Comprehensive Analysis of SLC35A2 in Pan-Cancer and Validation of Its Role in Breast Cancer.

Purpose: Elucidation of the oncogenic role of SLC35A2 in human tumors and the potential function and clinical significance in breast cancer. Methods: Pan-cancer analysis was performed via various bioinformatics tools to explain the pathogenic role of SLC35A2. A prognostic nomogram was also developed based on the SLC35A2 expression and clinicopathological characteristics in breast cancer patients. In addition, the role of SLC35A2 was validated in breast cancer by in vivo and in vitro experiments. Results: SLC35A2 expression is increased in 27 tumor types, and its high expression is substantially correlated with poor prognosis in patients with a variety of cancers. Receiver operating characteristic (ROC) curves showed that SLC35A2 expression levels could accurately distinguish most tumor tissues from normal tissues. High SLC35A2 expression was linked to increased immune infiltration in myeloid-derived suppressor cells (MDSC), as well as immune checkpoints, ferroptosis-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI). SLC35A2 may be involved in tumorigenesis by regulating the glycosylation process. Furthermore, multivariate Cox analysis showed that SLC35A2 was an independent prognostic factor for breast cancer. And the nomogram model had good predictive accuracy for the prognosis of breast cancer patients. Meanwhile, cellular experiments demonstrated that knockdown of SLC35A2 could significantly inhibit the proliferation, migration and invasion of breast cancer cells, while increasing the protein level of E-cadherin and decreasing N-cadherin. A nude mouse xenograft model showed that inhibition of SLA35A2 expression could significantly inhibit tumor growth. Conclusion: SLC35A2 has good diagnostic and prognostic values in multiple cancers and is closely related to tumor immune infiltration. In addition, SLA35A2 as an oncogene in breast cancer may be involved in the progression of epithelial mesenchymal transition (EMT).

Predictive Value of Serum Heat Shock Protein 90α on the Prognosis of Patients with Lung Adenocarcinoma.

Purpose: Heat shock protein 90α (HSP90α) is highly expressed in tumors, and predicts tumor progression. This study analyzed the correlation between the expression level of HSP90α in the serum and the prognosis of patients with lung adenocarcinoma. Patients and methods: The medical records of patients with 228 lung adenocarcinoma from September 2015 to December 2021 were analyzed. HSP90α expression in the patients' serum was detected by ELISA and the cut-off value (93.76 ng/mL) was determined according to the ROC curve, then the patients were divided into high- and low-level groups. The differences in the medical records of the two groups were compared using the X2 test, and Univariate and multivariate Cox regression analyses showed that serum HSP90α level were independent risk factors for both PFS and OS (P < 0.05). Results: HSP90α was positively correlated with TNM staging (P < 0.01) by One-way analysis of variance. The results of the correlation analysis and the Kaplan-Meier survival curve showed that the expression levels of HSP90α and CEA of patients were positively correlated (R=0.54, P < 0.001), and patients with high HSP90α and CEA levels had the worst OS (P < 0.001). Conclusion: HSP90α expression is negatively correlated with the prognosis of patients with lung adenocarcinoma and is a potential prognostic marker.

Risk of De Novo Hypertensive Disorders of Pregnancy After Exposure to PM1 and PM2.5 During the Period From Preconception to Delivery: Birth Cohort Study.

BACKGROUND: Particulate matter (PM) is detrimental to the respiratory and circulatory systems. However, no study has evaluated the lag effects of weekly exposure to fine PM during the period from preconception to delivery on the risk of hypertensive disorders of pregnancy (HDPs). OBJECTIVE: We set out to investigate the lag effect windows of PM on the risk of HDPs on a weekly scale. METHODS: Data from women with de novo HDPs and normotensive pregnant women who were part of the Peking University Retrospective Birth Cohort, based on the hospital information system of Tongzhou district, were obtained for this study. Meteorological data and data on exposure to fine PM were predicted by satellite remote sensing data based on maternal residential address. The de novo HDP group consisted of pregnant women who were diagnosed with gestational hypertension or preeclampsia. Fine PM was defined as PM2.5 and PM1. The gestational stage of participants was from preconception (starting 12 weeks before gestation) to delivery (before the 42nd gestational week). A distributed-lag nonlinear model (DLNM) was nested in a Cox regression model to evaluate the lag effects of weekly PM exposure on de novo HDP hazard by controlling the nonlinear relationship of exposure-reaction. Stratified analyses by employment status (employed or unemployed), education level (higher or lower), and parity (primiparity or multiparity) were performed. RESULTS: A total of 22,570 pregnant women (mean age 29.1 years) for whom data were available between 2013 and 2017 were included in this study. The prevalence of de novo HDPs was 6.7% (1520/22,570). Our findings showed that PM1 and PM2.5 were significantly associated with an elevated hazard of HDPs. Exposure to PM1 during the 5th week before gestation to the 6th gestational week increased the hazard of HDPs. A significant lag effect of PM2.5 was observed from the 1st week before gestation to the 6th gestational week. The strongest lag effects of PM1 and PM2.5 on de novo HDPs were observed at week 2 and week 6 (hazard ratio [HR] 1.024, 95% CI 1.007-1.042; HR 1.007, 95% CI 1.000-1.015, respectively, per 10 µg/m3 increase). The stratified analyses indicated that pregnant women who were employed, had low education, and were primiparous were more vulnerable to PM exposure for de novo HDPs. CONCLUSIONS: Exposure to PM1 and PM2.5 was associated with the risk of de novo HDPs. There were significant lag windows between the preconception period and the first trimester. Women who were employed, had low education, and were primiparous were more vulnerable to the effects of PM exposure; more attention should be paid to these groups for early prevention of de novo HDPs.

Effects of fine ambient particulate matters on de novo hypertensive disorders of pregnancy and blood pressure before 20 weeks.

The effects of fine particulate matter (PM) on de novo hypertensive disorders of pregnancy (HDP) were inconsistent during the first and second trimesters. This study aimed to assess the trimester-specific effects of PM2.5 and PM1 prior to diagnosis of de novo HDP. The exposure of fine PM was predicted by satellite remote sensing data according to maternal residential addresses. De novo HDP was defined as gestational hypertension and preeclampsia during the current pregnancy. A logistic regression model was performed to assess the association of PM2.5 and PM1 with HDP during the first and early second trimesters (0-13 weeks and 14-20 weeks). The generalized estimating equation model was conducted to assess the effect of PM2.5 and PM1 on blood pressure. The present study included 22,821 pregnant women (mean age, 29.1 years) from 2013 to 2017. PM2.5 and PM1 were significantly associated with an increased risk of de novo HDP during the first trimester (OR = 1.070, 95% CI: 1.013-1.130; OR = 1.264, 95% CI: 1.058-1.511 for per 10 µg/m3) and early second trimester (OR = 1.045, 95% CI: 1.003-1.088; OR = 1.170, 95% CI: 1.002-1.366 for per 10 µg/m3). Significant trends of increased de novo HDP risk was also observed with the increment of PM (all P for trend <0.05). The stratified analyses demonstrated that the associations between exposure to fine PM and the risk of HDP were more pronounced among the pregnant women with maternal age above 35 and low maternal education level (all OR >1.047). Each 10 µg/m3 increase of PM1 and PM2.5 before diagnosis of de novo HDP elevated 0.204 (95% CI: 0.098-0.310) and 0.058 (95%CI: 0.033-0.083) mmHg of systolic blood pressure. Exposure to PM2.5 and PM1 during the first and early second trimester were positively associated with the risk of de novo HDP. The fine PM before diagnosis of de novo HDP elevated the systolic blood pressure.

Prediction of Adverse Outcomes in De Novo Hypertensive Disorders of Pregnancy: Development and Validation of Maternal and Neonatal Prognostic Models.

Effectively identifying high-risk patients with de novo hypertensive disorder of pregnancy (HDP) is required to enable timely intervention and to reduce adverse maternal and perinatal outcomes. Electronic medical record of pregnant women with de novo HDP were extracted from a birth cohort in Beijing, China. The adverse outcomes included maternal and fetal morbidities, mortality, or any other adverse complications. A multitude of machine learning statistical methods were employed to develop two prediction models, one for maternal complications and the other for perinatal deteriorations. The maternal model using the random forest algorithm produced an AUC of 0.984 (95% CI (0.978, 0.991)). The strongest predictors variables selected by the model were platelet count, fetal head/abdominal circumference ratio, and gestational age at the diagnosis of de novo HDP; The perinatal model using the boosted tree algorithm yielded an AUC of 0.925 (95% CI (0.907, 0.945]). The strongest predictor variables chosen were gestational age at the diagnosis of de novo HDP, fetal femur length, and fetal head/abdominal circumference ratio. These prediction models can help identify de novo HDP patients at increased risk of complications who might need intense maternal or perinatal care.

The association between electronic cigarettes, sleep duration, and the adverse cardiovascular outcomes: Findings from behavioral risk factor surveillance system, 2020.

The joint effect of electronic cigarette smoking and insufficient sleep duration on cardiovascular disease (CVD) was unclear. This cross-sectional study aimed to evaluate the association between electronic cigarettes, sleep duration, and risk of CVD among American adults. The participants who completed the survey from the behavioral risk factor surveillance system in 2020 were included in this study. The status of electronic cigarette smoking was divided into never, former, and current use. The duration of sleep was categorized into insufficient (<6 h), appropriate (6-9 h), and excessive (>9 h) groups. The CVD group was defined as a patient having any of the following conditions: heart attack, coronary heart disease, or stroke according to self-report. The multivariate logistic regression model was adopted to determine the association between electronic cigarettes, sleep duration, and the risk of CVD. Sensitivity analyses were performed to assess the joint effects on the risk of CVD subtypes, including heart attack, coronary heart disease, and strokes, respectively. Subgroup analyses were performed to estimate the joint effects within the stratum of the age group. The total number of participants included in the present study was 253,561. Of which, 22,908 patients had CVD. In total, 61,293 participants had previously or currently used electronic cigarettes and 37,429 participants had inappropriate sleep duration. Former electronic cigarette users had a 10.8% increased risk of having CVD (OR = 1.108, 95% CI: 1.001-1.227) compared to users who never had electronic cigarettes. Insufficient and excessive sleep durations are associated with increased risks of CVD (OR = 1.592, 95% CI: 1.460-1.735; OR = 1.523, 95% CI: 1.320-1.758). The participants with current vaping status and lack of sleep had a 159.6% increased risk of CVD (OR = 2.596, 95% CI: 1.810-3.723). Sensitivity analyses found similar joint effects of current vaping and insufficient sleep on the risk of heart attack, coronary heart attack, and stroke. The subgroup analyses across each age stratum found that the middle-aged group is most vulnerable to the joint effect of current vaping and insufficient sleep. This study found that both current vaping and inappropriate sleep duration were associated with CVD. Additionally, there was a significant joint effect of current vaping and insufficient sleep on the risk of CVD, especially for middle-aged participants.

The Efficacy of the Systemic Immune-Inflammation Index and Prognosis Nutritional Index for the Diagnosis of Venous Thromboembolism in Gastrointestinal Cancers.

Purpose: This study aimed to analyze the association between venous thromboembolism (VTE) and inflammatory markers like systemic immune-inflammation index (SII) and prognosis nutritional index (PNI), and to evaluate their efficacy for the diagnosis of VTE in patients with gastrointestinal malignancies. Patients and Methods: A total of 1326 patients with the initial diagnosis of gastrointestinal cancer in the First Affiliated Hospital of Anhui Medical University (AHMU) were enrolled in the training cohort. Univariate and multivariate analysis was used to pinpoint independent predictors of VTE, which were eventually visualized as the nomogram models. The Akaike Information Criterion (AIC) was used to screen the best model. The receiver operating characteristic curve (ROC) and the clinical decision curve analysis (DCA) were utilized to evaluate the models' predictive performance in the training queue and another external sample of 250 patients at the Second Affiliated Hospital of AHMU. Results: A total of 476 patients were complicated with VTE in the training cohort. Multifactorial analysis of clinical characteristics and inflammatory markers showed that PNI, SII, age, tumor location, and therapy were independent risk factors of VTE, visualized as model A. Another model B was constructed by adding coagulation markers to the previous analysis. Model B was the best prediction model with the minimum AIC value, followed by model A with an AUC of 0.806 (95% CI 0.782~0.830) which was similar to model B's 0.832 (95% CI 0.810~0.855) but significantly higher than the currently widely used Khorana score's 0.592 (95% CI 0.562~0.621) and the CATS score's 0.682 (95% CI 0.653~0.712). The external verification yielded similar findings, with the AUC being 0.792 (95% CI 0.734~0.851), 0.834 (95% CI 0.778~0.890), 0.655 (95% CI 0.582~0.729), and 0.774 (95% CI 0.699~0.849) respectively. The DCA curves demonstrated that new models had excellent usefulness in screening patients with a high VTE risk. Conclusion: The SII and PNI were simple and viable inflammatory markers associated with VTE, and the nomogram based on them and clinical features had a meaningful clinical utility for VTE in patients with gastrointestinal malignancies.

Development and Validation of Multi-Stage Prediction Models for Pre-eclampsia: A Retrospective Cohort Study on Chinese Women.

Objective: The aim of this study is to develop multistage prediction models for pre-eclampsia (PE) covering almost the entire pregnancy period based on routine antenatal measurements and to propose a risk screening strategy. Methods: This was a retrospective cohort study that included 20582 singleton pregnant women with the last menstruation between January 1, 2013 and December 31, 2019. Of the 20582 women, 717 (3.48%) developed pre-eclampsia, including 46 (0.22%) with early-onset pre-eclampsia and 119 (0.58%) preterm pre-eclampsia. We randomly divided the dataset into the training set (N = 15665), the testing set (N = 3917), and the validation set (N = 1000). Least Absolute Shrinkage And Selection Operator (LASSO) was used to do variable selection from demographic characteristics, blood pressure, blood routine examination and biochemical tests. Logistic regression was used to develop prediction models at eight periods: 5-10 weeks, 11-13 weeks, 14-18 weeks, 19-23 weeks, 24-27 weeks, 28-31 weeks, 32-35 weeks, and 36-39 weeks of gestation. We calculated the AUROC (Area Under the Receiver Operating Characteristic Curve) on the test set and validated the screening strategy on the validation set. Results: We found that uric acid tested from 5-10 weeks of gestation, platelets tested at 18-23 and 24-31 weeks of gestation, and alkaline phosphatase tested at 28-31, 32-35 and 36-39 weeks of gestation can further improve the prediction performance of models. The AUROC of the optimal prediction models on the test set gradually increased from 0.71 at 5-10 weeks to 0.80 at 24-27 weeks, and then gradually increased to 0.95 at 36-39 weeks of gestation. At sensitivity level of 0.98, our screening strategy can identify about 94.8% of women who will develop pre-eclampsia and reduce about 40% of the healthy women to be screened by 28-31 weeks of pregnancy. Conclusion: We developed multistage prediction models and a risk screening strategy, biomarkers of which were part of routine test items and did not need extra costs. The prediction window has been advanced to 5-10 weeks, which has allowed time for aspirin intervention and other means for PE high-risk groups.

The First-Trimester Gestational Weight Gain Associated With de novo Hypertensive Disorders During Pregnancy: Mediated by Mean Arterial Pressure.

The relationship between first-trimester GWG ( T1GWG) and risk of hypertensive disorders of pregnancy (HDP) remained uncertain. This study aimed to investigate the association between T1GWG and risk of de novo HDP. Meanwhile, we explored the mediated effect and constructed an early GWG category to evaluate the predictive capacity for HDP. T1GWG was defined as the weight difference between 13 ± 1 gestational weeks and pre-conception. HDP group was defined as having diagnosis of de novo HDP, including gestational hypertension or de novo pre-eclampsia (PE) during the current pregnancy. Early GWG category was constructed according to the risk of HDP within each pre-pregnancy body mass index (BMI) group. Cox regression model was utilized to check the association between the T1GWG and HDP. Serial mediation model was adopted to evaluate the potential mediators including mean arterial pressure (MAP) at 13th and 20th week. The logistic regression model with bootstrap was performed to assess the predictive capacity of Early GWG category and MAP for the risk of HDP. A total of 17,901 pregnant women (mean age, 29.0 years) were recruited from 2013 to 2017 at the Tongzhou Maternal and Child Health Hospital in Beijing, China. Compared to women in Class 1 of early GWG category, women in the Class 2, 3, 4 have increased risks of HDP by 1.42, 4.27, and 4.62 times, respectively (hazard ratio [HR] = 2.42, 95% CI: 2.11-2.77; HR = 5.27, 95% CI: 4.05-6.86; HR = 5.62, 95% CI: 4.05-7.79). The MAP measured at 13th and 20th week totally mediated 33.1 and 26.7% of association between T1GWG GWG and HDP in total participants and overweight/obesity pregnancies, respectively. The area under receiver operator characteristic curve for predictive model utilizing early GWG category and MAP measured at 13th and 20th week for the risk of HDP is 0.760 (95% CI: 0.739-0.777). The T1GWG was associated with de novo HDP, which was partially mediated by MAP measured at 13th and 20th week. Early GWG category showed a better predictive capacity for the risk of HDP compared to the National Academy of Medicine criteria for T1GWG.

Association between IL-37 and Systemic Lupus Erythematosus Risk.

Interleukin-37 (IL-37) is an anti-inflammatory cytokine. In our former study, we found increased plasma IL-37 levels in systemic lupus erythematosus (SLE) patients. However, relationship between IL-37 levels and clinical laboratory characteristics of SLE patients has not been elucidated. In addition, association of IL37 gene polymorphism with SLE risk needs to be discussed. A group of 580 individuals (220 SLE patients and 360 healthy controls) in a Southern Chinese Han population were recruited. Plasma IL-37 levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Four single-nucleotide polymorphisms (rs3811047, rs2723186, rs2723176 and rs4364030) of IL37 gene were genotyped. Relationship of IL-37 expression, IL37 gene polymorphisms and clinical characteristics was discussed. We found that plasma levels of IL-37 were negatively associated with SLE disease activity index (SLEDAI) (rs = -0.352, P = .001), and were higher in less active patients compared with active patients (P = .003). Decreased levels of IL-37 were found in SLE patients with discoid rash when compared to patients who did not have this symptom (P < .001). Plasma IL-37 levels were significantly lower in patients with hypocomplementemia comparing to those without this feature (P = .009). Levels of IL-37 in SLE with positive proteinuria were lower than patients with negative proteinuria (P = .046). Furthermore, allele distribution of rs2723186, rs4364030 between SLE cases and healthy individuals was significantly different (P = .001, P = .010, respectively). Genotype of rs4364030 was different between SLE cases and controls (P = .015). Haplotype analysis revealed that the frequency of haplotype CG (rs2723176 (C) +rs2723186 (G)) was higher in SLE, as compared with healthy individuals (P = .002). In conclusion, the plasma levels of IL-37 were related to SLE severity, and IL37 gene polymorphisms (rs2723186, rs2723176 and rs4364030) may associate with SLE susceptibility.

Metal-free g-C3N4 nanosheets as a highly visible-light-active photocatalyst for thiol-ene reactions.

Thiol-ene click reactions are important for the construction of carbon-sulfur bonds. The use of visible-light photoredox catalysis for the formation of C-S bonds has attracted much attention. In this work, two-dimensional metal-free graphitic carbon nitride (g-C3N4) nanosheets are prepared through a simple thermal polymerization method and used to catalyze the thiol-ene click reaction under visible light-illumination. This green, atom-economic, and inexpensive approach for the hydrothiolation of alkenes is applicable for structurally different substrates and exhibits superior yields. In air or nitrogen atmosphere, the reaction yield decreases when a hole scavenging agent, CH3OH, is introduced, which indicates that photogenerated holes in the g-C3N4 nanosheets play an important role in the formation of thiyl radicals. The g-C3N4 nanosheets still show a good stability and favorable photocatalytic activity after five cycles of the reaction. Moreover, this approach can be scaled up to the gram-scale synthesis of benzyl(phenethyl)sulfane with a yield up to 93%. Our study suggests a good potential of semiconducting g-C3N4 nanosheets as a metal-free, efficient photocatalyst for various thiol-ene click reactions and even for other organic reactions.

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.

Compact optically pumped cesium beam atomic clock with a 5-day frequency stability of 7×10-15.

Compared to other commercial atomic clocks in the time keeping field, the greatest advantage of cesium beam atomic clocks is their superior long-term stability. Compared to magnetic state-selection clocks, optically pumped cesium beam atomic clocks have more interacting atoms, which results in better stability potential. To achieve good long-term stability, we propose methods including stabilization of laser power and reconstruction of circuits. They play a key role in the long-term stability of cesium beam atomic clocks. After 75 days of continuous running and measurement, we released the 5-day stability results (7×10-15 Allan deviation) of our optically pumped cesium beam atomic clock. To the best of our knowledge, this is the best 5-day stability result ever reported for compact optically pumped cesium beam atomic clocks.

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.

Microecological treatment of hyperuricemia using Lactobacillus from pickles.

BACKGROUND: Hyperuricemia is one of the important risk factors for gout, arteriosclerosis, cardiovascular and cerebrovascular disease. Lactobacillus has attracted much attention due to its role in the regulation of intestinal function and tumor resistance, but its ability to reduce uric acid is unclear. Pickles are a traditional fermented food rich in lactic acid bacteria (LAB). RESULTS: LAB strains were isolated from 18 pickles and their tolerance to acid bile salts, trypsin, pepsin were evaluated after screening by nucleoside degradation. 16S rDNA sequence analysis was used to identify LAB strains. Furthermore, we established rat model of hyperuricemia and demonstrated that Lactobacillus could alleviate hyperuricemia and reduce kidney injury. CONCLUSION: This study suggests that microecological treatment with Lactobacillus represents a feasible option for patients with chronic hyperuricemia.

Biology of IL-36 Signaling and Its Role in Systemic Inflammatory Diseases.

Interleukin (IL)-36 is a member of the IL-1 superfamily and includes three agonists (IL-36α, IL-36ß, and IL-36γ) and an antagonist (IL-36Ra). IL-36 agonists bind to heterodimeric receptor complexes. Then, the heterotrimer complexes signal via intracellular functional domains, binding to downstream signaling proteins and inducing inflammatory responses. In this review, we summarized the current knowledge about the biological role of IL-36 and its correlation with systemic inflammatory diseases. The information collected will help to increase the understanding of the potential of IL-36 and may give clues for developing novel therapeutic strategies.

Association of IRF5 rs2004640 polymorphism and systemic lupus erythematosus: A meta-analysis.

BACKGROUND: This study aimed to discuss the relationship between interferon regulatory factor (IRF)5 gene rs2004640 T/G polymorphism and systemic lupus erythematosus (SLE) susceptibility. METHODS: A meta-analysis was calculated on the association between rs2004640 polymorphism and SLE by allelic contrast (T vs G), additive model (TT vs GG), recessive model (TT vs TG + GG) and dominant model (TT + TG vs GG). RESULTS: A total of 28 comparisons were identified, including 11 228 SLE cases and 14 374 controls. Meta-analysis revealed a significant association between allele T and SLE in overall populations (odds ratio [OR] = 1.393, 95% CI: 1.276-1.522, P < 0.001). Stratification by ethnicity indicated strong associations between T allele and SLE in Asians, Europeans and Latin Americans (OR = 1.256, 95% CI: 1.073-1.469, P = 0.004; OR = 1.338, 95% CI: 1.080-1.659, P = 0.008; OR = 1.853, 95% CI: 1.488-2.308, P < 0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR = 1.999, 95% CI: 1.442-2.771, P < 0.001; OR = 1.544, 95% CI: 1.009-2.362, P < 0.045). In addition, we found significant associations between the dominant model and SLE in all populations and Asians (OR = 1.521, 95% CI: 1.257-1.841, P < 0.001; OR = 1.270, 95% CI: 1.136-1.421, P < 0.001). A marginal association was detected between the recessive mode and SLE in overall subjects (OR = 1.480, 95% CI: 1.022-2.144, P = 0.038). CONCLUSION: The current study suggested that individuals carrying rs2004640 T allele correlated with a high risk of SLE, and the IRF5 rs2004640 polymorphism was associated with SLE susceptibility.

Association between TL1A gene polymorphisms and systemic lupus erythematosus in a Chinese Han population.

Our previous studies showed elevated tumor necrosis factor-like ligand 1 aberrance (TL1A) expression in systemic lupus erythematosus (SLE). However, TL1A polymorphisms with SLE susceptibility remain to be elucidated. In addition, we made meta-analysis to evaluate the relationship of TL1A polymorphisms and autoimmune diseases owing to inconsistent results. The present research was carried out by 404 SLE, 150 primary Sjogren's syndrome (pSS) patients, and 574 healthy individuals. Three TL1A polymorphisms (rs3810936, rs6478109, rs7848647) were genotyped using TaqMan genotyping assay. Then, the meta-analysis was performed by collecting the present case-control study and previously published research. Results showed that genotypes of rs3810936, rs7848647 were different between SLE patients and healthy controls, whereas no significant association was observed in the three polymorphisms and pSS patients. Genotypes distribution of rs6478109, rs7848647 were strongly related to lupus nephritis within SLE (p = 0.004, p = 0.011), respectively. Moreover, combined meta-analysis consisted of ten comparative research involving 4,305 patients and 5,600 controls. An association between autoimmune diseases and rs6478109 polymorphism was found. Our findings indicate that gene polymorphisms (rs3810936, rs7848647) of TL1A might correlate with lupus.