BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Objective To understand the current situation and influencing factors of salary satisfaction of staff in tertiary public hospitals,and provide suggestions for improving the reform of salary system.Methods A questionnaire survey was conducted on 816 employees from 7 tertiary public hospitals in Hunan Province,and the basic situation,salary level,salary promotion,salary system and salary distribution were studied.Descriptive analysis and binary logistic regression model were used to analyze the status quo and influencing factors of employee salary satisfaction.Results The overall satisfaction score of the 816 survey respondents'salary was 71.56 points,at a relatively high level.There was a large difference in satisfaction levels among different regions.Salary level and salary increase satisfaction were 69.19 and 70.90 points respectively,and satisfaction was low.Region,affiliation with a university,cadre status,and title were the main factors affecting salary satisfaction.Conclusion The salary satisfaction of staff in tertiary public hospitals was generally higher in Hunan Province,and the reform had shown positive results.The satisfaction with salary increases and salary levels was relatively low,and it was suggested that the government reasonably determine the salary level of public hospitals and establish a scientific and reasonable salary increase mechanism.It will improve supporting reforms and promote equal pay for equal work.

Objective To compare the efficacy of Qwen2.5(model A)and GPT-4o model(model B)for converting free-text reports of thyroid ultrasound into structured reports.Methods Preoperative thyroid ultrasound data of 100 patients who then underwent thyroidectomy(236 thyroid nodules)were retrospectively collected.Free-text reports were written by an attending ultrasound physician in accordance with guidelines of American College of Radiology thyroid imaging reporting and data system(ACR TI-RADS)and input into both model A and B for 3 times to generate structured thyroid ultrasound reports.The quality of these structured reports output by 2 models were compared,including structured writing,ACR TI-RADS categories and management recommendations,while the consistency of 3 times structured reports output by the models were analyzed.Results Among 300 structured reports output by models,the total satisfaction rate of structured writing was 94.00％(282/300)for model A and 94.67％(284/300)for model B,and no significant difference was found(x2=0.045,P=0.832).Among 236 thyroid nodules,there were 36,47,33,39 and 81 in ACR TI-RADS categories 1,2,3,4 and 5,respectively.The total accuracy model A and B for 3 times categories of thyroid nodules was 88.28％(625/708)and 89.27％(632/708),respectively,with no significant difference(x2=0.582,P=0.505).Moderate consistencies of results of 3 times structured writing(ICC=0.531,0.673)and nodules categories(ICC=0.714,0.747)were noticed between 2 models.The coincidence rate of model A and B for providing management recommendations for thyroid nodules was 74.86％(530/708)and 67.51％(478/708),respectively,the former was higher than the latter(x2=4.567,P=0.033),and the consistencies of 3 times management recommendations provided by 2 models were both good(ICC=0.836,0.769).Conclusion The efficacy of structured writing and ACR TI-RADS categories of Qwen2.5 and GPT-4o models for converting thyroid ultrasound free-text reports into structured reports was comparable,while the former was more effective for providing management recommendations.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To analyze the effects of different gender,gestational age,birth weight and blood collection date on the value of 17-hydroxyprogesterone(17-OHP)in neonatal screening for congenital adrenal hyperplasia(CAH)and to develop a positive cut-off for CAH screening that is appropriate for the laboratory itself.Methods Time-resolved fluorescence immunoassay was used to detect 17-OHP concentration,and Mann-Whitney U test and Kruskal-Wallis H test were used to compare 17-OHP concentration of newborns with the different gender,birth weight,gestational age and blood collection age.The comparison of rates was conducted using the multi-set rate chi-square test and Fisher's exact probability method.The relationship between the clinical features and 17-OHP concentration was analyzed by multiple linear regression,and the cut-off value of 17-OHP screening was 99.5％percentile.Results The 17-OHP concentration of male neonates was higher than that of female neonates,and the difference was statistically significant(Z=-17.768,P<0.05).The 17-OHP concentration of neonates in groups with different gestational age,different birth weight,and different blood collection days were compared respectively,and the difference was statistically significant(χ2=5 235.187、3 682.665、493.414 respectively,P=0.00).Further pair comparison showed that there were statistically significant differences in 17-OHP concentration of neonates at different gestational weeks,gestational age and blood collection days(P<0.05),except that age of blood collection≥3 and<4 days and≥4 and<7 days(Z=-0.950,P=0.342).Neonatal 17-OHP concentration decreased with the gestational age and birth weight increase.There were statistically significant differences in the initial screening positive rate and screening positive rate of 17-OHP among different gestational ages and different birth weights groups(P<0.05),and they decreased with the increase of gestational age,birth weight and age at the time of blood collection.The results of multiple linear regression showed that 17-OHP concentration was related to the several factors,including the gestational age,birth weight,age of blood collection and gender in descending order.Conclusion The effects of various factors on the concentration of 17-OHP in neonatal peripheral blood should be comprehensively considered.The cut-off value of 17-OHP for CAH screening in the Screening Center for Neonatal Genetic Metabolic Diseases in the First Affiliated Hospital of Kunming Medical University is modified to≥14.00 nmol/L for full-term neonates of normal weight and≥36.00 nmol/L for premature or/and low-weight neonates so as to improve the specificity of neonatal CAH screening and reduce the false positives.

Objective:To develop a scale for assessing science popularization competency in traditional Chinese medicine (TCM) and to evaluate its reliability and validity.Methods:Based on Lasswell's "5W" communication theory, the scale was constructed through literature review, expert consultation, and a pilot survey. Using convenient sampling, 450 TCM-related professionals were selected from two ClassⅢ Grade ATCM hospitals and their affiliated medical alliance community health institutions in Hunan Province. A total of 450 questionnaires were distributed and 446 valid responses were collected (valid response rate: 99.11%). Of these, 222 questionnaires were used for item analysis, reliability testing, and exploratory factor analysis (EFA) ; the remaining 224 were used for confirmatory factor analysis (CFA) .Results:The final TCM Science Popularization Competency Scale comprised 26 items under 6 dimensions: namely popular science cognition; science content creation ability; communication ability; professional values and personality traits; quality of science communication products; evaluation and feedback of communication effectiveness. EFA extracted six common factors, explaining 86.85% of total variance, with all item factor loadings > 0.500. The overall Cronbach's α coefficient for the scale was 0.972, with subscale values all > 0.800. Split-half reliability was 0.948. CFA showed good model fit across indices, indicating high reliability and validity.Conclusions:The TCM Science Popularization Competency Scale demonstrates good psychometric properties and can be used to assess the science popularization competency of TCM professionals. It offers a scientific tool to support the dissemination of TCM knowledge and contribute to the goals of the Healthy China initiative.

Objective:To develop a scale for assessing science popularization competency in traditional Chinese medicine (TCM) and to evaluate its reliability and validity.Methods:Based on Lasswell's "5W" communication theory, the scale was constructed through literature review, expert consultation, and a pilot survey. Using convenient sampling, 450 TCM-related professionals were selected from two ClassⅢ Grade ATCM hospitals and their affiliated medical alliance community health institutions in Hunan Province. A total of 450 questionnaires were distributed and 446 valid responses were collected (valid response rate: 99.11%). Of these, 222 questionnaires were used for item analysis, reliability testing, and exploratory factor analysis (EFA) ; the remaining 224 were used for confirmatory factor analysis (CFA) .Results:The final TCM Science Popularization Competency Scale comprised 26 items under 6 dimensions: namely popular science cognition; science content creation ability; communication ability; professional values and personality traits; quality of science communication products; evaluation and feedback of communication effectiveness. EFA extracted six common factors, explaining 86.85% of total variance, with all item factor loadings > 0.500. The overall Cronbach's α coefficient for the scale was 0.972, with subscale values all > 0.800. Split-half reliability was 0.948. CFA showed good model fit across indices, indicating high reliability and validity.Conclusions:The TCM Science Popularization Competency Scale demonstrates good psychometric properties and can be used to assess the science popularization competency of TCM professionals. It offers a scientific tool to support the dissemination of TCM knowledge and contribute to the goals of the Healthy China initiative.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.