OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

Objective:To study and analyze the epidemiological regularity of acute poisoning in Tianjin-Hebei region from 2020 to 2022, and to provide reference for the treatment and prevention of related patients.Methods:In December 2023, the analysis results and clinical data of 4695 patients with drug poisoning from January 2020 to December 2022 in multiple centers of Tianjin-Hebei region were collected as research objects. Gender, age, type of drug poisoning, season and poisoning route of the research objects were analyzed, and statistical analysis was conducted as well.Results:The sex ratio of men and women was 1∶1.16 (2173/2522). The poisoning of antidepressants and benzodiazepines were the most common drug poisonings, accounting for 1550 and 1274 cases respectively (33%, 27.1%). Paraquat poisoning has decreased year by year, while the poisonings of herbicides with low toxicity such as diquat, glyphosate and cremart have increased. The number of cases reached a peak during May to August which was the poisoning season, while was relatively fewer during October to December.Conclusion:Effective intervention measures should be taken according to the age of high incidence of poisoning, different seasons and populations. Essential drug poisoning prevention measures should be established and improved. The systems of sedative drug management and use should be established, and pesticide management and storage need to be strengthened.

Objective:To study and analyze the epidemiological regularity of acute poisoning in Tianjin-Hebei region from 2020 to 2022, and to provide reference for the treatment and prevention of related patients.Methods:In December 2023, the analysis results and clinical data of 4695 patients with drug poisoning from January 2020 to December 2022 in multiple centers of Tianjin-Hebei region were collected as research objects. Gender, age, type of drug poisoning, season and poisoning route of the research objects were analyzed, and statistical analysis was conducted as well.Results:The sex ratio of men and women was 1∶1.16 (2173/2522). The poisoning of antidepressants and benzodiazepines were the most common drug poisonings, accounting for 1550 and 1274 cases respectively (33%, 27.1%). Paraquat poisoning has decreased year by year, while the poisonings of herbicides with low toxicity such as diquat, glyphosate and cremart have increased. The number of cases reached a peak during May to August which was the poisoning season, while was relatively fewer during October to December.Conclusion:Effective intervention measures should be taken according to the age of high incidence of poisoning, different seasons and populations. Essential drug poisoning prevention measures should be established and improved. The systems of sedative drug management and use should be established, and pesticide management and storage need to be strengthened.

Objective To explore the performance of domestic and international large language models(LLMs)in the context of ques-tion banks for clinical examination knowledge.Methods The performance of six domestic or international LLMs,in the question banks with a set of 330 questions for intermediate-level of clinical medical laboratory technology were assessed.The differences in accuracy and consistency among the different LLMs were evaluated using chi-square tests,Fisher's exact tests and logistic regression.Results The accuracy results for the four English LLMs along with 95％confidence intervals(95％CI)were as follows:the accuracy rates of ChatGPT,BingAI,Claude and GPT-4 were demonstrated as 0.56(95％CI:0.527-0.601),0.61(95％CI:0.572-0.644),0.64(95％CI:0.607-0.678)and 0.80(95％CI:0.767-0.833)respectively,while the performance of Xinghuo and Tiangong yielded accuracy rates of 0.52(95％CI:0.479-0.561)and 0.45(95％CI:0.408-0.482)respectively.Using ChatGPT as the reference model,we found that the odds ratios(OR)of correct answers of BingAI,Claude and GPT-4 were 1.272(95％CI:1.020-1.588),1.397(95％CI:1.119-1.743)and 3.270(95％CI:1.904-2.729)respectively.The differences of LLMs performance were statistically significant(P＜0.05)for all the three models.In terms of consistency,Tiangong and BingAI showed poor consistency,while GPT-4 appeared better.Conclusion A-mong the six LLMs,GPT-4 demonstrated the highest overall accuracy and consistency in each question category.

Objective : To analyze the expression and immune infiltration levels of the BMP7 gene ( BMP7) in e- sophageal squamous cell carcinoma(ESCC) ． Methods : Initially，in 274 cases of ESCC and 242 cases of normal tissues，the level of BMP7 was verified by immunohistochemistry ，and the relationship between the expression difference and the survival cycle and clinical pathological characteristics of patients with ESCC was explored，and BMP7 overexpression plasmid transfection of ESCC cells was established，and the effect of BMP7 on the biological behavior of ESCC cells was examined by CCK-8，Clone，and Transwell. Results : BMP7 expression in normal e- sophageal tissues was higher than that of ESCC(P＜0. 001) ，the expression level of BMP7 was correlated with the degree of differentiation of patients(P = 0. 006) and TNM staging(P ＜0. 001) ，and the survival of patients with high expression of BMP7 exceeded that of patients with low BMP7 (P = 0. 041) ，and the experiments of CCK-8 and Clone showed that the proliferation effect of cells in the overexpressed BMP7 group was lower than that of the control group．Transwell experiments confirmed that the cell invasion migration capacity of the overexpressed BMP7 group was less than that of the control one．The immune infiltration results showed that BMP7 was positively correlated with macrophages(P = 0. 008) and negatively correlated with γ-δT cells(P = 0. 028) ． Conclusion BMP7 is low in ESCC and associated with poor prognosis and immune infiltration levels in patients.

Chromatography, Gas ; methods ; Triazoles ; blood

Chemistry Techniques, Analytical ; instrumentation ; Herbicides ; analysis ; Humans ; Paraquat ; analysis

Humans ; Serum ; chemistry ; Spectrophotometry, Ultraviolet ; methods ; Sulpiride ; blood

Objective To establish a qualitative and quantitative determination of glyphosate in serum using ultraviolet spectro-photometry(UV) to provide basis for clinical diagnosing and treating glyphosate poisoning .Methods The mixture of 0 .5 mL serum and 0 .2 mL 10% methanol solution of perchloric acid was shocked and centrifuged with 10 000 r/min for 5 min .A nitrosyla-tion reaction conducted on supernatant and 50 μL serum nitrosylation liquid was detected by UV scanning .Results The results of serum theophylline absorption maxima was(243 ± l) nm and the concentration of 10 .0-60 .0 μg/mL range linear regression equa-tion was Y=0 .0173 8X+0 .036 3(r= 0 .999 8) .The recovery rate was from 85 .5% to 102 .4% and the relative standard deviation (RSD) was from 3 .50% to 4 .90% .The intra-day and inter-day RSD were 3 .79% -5 .10% and 3 .88% -4 .55% .The minimum de-tectable concentration was 5μg/mL .Conclusion This method is simple ,rapid and accurate results for detecting glyphosate poison-ing .