Objective To investigate the situation of HIV infection and epidemiological characteristics among voluntary blood donors and pre-transfusion patients in Yuxi prefecture between 2010 and 2021.Methods Da-te collected with the HIV/AIDS Case Reporting Cards and original record of blood station,HIV antibody positive rate,the demographic characteristics,and epidemiological data of blood donors and pre-transfusion patients,were analyzed accordingly,the related date were statistically analyzed.Results The HIV antibody positive ratio were 5.56? and 2.01? among pre-transfusion patients and voluntary blood donors(P<0.001),showing an downward trend year after year.The HIV-positive detection rate among blood donors aged<25 years was significantly higher at 3.72‰ compared to 1.60‰ for those aged≥25 years(P=0.003).Among HIV-positive blood recipients,the proportion of individuals aged 15-24 years(34.62%)was markedly higher than that among blood donors(1.96%),whereas no donors were aged≥50 years compared to 23.53%of recipients(P<0.001).Farmers showed a significantly higher HIV detection rate(3.18‰)than students(2.66‰)and other occupations(1.60‰)(P=0.041).Similarly,individuals with high school education or below showed a higher detection rate(2.52‰)than those with high school education or above(1.45‰)(P=0.045).Among HIV-positive cases,blood donors had a higher proportion of HIV-infected individuals(84.62%)versus AIDS cases(15.38%),whereas the recipients showed the opposite trend:41.18%HIV-infected versus 58.82%AIDS cases(P<0.001).Conclusion In recent years,the HIV positive detection rate in Yuxi area has shown a downward trend,but the occurrence of HIV in Yuxi area is characterized by youthfulness and low education.Among them,HIV infected individuals through same-sex contact account for an important reason for HIV infection.

Objective To investigate the correlation of postoperative cytokine levels with infarct size and reperfusion injury in acute myocardial infarction(AMI)patients having achieved success-ful recanalization after PCI.Methods Clinical data of 164 AMI patients who underwent successful PCI in our department between March 2022 and March 2024 were collected and retrospectively analyzed.The levels of IL-6 and TNF-α were measured at 1 d after PCI,and base on the cutoff level,the patients were categorized into a high IL-6 group(≥5.72 ng/L,93 cases)and a low IL-6 group(＜5.72 ng/L,71 cases),and also into a high TNF-α group(≥5.27 ng/L,108 cases)and a low TNF-α group(＜5.27 ng/L,56 cases).General information,infarct volume and reperfusion injury were compared between the groups.Multivariate logistic regression analysis was used to identify the influencing factors of IL-6 and TNF-α.Pearson correlation analysis was employed to assess the correlation of IL-6/TNF-α levels with infarct size,while Spearman correlation analysis was utilized to evaluate their correlation with reperfusion injury.ROC curves were plotted to de-termine the predictive value of the two cytokines for reperfusion injury.Results The high IL-6 group showed significantly higher ratio of diabetes,larger proportion of reperfusion injury,greater infarct size,increased cardiac troponin I(cTnI)level,and longer PCI time than the low IL-6 group(P＜0.01),and similar results were seen in the high TNF-α group when compared with the low TNF-α group(P＜0.01).Multivariate logistic regression analysis identified PCI time(OR=3.492,95％CI:2.253-5.411),cTnI(OR=5.126,95％CI:1.104-23.787),infarct size(OR=1.178,95％CI:1.026-1.352),and reperfusion injury(OR=3.283,95％CI:1.099-9.809)as independent risk factors for elevated IL-6,while PCI time(OR=3.101,95％CI:2.027-4.742),cTnI(OR=3.498,95％CI:1.730-7.072),infarct size(OR=1.234,95％CI:1.051-1.449),and reperfusion injury(OR=3.518,95％CI:1.017-12.170)as independent risk factors for increased TNF-α.Pear-son and Spearman analysis showed that the IL-6 and TNF-α levels were positively correlated with infarct volume and reperfusion injury(P＜0.01).ROC curve analysis indicated that the AUC value of IL-6 and TNF-α in predicting reperfusion injury was 0.693(95％CI:0.616-0.762)and 0.681(95％CI:0.604-0.752),with a sensitivity of 60.49％and 81.25％,and a specificity of 71.08％and 78.81％,respectively.Conclusion In AMI patients after PCI recanalization,elevated IL-6 and TNF-α levels are positively correlated with infarct size and reperfusion injury,and the levels can serve as biomarkers for assessing the occurrence of reperfusion injury.

Objective To investigate the correlations of resting electrocardiogram ST-T abnormality and stress hyperglycemia ratio(SHR)with short-term prognosis of acute left heart failure(ALHF).Methods The clinical data of 125 patients with ALHF were analyzed.According to the prognosis within 30 days after onset,the patients were divided into good prognosis group(n=59),poor prognosis group(n=42)and death group(n=24).The resting electrocardiogram indications,admission blood glucose and glycosylated hemoglobin at fasting on the next day were collected,and SHR was calculated for exploring the correlations of resting electrocardiogram ST-T abnormality and SHR with short-term prognosis of ALHF.Results and conclusion The differences in gender,blood pressure and other general data among 3 groups were trivial(P>0.05),but death group was at an older age as compared with good prognosis group(P<0.05).The resting electrocardiogram ST-T abnormality rate,QRS wave duration and QTc interval were lower/shorter in good prognosis group than in the other two group(P<0.05),and the above indicators were lower/shorter in poor prognosis group than in death group(P<0.05).Good prognosis group had the lowest SHR,followed by poor prognosis group and death group(P<0.05).Multivariate Logistic regression analysis revealed that ST-T abnormality,prolonged QRS wave duration,prolonged QTc interval and high SHR were independent risk factors for poor prognosis in ALHF patients(P<0.05).Resting electrocardiogram ST-T abnormality and SHR were significantly and positively correlated with ALHF short-term prognosis.

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*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.

Objective To investigate the correlation of postoperative cytokine levels with infarct size and reperfusion injury in acute myocardial infarction(AMI)patients having achieved success-ful recanalization after PCI.Methods Clinical data of 164 AMI patients who underwent successful PCI in our department between March 2022 and March 2024 were collected and retrospectively analyzed.The levels of IL-6 and TNF-α were measured at 1 d after PCI,and base on the cutoff level,the patients were categorized into a high IL-6 group(≥5.72 ng/L,93 cases)and a low IL-6 group(＜5.72 ng/L,71 cases),and also into a high TNF-α group(≥5.27 ng/L,108 cases)and a low TNF-α group(＜5.27 ng/L,56 cases).General information,infarct volume and reperfusion injury were compared between the groups.Multivariate logistic regression analysis was used to identify the influencing factors of IL-6 and TNF-α.Pearson correlation analysis was employed to assess the correlation of IL-6/TNF-α levels with infarct size,while Spearman correlation analysis was utilized to evaluate their correlation with reperfusion injury.ROC curves were plotted to de-termine the predictive value of the two cytokines for reperfusion injury.Results The high IL-6 group showed significantly higher ratio of diabetes,larger proportion of reperfusion injury,greater infarct size,increased cardiac troponin I(cTnI)level,and longer PCI time than the low IL-6 group(P＜0.01),and similar results were seen in the high TNF-α group when compared with the low TNF-α group(P＜0.01).Multivariate logistic regression analysis identified PCI time(OR=3.492,95％CI:2.253-5.411),cTnI(OR=5.126,95％CI:1.104-23.787),infarct size(OR=1.178,95％CI:1.026-1.352),and reperfusion injury(OR=3.283,95％CI:1.099-9.809)as independent risk factors for elevated IL-6,while PCI time(OR=3.101,95％CI:2.027-4.742),cTnI(OR=3.498,95％CI:1.730-7.072),infarct size(OR=1.234,95％CI:1.051-1.449),and reperfusion injury(OR=3.518,95％CI:1.017-12.170)as independent risk factors for increased TNF-α.Pear-son and Spearman analysis showed that the IL-6 and TNF-α levels were positively correlated with infarct volume and reperfusion injury(P＜0.01).ROC curve analysis indicated that the AUC value of IL-6 and TNF-α in predicting reperfusion injury was 0.693(95％CI:0.616-0.762)and 0.681(95％CI:0.604-0.752),with a sensitivity of 60.49％and 81.25％,and a specificity of 71.08％and 78.81％,respectively.Conclusion In AMI patients after PCI recanalization,elevated IL-6 and TNF-α levels are positively correlated with infarct size and reperfusion injury,and the levels can serve as biomarkers for assessing the occurrence of reperfusion injury.

Objective To investigate the correlations of resting electrocardiogram ST-T abnormality and stress hyperglycemia ratio(SHR)with short-term prognosis of acute left heart failure(ALHF).Methods The clinical data of 125 patients with ALHF were analyzed.According to the prognosis within 30 days after onset,the patients were divided into good prognosis group(n=59),poor prognosis group(n=42)and death group(n=24).The resting electrocardiogram indications,admission blood glucose and glycosylated hemoglobin at fasting on the next day were collected,and SHR was calculated for exploring the correlations of resting electrocardiogram ST-T abnormality and SHR with short-term prognosis of ALHF.Results and conclusion The differences in gender,blood pressure and other general data among 3 groups were trivial(P>0.05),but death group was at an older age as compared with good prognosis group(P<0.05).The resting electrocardiogram ST-T abnormality rate,QRS wave duration and QTc interval were lower/shorter in good prognosis group than in the other two group(P<0.05),and the above indicators were lower/shorter in poor prognosis group than in death group(P<0.05).Good prognosis group had the lowest SHR,followed by poor prognosis group and death group(P<0.05).Multivariate Logistic regression analysis revealed that ST-T abnormality,prolonged QRS wave duration,prolonged QTc interval and high SHR were independent risk factors for poor prognosis in ALHF patients(P<0.05).Resting electrocardiogram ST-T abnormality and SHR were significantly and positively correlated with ALHF short-term prognosis.

Gap junction proteins have a significant impact on the propagation of neuroinflammation after cerebral ischemia.Connexin 43(Cx43),the principal connexin in the central nervous system,typically assembles hexameric hemichannels in an oligomeric state that dock with hemichannels on adjacent cells to form gap junction channels.Ordinarily,the likelihood of cell surface hemichannels opening is minimal.However,during cerebral ischemia,the excessive activation of Cx43 hemichannels leads to the liberation of a substantial quantity of ions(Na+,Cl-,Ca2+,and K+),glutamate,aspartate,and adenosine triphosphate(ATP),thereby resulting in impairment of adjacent cells and aggravation of neuronal injury.Furthermore,the activation of Cx43 hemichannels triggers the release of inflammatory factors,which exhibits a strong association with the activation of NLRP3 inflammasome after cerebral ischemia.Hence,the modulation of Cx43 hemichannels presents a potential avenue for mitigating neuroinflammation and subsequently diminishing cerebral ischemic injury.This article focuses on the relationship between Cx43 hemichannels and NLRP3 inflammasome activation,as well as its role in cerebral ischemia,all of which provide novel insights and therapeutic approaches for managing cerebral ischemia.