Integration of network pharmacology, lipidomics, and transcriptomics analysis to reveal the mechanisms underlying the amelioration of AKT-induced nonalcoholic fatty liver disease by total flavonoids in vine tea.

Nonalcoholic fatty liver disease (NAFLD) is the main reason for chronic liver diseases and malignancies. Currently, there is a lack of approved drugs for the prevention or treatment of NAFLD. Vine tea (Ampelopsis grossedentata) has been used as a traditional Chinese beverage for centuries. Vine tea carries out several biological activities including the regulation of plasma lipids and blood glucose, hepato-protective function, and anti-tumor activity and contains the highest content of flavonoids. However, the underlying mechanisms of total flavonoids from vine tea (TF) in the attenuation of NAFLD remain unclear. Therefore, we investigated the interventions and mechanisms of TF in mice with NAFLD using an integrated analysis of network pharmacology, lipidomics, and transcriptomics. Staining and biochemical tests revealed a significant increase in AKT-overexpression-induced (abbreviated as AKT-induced) NAFLD in mice. Lipid accumulation in hepatic intracellular vacuoles was alleviated after TF treatment. In addition, TF reduced the hepatic and serum triglyceride levels in mice with AKT-induced NAFLD. Lipidomics results showed 32 differential lipids in the liver, mainly including triglycerides (TG), diglycerides (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Transcriptomic analysis revealed that 314 differentially expressed genes were commonly upregulated in the AKT group and downregulated in the TF group. The differential regulation of lipids by the genes Pparg, Scd1, Chpt1, Dgkz, and Pla2g12b was further revealed by network enrichment analysis and confirmed by RT-qPCR. Furthermore, we used immunohistochemistry (IHC) to detect changes in the protein levels of the key proteins PPARγ and SCD1. In summary, TF can improve hepatic steatosis by targeting the PPAR signaling pathway, thereby reducing de novo fatty acid synthesis and modulating the glycerophospholipid metabolism.

Safety and Efficacy of Inactivated SARS-CoV-2 Vaccine in Patients with Rheumatic Diseases and Serum Antibody Changes Post-Omicron Variant Infection.

INTRODUCTION: The purpose of this study was to investigate whether the inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has a similar effectiveness and safety profile in patients with rheumatic and musculoskeletal diseases (RMDs) and healthy controls (HCs). METHODS: Between August 10, 2021 and September 30, 2021, 134 HCs and 269 patients with RMDs were recruited. All participants who tested negative for COVID-19 were vaccinated with SARS-CoV-2 inactivated vaccine. Next, 150 patients with RMDs and 30 HCs infected with the SARS-CoV-2 Omicron variant within the previous 12 weeks were recruited between February 20, 2023 and March 1, 2023. Serum samples were collected from each participant, and the serum immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody titers against SARS-CoV-2 were determined using a chemiluminescence assay. RESULTS: No statistically significant difference was found in the titer of anti-SARS-CoV-2 IgG and IgM antibodies, or in the incidence of vaccination-related adverse events between the RMD and HC groups (P = 0.183, P = 0.903, and P = 0.27, respectively). Serum IgG titers of SARS-CoV-2 neutralizing antibodies were significantly higher in patients who received two or more doses of inactivated vaccine than in patients who were unvaccinated or had received one dose of vaccine (244.36 ± 109.79 vs. 66.20 ± 82.50; P < 0.001). CONCLUSIONS: SARS-CoV-2 inactivated vaccines have similar protective effects in HCs and patients with RMDs, with an appreciable safety profile. Fully vaccinated patients with RMDs infected with the Omicron variant were able to produce effective neutralizing antibody concentrations.

Abnormal presentation of pregnancy and postpartum initial-onset systemic lupus erythematosus combined with diffuse alveolar hemorrhage: A case report.

Systemic lupus erythematosus (SLE) is an autoimmune disease that most commonly occurs in women of childbearing age. However, cases of SLE with abnormal pregnancy as the initial manifestation, involving the development of diffuse alveolar hemorrhage (DAH), have rarely been reported. Herein, we report the case of a young woman who underwent a cesarean section for fetal distress and growth restriction at 35 + 1 weeks' gestation. Following discharge, she experienced progressive worsening of anemia and chest tightness, which was later diagnosed as SLE complicated by DAH.

Impact of short-term exposure to ambient air pollution on osteoarthritis: a multi-city time-series analysis in Central-Eastern China.

Osteoarthritis (OA) is a threat to public health issue with high morbidity and disability worldwide. However, unequivocal evidence on the link between air pollution and OA remains little, especially in multi-study sites. This study aimed to explore the relationship between short-term exposure to main air pollutants and the risk of OA outpatient visits in multi-study sites. A multi-city time-series analysis was performed in Anhui Province, Central-Eastern China from January 1, 2015, to December 31, 2020. We used a two-stage analysis to assess the association between air pollution and daily OA outpatient visits. City-specific associations were estimated with a distributed lag nonlinear model and then pooled by random-effects or fixed-effects meta-analysis. Stratified analysis was conducted by gender, age, and season. Additionally, the disease burden of OA attributable to air pollutant exposure was calculated. A total of 35,700 OA outpatients were included during the study period. The pooled exposure-response curves showed that PM2.5 and PM10 concentrations below the reference values could increase the risk of OA outpatient visits. Concretely, per 10 ug/m3 increase in PM2.5 concentration was linked to an elevated risk of OA outpatient visits at lag 2 and lag 3 days, where the effect reached its highest value on lag 2 day (RR: 1.023, 95%CI: 1.005-1.041). We observed that a 10 µg/m3 increase in PM10 was positively correlated with OA outpatient visits (lag2 day, RR: 1.011, 95%CI: 1.001-1.025). Nevertheless, no statistical significance was discovered in gaseous pollutants (including SO2, O3, and CO). Additionally, a significant difference was found between cold and warm seasons, but not between different genders or age groups. This study reveals that particulate matter is an important factor for the onset of OA in Anhui Province, China. However, there is no evidence of a relationship of gaseous pollutants with OA in this area.

Exploration of Sports Participation and Curriculum Resource Utilization in Primary Schools Before and After the "Double Reduction".

In order to eliminate capital chaos in the Education And Training (EAT) industry and ease parents' and students' excessive attention to subject achievements over physical quality, China government has launched the "Double Reduction" ("DR") policy which promotes students' Sports Participation (SP) in the Compulsory Education (CE) stage concerning students' physical and mental health. Firstly, based on the actual situation of students' SP before and after releasing the "DR" policy, this paper understands the exact needs of parents and children. Secondly, following empirical research and mathematical statistics, it analyzes the structure and characteristics of students' SP before and after the release of the "DR" policy. Mainly, the experiment focuses on the frequency, project types, and off-campus class expenditure. It also considers students' SP motivation in on-campus and off-campus sports classes before and after the "DR" policy proposal. Additionally the general curriculum resource utilization of PE teachers are surveyed in order to find out the current status of on-campus PE classes. Eventually, the strategies are put forward to optimize students' SP under the "DR" from the perspectives of family, school, and society. The results show that after the release of "DR", parents and schools gradually pay attention to student's physical health and better understand students' physical exercise in school. The consumption expenditure on sports off-campus classes has increased significantly. Meanwhile, family income and the father's occupation significantly impact the children's SP frequency in off-campus sports classes. Overall, "DR" is a protracted war. The existing difficulties need to be solved by families, schools, and the government. The research provides a practical basis for extending and managing on-campus sports classes and training. It helps timely uncover the problems in policy implementation. It guides the formulation of PE policy in the next stage of CE.

Risk factors of perioperative complications and management with enhanced recovery after primary surgery in women with epithelial ovarian carcinoma in a single center.

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I-IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4-5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3-5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3-5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3-5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3-5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.

Neuropsychological Performance Is Correlated With Tau Protein Deposition and Glucose Metabolism in Patients With Alzheimer's Disease.

Objective: This study characterizes glucose metabolism and tau protein deposition distribution in patients with Alzheimer's disease (AD) and to evaluate the relationships between neuropsychological performance and tau protein deposition or glucose metabolism using 18F-FDG and 18F-AV1451 positron emission tomography/computed tomography (PET/CT). Methods: Sixty-four patients with ß-amyloid-positive (Aß+) AD and twenty-five healthy participants were enrolled in this study. All participants underwent 18F-FDG and 18F-AV1451 PET/CT. Clinical data and neuropsychological scores were collected. Patients with AD were divided into mild, moderate, and severe groups according to mini-mental state examination (MMSE) scores. The standardized uptake value ratios (SUVRs) for both FDG and AV1451 PET images were calculated using the cerebellar vermis as reference. The SUVRs of the whole cerebral cortex and each brain region were calculated. The volume of interest (VOI) was obtained using automated anatomical atlas (AAL) and Brodmann regions. Student's t-test was used to perform intergroup comparisons of SUVR. The partial correlation coefficient between SUVR and neuropsychological scores was computed in an inter-subject manner using age and education as covariates. Results: The mild subgroup showed a reduction in glucose metabolism and aggregation of tau protein in the temporoparietal cortex. With a decline in neuropsychiatric performance, the SUVR on FDG PET decreased and SUVR on tau PET increased gradually. The areas of glucose metabolism reduction and tau protein deposition appeared first in the parietal cortex, followed by the temporal and frontal cortex, successively. Both FDG and tau SUVRs significantly correlated with MMSE, Montreal cognitive assessment (MOCA), auditory verbal learning test (AVLT), Boston naming test (BNT), clock drawing task (CDT), and verbal fluency test (VFT) (p < 0.05). The SUVR on FDG PET significantly correlated with activities of daily living (ADL) and the Hamilton depression scale (HAMD). There was no significant correlation between the tau SUVRs and ADL or HAMD. Conclusion: The extension of tau protein deposition was similar but not exactly consistent with the area of glucose metabolism reduction. Both tau and FDG SUVRs correlated with cognitive function in domain-specific patterns, and the results of FDG PET more closely correlated with neuropsychological function than tau PET results did.

Seroprevalence of SARS-CoV-2-specific antibodies and vaccination-related adverse events in systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: This study aimed to investigate the seroreactivity of Coronavirus disease 2019 (COVID-19) vaccination and its adverse events among systemic lupus erythematosus (SLE) patients, rheumatoid arthritis (RA) patients, and healthy controls (HCs). METHODS: A total of 60 SLE patients, 70 RA patients and 35 HCs, who received a complete inactivated COVID-19 vaccine (Vero cells) regimen, were recruited in the current study. Serum IgG and IgM antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2, and the self-reported vaccination-related adverse events among SLE patients, RA patients and HCs. The inactivated COVID-19 vaccines appeared to be well-tolerated and moderately immunogenic. In addition, case-only analysis indicated that in SLE patients, the disease manifestation of rash and anti-SSA autoantibody were associated with seroprevalence of IgG antibody against SARS-CoV-2, whereas the uses of ciclosporin and leflunomide had influence on the seroprevalence of IgM antibody against SARS-CoV-2. In RA patients, rheumatoid factor (RF) appeared to be associated with the seroprevalence of IgG antibody against SARS-CoV-2. CONCLUSION: Our study reveals that the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar among SLE, RA and HCs, suggesting that COVID-19 vaccine is safe and effective for SLE and RA patients to prevent from the pandemic of COVID-19.

Therapeutic Potential of Galectin-1 and Galectin-3 in Autoimmune Diseases.

Galectins are a highly conserved protein family that binds to ß-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. They can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies have indicated that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. This information may provide a novel and promising therapeutic target for autoimmune diseases.

Association between non-optimal temperature and hospitalizations for gout in Anqing, China: a time-series analysis.

Previous studies have found that non-optimal temperature influences the development of gout, but the results have been inconsistent. The present study aimed to explore the effects of high temperature and high temperature variation on hospitalizations for gout in Anqing, China. We collected daily data on air pollutants, meteorological factors, and hospitalizations for gout between 1January 2016 and 31 December 2020 in Anqing City, China. We used Poisson generalized linear regression model and a distributed lag non-linear model (DLNM) to explore the relationship of high temperature, diurnal temperature range (DTR), and temperature change between neighboring days (TCN) with hospitalizations for gout. Stratified analysis by gender (male, female) and age (<65 years, ≥65 years) was conducted. Hospitalizations for gout attributed to high temperature, high DTR, and high TCN were also quantified. A total of 8675 hospitalized patients with gout were reported during the study period. We observed that exposure to high temperature was linked with an increased risk of hospitalizations for gout (lag 0, RR: 1.081, 95% confidence interval (CI): 1.011, 1.155). Exposure to high DTR was also associated with increased risk of hospitalizations for gout (lag9, RR: 1.017, 95% CI: 1.001,1.035). A large drop in temperature between neighboring days was associated an increased risk of hospitalizations for gout (lag 0-2 days, RR: 1.234, 95% CI: 1.017, 1.493). Stratified analysis results revealed that older adults and men were more sensitive to high-level DTR exposure than their counterparts. Nearly 15% of hospitalizations for gout could be attributable to high temperature (attributable fraction: 14.93%, 95% CI: 5.99%, 22.11%). This study suggests that high temperature and high temperature variation may trigger hospitalizations for gout, indicating that patients with gout need to take proactive actions in the face of days with non-optimal temperature.

Multimodal Classification of Alzheimer's Disease and Amnestic Mild Cognitive Impairment: Integrated 18F-FDG PET and DTI Study.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and memory impairment. Amnestic mild cognitive impairment (aMCI) is the intermediate stage between normal cognitive aging and early dementia caused by AD. It can be challenging to differentiate aMCI patients from healthy controls (HC) and mild AD patients. OBJECTIVE: To validate whether the combination of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and diffusion tensor imaging (DTI) will improve classification performance compared with that based on a single modality. METHODS: A total of thirty patients with AD, sixty patients with aMCI, and fifty healthy controls were included. AD was diagnosed according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable. aMCI diagnosis was based on Petersen's criteria. The 18F-FDG PET and DTI measures were each used separately or in combination to evaluate sensitivity, specificity, and accuracy for differentiating HC, aMCI, and AD using receiver operating characteristic analysis together with binary logistic regression. The rate of accuracy was based on the area under the curve (AUC). RESULTS: For classifying AD from HC, we achieve an AUC of 0.96 when combining two modalities of biomarkers and 0.93 when using 18F-FDG PET individually. For classifying aMCI from HC, we achieve an AUC of 0.79 and 0.76 using the best individual modality of biomarkers. CONCLUSION: Our results show that the combination of two modalities improves classification performance, compared with that using any individual modality.

The Relationship Between Ambient Air Pollution and Hospitalizations for Gout in a Humid Subtropical Region of China.

OBJECTIVE: Gout is a chronic disease caused by the deposition of sodium urate (MSU) crystals. Available data on the association between environmental hazards and gout are scarce. The present study was present to investigate the relationship between short-term exposure to air pollution and hospitalizations for acute gout from 2016 to 2020 in Anqing City, China. METHODS: Daily records of hospital admissions for acute gout in Anqing from 1 January 2016 to 31 December 2020 were retrieved from the tertiary first-class hospitals in Anqing. Air pollutants and meteorological data were obtained from the China Environmental Monitoring Station and China Meteorological Data Service Center respectively. We used a time-series analysis to explore the association between air pollution (NO2, O3, and CO) and hospitalizations for acute gout, and conducted stratified analyses by gender, age and season. RESULTS: We observed an association between NO2 and hospitalizations for gout (lag 0, relative risk (RR):1.022, 95% confidence interval (CI):1.004-1.041). For every 1 mg/m3 increase in CO concentration, hospitalizations for gout increased by 3.9% (lag 11 days, RR=1.039, 95% CI: 1.004-1.076). Intriguingly, there was a negative association between O3 and hospitalizations for gout (lag0, RR=0.986, 95% CI: 0.976-0.996). Stratified analyses showed that exposure to high levels of NO2 was considered to be more vulnerable to gout in cold season. CONCLUSION: Our study showed that short-term exposure to NO2 and CO has a significant effect on hospitalizations for acute gout.

Enhancing Hydrogen Productivity of Photosynthetic Bacteria from the Formulated Carbon Source by Mixing Xylose with Glucose.

To develop an efficient photofermentative process capable of higher rate biohydrogen production using carbon components of lignocellulosic hydrolysate, a desired carbon substrate by mixing xylose with glucose was formulated. Effects of crucial process parameters affecting cellular biochemical reaction of hydrogen by photosynthetic bacteria (PSB), i.e., variation in initial concentration of total carbon, glucose content in initial carbon substrate, and light intensity, were experimentally investigated using response surface methodology (RSM) with a Box-Behnken design (BBD). Hydrogen production rate (HPR) in the maximum value of 30.6 mL h-1 L-1 was attained under conditions of 39 mM initial concentration of total carbon, 59% (mol/mol) glucose content in initial carbon substrate, and 12.6 W m-2 light intensity at light wavelength of 590 nm. Synergic effects of metabolizing such a well-formulated carbon substrate for sustaining the active microbial synthesis to sufficiently accumulate biomass in bioreactor, as well as stimulating enzyme activity of nitrogenase for the higher rate biohydrogen production, were attributed to this carbon substrate that can enable PSB to maintain the relatively consistent microenvironment in suitable culture pH condition during the optimized photofermentative process.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Preparation, Characterization, and In Vitro Pharmacodynamics and Pharmacokinetics Evaluation of PEGylated Urolithin A Liposomes.

Urolithin A (Uro-A), a metabolite of ellagitannins in mammals' intestinal tract, displays broad biological properties in preclinical models, including anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the clinical application of Uro-A is restricted because of its low aqueous solubility and short elimination half-life. Our purpose was to develop a delivery system to improve the bioavailability and anti-tumor efficacy of Uro-A. To achieve this goal, urolithin A-loaded PEGylated liposomes (Uro-A-PEG-LPs) were prepared for the first time and its physicochemical properties and anti-tumor efficacy in vitro were evaluated. The morphology of Uro-A-PEG-LPs displayed a uniform sphere under transmission electron microscope. The particle size, polydispersity index, zeta potential, and encapsulation efficiency of Uro-A-PEG-LPs were 122.8 ± 7.4 nm, 0.25 ± 0.16, - 25.5 ± 2.3 mV, and 94.6 ± 1.6%, respectively. Moreover, Uro-A-PEG-LPs possessed higher stability and could be stably stored at 4°C for a long time. In vitro release characteristics indicated that Uro-A-PEG-LPs possessed superior sustained release properties. The results of confocal laser scanning microscopy experiment showed that the coumarin 6-loaded PEGylated liposomes (C6-PEG-LPs) have superior cellular uptake than that of conventional liposomes. In addition, in vitro tests demonstrated that Uro-A-PEG-LPs elevated cytotoxicity and pro-apoptotic effect in human hepatoma cells comparing with free Uro-A. Furthermore, the results of pharmacokinetic experiments showed that the t1/2, AUC0-t, and MRT0-t of Uro-A-PEG-LPs increased to 4.58-fold, 2.33-fold, and 2.43-fold than those of free Uro-A solution, respectively. Collectively, these manifested that PEGylated liposomes might be a potential delivery system for Uro-A to prolonging in vivo circulation time, promoting cellular uptake, and enhancing its anti-tumor efficacy.

Impact of IL-10 gene polymorphisms and its interaction with environment on susceptibility to systemic lupus erythematosus.

This study aims to explore the impact of interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and its interaction with environment on the risk of systemic lupus erythematosus (SLE). Chi-square testing method was used to investigate whether the distributions for genotype of four SNPs were differed from Hardy-Weinberg equilibrium (HWE). Logistic regression was used to test the association between IL-10 SNPs and SLE risk. The best interaction combinations between IL-10 SNPs and environmental factors were assessed by generalized multifactor dimensionality reduction (GMDR). Both rs1800896-G and rs1800871-T alleles were associated with increased risk of SLE, the odds ratios (ORs) (95% confidence interval (CI)) for the two SNPs were 1.68 (1.25-2.09) and 1.47 (1.12-1.94), respectively. Then, we used the GMDR method to analyze the high-order interactions of four SNPs within IL-10 gene and environmental factors on SLE risk. We found a significant interaction combination (two-locus model with P = 0.001) between rs1800896 and smoking, after adjusting for gender, age, body mass index (BMI), and alcohol drinking. We also used two-variable stratified analysis by logistic regression to analyze the synergistic effect between two variables (rs1800896 and smoking), which had significant significance in GMDR model. We found that current smokers with rs1800896-AG or GG genotype have the highest SLE risk, compared with never smokers with the rs1800896-AA genotype, OR (95% CI) = 2.24 (1.52-3.58). The rs1800896-G and rs1800871-T alleles and interaction between rs1800896 and current smoking were all associated with increased risk of SLE.

The mechanism of Arhalofenate in alleviating hyperuricemia-Activating PPARγ thereby reducing caspase-1 activity.

Hyperuricemia (HUA) is an important risk factor for renal diseases and contributes to gout. Arhalofenate (Arha) has been proved to have uricosuric activity as an inhibitor of URAT1, organic anion transporter 4 (OAT4) and OAT10. However, the effects of Arha on HUA remain unknown. The objective of this study was to investigate whether Arha could alleviate HUA and uncovered the underlying mechanism in vitro. HK-2 cells were exposed to uric acid (UA) to simulate HUA in vitro. Then cells were treated with Arha, caspase-1 inhibitor Belnacasan (Beln), caspase-11 inhibitor Wedelolactone (Wede) and PPARγ inhibitor Mifobate, respectively. The alteration of cell proliferation, inflammation, pyroptosis and expression of related proteins were detected. Results showed that UA exposure inhibited cell viability and increased IL-1ß and IL-18 generation in a concentration dependent manner. Meanwhile, UA activated the cleavage of gasdermin D (GSDMD), enhanced the protein expression of URAT1, OAT4, TLR4, caspase-1, and caspase-11 and reduced PPARγ expression. While the presence of Arha or Beln enhanced cell viability and inhibited cleavage of GSDMD. Wede slightly increased cell viability but failed to prevent GSDMD cleavage. The expression of related proteins except caspase-11was also recovered by Arha. Beln and Wede partially rescued related proteins level except PPARγ compared with model group. Besides, the co-treatment of Mifobate blunted the effects of Arha on cell viability and expression of GSDMD, TLR4, and caspase-1. In conclusion, Arha inhibited UA transport as well as preventing inflammation and pyroptosis via activating PPARγ thereby blocking caspase-1 activation of HUA in vitro.

Incidence and potential predictors of thromboembolic events in epithelial ovarian carcinoma patients during perioperative period.

OBJECTIVE: To assess the incidence and the risk factors of venous thromboembolism (VTE) in patients with epithelial ovarian carcinoma (EOC) during the perioperative period. METHODS: A retrospective analysis was conducted on the patients with epithelial ovarian cancer treated in our hospital, between January 2017 and July 2019, and a comprehensive review of the medical documentation was performed to collect relevant data. We then analyzed the related factors of the thrombosis in the EOC patients, using univariate and multivariate analysis to identify significant risk factors for VTE, and bootstrap resampling method was used to verify the multivariate analysis results. The ROC curve methods were conducted to evaluate the diagnostic value for the prediction of VTE. RESULTS: We analyzed 233 cases of patients with EOC, of whom the incidence of VTE was 11.16%. According to multivariate and 5000 bootstrap samples analysis, preoperative D-dimer levels (>4.215 µg/ml, p = 0.041 and p = 0.032) and comorbid of cerebral infarction (p < 0.001 and p < 0.001) had statistical significance in predicting VTE events; bootstrap analysis also found the Alb, CA125, OCCC had statistical significance. While According to multivariate and 5000 bootstrap samples analysis, age (>50.5 years old, p = 0.019 and p = 0.002) and nonoptimal debulking surgery (p = 0.007 and p = 0.002) showed significance in predicting VTE after surgery; bootstrap analysis also found the D-dimer levels (>4.215 µg/ml) and tuberculosis had statistical significance. CONCLUSION: More effective thromboprophylaxis and pre-test assessment is necessary for EOC patients. For prediction VTE events, D-dimer levels (>4.215 µg/ml) were the independent predictors before operation. Age and debulking surgery were the independent predictors post operation.

Distinct relationships of amyloid-beta and tau deposition to cerebral glucose metabolic networks in Alzheimer's disease.

Extracellular accumulation of amyloid-beta peptides and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins are the two cardinally pathological hallmarks of Alzheimer's disease (AD). However, their exact roles in the mechanisms of AD progression are not well established. Given that AD is a disconnection syndrome and hypometabolism is one of its most important neurodegenerative indicators, we hypothesized amyloid-beta and tau burden may disturb the glucose metabolic network of AD. Here we investigated the relationship of these two factors to regional metabolic network properties using multimodal positron emission tomography (PET) imaging data. Participants included six groups covering from cognitively normal controls, patients with early cognitive impairment (MCI), late MCI, mild AD, moderate AD to severe AD who underwent amyloid-beta PET, tau PET and fluorodeoxyglucose (FDG) PET. Glucose metabolic network of each group was constructed and relations of amyloid-beta and tau to regional metabolic network measurements were investigated. Results revealed distinct associations of these two hallmarks to metabolic networks: amyloid-beta were positively related to metabolic network measurements at relative early phases of AD, while tau burden showed a negative relationship at late phase of AD. These results supported the notion that amyloid-beta and tau accumulation may contribute independently to mechanisms of AD. Furthermore, these findings might also provide connectivity evidence for the speculation that amyloid-beta deposition is protective to neuronal activity.

[Straw Returning Plus Nitrogen Fertilizer Affects the Soil Microbial Community and Organic Carbon Mineralization in Karst Farmland].

The use of straw returning plus nitrogen fertilizer on farmland is one of the important agronomic practices for adjusting soil organic carbon (SOC) transformations. To explore the mechanisms of straw and nitrogen fertilizer application on straw and SOC mineralization in long-term fertilized soils, an incubation experiment with the 13C isotope tracing technique was conducted, which involved three long-term fertilized models in typical karst soils (no fertilization, inorganic fertilization, and a combination of inorganic fertilization and straw). To study the mechanisms of 13C-labeled straw and SOC mineralization, four treatments were designed as follows:no straw and nitrogen (control), and straw combined with three levels of nitrogen fertilizer (0, 214.0, and 571.0 mg·kg-1 soil). The results showed that cumulative mineralization amounts of straw-derived organic carbon in long-term fertilized soils were markedly higher than those in non-fertilized soil. Straw-derived organic carbon mineralization was significantly affected by nitrogen fertilizer levels. The positive priming effects (PE) in long-term fertilized soils were much lower than those in non-fertilized soil. The PE was decreased at the low nitrogen fertilizer level but increased at the high nitrogen fertilizer level. The principal component analysis (PCA) of phospholipid fatty acids (PLFAs) indicated that the soil microbial community structure was greatly affected by the long-term fertilization models and combined straw and nitrogen fertilizer application. Moreover, the content of PLFAs in soil microorganisms, namely, bacteria and fungi, were remarkably increased by the straw plus nitrogen fertilizer (values increased by 40.3%-53.0%, 41.1%-62.6%, and 60.5%-148.6% compared with control), but levels were not significantly affected by nitrogen fertilizer levels alone. The ratios between PLFAs of soil gram-positive and gram-negative bacteria (G+/G-) decreased and were stable at around 0.8. The structure equation models (SEM) demonstrated that the combination of straw and nitrogen affected the soil gram-positive and gram-negative bacteria structure and increased the soil DOC content, which promoted the decomposition of straw and affected the mineralization of SOC. These results indicate that straw returning plus low nitrogen fertilizer can improve the SOC sequestration capacity in karst farmland.