ObjectiveTo analyze the protective effect of different types of influenza vaccines (InfV) against influenza A among the individuals aged between 3‒17 years old, and to provide a scientific basis for the prevention and control of influenza in the future. MethodsA retrospective cohort study was conducted to collect data on the incidence and InfV vaccination of the individuals aged between 3‒17 years during the influenza epidemic season from 2022 to 2023. Vaccine effectiveness (VE) was calculated, and a log-binomial regression model was used to calculate the corrected VE. ResultsThe incidence rate of influenza in InfV vaccinated and un-vaccinated groups was 7.32% (1 937/ 26 446) and 9.65% (4 421/45 837), respectively. After adjusting for age and gender factors, the unadjusted VE (95%CI) was 54.57% (52.24%‒56.78%). The unadjusted VE (95%CI) was 53.66% (50.36%‒56.74%) for males and 55.60% (52.24%‒58.72%) for females, respectively. The unadjusted VE (95%CI) for the age group of 3‒ years, 6‒ years, 9‒ years, 12‒ years, and 15‒17 years were 64.08% (60.89%‒67.01%), 57.40% (53.71%‒60.80%), 57.77% (52.49%‒62.47%), 24.36% (9.49%‒36.79%), and 24.09% (-17.59%‒51.00%), respectively. The unadjusted VE (95%CI) for quadrivalent split-virion inactivated influenza vaccine, trivalent split-virion inactivated influenza vaccine, trivalent subunit influenza vaccine, and trivalent live attenuated influenza vaccine were 53.84% (51.32%‒56.24%), 62.17% (56.28%‒67.26%), 79.83% (69.94%‒86.46%), and 31.59% (19.07%‒42.18%), respectively. ConclusionThe InfV used during the 2022‒2023 influenza season had a good protective effect against influenza A among the individuals aged between 3‒17 years old, especially in those aged between 3‒11 years old.

Objective To investigate the protective effect and mechanism of schisandrin A(SA)on hydrogen peroxide(H2O2)-induced oxidative stress injury in renal tubular epithelial cells(HK-2).Methods HK-2 cells were cultured in vitro and divided into five groups:blank control group,model control group(treated with 600 μmol·L-1 H2O2 for 2 h),low-dose SA group(0.125 μmol·L-1 SA,24 h pretreatment+H2O2),medium-dose SA group(0.5 μmol·L-1 SA,24 h pretreatment+H2 O2),high-dose SA group(0.75 μmol·L-1 SA,24 h pretreatment+H2O2).The cell survival was assessed by CCK-8 assay;apoptosis level was tested by Annexin V-FITC/PI double staining;cell cycle distribution was detected by propidium iodide staining;oxidative markers(ROS,SOD,MDA,GSH,LDH)was determined with commercial kits;and apoptosis-related proteins(Bax,Bcl-2,Caspase-3,Cytochrome C)was evaluated by Western blot.Results Compared with the blank control,the model group reduced in cell viability and increased in apoptosis(P＜0.01),elevated in the ratio of G0/G1-phase cells and decreased in S-phase cells(P＜0.05),decreased in SOD activity and GSH content(P＜0.01),and increased in the levels of ROS,LDH,and MDA levels(P＜0.01).In all SA dose,cell apoptosis reduced(P＜0.01).In medium/high dose groups,the G0/G1-phase arrest reduced(P＜0.05).In high dose group,the S-phase cells ratio increased(P＜0.05).And in medium/high dose groups,ROS(P＜0.01)decreased in a dose-dependent manner.The SOD activity increased non-significantly in all SA groups.In SA medium/high dose groups,the LDH activity decreased in a dose-dependent manner.In all SA groups,GSH increased(P＜0.01)and MDA decreased,both in a dose-dependent manner.The Bax/Bcl-2 ratio significantly decreased(P＜0.05)in all SA groups.The caspase-3 activity decreased in medium/high dose group(P＜0.05);and Cytochrome C reduced in all SA groups(P＜0.05).Conclusion SA protects HK-2 cells against H2O2-induced oxidative injury by modulating oxidative stress,inhibiting apoptosis,and ameliorating cell cycle arrest.

Objective:To investigate the regulatory role of miR-146a in the maintenance of homeostasis and function of conventional dendritic cells (cDCs).Methods:Bone marrow-derived dendritic cells (BMDCs) from wild-type (WT) and miR-146a knockout (miR-146a KO) mice were cultured in vitro. RT-PCR was used to analyze miR-146a expression in BMDCs stimulated by Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) or TLR9 ligand CpG oligonucleotide (CpG-ODN); flow cytometry was performed to assess the expression of MHCⅡ and co-stimulatory markers (CD86 and CD80); RT-PCR and ELISA were used to measure the expression of cytokines at mRNA and protein levels, respectively; the influence of miR-146a-deficient BMDCs on CD4 + OTⅡT cell proliferation and differentiation was analyzed through in vitro co-culture and in vivo adoptive transfer experiments; flow cytometry was used to analyze the changes in the proportions of splenic DCs subsets in mice; the regulatory role of miR-146a in maintaining splenic DC homeostasis was further investigated using miR-146a KO mice and bone marrow chimeric models. Two-tailed t test was used for statistical analysis. Results:Following the stimulation with TLR4/9 ligands, miR-146a expression was significantly enhanced in BMDCs from WT mice ( P<0.01); the expression of MHCⅡ and CD86 in BMDCs from miR-146a KO mice were higher than in those from WT mice (all P<0.01). Following CpG-ODN stimulation, IL-12 and IL-6 expression at both mRNA and protein levels were higher in BMDCs from miR-146a KO mice than in those from WT mice (all P<0.05). However, no statistically significant differences in IL-12 or IL-6 expression were observed after LPS stimulation (all P>0.05). CpG-ODN-activated BMDCs demonstrated a robust capability to promote the proliferation of CD4 + OTⅡT cells and induced Th1/Th17 cell polarization (all P<0.01). Compared with WT mice, miR-146a KO mice showed a significant reduction in the CD11c + CD11b highcDC subsets in the spleen ( P<0.01). Bone marrow chimeric mice further confirmed that miR-146a played a critical role in maintaining the homeostasis of splenic CD11c + CD11b highcDC subsets. Conclusion:miR-146a regulates the homeostasis and function of cDC subsets, suggesting its potential for developing novel DC-based therapeutic strategies against microbial infections.

Objective To investigate the protective effect and mechanism of schisandrin A(SA)on hydrogen peroxide(H2O2)-induced oxidative stress injury in renal tubular epithelial cells(HK-2).Methods HK-2 cells were cultured in vitro and divided into five groups:blank control group,model control group(treated with 600 μmol·L-1 H2O2 for 2 h),low-dose SA group(0.125 μmol·L-1 SA,24 h pretreatment+H2O2),medium-dose SA group(0.5 μmol·L-1 SA,24 h pretreatment+H2 O2),high-dose SA group(0.75 μmol·L-1 SA,24 h pretreatment+H2O2).The cell survival was assessed by CCK-8 assay;apoptosis level was tested by Annexin V-FITC/PI double staining;cell cycle distribution was detected by propidium iodide staining;oxidative markers(ROS,SOD,MDA,GSH,LDH)was determined with commercial kits;and apoptosis-related proteins(Bax,Bcl-2,Caspase-3,Cytochrome C)was evaluated by Western blot.Results Compared with the blank control,the model group reduced in cell viability and increased in apoptosis(P＜0.01),elevated in the ratio of G0/G1-phase cells and decreased in S-phase cells(P＜0.05),decreased in SOD activity and GSH content(P＜0.01),and increased in the levels of ROS,LDH,and MDA levels(P＜0.01).In all SA dose,cell apoptosis reduced(P＜0.01).In medium/high dose groups,the G0/G1-phase arrest reduced(P＜0.05).In high dose group,the S-phase cells ratio increased(P＜0.05).And in medium/high dose groups,ROS(P＜0.01)decreased in a dose-dependent manner.The SOD activity increased non-significantly in all SA groups.In SA medium/high dose groups,the LDH activity decreased in a dose-dependent manner.In all SA groups,GSH increased(P＜0.01)and MDA decreased,both in a dose-dependent manner.The Bax/Bcl-2 ratio significantly decreased(P＜0.05)in all SA groups.The caspase-3 activity decreased in medium/high dose group(P＜0.05);and Cytochrome C reduced in all SA groups(P＜0.05).Conclusion SA protects HK-2 cells against H2O2-induced oxidative injury by modulating oxidative stress,inhibiting apoptosis,and ameliorating cell cycle arrest.

Objective:To investigate the regulatory role of miR-146a in the maintenance of homeostasis and function of conventional dendritic cells (cDCs).Methods:Bone marrow-derived dendritic cells (BMDCs) from wild-type (WT) and miR-146a knockout (miR-146a KO) mice were cultured in vitro. RT-PCR was used to analyze miR-146a expression in BMDCs stimulated by Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) or TLR9 ligand CpG oligonucleotide (CpG-ODN); flow cytometry was performed to assess the expression of MHCⅡ and co-stimulatory markers (CD86 and CD80); RT-PCR and ELISA were used to measure the expression of cytokines at mRNA and protein levels, respectively; the influence of miR-146a-deficient BMDCs on CD4 + OTⅡT cell proliferation and differentiation was analyzed through in vitro co-culture and in vivo adoptive transfer experiments; flow cytometry was used to analyze the changes in the proportions of splenic DCs subsets in mice; the regulatory role of miR-146a in maintaining splenic DC homeostasis was further investigated using miR-146a KO mice and bone marrow chimeric models. Two-tailed t test was used for statistical analysis. Results:Following the stimulation with TLR4/9 ligands, miR-146a expression was significantly enhanced in BMDCs from WT mice ( P<0.01); the expression of MHCⅡ and CD86 in BMDCs from miR-146a KO mice were higher than in those from WT mice (all P<0.01). Following CpG-ODN stimulation, IL-12 and IL-6 expression at both mRNA and protein levels were higher in BMDCs from miR-146a KO mice than in those from WT mice (all P<0.05). However, no statistically significant differences in IL-12 or IL-6 expression were observed after LPS stimulation (all P>0.05). CpG-ODN-activated BMDCs demonstrated a robust capability to promote the proliferation of CD4 + OTⅡT cells and induced Th1/Th17 cell polarization (all P<0.01). Compared with WT mice, miR-146a KO mice showed a significant reduction in the CD11c + CD11b highcDC subsets in the spleen ( P<0.01). Bone marrow chimeric mice further confirmed that miR-146a played a critical role in maintaining the homeostasis of splenic CD11c + CD11b highcDC subsets. Conclusion:miR-146a regulates the homeostasis and function of cDC subsets, suggesting its potential for developing novel DC-based therapeutic strategies against microbial infections.

Objective To analyze the prognosis and influencing factors of patients with acute myocardial infarction(AMI)complicated with cardiogenic shock(CS)under extracorporeal membrane oxygenation(ECMO)support.Methods Retrospective analysis of the clinical data of ECMO supported coronary angiography and percutaneous coronary intervention(PCI)treatment for AMI complicated with CS patients who visited the department of emergency medicine of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking history,coronary heart disease,diabetes,hypertension,hyperlipidemia,cerebrovascular disease),acute physiological and chronic health evaluationⅡ(APACHEⅡ),vasoactive-inotropic score(VIS),the worst auxiliary examination indicators within 24 hours before ECMO[arterial lactate acid,white blood cell count(WBC),cardiac troponin I(cTnI),alanine transferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium(K+),left ventricular ejection fraction(LVEF)],time from onset to PCI,coronary angiography results(involved anterior descending branch,circumflex branch,right coronary artery,three-vessel lesions,left main artery lesions),whether to use intra aortic-balloon counterpulsation(IABP)and continuous renal replacement therapy(CRRT).Patients were divided into survival and death groups based on the prognosis after 30 days of onset.Univariate analysis was used to compare the differences in the above indicators between the two groups with different prognoses,Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of AMI patients with CS under ECMO support coronary angiography and PCI treatment,and the receiver operator characteristic curve(ROC curve)was drawn to evaluate the predictive value of risk factors on patient prognosis.Results Out of 39 patients,21 cases(53.8%)survived and 18 cases(46.2%)died.Compared with the survival group,the VIS score,lactate acid,time from onset to PCI,involvement of the circumflex artery,three-vessel disease,and left main artery lesions significantly increased in the death group(all P＜0.05).Logistic regression analysis showed that lactate acid and three-vessel lesions were independent risk factors affecting the 30-day prognosis of AMI patients with CS[odds ratio(OR)and 95%confidence interval(95%CI)were 1.845(1.018-3.342)and 107.171(1.307-8 785.901),all P＜0.05].ROC curve analysis showed that lactate acid and three-vessel lesions has predictive value for the prognosis of AMI combined with CS patients undergoing ECMO supported coronary angiography and PCI treatment,the area under the ROC curve(AUC)were 0.756 and 0.752,95%CI were 0.601-0.911 and 0.588-0.916,P value were 0.007 and 0.008.When the cut-off value of lactic acid was 5 mmol/L,the sensitivity and specificity of predicting the prognosis of AMI combined with CS patients undergoing coronary angiography and PCI treatment were 94.1%and 57.1%,respectively.Conclusions The indications for using ECMO in critically ill patients with AMI combined with CS need to be further refined.VIS score,lactate acid,time from onset to PCI,three-vessel lesions,and left main artery lesions are risk factors for patient death.When using ECMO support for high lactate,high VIS score,and three-vessel lesions,caution should be exercised.Early ECMO support can improve the prognosis of appropriate patients by reducing lactate,reducing the use of vasoactive drugs,and shortening the time from onset to PCI.

Objective To investigate the predictive value of geriatric nutritional risk index(GNRI)for stroke-associated pneumonia in elderly patients with acute ischemic stroke(AIS).Methods A total of 1505 elderly patients with AIS admitted to Department of Neurology of the Second Affili-ated Hospital of Nanchang University from January 2017 to October 2022 were included in this retrospective study.According to GNRI nutritional assessment,they were divided into T1(high nutritional risk,GNRI＜82,n=49),T2(moderate nutritional risk,GNRI 82-91,n=305),T3(low nutritional risk,GNRI 92-98,n=555),and T4(no nutritional risk,GNRL＞98,n=596)groups.Additionally,based on the discharge diagnosis,they were further classified into pulmonary infection group(150 cases)and non-infection group(1355 cases).These subjects were also ran-domly assigned into training,validation,and testing sets in a ratio of 16∶4∶5.Multivariate logis-tic regression analysis was performed to identify the risk factors for pulmonary infection in stroke patients.Logistic regression and XGBoost algorithms were used to establish prediction models for pulmonary infection.The models were evaluated with their AUC value,accuracy,sensitivity,and specificity based on ROC curve analysis.Results Multivariate logistic regression analysis revealed that hypertension,invasive procedures,consciousness disorders,CRP,lymphocyte count,hemoglo-bin and GNRI were independent risk factors for pulmonary infection in stroke patients(P＜0.05).The AUC value of the GNRI model for predicting pulmonary infection in the testing set was 0.742(95％CI:0.651-0.833),with an accuracy of 71.8％,sensitivity of 76.7％,and specificity of 71.2％.The combined model of clinical indicators(hypertension,invasive procedures,conscious-ness disorders,CRP,lymphocyte count,hemoglobin)and GNRI achieved an AUC value of 0.776(95％CI:0.700-0.853),accuracy of 74.8％,sensitivity of 83.3％,and specificity of 73.8％in the test set.Conclusion GNRI is an independent risk factor for pulmonary infection in elderly pa-tients with AIS and has a certain value in predicting pulmonary infection after AIS.

Reducing lactate accumulation has always been a goal of the mammalian cell biotechnology industry. When animal cells are cultured in vitro, the accumulation of lactate is mainly the combined result of two metabolic pathways. On one hand, glucose generates lactate under the function of lactate dehydrogenase A (LDHA); on the other hand, lactate can be oxidized to pyruvate by LDHB or LDHC and re-enter the TCA cycle. This study comprehensively evaluated the effects of LDH manipulation on the growth, metabolism and human adenovirus (HAdV) production of human embryonic kidney 293 (HEK-293) cells, providing a theoretical basis for engineering the lactate metabolism in mammalian cells. By knocking out ldha gene and overexpression of ldhb and ldhc genes, the metabolic efficiency of HEK-293 cells was effectively improved, and HAdV production was significantly increased. Compared with the control cell, LDH manipulation promoted cell growth, reduced the accumulation of lactate and ammonia, significantly enhanced the efficiency of substrate and energy metabolism of cells, and significantly increased the HAdV production capacity of HEK-293 cells. Among these LDH manipulation measures, ldhc gene overexpression performed the best, with the maximum cell density increased by about 38.7%. The yield of lactate to glucose and ammonia to glutamine decreased by 33.8% and 63.3%, respectively; and HAdV titer increased by at least 16 times. In addition, the ATP production rate, ATP/O₂ ratio, ATP/ADP ratio and NADH content of the modified cell lines were increased to varying degrees, and the energy metabolic efficiency was significantly improved.
Animals ; Humans ; L-Lactate Dehydrogenase/genetics* ; Lactic Acid ; Adenoviruses, Human ; Ammonia ; HEK293 Cells ; Glucose/metabolism* ; Adenosine Triphosphate/metabolism* ; Kidney/metabolism* ; Mammals/metabolism*

Objective To explore the predictive efficacy of XGboost model in predicting risk of relapse and re-admission within 90 d in patients with ischemic stroke,and provide basis for early screening and prevention of high-risk population with ischemic stroke.Methods The clinical data of 6070 primary ischemic stroke patients admitted to our hospital from January 2007 to July 2017 were retrospectively collected.XGboost model and multivariate Logistic regression model were utilized to screen out the influencing factors of relapse and re-admission within 90 d in patients with ischemic stroke.A predictive model was set up.Receiver operating characteristic (ROC) curve was drawn and compared.Sensitivity,specificity and Youden index were calculated and compared to evaluate the prediction performance of XGboost model.Results During the observation period,a total of 520 patients with relapsed ischemic stroke were observed within a period of 90 d,and the incidence density was 8.57％.Multivariate Logistic regression analysis showed that length of first hospital stay,hypertension,pulmonary infection,neutrophil percentage,red blood cell distribution width (variable coefficient),and alkaline phosphatase level were independent influencing factors for re-hospitalization within 90 d of ischemic stroke,(OR=1.016,P=0.000,95％CI:1.008-1.025;OR=4.598,P=0.000,95％CI:3.717-5.687;OR=1.452,P=0.025,95％CI:1.048-2.012;OR=1.013,P=0.006,95％CI:1.004-1.022;OR=1.161,P=0.000,95％CI:1.090-1.237;OR=1.003,P=0.023,95％CI:1.000-1.005).Analysis of importance of risk factors for re-admission of ischemic stroke using XGboost model showed that the top 6 factors were hypertension,red blood cell distribution width,direct bilirubin,length of hospital stay,pulmonary infection,and alkaline phosphatase,and the corresponding importance scores were 32,20,19,18,15 and 14,respectively.ROC curve analysis results indicated that the area under the ROC for re-admission for XGboost model was 0.792 (95％CI:0.717-0.762),which was improved by 5％ as compared with that for multivariate Logistic regression model (0.739 [95％CI:0.764-0.818]).The sensitivity was 89.30％ and the Youden index was 0.444 for XGboost model,which were significantly higher than those for multivariate Logistic regression model (77.3％,0.405).Conclusions XGboost model is superior to multivariate Logistic regression model in predicting recurrence and re-admission of first ischemic stroke patients within 90 d.This model is suitable for prediction and early diagnosis of re-admission of ischemic stroke,which is of great clinical value.