Mechanism of Zuogui pill enhancing ovarian function and skin elastic repair in premature aging rats based on artificial intelligence medical image analysis.

BACKGROUND: AI medical image analysis shows potential applications in research on premature aging and skin. The purpose of this study was to explore the mechanism of the Zuogui pill based on artificial intelligence medical image analysis on ovarian function enhancement and skin elasticity repair in rats with premature aging. MATERIALS AND METHODS: The premature aging rat model was established by using an experimental animal model. Then Zuogui pills were injected into the rats with premature aging, and the images were detected by an optical microscope. Then, through the analysis of artificial intelligence medical images, the image data is analyzed to evaluate the indicators of ovarian function. RESULTS: Through optical microscope image detection, we observed that the Zuogui pill played an active role in repairing ovarian tissue structure and increasing the number of follicles in mice, and Zuogui pill also significantly increased the level of progesterone in the blood of mice. CONCLUSION: Most of the ZGP-induced outcomes are significantly dose-dependent.

Clinical characteristics of KRAS mutation subtypes in non-small cell lung cancer population in Xinjiang, China, and their impact on the prognosis of immunotherapy.

PURPOSE: Non-small cell lung cancer (NSCLC) is a highly fatal malignancy. The Kirsten rat sarcoma viral oncogene (KRAS) gene profoundly impacts patient prognosis. This study aims to explore the correlation between KRAS mutation subtypes, clinical data, and the impact of these subtypes on immunotherapy. MATERIALS AND METHODS: Tumor samples from 269 NSCLC patients at the Affiliated Cancer Hospital of Xinjiang Medical University were analyzed. Patients received first- or second-line therapy without targeted therapy. Molecular and clinical data were used to analysis KRAS mutation subtypes and treatment outcomes. RESULTS: KRAS mutations predominantly included G12C, G12D, and G12V subtypes. TP53 had the highest mutation frequency among KRAS mutations, followed by MST1, STK11, and KMT2C. Gender differences were noted among KRAS mutation subtypes, with G12C and G12V mutations prevalent in males, while G12D mutations were less common among males. Smokers exhibited varied KRAS mutation subtypes, with G12C and G12V prevalent in smokers and G12D in nonsmokers. KRAS mutations were mainly in lung adenocarcinoma. TTF-1 and PD-L1 expression differed significantly among KRAS mutations. Patients with G12C and G12V mutations showed higher TMB levels and better immunotherapy outcomes compared to those without KRAS mutations. Conversely, patients with G12D mutations had poorer immunotherapy responses. CONCLUSIONS: KRAS mutation subtypes exhibit distinct clinical and molecular characteristics and varying responses to immunotherapy. G12C and G12V mutations correlate with better immunotherapy outcomes, while G12D mutations are associated with poorer responses.

Association of maternal infection of SARS-CoV-2 and neonatal susceptibility: A retrospective cohort study.

Objective: This study aims to assess the risk of neonatal susceptibility to COVID-19 among pregnant women. Methods: We conducted a retrospective cohort study involving 1089 pregnant women ≥28 weeks of gestational age, who were categorized into infected and uninfected groups. Data for all participants were collected through a comprehensive review of electronic medical records and follow-up phone calls. The primary outcome was neonatal infection with SARS-CoV-2, while secondary outcomes included delivery patterns and gestational age at delivery. Results: Maternal vaccination (OR 95%CI:0.63[0.46, 0.85]) and maternal infection with SARS-CoV-2 (OR 95%CI: 0.45[0.34, 0.60]) were found to be associated with a decreased risk of neonatal infection. The infected group exhibited a lower neonatal SARS-CoV-2 infection rate (25.93%) compared to the uninfected group (45.15%). Logistic regression analysis identified several risk factors associated with an increased risk of neonatal infection, including pregnancy BMI (OR 95%CI: 1.04[1.01, 1.08]), age at first pregnancy (OR 95%CI: 1.05[1.01, 1.10]), age at menarche (OR 95%CI: 1.13[1.02, 1.26]), and parturition (Yes vs. No) (OR 95%CI:1.4 [1.04,1.88]). Conclusion: Maternal vaccination and perinatal infection with SARS-CoV-2 play a protective role in preventing neonatal SARS-CoV-2 infection.

Diagnostic lncRNA high expression for liver patients prognosis and medication guidance: a systematic review and meta-analysis.

Background: The study of long non-coding RNAs (lncRNAs) has gained significant attention due to their roles in regulating gene expression and their potential as diagnostic biomarkers. This systematic review and meta-analysis aimed to evaluate the diagnostic value of high-expression lncRNAs in liver disease patients, including those with hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Methods: A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, up to July 2024. Studies were included if they investigated the expression of lncRNAs in liver disease patients and evaluated their diagnostic performance. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of included studies. Pooled sensitivity, specificity, diagnostic odds ratios (DOR), and summary receiver operating characteristic (SROC) curves were calculated using a bivariate random-effects model. Results: Nine studies involving 888 samples were included in the meta-analysis. The pooled hazard ratio (HR) for overall survival (OS) was 2.01 (95% CI: 1.71-2.36), indicating a significant association between high lncRNA expression and poor liver disease outcomes. Subgroup analyses revealed a pooled odds ratio (OR) of 1.99 (95% CI: 1.53-2.60) for tissue samples and 8.62 (95% CI: 1.16-63.71) for blood samples, suggesting a stronger diagnostic value for blood-based lncRNAs. The funnel plots indicated minimal publication bias, and sensitivity analyses confirmed the robustness of the findings. Conclusion: High-expression lncRNAs show significant potential as diagnostic biomarkers for liver diseases, offering non-invasive, accurate, and timely diagnostic information. Despite the promising results, further research is needed to standardize detection methods, elucidate the biological functions of lncRNAs, and validate their clinical utility in diverse patient populations. Integrating lncRNA biomarkers with traditional diagnostic approaches could enhance diagnostic accuracy and improve patient management and outcomes in liver disease.

Meteorin­like/meteorin­ß protects against cardiac dysfunction after myocardial infarction in mice by inhibiting autophagy.

Meteorin-ß (Metrnß) is a protein that is secreted by skeletal muscle and adipose tissue, and participates in cardiovascular diseases. However, its role in myocardial infarction (MI) has not been fully elucidated to date. The aim of the present study was to investigate the role and underlying mechanism of Metrnß in MI. In the present study, mice were subjected to left coronary ligation to induce a MI model before being injected with adeno-associated virus 9 (AAV9)-Metrnß to overexpress Metrnß. Mice were subjected to echocardiography and pressure-volume measurements 2 weeks after ligation. Cardiac injury was measured from the levels of cardiac troponin T and pro-inflammatory factors, which were detected using ELISA kits. Cardiac remodelling was determined from the cross-sectional areas detected using H&E and wheat germ agglutinin staining as well as from the transcriptional levels of hypertrophic and fibrosis markers detected using reverse transcription-quantitative PCR. Cardiac function was detected using echocardiography and pressure-volume measurements. In addition, H9c2 cardiomyocytes were transfected with Ad-Metrnß to overexpress Metrnß, before being exposed to hypoxia to induce ischaemic injury. Apoptosis was determined using TUNEL staining and caspase 3 activity. Cell inflammation was detected using ELISA assays for pro-inflammatory factors. Autophagy was detected using LC3 staining and assessing the protein level of LC3II using western blotting. H9c2 cells were also treated with rapamycin to induce autophagy. It was revealed that Metrnß expression was reduced in both mouse serum and heart tissue 2 weeks post-MI. Metrnß overexpression using AAV9-Metrnß delivery reduced the mortality rate, decreased the infarction size and reduced the extent of myocardial injury 2 weeks post-MI. Furthermore, Metrnß overexpression inhibited cardiac hypertrophy, fibrosis and inflammation post-MI. In ischaemic H9c2 cells, Metrnß overexpression using adenovirus also reduced cell injury, cell death and inflammatory response. Metrnß overexpression suppressed MI-induced autophagy in vitro. Following autophagy activation using rapamycin in vitro, the protective effects induced by Metrnß were reversed. Taken together, these results indicated that Metrnß could protect against cardiac dysfunction post-MI in mice by inhibiting autophagy.

ß-Thalassemia gene editing therapy: Advancements and difficulties.

ß-Thalassemia is the world's number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of ß-pearl protein chains. This results in intramedullary destruction and premature lysis of red blood cells in peripheral blood. Among them, patients with transfusion-dependent ß-thalassemia face the problem of long-term transfusion and iron chelation therapy, which leads to clinical complications and great economic stress. As gene editing technology improves, we are seeing the dawn of a cure for the disease, with its reduction of ineffective erythropoiesis and effective prolongation of survival in critically ill patients. Here, we provide an overview of ß-thalassemia distribution and pathophysiology. In addition, we focus on gene therapy and gene editing advances. Nucleic acid endonuclease tools currently available for gene editing fall into 3 categories: zinc finger nucleases, transcription activator-like effector nucleases, and regularly interspaced short palindromic repeats (CRISPR-Cas9) nucleases. This paper reviews the exploratory applications and exploration of emerging therapeutic tools based on 3 classes of nucleic acid endonucleases in the treatment of ß-thalassemia diseases.

Internet of things-based management versus standard management of home noninvasive ventilation in COPD patients with hypercapnic chronic respiratory failure: a multicentre randomized controlled non-inferiority trial.

Background: Effective monitoring and management are crucial during long-term home noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic chronic obstructive pulmonary disease (COPD). This study investigated the benefit of Internet of Things (IOT)-based management of home NPPV. Methods: This multicenter, prospective, parallel-group, randomized controlled non-inferiority trial enrolled patients requiring long-term home NPPV for hypercapnic COPD. Patients were randomly assigned (1:1), via a computer-generated randomization sequence, to standard home management or IOT management based on telemonitoring of clinical and ventilator parameters over 12 months. The intervention was unblinded, but outcome assessment was blinded to management assignment. The primary outcome was the between-group comparison of the change in health-related quality of life, based on severe respiratory insufficiency questionnaire scores with a non-inferiority margin of -5. This study is registered with Chinese Clinical Trials Registry (No. ChiCTR1800019536). Findings: Overall, 148 patients (age: 72.7 ± 6.8 years; male: 85.8%; forced expiratory volume in 1 s: 0.7 ± 0.3 L; PaCO2: 66.4 ± 12.0 mmHg), recruited from 11 Chinese hospitals between January 24, 2019, and June 28, 2021, were randomly allocated to the intervention group (n = 73) or the control group (n = 75). At 12 months, the mean severe respiratory insufficiency questionnaire score was 56.5 in the intervention group and 50.0 in the control group (adjusted between-group difference: 6.26 [95% CI, 3.71-8.80]; P < 0.001), satisfying the hypothesis of non-inferiority. The 12-month risk of readmission was 34.3% in intervention group compared with 56.0% in the control group, adjusted hazard ratio of 0.56 (95% CI, 0.34-0.92; P = 0.023). No severe adverse events were reported. Interpretation: Among stable patients with hypercapnic COPD, using IOT-based management for home NPPV improved health-related quality of life and prolonged the time to readmission. Funding: Air Liquide Healthcare (Beijing) Co., Ltd.

Serum oxidative biomarkers associated with genital HPV infection and cervical lesions in women.

Human papillomavirus (HPV) infection is a major cause of cervical cancer. Studies showed HPV carcinogenesis may be induced by oxidative stress affecting the host immune system. The objective of this study is to evaluate levels of four circulating oxidative stress biomarkers associated with the HPV infection, persistence, and cervical lesion status in women. The three serum biomarkers measuring oxidative damage to biomolecules (8-oxodG, 8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG] for DNA, 4-hydroxy-2-nonenal [4-HNE] for lipid, and protein carbonyl [PC] for protein) and one antioxidant (glutathione, GSH) collected from 38 women were evaluated. The PC levels were significantly higher for women with oncogenic HPV infection (p = 0.047) and persistence (p = 0.053) based on the unadjusted linear model. In particular, women with ≥3 oncogenic HPV types had a higher PC level than those without HPV infection (p = 0.041). Women with low-grade squamous intraepithelial lesions showed an elevated PC (p = 0.058). These trends remained similar after adjusting for age. The GSH levels were lower for women infected with ≥3 oncogenic HPV types based on age-adjusted results (p = 0.061). This study supported that serum PC was associated with HPV infection, persistence, and cervical lesions, so it can potentially be used to monitor HPV carcinogenesis. Further large-scale studies will be needed to confirm these findings.

Mechanism Exploration of Environmental Pollutants on Premature Ovarian Insufficiency: a Systematic Review and Meta-analysis.

As a public health problem, premature ovarian insufficiency leads to infertility or sub-fertility. In addition to premature ovarian insufficiency (POI) increases the lifetime risk of bone fragility, cardiovascular disease, and cognitive impairment. To investigate the effects of environmental pollutants on the occurrence of POI and explore its mechanism, we conducted a computer search for articles published in electronic databases by December 13, 2022. Three reviewers independently examined all included studies and scored the qualities of included studies using the Newcastle-Ottawa Scale criteria. In this meta-analysis, eight clinical studies as well as ten preclinical findings showed a pooled OR of 2.331 and 95% CI of 1.968-2.760. This confirms that environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI. In addition, it is demonstrated from the results of this study that signaling pathway of calcium and PI3K Akt and Xpnpep2, Col1, Col3, Col4, Cx43, Egr3, Tff1, and Ptgs2 genes may all be involved in the process. Environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI.

The Relationship Between Level of Education, Cognitive Function and Medication Adherence in Patients with Schizophrenia.

Purpose: Several studies have explored the relationship between level of education and medication adherence, as well as the relationship between level of education and cognitive function. However, there have been few studies on the relationships between level of education, cognitive function, and medication adherence. This study aimed to explore whether cognitive function has a mediating effect between level of education and medication adherence in patients with schizophrenia. Patients and Methods: A total of 329 participants were included in this study. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia, and medication adherence using the Medication Adherence Questionnaire. The relationships between the clinical factors and cognitive function that contributed to medication adherence were tested through multivariable linear regression analysis. The mediating effect of medication adherence was tested using the bootstrapping approach with the PROCESS macro. Results: Family history, insight and executive function were associated with medication adherence in individuals with schizophrenia, and executive function had a mediating effect between level of education and medication adherence. Conclusion: Adopting specific education programs that promote cognitive development as well as actively intervening in executive function might be conducive to improve medication adherence in patients with schizophrenia.

Dietary and Serum Antioxidants Associated with Prostate-Specific Antigen for Middle-Aged and Older Men.

High prostate-specific antigen (PSA) levels can indicate potential prostate problems and are a warning sign of prostate cancer. The impact of antioxidants on the PSA of generally healthy men is understudied. This study aims to evaluate 14 dietary and endogenous antioxidants associated with PSA levels for United States (US) men. We assessed 7398 men using the 2003-2010 US population-based National Health and Nutrition Examination Survey (NHANES). The PSA levels were categorized into three groups: Normal, borderline, and elevated levels. We performed analyses for middle-aged and older groups aged 40-64.9 and ≥65, respectively. The weighted multinomial regressions were performed to evaluate antioxidants associated with the PSA status. For results, 0.3% and 3.4% of middle-aged and older men, respectively, had elevated PSA (>10 ng/mL). Men with a higher serum albumin level had a lower risk of an elevated PSA, adjusting for age. The magnitude of albumin's impact on PSA is larger in middle-aged men than in older men (OR of elevated PSA = 0.82 and 0.90, respectively, interaction p = 0.002). Other antioxidants are not associated with PSA. Our findings support men with low serum albumin tend to have an elevated PSA level, so related interventions can be considered to decrease PSA for maintaining prostate health.

Ticlopidine induces embryonic development toxicity and hepatotoxicity in zebrafish by upregulating the oxidative stress signaling pathway.

Ticlopidine exerts its anti-platelet effects mainly by antagonizing platelet p2y12 receptors. Previously, a few studies have shown that ticlopidine can induce liver injury, but the exact mechanism of hepatotoxicity remains unclear. Oxidative stress, metabolic disorders, hepatocyte apoptosis, lipid peroxidation, and inflammatory responses can all lead to hepatic liver damage, which can cause hepatotoxicity. In this study, in order to deeply explore the potential molecular mechanisms of ticlopidine -induced hepatotoxicity, we used zebrafish as a model organism to comprehensively evaluate the hepatotoxicity of ticlopidine and its associated mechanism. Three days post-fertilization, zebrafish larvae were exposed to varying concentrations (1.5, 1.75 and 2 µg/mL) of ticlopidine for 72 h, in contrast, adult zebrafish were exposed exposure to 4 µg/mL of ticlopidine for 28 days. Ticlopidine-exposed zebrafish larvae showed changes in liver morphology, shortened body length, and delayed development of the swim bladder development. Liver tissues of ticlopidine-exposed zebrafish larvae and adults stained with Hematoxylin & Eosin revealed vacuolization and increased cellular interstitial spaces in liver tissues. Furthermore, using Oil Red O and periodic acid-Schiff staining methods and evaluating different metabolic enzymes of ticlopidine-exposed zebrafish larvae and adults suggested abnormal liver metabolism and liver injury in both ticlopidine-exposed zebrafish larvae and adults. Ticlopidine also significantly elevated inflammation and oxidative stress and reduced hepatocyte proliferation. During the rescue intervention using N-acetylcysteine, we observed significant improvement in ticlopidine-induced morphological changes in the liver, shortened body length, delayed swim bladder development, and proliferation of liver tissues showed significant improvement. In conclusion, ticlopidine might inhibit normal development and liver proliferation in zebrafish by upregulation of oxidative stress levels, thus leading to embryonic developmental toxicity and hepatotoxicity. In this study, we used zebrafish as a model organism to elucidate the developmental toxicity and hepatotoxicity induced by ticlopidine upregulation of oxidative stress signaling pathway in zebrafish, providing a theoretical basis for clinical application.

Screening biomarkers for predicting the efficacy of immunotherapy in patients with PD-L1 overexpression.

PURPOSE: Immunotherapy plays an important role in non-small cell lung cancer (NSCLC); in particular, immune checkpoint inhibitors (ICIs) therapy has good therapeutic effects in PD-L1-positive patients. This study aims to screen NSCLC patients with PD-L1-positive expression and select effective biomarkers for ICI immunotherapy. METHODS: Collected tumor samples from the Affiliated Cancer Hospital of Xinjiang Medical University and 117 patients with stage III-IV NSCLC were included in the study. All patients were on first- or second-line therapy and not on targeted therapy. Based on the molecular profiles and clinical features, we screened biomarkers for predicting the efficacy of immunotherapy in patients with PD-L1 overexpression. RESULTS: 117 NSCLC patients receiving ICIs immunotherapy were enrolled. First, we found that immunotherapy was more effective in patients with positive PD-L1 expression. Second, we found that ROS1 gene mutations, KRAS gene mutations, tumor stage, and the endocrine system diseases history are independent prognostic factors for PD-L1 positive patients. Then we combined independent risk factors and constructed a new Nomogram to predict the therapeutic efficacy of ICIs immunotherapy in PD-L1 positive patients. The Nomogram integrates these factors into a prediction model, and the predicted C-statistic of 3 months, 6 months and 12 months are 0.85, 0.84 and 0.85, which represents the high predictive accuracy of the model. CONCLUSIONS: We have established a model that can predict the efficacy of ICIs immunotherapy in PD-L1 positive patients. The model consists of ROS1 gene mutations, KRAS gene mutations, tumor staging, and endocrine system disease history, and has good predictive ability.

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer.

Background: Colorectal cancer (CRC) is a heterogeneous cancer. Its treatment depends on its anatomical site and molecular features. Carcinomas of the rectosigmoid junction are frequent; however, specific data on these tumors are sparse, as they are frequently assigned to either the colon or rectum. This study sought to identify the molecular features of rectosigmoid junction cancer to determine whether there should be any difference between the therapeutic management of rectosigmoid junction cancer and that of sigmoid colon or rectum cancer. Methods: The data of 96 CRC patients with carcinomas in the sigmoid colon, rectosigmoid junction, and rectum were retrospectively summarized. The next-generation sequencing (NGS) data of the patients were analyzed to study the molecular characteristics of the carcinomas in different locations of the bowel. Results: In total, there was no difference in the clinicopathologic characteristics of the three groups. TP53, APC, and KRAS genes were the top 3 alteration genes in sigmoid colon, rectosigmoid junction, and rectum cancer. The rates of the KRAS, NRAS, and PIK3CA increased as the location moved distally, while the rates of APC and BRAF decreased. Almost no significant molecular differences were found among the three groups. The prevalence of the FLT3, fms-related tyrosine kinase 1 (FLT1), and phosphoenolpyruvate carboxykinase 1 (PCK1) mutation was lower in the rectosigmoid junction group than the sigmoid colon and rectum groups (P>0.05). The proportion of the transforming growth factor beta pathway was higher in the rectosigmoid junction and rectum groups than the sigmoid colon group (39.3% vs. 34.3% vs. 18.2%, respectively, P=0.121, P=0.067, P=0.682); a higher proportion of MYC pathway was also observed in the rectosigmoid junction than that in rectum and sigmoid colon (28.6% vs. 15.2% vs. 17.1%, P=0.278, P=0.202, P=0.171). Regardless of the clustering method employed, the patients were divided into two clusters, and the composition of clusters revealed no significant differences in terms of the different locations. Conclusions: Rectosigmoid junction cancer has a distinctive molecular profile compared to the molecular profiles of the adjacent bowel segment cancers.

Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy.

Purpose: To determine the mechanism that long noncoding RNA NEAT1 (lncNEAT1)/miR-320a competitive endogenous RNA (ceRNA) network regulates hypoxia-inducible factor-1α (HIF-1α) in ARPE-19 cells and its potential role in diabetic retinopathy (DR). Methods: ARPE-19 cells were cultured in a normal or high-glucose (HG) medium, and cell migration, invasion, and permeability were detected by scratch, transwell, and FITC-dextran staining assays. LncNEAT1, HIF-1α, ZO-1, occludin, N-cadherin, and vimentin levels were tested. The binding of lncNEAT1 to miR-320a was verified by dual-luciferase reporter assay, and the binding of miR-320a to HIF-1α by RIP assay. ARPE-19 cells were treated with lncNEAT1 or HIF-1α shRNA or miR-320a agomir to determine the activation of ANGPTL4/p-STAT3 pathway. The effect of lncNEAT1 in DR and its regulations on miR-320a and HIF-1α were determined in a rat model of DR. Results: HG treatment promoted the migration, invasion, and permeability of ARPE-19 cells. After lncNEAT1 silencing, HIF-1α, N-cadherin, and vimentin levels were downregulated, ZO-1 and occludin levels were upregulated, and the migration, permeability, and invasion of HG-treated ARPE-19 cells were inhibited. However, HIF-1α overexpression increased N-cadherin and vimentin expression, reduced ZO-1 and occludin expression, and promoted the migration, permeability, and invasion of ARPE-19 cells. The binding of miR-320a with both lncNEAT1 and HIF-1α was predicted and confirmed. In a diabetic rat model, silencing lncNEAT1 inhibited HIF-1α/ANGPTL4/p-STAT3 pathway activation and alleviated retinopathy. Conclusions: The lncNETA1/miR-320a/HIF-1α ceRNA network activates the ANGPTL4/p-STAT3 pathway and promotes HG-induced ARPE-19 cell invasion and migration.

Protective Effect and Mechanism of Autophagy in Endothelial Cell Injury Induced by Hyperoxia.

OBJECTIVE: Bronchopulmonary dysplasia is a chronic lung disease in premature infants with alveolar simplification and pulmonary vascular development disorder as the main pathological feature and hyperoxia as the main etiology. Autophagy is a highly conserved cytological behavior of self-degrading cellular components and is accompanied by oxidative stress. Studies have reported that autophagy is regulated by FOXO1 posttranslational modification. However, whether autophagy can be involved in the regulation of endothelial cell injury induced by hyperoxia and its mechanism are still unclear. STUDY DESIGN: We have activated and inhibited autophagy in human umbilical vein endothelial cells under hyperoxia and verified the role of autophagy in endothelial cell-related functions from both positive and negative aspects. RESULTS: Our research showed that the expression level of autophagy-related proteins decreased, accompanied by decreased cell migration ability and tube formation ability and increased cell reactive oxygen species level and cell permeability under hyperoxia conditions. Using an autophagy agonist alleviated hyperoxia-induced changes and played a protective role. However, inhibition of autophagy aggravated the cell damage induced by hyperoxia. Moreover, the decrease in autophagy proteins was accompanied by the upregulation of FOXO1 phosphorylation and acetylation. CONCLUSION: We concluded that autophagy was a protective mechanism against endothelial cell injury caused by hyperoxia. Autophagy might participate in this process by coregulating posttranslational modifications of FOXO1. KEY POINTS: · Hyperoxia induces vascular endothelial cell injury.. · Autophagy may has a protective role under hyperoxia conditions.. · FOXO1 posttranslational modification may be involved in the regulation of autophagy..

Automatic depression severity assessment with deep learning using parameter-efficient tuning.

Introduction: To assist mental health care providers with the assessment of depression, research to develop a standardized, accessible, and non-invasive technique has garnered considerable attention. Our study focuses on the application of deep learning models for automatic assessment of depression severity based on clinical interview transcriptions. Despite the recent success of deep learning, the lack of large-scale high-quality datasets is a major performance bottleneck for many mental health applications. Methods: A novel approach is proposed to address the data scarcity problem for depression assessment. It leverages both pretrained large language models and parameter-efficient tuning techniques. The approach is built upon adapting a small set of tunable parameters, known as prefix vectors, to guide a pretrained model towards predicting the Patient Health Questionnaire (PHQ)-8 score of a person. Experiments were conducted on the Distress Analysis Interview Corpus - Wizard of Oz (DAIC-WOZ) benchmark dataset with 189 subjects, partitioned into training, development, and test sets. Model learning was done on the training set. Prediction performance mean and standard deviation of each model, with five randomly-initialized runs, were reported on the development set. Finally, optimized models were evaluated on the test set. Results: The proposed model with prefix vectors outperformed all previously published methods, including models which utilized multiple types of data modalities, and achieved the best reported performance on the test set of DAIC-WOZ with a root mean square error of 4.67 and a mean absolute error of 3.80 on the PHQ-8 scale. Compared to conventionally fine-tuned baseline models, prefix-enhanced models were less prone to overfitting by using far fewer training parameters (<6% relatively). Discussion: While transfer learning through pretrained large language models can provide a good starting point for downstream learning, prefix vectors can further adapt the pretrained models effectively to the depression assessment task by only adjusting a small number of parameters. The improvement is in part due to the fine-grain flexibility of prefix vector size in adjusting the model's learning capacity. Our results provide evidence that prefix-tuning can be a useful approach in developing tools for automatic depression assessment.

Impact of Dietary Quality on Genital Oncogenic Human Papillomavirus Infection in Women.

BACKGROUND: Most cervical cancers are directly linked to oncogenic or high-risk human papillomavirus (HR-HPV) infection. This study evaluates associations between diet quality and genital HPV infection in women. METHODS: This study included 10 543 women from the 2003-2016 National Health and Nutrition Examination Survey. The outcome was the genital HPV infection status (HPV-negative, low-risk [LR] HPV, and HR-HPV). Dietary quality was evaluated using the Healthy Eating Index (HEI), in which a higher score indicates a better diet quality. RESULTS: Women who did not consume total fruits (15.8%), whole fruits (27.5%), or green vegetables and beans (43%) had a significantly higher risk of HR-HPV infection than women who complied with the Dietary Guidelines for Americans (HR-HPV odds ratio = 1.76, 1.63, and 1.48 for a HEI score of 0 vs 5, respectively) after adjusting confounding factors. Similar results of these food components on LR-HPV infection were found. In addition, intake of whole grains and dairy was inversely associated with LR-HPV infection. CONCLUSIONS: This study showed that women who did not eat fruits, dark-green vegetables, and beans had a higher risk of genital HR-HPV infection. Intake of these food components is suggested for women to prevent HPV carcinogenesis.

MicroRNA-130a-3p impedes the progression of papillary thyroid carcinoma through downregulation of KPNB1 by targeting PSME3.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the main type of thyroid cancer (THCA). Despite the good prognosis, some PTC patients may deteriorate into more aggressive disease, leading to poor survival. Our study aimed to explore the role of microRNA (miR)-130a-3p in regulating PTC. METHODS: After transfection with miR-130a-3p-mimic, OE-PSME3, or miR-130a-3p-mimic + OE-KPNB1 in PTC cells (TPC-1), CCK-8, Transwell, scratch, and flow cytometry experiments were performed to analyze TPC-1 cell proliferation, invasion, migration, and apoptosis. Western blotting was used to detect proliferation or invasion-related protein markers (PCNA, E-cadherin, and N-cadherin). The RNA22 database, dual-luciferase reporter assay, and RNA pull-down assay were applied for the prediction and verification of the binding site between miR-130a-3p and PSME3. Pan-cancer software identified a positive correlation between PSME3 and KPNB1 in THCA. Co-immunoprecipitation was utilized to verify the interaction of PSME3 with KPNB1. Nude mice were transplanted with TPC-1 cells overexpressing miR-130a-3p. The tumors were isolated for detection of the expression of miR-130a-3p, PSME3, KPNB1, Ki-67, and CD31. RESULTS: miR-130a-3p was lowly expressed in PTC cell lines. Upregulation of miR-130a-3p repressed the expression of PSME3 and KPNB1 and reduced the malignancy of TPC-1 cells in vitro, shown by inhibited cell proliferation, invasion, migration, and the expression of PCNA and N-cadherin. Also, overexpressed miR-130a-3p inhibited the growth of xenograft tumors in nude mice. miR-130a-3p bound to PSME3 which interacted with KPNB1. CONCLUSION: miR-130a-3p impedes the progression of PTC by downregulating PSME3/KPNB1.