Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Automatic detection of small bowel lesions with different bleeding risks based on deep learning models.

BACKGROUND: Deep learning provides an efficient automatic image recognition method for small bowel (SB) capsule endoscopy (CE) that can assist physicians in diagnosis. However, the existing deep learning models present some unresolved challenges. AIM: To propose a novel and effective classification and detection model to automatically identify various SB lesions and their bleeding risks, and label the lesions accurately so as to enhance the diagnostic efficiency of physicians and the ability to identify high-risk bleeding groups. METHODS: The proposed model represents a two-stage method that combined image classification with object detection. First, we utilized the improved ResNet-50 classification model to classify endoscopic images into SB lesion images, normal SB mucosa images, and invalid images. Then, the improved YOLO-V5 detection model was utilized to detect the type of lesion and its risk of bleeding, and the location of the lesion was marked. We constructed training and testing sets and compared model-assisted reading with physician reading. RESULTS: The accuracy of the model constructed in this study reached 98.96%, which was higher than the accuracy of other systems using only a single module. The sensitivity, specificity, and accuracy of the model-assisted reading detection of all images were 99.17%, 99.92%, and 99.86%, which were significantly higher than those of the endoscopists' diagnoses. The image processing time of the model was 48 ms/image, and the image processing time of the physicians was 0.40 ± 0.24 s/image (P < 0.001). CONCLUSION: The deep learning model of image classification combined with object detection exhibits a satisfactory diagnostic effect on a variety of SB lesions and their bleeding risks in CE images, which enhances the diagnostic efficiency of physicians and improves the ability of physicians to identify high-risk bleeding groups.

Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury.

BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Short-term efficacy and influencing factors of conventional chemotherapy combined with irinotecan in patients with advanced gastric cancer.

BACKGROUND: Gastric cancer is one of the most common cancers worldwide, with a 5-year survival rate of only 20%. The age of onset of gastric cancer is in line with the general rule of cancer. Most of them occur after middle age, mostly between 40 and 60 years old, with an average age of about 50 years old, and only 5% of patients are under 30 years old. The incidence of male is higher than that of female. AIM: To investigate the short-term efficacy and influencing factors of chemotherapy combined with irinotecan in patients with advanced gastric cancer. METHODS: Eighty patients with advanced gastric cancer who were treated in our hospital from January 2019 to January 2022 were selected. The patients were divided into an observation group (n = 40) and control group (n = 40) by the envelope method. The control group was given preoperative routine chemotherapy. The observation group was treated with irinotecan in addition to the chemotherapy given to the control group. The short-term efficacy of treatment in the two groups, as well as tumor marker levels and quality of life before and after treatment were evaluated. RESULTS: The short-term treatment effect in the observation group was better than that in the control group (P < 0.05), and the total effective rate was 57.50%. The age and proportion of tumor node metastasis (TNM) stage IV patients with ineffective chemotherapy in the observation group were (65.12 ± 5.71) years and 52.94%, respectively, which were notably higher than those of patients with effective chemotherapy (P < 0.05), while the Karnofsky Performance Scale score was (67.70 ± 3.83) points, which was apparently lower than that of patients with effective chemotherapy (P < 0.05). After 3 mo of treatment, the SF-36 scale scores of physiological function, energy, emotional function, and mental health in the observation group were 65.12 ± 8.14, 54.76 ± 6.70, 47.58 ± 7.22, and 66.16 ± 8.11 points, respectively, which were considerably higher than those in the control group (P < 0.05). The incidence rates of grade III-IV diarrhea and grade III-IV thrombocytopenia in the observation group were 32.50% and 25.00%, respectively, which were markedly higher than those in the control group (P < 0.05). CONCLUSION: Chemotherapy combined with irinotecan in patients with advanced gastric cancer has a good short-term efficacy and can significantly reduce serum tumor markers and improve the quality of life of patients. The efficacy may be affected by the age and TNM stage of the patients, and its long-term efficacy needs further study.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Controlling the atomic-orbital-resolved photoionization for neon atoms by counter-rotating circularly polarized attosecond pulses.

We theoretically investigate the atomic-orbital-resolved vortex-shaped photoelectron momentum distributions (PMDs) and ionization probabilities by solving the two-dimensional time-dependent Schrödinger equation (2D-TDSE) of neon in a pair of delayed counter-rotating circularly polarized attosecond pulses. We found that the number of spiral arms in vortex patterns is twice the number of absorbed photons when the initial state is the ψm=±1 state, which satisfy a change from c2n+2 to c2n (n is the number of absorbed photons) rotational symmetry of the vortices if the 2p state is replaced by 2p+ or 2p- states. For two- and three-photon ionization, the magnetic quantum number dependence of ionization probabilities is quite weak. Interestingly, single-photon ionization is preferred when the electron and laser field corotate and ionization probabilities of 2p- is much larger than that of 2p+ if the proper time delay and wavelength are used. The relative ratio of ionization probabilities between 2p- and 2p+ is insensitive to laser peak intensity, which can be controlled by changing the wavelength, time delay, relative phase and amplitude ratio of two attosecond pulses.

Novelelectronic health records applied for prediction of pre-eclampsia: Machine-learning algorithms.

OBJECTIVE: To predict risk of pre-eclampsia (PE) in women using machine learning (ML) algorithms, based on electronic health records (EHR) collected at the early second trimester. STUDY DESIGN: A total of 3759 cases of pregnancy who received antenatal care at Xinhua hospital Chongming branch Affiliated to Shanghai Jiaotong University were included in this retrospective EHR-based study. Thirty-eight candidate clinical parameters routinely available at the first visit in antenatal care were collected by manual chart review. Logistic regression (LR), random forest (RF), support vector machine (SVM) and extreme gradient boosting (XGBoost) were used to construct the prediction model. Features that contributed to the model predictions were identified using XGBoost. OUTCOME MEASURES: The performance of ML models to predict women at risk of PE was quantified in terms of accuracy, precision, recall, false negative score, f1_score, brier score and the area under the receiver operating curve (auROC). RESULTS: The XGboost model had the best prediction performance (accuracy = 0.920, precision = 0.447, recall = 0.789, f1_score = 0.571, auROC = 0.955). The most predictive feature of PE development was fasting plasma glucose, followed by mean blood pressure and body mass index. An easy-to-use model that a patient could answer independently still enabled accurate prediction, with auROC of 0.83. CONCLUSION: risk of PE development can be predicted with excellent discriminative ability using ML algorithms based on EHR collected at the early second trimester. Future studies are needed to assess the real-world clinical utility of the model.

UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1.

Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.

Preparation and Photocatalytic Application of the Composites PMo12/AgNPs Based on Polyoxometalates.

Supported catalysts, consisting of PMo12 immobilized on silver nanomaterials at different recombination time and the silver nanomaterials with different template sodium citrate amount characterized by FT-IR, XRD, SEM, UV-vis and other test methods. The results show that the AgNPs are relatively uniformed with sizes between 100-300 nm when the sodium citrate addition amount is 9.0 mL. As the reaction time of PMo12/AgNPs increases, the adhesion of AgNPs on the surface of PMo12 becomes more complete. Using PMo12 and PMo12/AgNPs composite materials as catalysts, methylene blue (MB) is photocatalytically degraded under simulated visible light conditions. The results show that PMo12 can catalyze MB effectively, and the decolorization rate reached 98.6% when the catalyst content is 2 g/L, the solution pH is 3 and the MB concentration is 5 mg/L. Under the same experimental conditions, photocatalytic performance of the PMo12/AgNPs system is better than that of the PMo12 further improved the photocatalytic degradation effect of the MB solution with a decolorization rate of 100%. The composite still keeps good photocatalytic activity and stability after three cycles of use. Finally, the catalytic mechanism of the POMs composite material is preliminarily discussed.

Association between ambient air pollution and multiple sclerosis: a systemic review and meta-analysis.

Recently, increasing attention has been paid to the effects of air pollutants on autoimmune diseases. The results of relationship between ambient air pollution and multiple sclerosis (MS) showed a variety of differences. Thus, the purpose of this study is to further clarify and quantify the relationship between ambient air pollutants and MS through meta-analysis. Through electronic literature search, literature related to our research topic was collected in Cochrane Library, Embase, and PubMed till August 18, 2020, according to certain criteria. Pooled risk estimate and 95% confidence intervals (95%CI) were calculated by random-effect model analysis. After removing copies, browsing titles and abstracts, and reading full text, 6 studies were finally included. The results showed that only particulate matter (PM) with aerodynamic diameter ≤ 10 (PM10) was related to MS (pooled HR = 1.058, 95% CI = 1.050-1.066), and no correlation was found between PM with aerodynamic diameter < 2.5 (PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), benzene (C6H6), major road < 50 m, and MS. There was no publication bias, and the heterogeneity analysis results were stable. PM10 is correlated with the disease MS, while other pollution is not connected with MS. Therefore, it is important for MS patients to take personal protection against particulate pollution and avoid exposure to higher levels of PM.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

IL-21 mediates microRNA-423-5p /claudin-5 signal pathway and intestinal barrier function in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of chronic and recurrent nonspecific inflammatory disorders, including Crohn's disease (CD) and ulcerative colitis (UC). Due to the persistent inflammation of intestinal mucosa caused by immune disorders, barrier dysfunction may be an essential cause of the pathogenesis of IBD. Therefore, exploring the mechanism is very important to clarify the pathogenesis of IBD. In our research, we provided evidence of IL-21 function in IBD. The junction complex protein claudin-5 may be a downstream gene of the IL-21. Anti-IL-21 administrated prevented DSS-simulative colitis via recovering claudin-5 expression in the human colonic epithelial cells. Meanwhile, we described that miR-423-5p could be involved in IL-21/ claudin-5 pathway by regulating NF-κB/MAPKs/JNK signaling pathway, which may provide a new therapeutic target for IBD.

Elevated Urinary and Blood Vascular Cell Adhesion Molecule-1 as Potential Biomarkers for Active Systemic Lupus Erythematosus: A Meta-analysis.

OBJECTIVE: Due to the inconsistent results of current studies on the association between urinary and blood vascular cell adhesion molecule-1 (VCAM-1) and systemic lupus erythematosus (SLE) disease activity, we conducted this study and analyzed its influencing factors. METHODS: A literature search was conducted in PubMed, EMBASE, Web of Science, and Cochrane Library. Data were extracted from eligible studies to calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Cochrane Q test and I2 statistics were used to examine heterogeneity. The sources of heterogeneity were assessed through sensitivity analysis and subgroup analysis. Publication bias was evaluated by funnel plots and Egger's test. RESULTS: A total of 15 studies met the inclusion criteria, including 473 active SLE patients and 674 inactive SLE patients. The random effects model was used for data analysis. In both urine and blood samples, VCAM- 1 level in active SLE patients was significantly higher than those in inactive SLE patients (urine: SMD: 0.769; 95% CI: 0.260-1.278; blood: SMD=0.655, 95% CI: 0.084-1.226). No publication bias was found in this study. CONCLUSION: Compared with inactive SLE patients, patients with active SLE have higher levels of VCAM-1 in both urine and blood. VCAM-1 may be a potential indicator of SLE disease activity.

Formation and migration of α-dicarbonyl compounds during storage and reheating of a sugary food simulation system.

BACKGROUND: The thermal processing of food results in the formation of α-dicarbonyl compounds (α-DCs) such as glyoxal (GO), methylglyoxal (MGO), 2,3-butanedione (2,3-BD), and 3-deoxyglucosone (3-DG), which are precursors of potentially harmful advanced glycation end products. Some of the α-DCs found in food products might result from chemical deterioration reactions during storage and reheating. A range of sugary food simulation systems were stored at three different temperatures (4, 25, and 37 °C) and reheated using three different processing methods to investigate the formation and migration of α-DCs. RESULTS: During 20 days of storage, the concentration of α-DCs declined, following which the concentration remained approximately constant. Methylglyoxal was the major α-DC affected during storage, its relative content decreasing from 233.71 to 44.12 µg mL-1 in the glucose-lysine system. The concentration of α-DCs decreased with increasing temperature. Microwave reheating increased the formation of α-DC compounds. The largest increases in 3-DG concentrations were observed in the maltose-lysine systems (24.94 to 35.74 µg mL-1 ). The concentration of α-DCs only changed a little in response to reheating at 100 °C, but declined when reheated at 150 °C. CONCLUSION: The concentration of α-DCs following storage and reheating depends on the type of sugar, lysine content, temperature, and method of reheating. © 2020 Society of Chemical Industry.

Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis.

OBJECTIVES: CXC ligand 13 (CXCL13) is known as B cell chemotactic factor (BLC), promoting the migration of B lymphocytes by communicating with its receptor CXCR5, which can be regarded as part of pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This meta-analysis was to evaluate the circulating CXCL13 levels in SLE and RA. METHODS: All articles were respectively gathered from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) (by the end of 10 April 2019). According to random effects model, standardized mean difference (SMD) and 95% confidence interval (CI) of CXCL13 levels in SLE and RA were calculated by Stata 12.0 software. RESULTS: Totally, 15 studies were selected (981 SLE patients and 380 healthy controls, 332 RA patients and 147 healthy controls). SLE and RA patients were significantly increased in circulating CXCL13 levels (SMD = 1.851, 95% CI 0.604-3.098; SMD = 1.801, 95% CI = 1.145-2.457). Subgroup analyses showed that SLE patients from the Chinese group and systemic lupus erythematosus disease activity index (SLEDAI) score ≥ 6 group had higher circulating CXCL13 levels (SMD = 2.182, 95% CI 0.135-4.229; SMD = 0.767, 95% CI 0.503-1.030). However, there were no significant changes in CXCL13 concentrations in SLE patients from the English and SLEDAI score < 6 group. Similarly, subgroup analyses presented that RA patients from different classifications showed higher circulating CXCL13 levels. There was no publication bias. CONCLUSIONS: This meta-analysis demonstrated increased circulating CXCL13 concentrations in SLE and RA patients. Circulating CXCL13 levels may act as biomarkers and therapy targets in the diagnosis and treatment of SLE and RA.Key Point• First, CXC ligand 13 (CXCL13) is closely related to the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), Second, this study may provide novel therapeutic targets for the treatment of SLE and RA patients. This meta-analysis provides a comprehensive analysis of circulating CXCL13 levels in patients with SLE and RA and also explores related influencing factors.

Ubiquitin-conjugating enzyme E2T knockdown suppresses hepatocellular tumorigenesis via inducing cell cycle arrest and apoptosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is now the most common primary liver malignancy worldwide, and multiple risk factors attribute to the occurrence and development of HCC. Recently, increasing studies suggest that ubiquitin-conjugating enzyme E2T (UBE2T) serves as a promising prognostic factor in human cancers, although the molecular mechanism of UBE2T in HCC remains unclear. AIM: To investigate the clinical relevance and role of UBE2T in HCC development. METHODS: UBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed. A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells. qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells. Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay, respectively. Cell cycle distribution and apoptosis were determined by flow cytometry. The genes regulated by UBE2T were profiled by microarray assay. RESULTS: UBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues. High expression of UBE2T predicted a poor overall survival in HCC patients. In vitro, lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells. In vivo, the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing. The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown. Furthermore, apoptosis was increased by UBE2T knockdown. At the molecular level, numerous genes were dysregulated after UBE2T silencing, including IL-1B, FOSL1, PTGS2, and BMP6. CONCLUSION: UBE2T plays an important role in cell cycle progression, apoptosis, and HCC development.

MiR-32-5p aggravates intestinal epithelial cell injury in pediatric enteritis induced by Helicobacter pylori.

BACKGROUND: Pediatric enteritis is one of the infectious diseases in the digestive system that causes a variety of digestive problems, including diarrhea, vomiting, and bellyache in children. Clinically, Helicobacter pylori (H. pylori) infection is one of the common factors to cause pediatric enteritis. It has been demonstrated that aberrant expression of microRNAs (miRNAs) is found in gastrointestinal diseases caused by H. pylori, and we discovered a significant increase of miR-32-5p in H. pylori-related pediatric enteritis. However, the exact role of miR-32-5p in it is still unknown. AIM: To investigate the role of aberrant miR-32-5p in pediatric enteritis induced by H. pylori. METHODS: MiR-32-5p expression was detected by quantitative real time-polymerase chain reaction. The biological role of miR-32-5p in H. pylori-treated intestinal epithelial cells was evaluated by Cell Counting Kit-8 assay and flow cytometry. The potential target of miR-32-5p was predicted with TargetScanHuman and verified by luciferase assay. The downstream mechanism of miR-32-5p was explored by using molecular biology methods. RESULTS: We found that miR-32-5p was overexpressed in serum of H. pylori-induced pediatric enteritis. Further investigation revealed that H. pylori infection promoted the death of intestinal epithelial cells, and increased miR-32-5p expression. Moreover, miR-32-5p mimic further facilitated apoptosis and inflammatory cytokine secretion of intestinal epithelial cells. Further exploration revealed that SMAD family member 6 (SMAD6) was the direct target of miR-32-5p, and SMAD6 overexpression partially rescued cell damage induced by H. pylori. The following experiments showed that miR-32-5p/SMAD6 participated in the apoptosis of intestinal epithelial cells induced by transforming growth factor-ß-activated kinase 1 (TAK1)-p38 activation under H. pylori infection. CONCLUSION: Our work uncovered the crucial role of aberrant expression of miR-32-5p in H. pylori-related pediatric enteritis, and suggested that the TAK1-p38 pathway is involved in it.