Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

BACKGROUND: High temperatures are known to be associated with an increased risk of self-harm, but the influence of demographic changes and country-level indicators on the burden of heat-related self-harm remains unclear. This study examined the key factors driving changes in self-harm mortality linked to high temperatures and explored their impact at the country level. METHODS: This is an ecological study that analyzes data from the 2021 Global Burden of Disease (GBD) study, the World Bank, and the Climate Research Unit (CRU) were analyzed. Decomposition analyses were used to identify key factors driving changes in high temperature-related self-harm mortality between 1990 and 2021. A panel data model assessed the impact of national indicators on heat-related self-harm mortality. RESULTS: In 2021, 14,885 deaths globally were attributed to heat-related self-harm, a 41.94% increase from 1990, with low-middle SDI regions accounting for 47.84% of these deaths. While the global death rate from heat-related self-harm declined slightly over this period, South Asia and low-middle SDI regions contributed most to the decline. However, population aging exacerbated mortality rates. Demographic and meteorological factors were also linked to heat-related self-harm. CONCLUSION The global decline in heat-related self-harm mortality is largely driven by reductions in females, low-middle SDI regions, and South Asia. However, population aging and growth in these regions have added to the mortality burden, slowing the overall decline. Factors such as population density are also associated with heat-related self-harm. Targeted measures are needed to mitigate heat-induced self-harm more effectively in future.
Humans ; Self-Injurious Behavior/etiology* ; Hot Temperature/adverse effects* ; Global Health/statistics & numerical data* ; Female ; Male ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent

There is a large gap between production and demand of plant oil in China, which leads to the heavy reliance on imports. Diacylglycerol acyltransferase (DGAT) and phospholipid: diacylglycerol acyltransferase (PDAT) are two key enzymes responsible for the synthesis of triacylglycerol, thereby affecting the yield and quality of plant oil. This paper comprehensively reviews the research progress in DGAT and PDAT in terms of their biological functions in plant oil synthesis, the molecular mechanisms of regulating plant lipid metabolism, growth, and development under stress, and their roles in driving oil synthesis under the background of synthetic biology. Furthermore, future research and application of DGAT and PDAT are prospected. This review aims to provide a basis for deeply understanding the molecular mechanism of plant oil synthesis and improving the quality and productivity of oil crops by the utilization of DGAT and PDAT genes.
Diacylglycerol O-Acyltransferase/physiology* ; Plant Oils/metabolism* ; Acyltransferases/metabolism* ; Lipid Metabolism/genetics* ; Gene Expression Regulation, Plant ; Triglycerides/biosynthesis*

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

[Objective] To explore the feasibility of exemption from radiotherapy after breast-conserving surgery for hormone receptor-negative elderly breast cancer. [Methods] A total of 139 estrogen receptor (ER) and progesterone receptor (PR)-negative older adults with breast cancer who underwent breast-conserving surgery admitted to the Second Affiliated Hospital of Nanchang University from December 1, 2013 to December 1, 2018 were recruited as the subjects of the study, and were divided into a case group of 67 patients who did not undergo postoperative radiotherapy and a control group of 72 ones who underwent postoperative radiotherapy, according to whether they received postoperative radiotherapy or not. Clinicopathological data including age, tumor T stage, tumor N stage, tumor Nottingham grade, pathology type, human epidermal growth factor receptor 2 (HER2) expression status, and chemotherapy regimen were collected and compared between the two groups. The study analyzed the 5-year disease-free survival (DFS) and 5-year overall survival (OS) of two groups of patients. The log-rank test was used to compare the survival rate, and a multifactorial COX proportional hazards regression model was used to analyze the effect of exempted radiotherapy after breast-conserving surgery on DFS and OS of hormone receptor-negative elderly breast cancer mammary carcinoma. [Results] The two groups did not significantly differ in age, tumor T-stage, tumor N-stage, pathological type, tumor Nottingham grade, HER2 status, or chemotherapeutic regimen (all P>0.05). The 5-year DFS rate of 139 hormone receptor-negative elderly breast cancer cases was 74.1% and the 5-year OS rate was 83.5%. The difference in the 5-year DSF rate between the case group and the control group was statistically significant (65.7 vs. 81.9%, P=0.023), but the difference in the 5-year OS rate was not statistically significant (79.1% vs. 87.5%, P=0.186). The results of multifactorial COX proportional risk regression model analysis showed that exemption from radiotherapy after breast-conserving surgery was an independent risk factor for DFS (HR=2.298, 95% CI: 1.113-4.746, P=0.024), but not for OS (HR=1.831, 95% CI: 0.740-4.532, P=0.191). [Conclusion] Hormone receptor-negative elderly breast cancer according to exemption of radiotherapy after breast-conserving surgery has a higher local recurrence rate, but OS has no significant effect. Therefore, whether hormone receptor-negative elderly breast cancer can be exempted from radiotherapy after breast-conserving surgery still needs to be verified by further clinical trials.

ObjectiveTo investigate the risk factors and construct a predictive model for severe myelosuppression due to chemotherapy in triple negative breast cancer （TNBC）. MethodsPatients with TNBC who received anthracycline combined with cyclophosphamide sequential paclitaxel chemotherapy regimen at the Second Affiliated Hospital of Nanchang University from September 2， 2016 to September 2， 2021 were selected and assigned to severe myelosuppression group and no/mild myelosuppression group. The χ² test and binary logistic regression were used to analyze the risk factors for severe myelosuppression due to chemotherapy and to develop a prediction model. Hosmer-Lemeshow test and receiver operating characteristic （ROC） curve were used to evaluate the predictive efficiency of the regression model. Kappa consistency test was used to verify the regression model externally. ResultsA total of 207 patients who met the inclusion were enrolled and 106 patients （51%） had severe myelosuppression. Binary logistic regression multivariate analysis showed that age 40 to 60 years （OR = 3.463， 95% CI： 1.144 to 10.486， P = 0.028）， age >60 years （OR = 3.474， 95% CI： 1.004 to 12.020， P = 0.049）， body mass index （BMI） 18.5 to 24.0 （OR = 1.445， 95% CI： 0.686 to 3.087， P = 0.328）， BMI <18.5 （OR = 3.582， 95% CI： 1.260 to 10.182， P = 0.017）， tumor TNM stage Ⅱ （OR = 1.698， 95% CI： 0.831 to 3.468， P = 0.146）， tumor TNM stage Ⅲ （OR = 2.943， 95% CI： 1.199 to 7.227， P = 0.019）， previous diabetes （OR = 2.441， 95% CI： 1.076 to 5.539， P = 0.033）， low pre-treatment albumin level （OR = 2.759， 95% CI： 1.141 to 6.669， P = 0.024） and low pre-treatment lymphocytes （OR = 3.428， 95% CI： 1.689 to 6.958， P = 0.001） were independent risk factors for severe myelosuppression due to chemotherapy. The χ² value for the logistic regression model Hosmer-Lemeshow test was 11.507， P= 0.175， the area under the ROC curve was 0.763， standard error 0.033， 95% CI： 0.698-0.828， P=0.000. External validation showed that the prediction model had a specificity of 88% and a sensitivity of 80%； the kappa value was 0.679， standard error 0.081， P=0.000. conclusionThis logistic regression model had high predictive efficacy and is useful for clinicians to predict whether patients with TNBC develop severe myelosuppression.

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

OBJECTIVES: Adolescents are at high risk of non-suicidal self-injury (NSSI). Currently, there is no clinical assessment tool for adolescent NSSI behaviors measurement with global consistency. The Ottawa Self-injury Inventory (OSI) is considered as a relatively comprehensive assessment tool for NSSI, but the questionnaire is discussed with excessive content and timecostly, which may affect the reliability of the measurement results for adolescent.Thus, this study, based on OSI, aims to revise the assessment tool for adolescent with NSSI that is suitable for both clinically and scientifically, referring to the diagnostic criteria for NSSI in the 5th Diagnostic and Statistical Manual of Mental Disorder (DSM-5). METHODS: This study was led by the Second Xiangya Hospital of Central South University and collaborated with 6 mental health service institutions in China from August to December 2020. Adolescent aged from 12 to 24 years old who had self-injury behavior and met the DSM-5 diagnostic criteria for NSSI were continuously recruited in the psychiatric outpatient department or ward. After clinical diagnosis by an experienced attending psychiatrist or above, the general information and OSI were collected by questionnaires. SPSS 24.0 and AMOS structural equation model statistical softwares were used to conduct item analysis and exploratory factor analysis on the obtained data to complete the revision of the scale. Cronbach's alpha coefficient, split-half reliability, test-retest reliability, and content validity and structure validity were performed to analyze the reliability and validity and confirmatory factor analysis was carried out to test the structure validity for the revised scale. RESULTS: A total of 234 adolescent with NSSI were enrolled, including 33 (14.1%) males and 201 (85.9%) females with the mean age of (16.2±2.6) years old. The most common clinical diagnoses were depression disorder (57.4%), bipolar disorder (20.9%), adolescent mood disorder (17.1%), etc. Nine items (item 2, 7, 11, 13, 23, 24, 10, 17, 18) in the functional scale of OSI were deleted according to extreme grouping method, correlation analysis, and principal component analysis in exploratory factor analysis. The revised functional scale for NSSI consisted of 15 items. The reliability analysis showed that the Cronbach's alpha coefficients of NSSI thought and behavior frequency, addiction characteristics, and function scales were 0.799, 0.798, and 0.835, respectively, and the split-half coefficients were 0.714, 0.727, and 0.852, respectively. The test-retest coefficients of the latter 2 scales were 0.466 and 0.560, respectively. The correlation coefficient between sub-items and total scores in each part of the scale showed good content validity. The exploratory factor analysis showed that a component was extracted from the frequency of thoughts and behaviors of NSSI, one component was extracted from the addictive characteristics, and three components were extracted from the functional part. The three functional subscales were social influence, external emotion regulation, and internal emotion regulation. The factor load of each item was >0.400. CONCLUSIONS The revised Chinese version OSI targeted the adolescent patients with mental disorders has relatively ideal reliability and validity. The scale shows high stability, dependability, and a reasonable degree of fit. It is a suitable assessment tool for clinical and scientific research on adolescent with NSSI.
Adolescent ; Adult ; Child ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Mental Disorders/diagnosis* ; Psychometrics/methods* ; Reproducibility of Results ; Self-Injurious Behavior/psychology* ; Surveys and Questionnaires ; Young Adult