AIM: To investigate the correlation of serum Silent mating-type information regulation 2 homolog 1(SIRT1)and Vasostatin-2 content with pathological changes in diabetic retinopathy(DR)patients.METHODS: A total of 104 DR patients(104 eyes)admitted to our hospital from April 2021 to April 2024 were included as the DR group. According to different disease stages, they were assigned into a non-proliferative DR(NPDR)group of 44 cases(44 eyes)and a proliferative DR(PDR)group of 60 cases(60 eyes). Meantime, 104 patients(104 eyes)with simple diabetes were treated as non-DR group. ELISA was applied to detect the levels of SIRT1 and Vasostatin-2 in serum. The diagnostic value of serum SIRT1 and Vasostatin 2 in DR was analyzed by ROC curve. Multivariate Logistic regression was applied to analyze the factors that affected the occurrence of DR. Pearson correlation was applied to analyze the relationship between the levels of SIRT1 and Vasostatin-2 in the serum of DR patients and angiogenesis indicators(VEGF, Ang-2).RESULTS: Compared with the non-DR group, the levels of SIRT1 and Vasostatin-2 in the serum of the DR group were significantly decreased(P<0.05). Compared with the NPDR group, the levels of SIRT1 and Vasostatin-2 in the serum of the PDR group were significantly decreased(P<0.05). Compared with the non-DR group, the levels of VEGF and Ang-2 in the serum of the DR group were obviously higher(P<0.05). Compared with the single detection of serum SIRT1 and Vasostatin-2 levels, combined detection significantly increased the AUC in the diagnosis of DR(Z=4.180, 5.128, all P<0.05). Multivariate Logistic regression analysis showed that HOMA-IR(OR=3.455), fasting blood glucose(OR=1.467), SIRT1(OR=0.836), Vasostatin-2(OR=0.767), VEGF(OR=2.564), and Ang-2(OR=1.834)levels were the influencing factors on the occurrence of DR(all P<0.05). Pearson correlation analysis showed that the levels of SIRT1 and Vasostatin-2 in the serum of DR patients were negatively correlated with VEGF and Ang-2(rSIRT1 vs VEGF=-0.395, rSIRT1 vs Ang-2=-0.474, rVasostatin-2 vs VEGF=-0.323, rVasostatin-2 vs Ang-2=-0.583, all P<0.001).CONCLUSION: The abnormal decrease of serum SIRT1 and Vasostatin 2 levels in DR patients is closely related to the stage of DR lesions and angiogenesis.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.

Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".

Objective:To evaluate the effect of esketamine on caspase-11-mediated non-canonical pathway pyroptosis in sepsis-induced acute lung injury in rats.Methods:Eighteen SPF healthy Sprague-Dawley rats, aged 8-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), cecal ligation and puncture (CLP) group and CLP+ esketamine group (CLP+ ES group). Sepsis was induced by CLP in anesthetized animals. Esketamine 10 mg/kg was injected via the tail vein immediately after development of the model, and the equal volume of normal saline was injected via the tail vein in the other two groups. At 24 h after development of the model, the rats were sacrificed under anesthesia, and the lung tissues and blood samples were taken. The wet to dry lung weight ratio (W/D ratio) was calculated, and the pathological changes were observed and the lung injury was scored. The expression of caspase-11, gasdermin D-N (GSDMD-N), phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) was detected by Western blot. The expression of caspase-11 and GSDMD-N mRNA was detected by quantitative real-time polymerase chain reaction. The serum concentration of interleukin-1β (IL-1β) was determined by enzyme-linked immunosorbent assay. Results:Compared with Sham group, the lung injury score and W/D ratio were significantly increased, the expression of caspase-11 and GSDMD-N protein and mRNA was up-regulated, the expression of p-PI3K and p-AKT was down-regulated, and the concentration of IL-1β was increased in CLP group ( P<0.05). Compared with CLP group, the lung injury score and W/D ratio were significantly decreased, the expression of caspase-11 and GSDMD-N protein and mRNA was down-regulated, the expression of p-PI3K and p-AKT was up-regulated, and the concentration of IL-1β was decreased in CLP+ ES group ( P<0.05). Conclusions:The mechanism by which esketamine alleviates sepsis-induced acute lung injury may be related to the inhibition of caspase-11-mediated non-canonical pathway pyroptosis in rats.

Objective:To evaluate the effect of esketamine on caspase-11-mediated non-canonical pathway pyroptosis in sepsis-induced acute lung injury in rats.Methods:Eighteen SPF healthy Sprague-Dawley rats, aged 8-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), cecal ligation and puncture (CLP) group and CLP+ esketamine group (CLP+ ES group). Sepsis was induced by CLP in anesthetized animals. Esketamine 10 mg/kg was injected via the tail vein immediately after development of the model, and the equal volume of normal saline was injected via the tail vein in the other two groups. At 24 h after development of the model, the rats were sacrificed under anesthesia, and the lung tissues and blood samples were taken. The wet to dry lung weight ratio (W/D ratio) was calculated, and the pathological changes were observed and the lung injury was scored. The expression of caspase-11, gasdermin D-N (GSDMD-N), phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) was detected by Western blot. The expression of caspase-11 and GSDMD-N mRNA was detected by quantitative real-time polymerase chain reaction. The serum concentration of interleukin-1β (IL-1β) was determined by enzyme-linked immunosorbent assay. Results:Compared with Sham group, the lung injury score and W/D ratio were significantly increased, the expression of caspase-11 and GSDMD-N protein and mRNA was up-regulated, the expression of p-PI3K and p-AKT was down-regulated, and the concentration of IL-1β was increased in CLP group ( P<0.05). Compared with CLP group, the lung injury score and W/D ratio were significantly decreased, the expression of caspase-11 and GSDMD-N protein and mRNA was down-regulated, the expression of p-PI3K and p-AKT was up-regulated, and the concentration of IL-1β was decreased in CLP+ ES group ( P<0.05). Conclusions:The mechanism by which esketamine alleviates sepsis-induced acute lung injury may be related to the inhibition of caspase-11-mediated non-canonical pathway pyroptosis in rats.