1.858-4.943), and MELD (HR = 1.222; 95%CI: 1.073-1.393) scores. ROC analysis confirmed that, compared to those of the classic prognostic models for Child-Pugh and MELD scores, the predictive accuracy of Cys C for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites was slightly lower. This analysis yielded sensitivity and specificity values of 83.33% and 82.22%, respectively. The area under the curve value at this juncture was 0.883, with an optimal cutoff value set at 1.95 mg/L. CONCLUSION: Monitoring the serum Cys C concentration is valuable for assessing the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. Predictive models based on serum Cys C levels, as opposed to Scr levels, are more beneficial for evaluating the condition and prognosis of patients with ascites due to cirrhosis.

Efficacy of transjugular intrahepatic portosystemic shunts in treating cirrhotic esophageal-gastric variceal bleeding.

BACKGROUND: Esophageal-gastric variceal bleeding (EGVB) represents a severe complication among patients with cirrhosis and often culminates in fatal outcomes. Interventional therapy, a rapidly developing treatment modality over the past few years, has found widespread application in clinical practice due to its minimally invasive characteristics. However, whether transjugular intrahepatic portosystemic shunt (TIPS) treatment has an impact on patient prognosis remains controversial. AIM: To probing the efficacy of TIPS for treating cirrhotic EGVB and its influence on the prognosis of patients afflicted by this disease. METHODS: A retrospective study was conducted on ninety-two patients presenting with cirrhotic EGVB who were admitted to our hospital between September 2020 and September 2022. Based on the different modes of treatment, the patients were assigned to the study group (TIPS received, n = 50) or the control group (percutaneous transhepatic varices embolization received, n = 42). Comparative analyses were performed between the two groups preoperatively and one month postoperatively for the following parameters: Varicosity status; hemodynamic parameters [portal vein flow velocity (PVV) and portal vein diameter (PVD); platelet count (PLT); red blood cell count; white blood cell count (WBC); and hepatic function [albumin (ALB), total bilirubin (TBIL), and aspartate transaminase (AST)]. The Generic Quality of Life Inventory-74 was utilized to assess quality of life in the two groups, and the 1-year postoperative rebleeding and survival rates were compared. RESULTS: Following surgical intervention, there was an improvement in the incidence of varicosity compared to the preoperative status in both cohorts. Notably, the study group exhibited more pronounced enhancements than did the control group (P < 0.05). PVV increased, and PVD decreased compared to the preoperative values, with the study cohort achieving better outcomes (P < 0.05). PLT and WBC counts were elevated postoperatively in the two groups, with the study cohort displaying higher PLT and WBC counts (P < 0.05). No differences were detected between the two groups in terms of serum ALB, TBIL, or AST levels either preoperatively or postoperatively (P < 0.05). Postoperative scores across all dimensions of life quality surpassed preoperative scores, with the study cohort achieving higher scores (P < 0.05). At 22.00%, the one-year postoperative rebleeding rate in the study cohort was significantly lower than that in the control group (42.86%; P < 0.05); conversely, no marked difference was observed in the 1-year postoperative survival rate between the two cohorts (P > 0.05). CONCLUSION: TIPS, which has demonstrated robust efficacy in managing cirrhotic EGVB, remarkably alleviates varicosity and improves hemodynamics in patients. This intervention not only results in a safer profile but also contributes significantly to a more favorable prognosis.

Effects of intensive glycemic control on microvascular outcomes in type 2 diabetes mellitus are modified by long-term HbA1c variability: A post hoc analysis of the ACCORD trial.

AIMS: To assess the impact of long-term visit-to-visit variability in HbA1c on microvascular outcomes in type 2 diabetes mellitus (T2DM), and its influence on the effects of intensive glycemic control. METHODS: Included were participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) who had at least three measurements of HbA1c prior to new-onset microvascular outcomes, namely nephropathy, retinopathy and neuropathy. Variability in HbA1c was defined as the coefficient of variation (CV) across HbA1c measurements obtained from enrollment to the transition from intensive to standard glycemic therapy. RESULTS: During a median of 22,005, 23,121, and 13,080 person-years of follow-up, 2,905 nephropathy, 2,655 retinopathy, and 1,974 neuropathy cases were recorded, respectively. Median CV (IQR) was 7.91 % (5.66 %-10.76 %) in the standard treatment group and 9.79 % (7.32 %-13.35 %) in the intensive treatment group. In the standard treatment group, lower HbA1c-CV (the first versus the second quartile) was associated with a higher risk of all microvascular outcomes, while higher HbA1c-CV (the fourth quartile) was associated with a higher risk of nephropathy only. In the intensive treatment group, only higher HbA1c-CV was associated with a higher risk of developing the microvascular outcomes. Intensive therapy reduced all microvascular outcomes among individuals with lower HbA1c-CV, but increased the risk among those with the highest HbA1c-CV (all P values for interaction < 0.0001). For example, hazard ratios (95 % CI) of retinopathy comparing intensive with standard treatments were 0.65 (0.56-0.75), 0.84 (0.71-0.98), 0.97 (0.82-1.14) and 1.28 (1.08-1.53) across the lowest to the highest quartiles of HbA1c variability. CONCLUSIONS: The effects of intensive glycemic control on microvascular outcomes in T2DM appear to be modified by the variability of HbA1c during the treatment process, suggesting the significance of dynamic monitoring of HbA1c levels and timely adjustments to the therapeutic strategy among individuals with a high HbA1c variability.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

Analysis of risk factors and development of a nomogram prediction model for lupus nephritis in systemic lupus erythematosus patients.

BACKGROUND: This study aimed to explore risk factors for lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients and establish a Nomogram prediction model based on LASSO-logistic regression. METHODS: The clinical and laboratory data of SLE patients in Meishan People's Hospital from July 2012 to December 2021 were analyzed retrospectively. All SLE patients were divided into two groups with or without LN. Risk factors were screened based on LASSO-logistic regression analysis, and a Nomogram prediction model was established. The receiver operating characteristic curve, calibration curves, and decision curve analysis were adopted to evaluate the performance of the Nomogram model. RESULTS: A total of 555 SLE patients were enrolled, including 303 SLE patients with LN and 252 SLE patients without LN. LASSO regression and multivariate logistic regression analyses showed that ESR, mucosal ulcer, proteinuria, and hematuria were independent risk factors for LN in SLE patients. The four clinical features were incorporated into the Nomogram prediction model. Results showed that calibration curve was basically close to the diagonal dotted line with slope 1 (ideal prediction case), which proved that the prediction ability of the model was acceptable. In addition, the decision curve analysis showed that the Nomogram prediction model could bring net clinical benefits to patients when the threshold probability was 0.12-0.54. CONCLUSION: Four clinical indicators of ESR, mucosal ulcer, proteinuria, and hematuria were independent risk factors for LN in SLE patients. The predictive power of the Nomogram model based on LASSO-logistic regression was acceptable and could be used to guide clinical work.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease.

BACKGROUND: Although many studies have investigated the impact of chronic hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) on liver disease, few have investigated the relationship between nonalcoholic steatohepatitis (NASH) defined by liver pathology and the prognosis of chronic HBV infection. Most patients were followed up for a short time. This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection. AIM: To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events [cirrhosis, hepatocellular carcinoma (HCC), and death] in patients with chronic hepatitis B (CHB) virus infection. METHODS: We enrolled patients with chronic hepatitis B virus (HBV) infection who underwent liver biopsy at the Third People's Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020. Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected. Propensity score matching (PSM) was used to balance baseline parameters, Kaplan-Meier (K-M) survival analysis was used to evaluate the risk of clinical events, and Cox regression was used to analyze the risk factors of events. RESULTS: Overall, 456 patients with chronic HBV infection were included in the study, of whom 152 (33.3%) had histologically confirmed NAFLD. The median follow-up time of the entire cohort was 70.5 mo. Thirty-four patients developed cirrhosis, which was diagnosed using ultrasound during the follow-up period. K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis (log-rank test, P > 0.05). Patients with CHB with fibrosis at baseline were more prone to cirrhosis (log-rank test, P = 0.046). After PSM, multivariate analysis showed that diabetes mellitus, ballooning deformation (BD), and platelet (PLT) were independent risk factors for cirrhosis diagnosed using ultrasound (P < 0.05). A total of 10 patients (2.2%) developed HCC, and six of these patients were in the combined NAFLD group. K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher (log-rank test, P < 0.05). Hepatocyte ballooning, and severe liver fibrosis were also associated with an increased risk of HCC (log-rank test, all P < 0.05). Cox multivariate analysis revealed that hepatocyte ballooning, liver fibrosis, and diabetes mellitus were independent risk factors for HCC. CONCLUSION: There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD. Diabetes mellitus, BD, and PLT were independent risk factors for liver cirrhosis. Patients with chronic HBV infection and NASH have an increased risk of HCC. BD, liver fibrosis, and diabetes mellitus are independent risk factors for HCC.

IFITM3 promotes NiV envelope protein-mediated entry into MDCK cells and interacts with the fusion subunit of the F protein.

IFITM proteins are a host restriction factor with broad-spectrum antiviral activity, but the role in the paramyxovirus entry remains unclear. Nipah virus (NiV) is a zoonotic virus of the paramyxoviridae with extremely high lethality. Here, we assessed the role of IFITM3 on NiV G and F glycoprotein-mediated virus entry. Using NiV pseudovirus bearing NiV G and F proteins to infect IFITM3-induced MDCK cells, we found that overexpression of IFITM3 promotes NiV G and F proteins-mediated virus entry. Mechanistically, the subcellular distribution showed that F protein completely co-localized with IFITM3, but G protein does not. Immunoprecipitation further indicated that IFITM3 strongly captures F protein rather than G protein. F protein truncation found that the F1 subunit completely co-localized and captures with IFITM3, but not the F2 subunit. Furthermore, IFITM3 strongly binds to F1 truncations containing fusion peptide (FP), and F1 strongly captures IFITM3 truncation with the intramembrane domain (IMD). Together, the results suggest that IFITM3 can promote NiV G and F proteins-mediated virus entry into MDCK cells, and IFITM3 directly interacts with the F1 subunit of NiV F protein dependent on the former's IMD and the latter's FP, which may occur after incorporation of fusion peptides into the cell membrane following virus fusion activation.

The feasibility and safety of disposable endoscope vs. conventional endoscope for upper gastrointestinal tract examination: a multicenter, randomized, parallel, non-inferiority trial.

BACKGROUND: A disposable upper gastrointestinal endoscope can effectively decrease infectious outbreaks associated with endoscope reuse. In the present study, we aimed to evaluate the feasibility and safety of a disposable endoscope for upper gastrointestinal examination. METHODS: In a prospective, randomized trial, 144 upper endoscopic procedures were allocated to either the disposable endoscope group or the conventional endoscope group. The primary outcomes were rates of excellent and good image qualities and maneuverability satisfaction. The second outcome included procedure duration, endoscopic diagnosis, and adverse events. RESULTS: A total of 144 subjects were enrolled in the present analysis and prospectively randomized to 2 study groups. Finally, 70 and 69 subjects were enrolled in the novel disposable endoscope group and the conventional endoscope group, respectively, due to the schedule cancellation of 5 subjects. The baseline characteristics of the patients were similar in both groups. The excellent and good image quality rates and maneuverability satisfaction of the novel disposable endoscope were not inferior to the conventional endoscope (p = 0.99 and p = 0.99, respectively). Moreover, no significant between-group difference was observed in the endoscopic results and adverse events (p = 0.30 and p = 1, respectively). However, the procedure duration in the novel disposable endoscope was longer compared with the conventional endoscope (8.40 ± 4.28 min vs. 5.12 ± 2.65 min, p < 0.001). CONCLUSIONS: The novel disposable endoscope was as safe, effective, and maneuverable as a conventional endoscope. However, the novel disposable endoscope was associated with a longer procedure duration.

Chemical constituents from the aerial part of Polygala tenuifolia.

Three new compounds, polygalapyrone A (1), tenuiside G (2) and polygalapyrrole A (3), together with two known compounds (4-5) were isolated by silica gel, ODS and preparative HPLC from the aerial part of Polygala tenuifolia. Their structures were elucidated by spectrum analysis and compared with findings from the literature. The anti-inflammatory effects of those compounds were investigated in vitro.

Is simultaneous presence of IgG4-positive plasma cells and giant-cell hepatitis a coincidence in autoimmune hepatitis? A case report.

BACKGROUND: The immune-mediated invasion of IgG4-positive plasma cells in the liver is found in some autoimmune hepatitis. Giant-cell hepatitis (GCH) is a very rare pathological feature in adults, and the clinical characteristics of the simultaneous appearance of the two pathological phenomena are not clear. CASE SUMMARY: A 68-year-old woman was hospitalized with fatigue, poor appetite, and yellow urine for 20 d. Liver function tests and immunological indexes were significantly abnormal and accompanied by elevated serum IgG4 levels. Liver pathology revealed severe inflammation of the interface between the portal tract and hepatocytes, portal area inflammation, plasma cell infiltration, formation of rosette cells, IgG4-positive plasma cells > 10/high-power field, IgG4/IgG > 40%, and multinucleated liver cell swelling. IgG4-related autoimmune hepatitis (AIH) combined with GCH was diagnosed, and methylprednisolone was administered at 40 mg/day. Two weeks later, the clinical symptoms disappeared, and the liver function and immunological indicators were significantly improved. Methylprednisolone was reduced at a rate of 4-8 mg per week to 8 mg/day for maintenance. A second liver biopsy 48 wk later indicated that liver inflammation and fibrosis were significantly improved. IgG4-positive plasma cells and GCH were not detected. A literature search was conducted to analyze articles reporting similar pathological phenomena. CONCLUSION: AIH with simultaneous IgG4-positive plasma cell infiltration and GCH, liver inflammation, and fibrosis is possibly more severe than typical AIH but sensitive to corticosteroids.

[Application of Array-based Comparative Genomic Hybridization in Diagnostic Assessment of Abnormal Prenatal Serological Screening Results of Down's Syndrome].

OBJECTIVE: To explore the application of array-based comparative genomic hybridization (a-CGH) technology in the prenatal diagnostic assessment of abnormal serological prenatal screening results of Down's syndrome (DS). METHODS: A total of 3 578 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal serological prenatal screening results were selected. The samples were categorized into 3 groups, 2 624 in the high-risk group, 662 in the borderline-risk group, and 292 in the abnormal multiple of median (MoM) group. a-CGH was performed on the Agilent CGX ™ (8×60K) platform and the data were analyzed by the Genoglyphix ® software. RESULTS: The overall detection rate of chromosomal abnormalities was 3.38% (121/3 578). Among the chromosomal abnormalities, 49.59% (60/121) was aneuploidies, 42.15% (51/121) was pathogenic copy number variants (pCNVs), and 8.26% (10/121) was likely pathogenic CNVs (lpCNVs). The detection rate of copy number variant of uncertain significance (VUS) was 1.03% (37/3 578). In the high-risk, the borderline-risk and the abnormal MoM groups, the detection rate of chromosomal abnormalities was 3.54% (93/2 624), 2.87% (19/662) and 3.08% (9/292), respectively; the detection rate of p/lp CNVs was 1.64% (43/2 624), 1.81% (12/662) and 2.05% (6/292), respectively; the detection rate of trisomy 21 and trisomy 18 was 1.37% (36/2 624), 0.76% (5/662) and 0.34% (1/292) in the three groups, respectively. There were no significant differences in all the detection rate among these groups ( P>0.05). One sample with X(51)/XYY(49) confirmed by fluorescence in situ hybridization (FISH) was misdiagnosed by a-CGH. CONCLUSION: Prenatal diagnosis with a-CGH is of great significance for reducing birth defects in pregnancies with abnormal serological prenatal screening results of DS. It can also be used to detect CNVs of microdeletion/microduplication syndromes.

[Application of Array-based Comparative Genomic Hybridization in the Prenatal Diagnosis of Fetal Chromosomal Aberration in Gravidas with Advanced Age].

OBJECTIVE: To evaluate the clinical application of array-based comparative genomic hybridization (a-CGH) in the prenatal diagnosis of fetal chromosomal aberrations in gravidas with advanced maternal age (AMA). METHODS: A total of 3 677 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to AMA were selected. Array-CGH was performed on the Agilent CGX TM (8X60K) platform and the data were analyzed by the Genoglyphix software. RESULTS: The overall detection rate of chromosomal aberration was 2.04% (75/3677), with 53.33% (40/75) being aneuploidies, including 22 cases of trisomy-21, 5 cases of trisomy-18, 8 cases with XXY, 3 cases of XYY and 2 cases of mosaic monosomy X, 32.00% (24/75) being pathogenic copy number variations (pCNVs), including 19 cases of microdeletion and 5 cases of microduplication, with the fragment size ranging from 323 kb to 26 780 kb, and 14.67% (11/75) being likely pathogenic CNVs (lpCNVs), including 7 cases of microdeletion and 7 cases of microduplication, with the fragment size ranging from 358 kb to 16 873 kb. Besides, the detection rate of CNVs of unknown clinical significance (VUS) was 0.84% (31/3 677). The detection rate of aneuploidies increased significantly with increased maternal age ( P<0.05). However, there were no significant differences in the detection rate of p/lpCNVs among different maternal age groups ( P>0.05). CONCLUSION: Our findings suggest that, compared with traditional karyotype analysis, a-CGH not only detects aneuploidies, but also detect pathogenic CNVs, including microdeletion/microduplication syndromes. The detection rate of fetal aneuploidies was closely correlated to maternal age. However, no correlation was found between the detection rate of p/lpCNVs and maternal age.

Serum levels and gene polymorphisms of angiopoietin 2 in systemic lupus erythematosus patients.

This study aimed to discuss association between serum Angiopoietin2 (Ang2) levels, Ang2 gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility. It was carried out by 235 SLE, 342 other inflammatory autoimmune diseases patients and 380 healthy individuals. Serum Ang2 levels was examinated by ELISA, and Ang2 rs12674822, rs1823375, rs1868554, rs2442598, rs3739390 and rs734701 polymorphisms were genotyped using KASP. Increased Ang2 concentrations in SLE patients were observed compared with healthy controls and patients with other inflammatory autoimmune diseases. For allelic contrast, except for rs1823375 (P = 0.058) and rs2442598 (P = 0.523), frequencies of alleles for other polymorphisms were significantly different between SLE patients and controls. Genotypes for rs12674822 (TT), rs1868554 (TT, TA and TT+TA), rs734701 (TT) were negatively correlated with SLE susceptibility (OR = 0.564 for rs12674822; OR = 0.572, OR = 0.625, OR = 0.607 for rs1868554; OR = 0.580 for rs734701). Patients carrying rs1868554 T allele and rs3739390 G allele were more likely to develop hematuria (P = 0.039; P = 0.003). The G allele frequencies of rs12674822 and rs2442598 were higher in SLE patients with proteinuria (P = 0.043; P = 0.043). GC genotype frequency of rs3739390 was higher in patients with ds-DNA (+) (P = 0.024). In summary, SLE had increased serum Ang2, which may be a potential biomarker, and the polymorphisms correlated with SLE.

Association of STAT4 Gene Rs7574865, Rs10168266 Polymorphisms and Systemic Lupus Erythematosus Susceptibility: A Meta-analysis.

Association of signal transducer and activator of transcription 4 (STAT4) gene rs7574865, rs10168266 polymorphisms with systemic lupus erythematosus (SLE) risk remains unclear. A meta-analysis was conducted on the correlation between rs7574865, rs10168266 polymorphisms and SLE. Twenty-six studies were recruited in our study (17,389 patients and 29,273 controls). For rs7574865, results showed significant associations between T allele and SLE susceptibility in overall population, Asians and Europeans (OR=1.557, 95%CI: 1.505-1.611, P<0.001; OR=1.557, 95%CI: 1.498-1.661, P<0.001; OR=1.548, 95%CI: 1.474-1.625, P<0.001). Significant associations of genotypes TT, GT, TT+TG and SLE risk were observed in general subjects, Asians and Europeans (all P<0.001). Regarding rs10168266, increased T allele frequencies were detected in overall SLE cases and those from Asian origin (OR=1.532, 95%CI: 1.440-1.631, P<0.001; OR=1.575, 95%CI: 1.445-1.717, P<0.001). The overall data showed that TT genotype, CT genotype and TT+CT genotype were significantly correlated with SLE (all P < 0.001). In conclusion, the present study verified strong association of STAT4 gene rs7574865, rs10168266 polymorphisms and SLE susceptibility.

Association of MBL2 gene polymorphisms and systemic lupus erythematosus susceptibility: A meta-analysis.

OBJECTIVES: Mannose binding lectin (MBL) gene single nucleotide polymorphisms have been associated with systemic lupus erythematosus (SLE) risk with inconsistent results. This study aimed to explore whether MBL2 A\B, A\C, A\D, A\O, L\H and Y\X polymorphisms affected SLE susceptibility. METHODS: A meta-analysis was performed on 20 studies, containing allelic contrast, additive, dominant and recessive models. Odds ratio (OR) was calculated to reflect the effect of association. RESULTS: A total of 64 pooled comparisons were conducted, including 7194 SLE patients and 7401 healthy controls. The meta-analysis inducted a significant association between allele B and SLE (OR = 0.766, 95% CI = 0.681-0.862, P < .001). The genotype BB in the additive model and AB + BB in the recessive model both reduced the risk of SLE (OR = 0.611, 95% CI = 0.422-0.882, P = .009; OR = 0.806, 95% CI = 0.688-0.944, P = .008). Regarding A\O polymorphisms, results revealed statistical differences in allelic contrast, additive model and recessive models (OR = 0.826, 95% CI = 0.732-0.931, P = .002; OR = 0.737, 95% CI = 0.557-0.977, P = .034 and OR = 0.793, 95% CI = 0.683-0.921, P = .002, respectively). As for L\H, meta-analysis revealed that allele H and genotype HH both decreased SLE susceptibility in allelic contrast and dominant models (OR = 1.463, 95% CI = 1.097-2.007, P = .018; OR = 1.383, 95% CI = 1.124-1.701, P = .002). Stratification by ethnicity indicated that allele H related to SLE in European populations (OR = 0.736, 95% CI = 0.617-0.879, P = .001), and the recessive model correlated with SLE in Asians (OR = 0.808, 95% CI = 0.667-0.979, P = .03). CONCLUSION: The present study suggests that A\B and A\O polymorphisms were associated with SLE susceptibility, and the allele H may be a protective factor in SLE.

IL-38: A novel cytokine in systemic lupus erythematosus pathogenesis.

IL-38 is a newly identified cytokine that belongs to the IL-1 family. In our previous study, we found elevated plasma levels of IL-38 in patients with systemic lupus erythematosus (SLE). However, the clear relationship of IL-38 expression in plasma, peripheral blood mononuclear cells (PBMCs) and clinical and laboratory features needs elucidation. Additionally, we evaluated the possible role of IL-38 in regulating production of inflammatory cytokines in PBMCs in vitro. A pristane-induced murine lupus model was used to further demonstrate the effects of IL-38 on cytokines in vivo and discuss the significance of IL-38 in lupus development. The results showed that mRNA expression of IL-38 in PBMCs of patients with SLE was elevated compared with volunteers, and expression of IL-38 in both plasma and PBMCs was strongly related to clinical features, such as haematuria and proteinuria, and correlated with a SLEDAI score. Plasma levels of TNF-α, IL-1ß, IL-6 and IL-23 were elevated in patients with SLE and were related to plasma levels of IL-38. In vitro, PBMCs of patients with SLE stimulated with IL-38 showed a decreased expression of the four inflammatory cytokines compared with PBMCs of patients without treatment. Interestingly, IL-38 administration in lupus mice significantly reduced the development of lupus, such as reduced proteinuria, improved histological examinations of the kidneys and down-regulated inflammatory cytokines. In conclusion, IL-38 may suppress synthesis of pro-inflammatory cytokines and therefore regulate lupus pathogenesis.

Gene polymorphisms and serum levels of sVEGFR-1 in patients with systemic lupus erythematosus.

Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case-control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.

HPLC-DAD-Guided Isolation of Diversified Chaetoglobosins from the Coral-Associated Fungus Chaetomium globosum C2F17.

Cytochalasans have continuously aroused considerable attention among the chemistry and pharmacology communities due to their structural complexities and pharmacological significances. Sixteen structurally diverse chaetoglobosins, 10-(indol-3-yl)-[13]cytochalasans, including a new one, 6-O-methyl-chaetoglobosin Q (1), were isolated from the coral-associated fungus Chaetomium globosum C2F17. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations. Meanwhile, the structures and absolute configurations of the previously reported compounds 6, 12, and 13 were confirmed by single-crystal X-ray analysis for the first time. Chaetoglobosins E (6) and Fex (11) showed significant cytotoxicity against a panel of cancer cell lines, K562, A549, Huh7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4, with the IC50 values ranging from 1.4 µM to 9.2 µM.