BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Purpose To explored the correlation between imaging features and patient's blood markers based on quantitative analysis of urate deposition in acute exacerbations of gouty arthritis of the knee by dual-energy spectrum CT(DECT).Materials and Methods A retrospective analysis was conducted on energy spectrum CT imaging of 72 patients clinically diagnosed with acute gouty knee osteoarthritis and 87 patients with non-gouty knee disease during the acute exacerbation period at the First Hospital of Qiqihar from January 2020 to September 2023.The analysis aimed to evaluate urate deposition in different parts of the knee joints and to analyze the influencing factors of urate deposition combined with the blood test indexes of the patients via receiver operating characteristic curves.Results The neutrophil lymphocyte ratio showed a positive correlation with C-reactive protein,erythrocyte sedimentation rate,and urate concentration at the site of urate deposition in gouty nodules of the knee(r=0.354,0.326,0.260,respectively,all P<0.05).The mean platelet volume was significantly positive correlated with the semi-quantitative data of monosodium urate crystals and urate concentration in the knee(r=0.563,0.257,respectively,P<0.05).In the gout group,C-reactive protein was positively correlated with pararticular soft tissue urate concentration and bone urate concentration(r=0.498,0.166,P<0.05),while erythrocyte sedimentation rate was positively correlated with pararticular soft tissue(tendons,ligaments,etc)urate concentration(r=0.325,P<0.01).Additionally,serum uric acid was positively correlated with gouty nodules in the knee joints and pararticular soft tissue(tendons,ligaments,etc)(r=0.264,0.243,respectively,P<0.05).The cut-off values of neutrophil lymphocyte ratio,platelet lymphocyte ratio and mean platelet volume combined with dual-energy energetic spectroscopic CT imaging data in the diagnosis of gouty knee osteoarthritis points were 2.190,122.96 and 9.049,respectively.Conclusion Energetic spectrum CT can identify and quantify urate crystals at the early stage.And blood test indexes such as mean platelet volume,erythrocyte sedimentation rate and serum uric acid have potential value in evaluating the activity of gout and the degree of migration of the disease in gouty knee osteoarthritis.

As an intermediate phenotype for multiple cardiovascular diseases, left ventricular hypertrophy (LVH) benefits from early diagnosis, which allows for timely intervention to prevent worsening of the condition, mitigate severe complications like heart failure and arrhythmias, and consequently improve patient outcomes. Preliminary advances have been made using deep learning for the early diagnosis and identification of etiology in LVH. This paper reviews the pathophysiology, causes, and diagnostic standards for LVH, discusses the strengths and weaknesses of applying deep learning to diagnostic tools such as echocardiography, cardiac magnetic resonance imaging, and electrocardiogram, examines its use in prognostic evaluation, and concludes by summarizing current achievements and suggesting future research avenues.

Hepatitis B virus(HBV)is the most common cause of hepatocellular carcinoma(HCC),which is the predominant liver cancer type in Southeast Asia.Approximately 350 million individuals suffer from persistent hepatitis B infection worldwide.HBV promotes HCC development through direct and indirect mechanisms.HBV DNA integrates into the host genome during the initial stages of tumorigenesis,causing insertional mutagenesis of cancer-related genes and genomic instability.Extrachromosomal circular DNA(ecDNA)is formed,which is efficiently amplified in large quantities to express viral genes and host oncogenes.Moreover,virus-associated proteins,such as the regulatory HBV X(HBx)protein and/or the modified preS/S envelope protein,alter the expression of genes associated with multiple functions in host cells.In this review,we summarize the role of the HBx and preS/S proteins in pro-moting tumorigenesis.In addition to summarizing the specific mechanism of HBV-related tumorigen-esis,the concerns and perspectives for future study are discussed.

Purpose To explored the correlation between imaging features and patient's blood markers based on quantitative analysis of urate deposition in acute exacerbations of gouty arthritis of the knee by dual-energy spectrum CT(DECT).Materials and Methods A retrospective analysis was conducted on energy spectrum CT imaging of 72 patients clinically diagnosed with acute gouty knee osteoarthritis and 87 patients with non-gouty knee disease during the acute exacerbation period at the First Hospital of Qiqihar from January 2020 to September 2023.The analysis aimed to evaluate urate deposition in different parts of the knee joints and to analyze the influencing factors of urate deposition combined with the blood test indexes of the patients via receiver operating characteristic curves.Results The neutrophil lymphocyte ratio showed a positive correlation with C-reactive protein,erythrocyte sedimentation rate,and urate concentration at the site of urate deposition in gouty nodules of the knee(r=0.354,0.326,0.260,respectively,all P<0.05).The mean platelet volume was significantly positive correlated with the semi-quantitative data of monosodium urate crystals and urate concentration in the knee(r=0.563,0.257,respectively,P<0.05).In the gout group,C-reactive protein was positively correlated with pararticular soft tissue urate concentration and bone urate concentration(r=0.498,0.166,P<0.05),while erythrocyte sedimentation rate was positively correlated with pararticular soft tissue(tendons,ligaments,etc)urate concentration(r=0.325,P<0.01).Additionally,serum uric acid was positively correlated with gouty nodules in the knee joints and pararticular soft tissue(tendons,ligaments,etc)(r=0.264,0.243,respectively,P<0.05).The cut-off values of neutrophil lymphocyte ratio,platelet lymphocyte ratio and mean platelet volume combined with dual-energy energetic spectroscopic CT imaging data in the diagnosis of gouty knee osteoarthritis points were 2.190,122.96 and 9.049,respectively.Conclusion Energetic spectrum CT can identify and quantify urate crystals at the early stage.And blood test indexes such as mean platelet volume,erythrocyte sedimentation rate and serum uric acid have potential value in evaluating the activity of gout and the degree of migration of the disease in gouty knee osteoarthritis.

BACKGROUND:Ischemic postconditioning is one of the effective ways to reduce ischemia-reperfusion injury and has been more and more widely used in clinical practice in recent years,but its specific molecular mechanism has yet to be studied. OBJECTIVE:To investigate the role and mechanism of piRNA-005854 in the aging cardiomyocytes caused by hypoxic postconditioning. METHODS:In vitro,cardiomyocytes were administered 8 mg/mL D-galactose for 9 days to induce their aging.β-Galactosidase staining was used to observe the aging of cardiomyocytes.Senescent cells were treated with hypoxia/reoxygenation and hypoxic postconditioning.ELISA was utilized to detect changes in myocardial injury markers creatine kinase isoenzyme MB and lactate dehydrogenase levels.Western blot assay was applied to detect the expression changes of autophagy-related proteins LC3II,p62,ULK1 and phosphorylated ULK1 in aging cardiomyocytes.qRT-PCR was employed to determine the expression level of piRNA-005854.piRNA-005854 inhibitor and piRNA-005854 mimics were transferred into aging cardiomyocytes and followed with hypoxic postconditioning.Western blot assay was used to examine the expression of LC3II,p62,ULK1 and phosphorylated ULK1. RESULTS AND CONCLUSION:(1)D-galactose induced obvious senescence of cardiomyocytes 9 days later.(2)Compared with the normoxia group,creatine kinase isoenzyme MB and lactate dehydrogenase levels increased in the hypoxia/reoxygenation group(P<0.01);LC3 II/I expression was increased;p62 expression was decreased;ULK1 phosphorylation level was increased,and piRNA-005854 expression was increased(P<0.01).(3)Compared with the hypoxia/reoxygenation group,creatine kinase isoenzyme MB and lactate dehydrogenase levels significantly reduced in the hypoxic postconditioning group(P<0.01);LC3 II/I expression significantly decreased(P<0.05);p62 expression increased(P<0.01);ULK1 phosphorylation level decreased(P<0.05),and piRNA-005854 expression decreased(P<0.01).(4)After transfection of piRNA-005854 inhibitor,LC3II/I expression was decreased(P<0.01);the expression of p62 was increased significantly(P<0.05);the phosphorylation level of ULK1 was decreased significantly(P<0.01).After transfection of piRNA-005854 mimics,LC3II/I expression was increased significantly;the expression of p62 was decreased,and the phosphorylation level of ULK1 was increased significantly(P<0.01).(5)The results show that piRNA-005854-mediated reduction of ULK1-dependent autophagy level is a possible mechanism that hypoxic postconditioning exerts its protective effect on aging cardiomyocytes.

BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.

Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

AIM:To investigate the role of specific long noncoding RNA SLC25a6(lncSLC25a6)in homocys-teine(Hcy)-induced cuproptosis in cardiomyocytes.METHODS:Rat cardiomyocytes were cultured in vitro and divided into control group and Hcy group.After 48 h of intervention,the expression levels of cuproptosis-related proteins,ferre-doxin 1(FDX1)and heat shock protein 70(HSP70),were detected by Western blot and immunofluorescence staining.The oxidative stress state of cardiomyocytes was assessed using fluorescence staining,and the intracellular Cu2+levels were measured using a copper ion assay kit.Furthermore,the impact of Hcy on the expression of cuproptosis-related proteins in cardiomyocytes was analyzed following overexpression of lncSLC25a6.RESULTS:Compared with the control group,80 μmol/L Hcy significantly accelerated cardiomyocyte damage,with a notable underexpression of lncSLC25a6(P<0.05).Western blot results indicated that,compared with the control group,the expression level of FDX1 in the Hcy intervention group was significantly reduced(P<0.05),while the expression level of HSP70 was significantly elevated(P<0.05),and the expression level of copper ions in cardiomyocytes of the Hcy group was increased(P<0.05).Immunofluorescence staining showed a significant reduction in FDX1 fluorescence intensity and a significant increase in HSP70 fluorescence in-tensity in the Hcy group.Further overexpression of lncSLC25a6 significantly mitigated Hcy-induced cuproptosis in cardio-myocytes,resulting in elevated expression of FDX1 and reduced expression of HSP70(P<0.05).Pearson correlation analysis demonstrated that the expression level of lncSLC25a6 was negatively correlated with FDX1 protein expression(r=-0.676,P=0.046)and positively correlated with HSP70 expression(r=0.680,P=0.044).CONCLUSION:lnc-SLC25a6 significantly mitigates Hcy-induced cuproptosis in cardiomyocytes,positioning it as a potential therapeutic target for managing Hcy-induced cardiac injury.

Background Acute exposure to mercury chloride (HgCl₂) can cause liver damage. Whether oleanolic acid (OA) as a hepatoprotective drug can protect against liver injury induced by acute exposure to HgCl₂ and related mechanism of action remain unclear. Objective To investigate the protective effect and possible mechanism of OA on liver injury in mice caused by acute exposure to HgCl₂. Methods Forty SPF C57BL/6 male mice were randomly divided into four groups with 10 mice in each group according to body weight. The four groups were named control group, OA group (300 mg·kg⁻¹), HgCl₂ group (5 mg·kg⁻¹), and OA + HgCl₂ group (300 mg·kg⁻¹ OA + 5mg·kg⁻¹ Hgcl₂). Soybean oil and OA solution were administered intragastric once a day for two consecutive days. HgCl₂ solution was injected intraperitoneally 2 h after the second intragastric administration. Mice were sacrificed after 48 h, and their serum and liver were collected. Liver coefficient was calculated. The changes of liver structure and iron deposition were observed by hematoxylin-eosin (HE) staining and Prussian blue staining. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total superoxide dismutase (T-SOD), reduced glutathione (GSH), malondialdehyde (MDA), and tissue iron content were measured with commercial kits. Western blotting was used to detect nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (Gpx4), transferrin receptor 1 (TFR1,) and solute carrier family 7 member 11 (SLC7A11). Results The AST and ALT levels of the HgCl₂ group were (76.447±9.695) U·g⁻¹ and (98.563±24.673)U·g⁻¹, respectively, which were higher than those of the control group (P<0.05). After the OA pretreatment, the liver coefficient and the above indexes were decreased to (4.769±0.237)%, (57.086±10.087) U·g⁻¹, and (87.294±27.181)U·g⁻¹, respectively. The liver coefficient and AST level of the OA + HgCl₂ group were significantly different from those of the HgCl₂ group (P<0.05). After acute exposure to HgCl₂, the hepatocytes of mice were disordered, accompanied by inflammatory infiltration, positive blue particles appeared in Prussian blue staining of liver tissue, and the above changes in liver tissue were alleviated after the OA pretreatment. The iron content in the HgCl₂ group was (3.646±0.238) μmol·g⁻¹, which was higher than that in the control group, (2.948±0.308) μmol·g⁻¹. After the OA pretreatment, the iron content decreased to (3.429±0.415) μmol·g⁻¹. Compared with the control group, acute exposure to HgCl₂ resulted in decreased levels of GSH and T-SOD, decreased protein expression levels of Nrf2, HO-1, SLC7A11, and Gpx4, increased level of MDA, and increased protein expression level of TFR1 (P<0.05). After the OA pretreatment, all indicators were improved including increased GSH level, decreased MDA level, increased Nrf2, HO-1, and SLC7A11 protein expression levels, and decreased TFR1 protein expression level; compared with the HgCl₂ group, the differences were statistically significant (P<0.05). Conclusion Acute HgCl₂ exposure could induce liver injury in mice, and its mechanism may involve iron overload and ferroptosis. OA may alleviate the liver injury caused by acute HgCl₂ exposure by affecting iron overload and the ferroptosis-related protein expression.