Comparative efficacy of THR-ß agonists, FGF-21 analogues, GLP-1R agonists, GLP-1-based polyagonists, and Pan-PPAR agonists for MASLD: A systematic review and network meta-analysis.

AIMS: To compare the efficacy of thyroid hormone receptor beta (THR-ß) agonists, fibroblast growth factor 21 (FGF-21) analogues, glucagon-like peptide-1 receptor agonists (GLP-1RAs), GLP-1-based polyagonists, and pan-peroxisome proliferator-activated receptor (Pan-PPAR) agonists in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: A database search for relevant randomized double-blind controlled trials published until July 11, 2024, was conducted. Primary outcomes were the relative change in hepatic fat fraction (HFF) and liver stiffness assessed non-invasively by magnetic resonance imaging proton density fat fraction and elastography. Secondary outcomes included histology, liver injury index, lipid profile, glucose metabolism, blood pressure, and body weight. RESULTS: Twenty-seven trials (5357 patients with MASLD) were identified. For HFF reduction, GLP-1-based polyagonists were most potentially effective (mean difference [MD] -51.47; 95 % confidence interval [CI]: -68.25 to -34.68; surface under the cumulative ranking curve [SUCRA] 84.9) vs. placebo, followed by FGF-21 analogues (MD -47.08; 95 % CI: -58.83 to -35.34; SUCRA 75.5), GLP-1R agonists (MD -37.36; 95 % CI: -69.52 to -5.21; SUCRA 52.3) and THR-ß agonists (MD -33.20; 95 % CI: -43.90 to -22.51; SUCRA 36.9). For liver stiffness, FGF-21 analogues were most potentially effective (MD -9.65; 95 % CI: -19.28 to -0.01; SUCRA 82.2) vs. placebo, followed by THR-ß agonists (MD -5.79; 95 % CI: -9.50 to -2.09; SUCRA 58.2), and GLP-1RAs (MD -5.58; 95 % CI: -15.02 to 3.86; SUCRA 54.7). For fibrosis improvement in histology, GLP-1-based polyagonists were most potentially effective, followed by FGF-21 analogues, THR-ß agonists, Pan-PPAR agonists, and GLP-1R agonists; For MASH resolution in histology, GLP-1-based polyagonists were most potentially effective, followed by THR-ß agonists, GLP-1R agonists, FGF-21 analogues, and Pan-PPAR agonists. THR-ß agonists are well-balanced in liver steatosis and fibrosis, and excel at improving lipid profiles; FGF-21 analogues are effective at improving steatosis and particularly exhibit strong antifibrotic abilities. GLP-1R agonists showed significant benefits in improving liver steatosis, glucose metabolism, and body weight. GLP-1-based polyagonists have demonstrated the most potential efficacy overall in terms of comprehensive curative effect. Pan-PPAR agonists showed distinct advantages in improving liver function and glucose metabolism. CONCLUSION: These results illustrate the relative superiority of the five classes of therapy in the treatment of MASLD and may serve as guidance for the development of combination therapies.

FTH1P8 induces and transmits docetaxel resistance by inhibiting ferroptosis in prostate cancer.

Overcoming docetaxel resistance remains a significant challenge in the management of prostate cancer. Previous studies have confirmed a link between ferroptosis and the development of docetaxel resistance. This study revealed that docetaxel-resistant prostate cancer cells presented increased FTH1P8 expression compared with docetaxel-sensitive cells. Decreasing the level of FTH1P8 counteracted docetaxel resistance and facilitated docetaxel-induced ferroptosis, which is characterized by an increase in intracellular Fe2+ concentration, lipid peroxidation levels (lipid ROS), reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) production and mitochondrial damage, a decrease in the Fe3+ concentration and glutathione (GSH) content, and the ability to inhibit hydroxyl radical (·OH) and the mitochondrial membrane potential (MMP). Conversely, increasing the level of FTH1P8 had the opposite effect. A positive correlation was revealed between the expression of FTH1P8 and its parental gene FTH1 in prostate cancer tissues in The Cancer Genome Atlas (TCGA) database. Molecular investigations revealed that FTH1P8 expression increased through miR-1252-5p. Furthermore, rescue experiments confirmed that FTH1 mediated the inhibitory effect of FTH1P8 on ferroptosis. Moreover, FTH1P8 was discovered to play a role in the spread of docetaxel resistance via exosomes. Docetaxel-siRNA targeting FTH1P8 (siFTH1P8)-nanoliposomes (DOC-siFTH1P8-LIP), which can codeliver docetaxel and siFTH1P8, significantly inhibited docetaxel resistance in cells. These results indicated that FTH1P8 can function as both an indicator and a treatment target for docetaxel resistance. The use of DOC-siFTH1P8-LIP demonstrated promising therapeutic effects on docetaxel-resistant cells, suggesting a novel option for treating docetaxel-resistant prostate cancer.

Development and Validation of a Nomogram for Evaluating the Incident Risk of Pain Catastrophizing Among Patients Who Have Severe Knee Osteoarthritis Awaiting Primary Total Knee Arthroplasty.

BACKGROUND: It is clinically important to anticipate the likelihood of pain catastrophizing in patients who undergo total knee arthroplasty (TKA). Persistent pain and diminished physical function following TKA are independently associated with preoperative pain catastrophizing. The purpose of this study was to develop and validate a nomogram model to predict pain catastrophizing in patients who have severe osteoarthritis undergoing primary TKA. METHODS: Data were collected from patients who have severe osteoarthritis undergoing primary TKA at four tertiary general hospitals in Changsha, China, from September to December 2023. The study cohort was randomly divided into a training group and a validation group in the proportion of 70 to 30%. Least absolute shrinkage and selection operator regression analysis was utilized to select the optimal predictive variables for the model. A nomogram model was created using independent risk factors that were identified through multivariate regression analysis. Their performance was assessed using the concordance index and calibration curves, and their clinical utility was analyzed using decision curve analysis. RESULTS: A total of 416 patients were included, 291 in the training group and 125 in the validation group. There were 115 (27.6%) who had pain catastrophizing. The predictors contained in the nomogram were pain intensity during activity, anxiety and depression, body mass index, social support, and household. The area under the curve of the nomogram was 0.976 (95% confidence interval = 0.96 to 0.99) for the training group and 0.917 (95% confidence interval = 0.88 to 0.96) for the validation group. The calibration curves confirmed the nomogram's accuracy, and decision curve analysis showed its strong predictive performance. CONCLUSIONS: The comprehensive nomogram generated in this study was a valid and easy-to-use tool for assessing the risk of pain catastrophizing in preoperative TKA patients, and helped healthcare professionals to screen the high-risk population.

Transcriptome analysis reveals the anti-Parkinson's activity of Mangiferin in zebrafish.

As the global population ages, the incidence of Parkinson's Disease (PD) continues to rise, imposing significant social and economic burdens. Mangiferin (MGF), a polyphenolic, bioactive compound has been shown to play a role in the prevention and treatment of PD. This study investigates the neuroprotective effects of MGF in an MPTP-induced zebrafish model of PD through transcriptome analysis. Initially, optimal concentrations for modeling were determined using various MPTP and MGF combinations. The zebrafish were then divided into control, MPTP-treated, and MGF co-treated groups. Subsequent evaluations included hatching rates, mortality rates, growth and development conditions, spontaneous motor abilities, as well as measurements of enzymatic activities of SOD, CAT, and levels of GSH. Ultimately, the therapeutic efficacy of MGF on the PD model in zebrafish was assessed through transcriptome sequencing. The results demonstrated that MPTP treatment induced PD-associated symptoms in zebrafish, while MGF treatment significantly improved the motor abilities and survival rates of the PD model zebrafish, effectively reducing oxidative stress and ameliorating PD symptoms. Transcriptome sequencing further revealed that MGF may mitigate mitochondrial-related oxidative stress in PD zebrafish by modulating the expression of critical genes including lrrk2, vps35, atp13a, dnajc6, and uchl1. Differential gene expression analysis indicated that these genes are primarily involved in vital signaling pathways, such as neuroactive ligand-receptor interaction, and the calcium signaling pathway. In summary, our study provides robust scientific evidence supporting MGF as a potential therapeutic candidate for PD by preserving mitochondrial homeostasis and elucidating its mechanisms of action.

Evaluating PAX1 methylation for cervical cancer screening triage in non-16/18 hrHPV-positive women.

BACKGROUND: In China, the national cervical cancer screening protocol involves initial testing for high-risk human papillomavirus (hrHPV), followed by cytology for hrHPV-positive cases. This study evaluates the effectiveness of PAX1 methylation (PAX1m) analysis in identifying precancerous or cancerous lesions in cervical samples from Chinese women positive for non-16/18 hrHPV strains. METHODS: Between February 2022 and March 2023, 281 cervical samples from non-16/18 hrHPV-positive women underwent cytological examination and PAX1m analysis. The study assessed the statistical relationship between PAX1m levels and the presence of cervical lesions, comparing the diagnostic performance of PAX1m to conventional cytology. RESULTS: A significant association was found between PAX1 methylation levels and the risk of CIN2 + and CIN3 + lesions, with 47 instances of CIN2 + detected. Odds ratios (ORs) for moderate and high PAX1m levels were 8.86 (95% CI: 2.24-42.17) and 166.32 (95% CI: 47.09-784.97), respectively. The area under the ROC curve for PAX1m in identifying CIN2 + lesions was 0.948 (95% CI: 0.895-0.99). PAX1m demonstrated similar sensitivity and negative predictive value (NPV) to cytology but reduced the colposcopy referral rate from 47.7% with cytology alone to 25.6% with PAX1m, showing superior specificity and positive predictive value across age groups. CONCLUSIONS: PAX1 methylation is a strong indicator of CIN2 + and CIN3 + risk, offering diagnostic performance comparable to cytology with the added benefit of reduced unnecessary colposcopy referrals. These findings support the use of PAX1m analysis as a reliable tool for triaging non-16/18 hrHPV-positive women in outpatient settings.

[Active constituents of essential oil from Curcuma phaeocaulis for treatment of dysmenorrhea].

This study aims to identify the active constituents of essential oil from the rhizomes of Curcuma phaeocaulis for the treatment of dysmenorrhea. The compounds were separated and purified by molecular distillation, silica gel and Sephadex LH-20 column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography. Their structures were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. The animal model of primary dysmenorrhea and the contraction model of isolated uterine smooth muscle of rats were established to examine the active constituents in the essential oil for treating dysmenorrhea. Six sesquiterpenes were isolated and identified as dehydrocommiterpene A(1), comosone Ⅱ(2), 5α(H)-eudesma-3(4),7(11)-dien-9ß-ol-6-one(3), guaia-6(7)-en-11-ol(4), curcumenol(5), and isocurcumenol(6), among which compound 1 was a novel compound. The animal experiments showed that the essential oil from C. phaeocaulis significantly lowered the level of PGF_(2α) in uterine tissue compared with the model group. The experiment with the contraction model of isolated uterine smooth muscle demonstrated that the components with high boiling points outperformed those with low boiling points in relaxing the uterine smooth muscle, and compounds 1, 2, 5, and 6 isolated from the fraction with a high boiling point had the effect of relaxing the uterine smooth muscle. Among them, compounds 5 and 6 inhibited the extracellular Ca~(2+) influx and intracellular Ca~(2+) release to relax the uterine smooth muscle. In conclusion, the components with high boiling points and sesquiterpenes are the active components in the essential oil of C. phaeocaulis for treating dysmenorrhea.

A strategy to build a library of oil tracers by oleophilic silica-encapsulated DNA nanoparticles.

Artificially synthesized DNA is involved in the construction of a library of oil tracers due to their unlimited number and no-biological toxicity. The strategy of the construction is proposed by oleophilic Silica-encapsulated DNA nanoparticles, which offers fresh thinking in developing novel tracers, sensors, and molecular machines in engineering & applied sciences based on artificially synthesized DNA blocks.

Automatic in situ short-distance deposition of PLGA/PLLA composite nanofibrous membranes for personalized wound dressings.

Improving the mechanical properties of wound dressings and achieving personalized automatic real-time in situ deposition are important for accelerating wound management and repair. In this study, we report a self-designed automatic in situ deposition device based on solution blow spinning (SBS) to prepare poly(lactic-co-glycolic acid) (PLGA) and poly-L-lactic acid (PLLA) composite (PLGA/PLLA) nanofibrous membranes for wound dressing at a short distance. Polymer solution and in situ deposition conditions, including air pressure, spinning distance, solvent extrusion rate, and spinning rate, were optimized using orthogonal experiments and characterized via dynamic mechanical analysis. The microscopic morphology and physical properties of the prepared PLGA/PLLA composite nanofibrous membranes show that their strength, adhesion, water vapor transmission rate (WVTR), water retention, water absorption, degradation, and other properties were sufficient for wound-dressing applications. To investigate the possibility of a biomedical wound-dressing material, tannic acid (TA) was incorporated into the PLGA/PLLA composite nanofibrous membranes. The resultant PLGA/PLLA/TA composite nanofibrous membranes exhibited good biocompatibility and exceptional antibacterial properties against both Escherichia coli and Staphylococcus aureus. A pilot animal study illustrated the potential of this in situ deposition of PLGA/PLLA/TA composite nanofibrous membranes across multiple applications in wound healing/repair by reducing wound scar tissue formation and fibroblast overactivation.

Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Evaluation of endometrial receptivity in women with unexplained infertility by shear wave elastography.

OBJECTIVES: The endometrium of most unexplained infertility (UI) patients has been altered histologically. Shear wave elastography (SWE) is utilized to assess the signature of living tissue. This study aimed to explore the value of SWE in evaluating endometrial receptivity (ER) in UI patients. METHODS: In total, 59 UI patients (UI group) and 52 normal control women (NC group) who received fertility consultation in our hospital were included between January 2022 and June 2023. We divided them into the late-proliferative phase of UI group (LPUI; n = 59), mid-secretory phase of UI group (MPUI; n = 41), late-proliferative phase of NC group (LPNC; n = 52), and mid-secretory phase of NC group (MPNC; n = 45). Transvaginal ultrasonography and SWE were performed during the LP and MP. Endometrial thickness (EMT), uterine artery pulsatility index (UA-PI), endometrial mean elasticity (E-mean), and mean shear wave velocities (SWV-mean) were measured. RESULTS: There were significant differences in E-mean, SWV-mean, EMT, and UA-PI between the UI group and the NC group during both the LP and MP (p MPNC vs MPUI < 0.05, p LPNC vs LPUI < 0.05). E-mean and SWV-mean decreased with increasing EMT but increased with increasing UA-PI (p < 0.05). The most effective parameter for evaluating ER in UI patients is the E-mean (AUC = 0.89). CONCLUSIONS: UI patients exhibited thinner endometrium, increased endometrial stiffness, and poor endometrial blood perfusion. E-mean was the most effective parameter to evaluate ER in UI patients. The study preliminarily proved that SWE is a promising non-invasive tool for evaluating the condition of endometrium. CRITICAL RELEVANCE STATEMENT: This study aimed to explore the significance of endometrial elasticity measured by SWE in evaluating patients with UI. The findings revealed a correlation between EMT, UA-PI, and E-mean. Endometrial elasticity can serve as an effective indicator for predicting ER. KEY POINTS: 1. To explore the significance of endometrial elasticity in assessing patients with UI. 2. The endometrium of UI patient exhibited thinness, stiffness, and poor blood perfusion. 3. Endometrial elasticity serves as a valuable indicator for evaluating endometrial receptivity.

RNA editing events and expression profiles of mitochondrial protein-coding genes in the endemic and endangered medicinal plant, Corydalis saxicola.

Corydalis saxicola, an endangered medicinal plant endemic to karst habitats, is widely used in Traditional Chinese Medicine to treat hepatitis, abdominal pain, bleeding hemorrhoids and other conditions. However, to date, the mitochondrial (mt) genome of C. saxicola has not been reported, which limits our understanding of the genetic and biological mechanisms of C. saxicola. Here, the mt genome of C. saxicola was assembled by combining the Nanopore and Illumina reads. The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. Twelve homologous fragments were identified between the mt and ct genomes of C. saxicola, accounting for 1.04% of the entire mt genome. Phylogenetic examination of the mt genomes of C. saxicola and 30 other taxa provided an understanding of their evolutionary relationships. We also predicted 779 RNA editing sites in 40 C. saxicola mt PCGs and successfully validated 506 (65%) of these using PCR amplification and Sanger sequencing. In addition, we transcriptionally profiled 24 core mt PCGs in C. saxicola roots treated with different concentrations of CaCl2, as well as in other organs. These investigations will be useful for effective utilization and molecular breeding, and will also provide a reference for further studies of the genus Corydalis.

Prediction of cervical lymph node metastasis in solitary papillary thyroid carcinoma based on ultrasound radiomics analysis.

Objective: To assess the utility of predictive models using ultrasound radiomic features to predict cervical lymph node metastasis (CLNM) in solitary papillary thyroid carcinoma (PTC) patients. Methods: A total of 570 PTC patients were included (456 patients in the training set and 114 in the testing set). Pyradiomics was employed to extract radiomic features from preoperative ultrasound images. After dimensionality reduction and meticulous selection, we developed radiomics models using various machine learning algorithms. Univariate and multivariate logistic regressions were conducted to identify independent risk factors for CLNM. We established clinical models using these risk factors. Finally, we integrated radiomic and clinical models to create a combined nomogram. We plotted ROC curves to assess diagnostic performance and used calibration curves to evaluate alignment between predicted and observed probabilities. Results: A total of 1561 radiomics features were extracted from preoperative ultrasound images. After dimensionality reduction and feature selection, 16 radiomics features were identified. Among radiomics models, the logistic regression (LR) model exhibited higher predictive efficiency. Univariate and multivariate logistic regression results revealed that patient age, tumor size, gender, suspicious cervical lymph node metastasis, and capsule contact were independent predictors of CLNM (all P < 0.05). By constructing a clinical model, the LR model demonstrated favorable diagnostic performance. The combined model showed superior diagnostic efficacy, with an AUC of 0.758 (95% CI: 0.712-0.803) in the training set and 0.759 (95% CI: 0.669-0.849) in the testing set. In the training dataset, the AUC value of the nomogram was higher than that of the clinical and radiomics models (P = 0.027 and 0.002, respectively). In the testing dataset, the AUC value of the nomogram model was also greater than that of the radiomics models (P = 0.012). However, there was no significant statistical difference between the nomogram and the clinical model (P = 0.928). The calibration curve indicated a good fit of the combined model. Conclusion: Ultrasound radiomics technology offers a quantitative and objective method for predicting CLNM in PTC patients. Nonetheless, the clinical indicators persists as irreplaceable.

Purification of the secondary treatment tail water for wastewater reclamation by integrated subsurface-constructed wetlands.

A whole-year investigation of full-scale integrated subsurface-constructed wetlands (ISCWs) was carried out to purify the tail water from a wastewater treatment plant (WWTP) for wastewater reclamation under four plant species, four hydraulic loading rates (HLRs), and four seasons. The results showed that ISCWs were effective for the purification of WWTP discharge, with the average removal efficiencies of COD, NH4+-N, TN, and TP being 48%, 49%, 9%, and 30%, respectively. Typical pollutant concentrations in the treated effluent of ISCWs were 8.19 mg/L COD, 1.76 mg/L NH4+-N, 11.57 mg/L TN, and 0.36 mg/L TP, which met most of the water quality standards for reusing recycling water. Emergent plants with well-developed root systems may be capable of promoting the decontamination of ISCWs. Seasonal change played an important role in the treatment process: the removal of phosphorus by plant uptake and microbial utilization was more active in the warm season and the co-occurrence of organic degradation and nitrification, whereas the cold season is conducive to exothermic adsorption process of pollutants to substrates. Properly increasing the HLRs may improve the availability of ISCWs according to the requirement of effluent quality. Furthermore, the C/N ratio might be the key factor for the purification effect of ISCWs, because the COD level of WWTP discharge may change the process of NH4+-N biotransformation.

Essential oil from Ligusticum chuanxiong Hort. Alleviates lipopolysaccharide-induced neuroinflammation: Integrating network pharmacology and molecular mechanism evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong, the rhizome of Ligusticum chuanxiong Hort., is an ancient herbal medicine that has gained extensive popularity in alleviating migraines with satisfying therapeutic effects in China. As the major bioactive component of Chuanxiong, the essential oil also exerts a marked impact on the treatment of migraine. It is widely recognized that neuroinflammation contributes to migraine. However, it remains unknown whether Chuanxiong essential oil has anti-neuroinflammatory activity. AIM OF THE STUDY: To explore the anti-neuroinflammatory properties of Chuanxiong essential oil and its molecular mechanisms by network pharmacology analysis and in vitro experiments. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical components of Chuanxiong essential oil. Public databases were used to predict possible targets, build the protein-protein interaction network (PPI), and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Moreover, cytological experiments, nitric oxide assay, enzyme-link immunosorbent assay, western blotting, and immunofluorescence assay were adopted to prove the critical signaling pathway in lipopolysaccharide (LPS)-induced BV2 cells. RESULTS: Thirty-six compounds were identified from Chuanxiong essential oil by GC-MS, and their corresponding putative targets were predicted. The network pharmacology study identified 232 candidate targets of Chuanxiong essential oil in anti-neuroinflammation. Furthermore, Chuanxiong essential oil was found to potentially affect the C-type lectin receptor, FoxO, and NF-κB signaling pathways according to the KEGG analysis. Experimentally, we verified that Chuanxiong essential oil could significantly reduce the overproduction of inflammatory mediators and pro-inflammatory factors via the NF-κB signaling pathway. CONCLUSION: Chuanxiong essential oil alleviates neuroinflammation through the NF-κB signaling pathway, which provides a theoretical foundation for a better understanding of the clinical application of Chuanxiong essential oil in migraine treatment.

Comprehensive Analyses and Experiments Confirmed IGFBP5 as a Prognostic Predictor Based on an Aging-genomic Landscape Analysis of Ovarian Cancer.

BACKGROUND: Ovarian cancer (OC) is one of the malignant diseases of the reproductive system in elderly women. Aging-related genes (ARGs) were involved in tumor malignancy and cellular senescence, but the specifics of these mechanisms in OC remain unknown. METHODS: ARGs expression and survival data of OC patients were collected from TCGA and CPTAC databases. Subtype classification was used to identify the roles of hub ARGs in OC progression, including function enrichment, immune infiltration, and drug sensitivity. LASSO regression was utilized to confirm the prognosis significance for these hub ARGs. MTT, EdU, Transwell, and wounding healing analysis confirmed the effect of IGFBP5 on the proliferation and migration ability of OC cells. RESULTS: ARGs were ectopically expressed in OC tissues compared to normal ovary tissues. Three molecular subtypes were divided by ARGs for OC patients. There were significant differences in ferroptosis, m6A methylation, prognosis, immune infiltration, angiogenesis, differentiation level, and drug sensitivity among the three groups. LASSO regression indicated that 4 signatures, FOXO4, IGFBP5, OGG1 and TYMS, had important prognosis significance. Moreover, IGFBP5 was significantly correlated with immune infiltration. The hub ARG, IGFBP5, expression was significantly decreased in OC patients compared to normal women. IGFBP5 could also reduce the migration and proliferation ability of OC cells compared to vector and NC groups. CONCLUSION: IGFBP5 was correlated with OC prognosis and associated with OC migration and proliferation. This gene may serve as potential prognostic biomarkers and therapeutic targets for OC patients.

Effect of visual perception training on binocular visual function reconstruction in patients after strabismus surgery.

AIM: To explore the effect of visual perception learning software training (VPT) on binocular visual function reconstruction in children with intermittent exotropia after strabismus surgery. METHODS: Ninety children with intermittent exotropia admitted to our hospital from June 2018 to December 2018 were included, and randomly divided into VPT and control groups. Children in the control group received basic binocular vision training, while those in the VPT group received VPT after strabismus surgery. Tertiary visual function, visual perception function, Newcastle Control Score (NCS), and ocular position retraction rate were compared at 3 and 12mo after the surgery. RESULTS: At 3 and 12mo after the surgery, the proportion of simultaneous perception, binocular fusion version and binocular stereo vision in the VPT group was conspicuously higher than that in the control group (P<0.05). After the vision training, the binocular visual perception functions of children in both groups were significantly improved compared with that before training (P<0.05). Interestingly, the grating sharpness, texture perception and texture motion perception in the VPT group were dramatically better than control group (P<0.01). The NCS in the VPT group was significantly lower than that in the control group (P<0.05). The ocular position retraction rate in the VPT group was significantly lower than that in the control group at 12mo (8.89% vs 26.67%, P=0.03). CONCLUSION: VPT effectively promotes binocular visual function reconstruction in intermittent exotropia children after strabismus surgery and reduces the strabismus severity and ocular position retraction rate.

Puerarin Prevents Bisphenol S Induced Lipid Accumulation by Reducing Liver Lipid Synthesis and Promoting Lipid Metabolism in C57BL/6J Mice.

Bisphenol S (BPS) is an environmental pollutant that can accumulate in the human body and cause harm. Puerarin (PUE) is a flavonoid with anti-inflammatory and antioxidant effects. In this study, we used 50 mg/kg/d BPS as a poison and PUE as an intervention for model mice for 42 d. BPS exposure significantly increased the levels of the impairment of the mice's liver function, T-CHO, TG, LDL-C, ALT, and AST in the BPS group were significantly increased (p < 0.05). Additionally, BPS exposure caused inflammatory cell infiltration in the mice liver tissue and enhanced oxidative stress response, the level of MDA was significantly increased (p < 0.05). The expression of CD36 and pparγ was stimulated after BPS exposure. Moreover, the expression of cpt1a and cpt1b, which promote fatty acid oxidation, was downregulated. After PUE intervention, the levels of genes and proteins involved in lipid synthesis (PPARγ, SREBP1C, and FASN) and metabolism (Cpt1a, Cpt1b, and PPARα) in mice returned to those of the control group, or much higher than those in the BPS group. Therefore, we hypothesized that BPS causes lipid accumulation in the liver by promoting lipid synthesis and reducing lipid metabolism, whereas PUE reduces lipid synthesis and promotes lipid metabolism. Conclusively, our results imply that long-term exposure to BPS in mice affects liver lipid metabolism and that PUE intervention could maintain the liver function of mice at normal metabolic levels.

Clinical Manifestations and Risk Factors Associated with 14 Deaths following Swarm Wasp Stings in a Chinese Tertiary Grade A General Hospital: A Retrospective Database Analysis Study.

INTRODUCTION: The objective was to evaluate the poisoning severity score (PSS) as an early prognostic predictor in patients with wasp stings and identify associated clinical characteristics and risk factors for mortality. METHODS: A total of 363 patients with wasp stings at Suining Central Hospital between January 2016 and December 2018 were enrolled. Within the first 24 h of admission, the poisoning severity score (PSS) and the Chinese expert consensus on standardized diagnosis and treatment of wasp stings (CECC) were utilized for severity classification, and their correlation was examined. Patients were then divided into survival and death groups based on discharge status. Logistic regression analysis was employed to analyze factors influencing patients' outcomes. RESULTS: The mortality of wasp sting patients was 3.9%. The PSS and CECC were found to correlate for severity classification. Additionally, female gender, age, number of stings, and PSS were identified as independent risk factors for mortality in wasp sting patients. Combining these four factors yielded an AUC of 0.962 for predicting death. CONCLUSIONS: PSS aids in early severity classification of wasp stings. Female gender, age, number of stings, and PSS were independent mortality risk factors in these patients.

New indolizidine- and pyrrolidine-type alkaloids with anti-angiogenic activities from Anisodus tanguticus.

Eleven alkaloids, including five previously undescribed indolizidine alkaloids (1, 2a, 2b, 3a, and 3b) and four new pyrrolidine alkaloids (5-8), were isolated from the roots of Anisodus tanguticus. Of these, two new pairs of enantiomeric alkaloids (2a/2b and 3a/3b) are the first examples of alkaloids containing both indolizidine and pyrrolidine structural fragments. The one-carbon bridge connections with two pyrrolidine rings (6) or with a pyrrolidine ring and a pyridine ring (8) are the first reported from nature. Extensive spectroscopic techniques were used to elucidate their structures, and NMR and ECD calculations were used to determine the absolute configurations. The viability of human umbilical vein endothelial cells (HUVECs) was inhibited by compounds 2a, 2b, 3a, 4b, and 5, and compound 2b exhibited a potential anti-angiogenic effect by inhibiting the proliferation, migration, and tube formation of HUVECs. A chorioallantoic membrane assay also demonstrated the anti-angiogenic activity of 2b. In addition, compounds 2a, 2b, 3a, and 4b exhibited moderate cytotoxicity against A2780 cells.

Disease burden contributed by dietary exposure to aflatoxins in a mountainous city in Southwest China.

Introduction: Aflatoxins (AFT) identified as a Group 1 human carcinogen naturally contaminate various types of food and could increase the risk of hepatocellular carcinoma (HCC) through dietary intake. Chongqing municipality is located in Southwest China with subtropical monsoon climate which is conducive to AFT contamination in crops. However, the burden of HCC caused by the dietary exposure of the population in Chongqing to AFT has not been quantified. Methods: The burden of HCC was estimated in terms of Disability Adjusted Life Year (DALY) using FDA-iRISK software. Dietary exposure to AFT in three food categories including grain and its products, nuts and seeds, and spices was assessed. Results: The lifetime average daily dose (LADD) of AFT exposure for the population ranged from 2.40 to 8.25 ng/kg bw/day and 9.51 to 15.10 ng/kg bw/day at the mean and heavy (P95) AFT contamination levels, respectively. Among the three food categories, grain and its products contributed most to AFT exposure of the population. The estimated DALYs related to HCC induced by AFT were 162,000-556,000 and 641,000-1,020,000; the DALY rates were 6.47-22.20 and 25.59-40.72 per 100,000 persons per year; and the population attribution fractions (PAF) were 1.68-5.78% and 6.66-10.60%. Discussion: Although the burden of HCC caused by dietary AFT was estimated to be relatively low among the population, the overall health burden might be underestimated owing to the uncertainties of this dataset. Thus, the overall health burden associated with AFT intake should still be of concern in further studies.