Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Objective To explore the short-term prognosis and risk factors for in-hospital mortality in patients with fulminant myocarditis induced refractory cardiogenic shock(FM-RCS)receiving veno-arterial extracorporeal membrane oxygenation(VA-ECMO)treatment,and to construct an early prognosis prediction model using relevant indicators.Methods A total of 61 FM-RCS patients treatment by VA-ECMO in the department of intensive care unit of the Second Affiliated Hospital of Zhengzhou University from January 2017 to February 2024,excluding 15 cases with age less than 18 years and 3 cases with ECMO treatment duration less than 24 hours,a total of 43 patients were finally included.Participants were stratified into survival(n=19)and mortality(n=24)groups according to discharge outcomes.Demographic data,chronic disease history,early laboratory indicators,left ventricular function indicators,and basic reference values of hemodynamics were systematically compared between the two groups.Variable selection was performed using LASSO regression,followed by multivariate COX regression analysis to screen independent risk factors for in-hospital mortality in ECMO-treatment FM-RCS patients.A nomogram prediction model was subsequently developed using R software and validated through calibration curves,concordance index(C-index),and receiver operator characteristic curve(ROC curve)analysis.Results The overall survival rate of the 43 enrolled patients was 44.2%,with 19 cases in the survival group and 24 cases in the mortality group.In early laboratory indicators,the survival group exhibited significantly lower levels of initial lactic acid(Lac),24-hour Lac(Lac 24 h),24-hour MB isoenzyme of creatine kinase(CK-MB 24 h),24-hour cardiac troponin T(cTnT 24 h),24-hour total bilirubin(TBil 24 h),24-hour serum creatinine(SCr 24 h),and lactate albumin ratio(LAR)compared to the mortality group[initial Lac(mmol/L):2.7(1.3,7.6)vs.9.2(5.9,14.0),Lac 24 h(mmol/L):2.4(2.0,3.6)vs.5.4(3.3,9.2),CK-MB 24 h(U/L):58.0(28.0,115.0)vs.167.7(68.5,280.3),cTnT 24 h(μg/L):0.53(0.37,2.41)vs.3.92(3.10,8.86),TBil 24h(μmol/L):18.3(9.9,37.8)vs.40.2(24.6,67.0),SCr 24 h(μmol/L):90.63±42.49 vs.177.76±70.76,LAR:0.09(0.04,0.23)vs.0.31(0.20,0.38),all P<0.05],serum albumin(Alb)levels were significantly higher in the survival group[g/L:36.0(31.9,39.2)vs.31.7(26.4,34.4),P<0.05].The mortality group had a higher incidence of malignant arrhythmias[66.7%(16/24)vs.31.6%(6/19),P<0.05].The LASSO regression model identified four non-zero coefficient variables-Lac 24 h,CK-MB 24 h,cTnT 24 h,and SCr 24 h-which were included in the subsequent multivariate COX regression analysis.The results demonstrated that Lac 24 h[hazard ratio(HR)and 95%confidence interval(95%CI)was 1.186(1.074-1.310),P<0.001]and cTnT 24 h(HR=1.230,95%CIwas 1.078-1.404,P=0.002)were independent risk factors for in-hospital mortality in VA-ECMO treatment FM-RCS patients.A predictive model constructed using these two indicators showed a C-index of 0.812,area under the curve(AUC)=0.941,with 91.7%sensitivity and 94.7%specificity.Furthermore,compared to the survival group,the mortality group exhibited significantly higher incidences of acute kidney injury[91.7%(22/24)vs.36.8%(7/19)]and hypoxic-ischemic encephalopathy[62.5%(15/24)vs.10.5%(2/19),both P<0.05].The mortality group also required greater transfusion volumes[mL:3 800(1 420,8 515)vs.1 200(400,3 020),P<0.05],but had shorter total hospitalization durations[days:7(3,13)vs.23(20,44),P<0.05].Conclusion For FM-RCS patients receiving VA-ECMO treatment,Lac 24 h and cTnT 24 h after ECMO initiation are independent predictors of in-hospital mortality.Clinicians should be vigilant about poor prognosis in FM-RCS patients with high Lac 24 h hours(>2.5 mmol/L)and cTnT 24 hours(>3.01 μg/L)after ECMO treatment.

Objective To explore the short-term prognosis and risk factors for in-hospital mortality in patients with fulminant myocarditis induced refractory cardiogenic shock(FM-RCS)receiving veno-arterial extracorporeal membrane oxygenation(VA-ECMO)treatment,and to construct an early prognosis prediction model using relevant indicators.Methods A total of 61 FM-RCS patients treatment by VA-ECMO in the department of intensive care unit of the Second Affiliated Hospital of Zhengzhou University from January 2017 to February 2024,excluding 15 cases with age less than 18 years and 3 cases with ECMO treatment duration less than 24 hours,a total of 43 patients were finally included.Participants were stratified into survival(n=19)and mortality(n=24)groups according to discharge outcomes.Demographic data,chronic disease history,early laboratory indicators,left ventricular function indicators,and basic reference values of hemodynamics were systematically compared between the two groups.Variable selection was performed using LASSO regression,followed by multivariate COX regression analysis to screen independent risk factors for in-hospital mortality in ECMO-treatment FM-RCS patients.A nomogram prediction model was subsequently developed using R software and validated through calibration curves,concordance index(C-index),and receiver operator characteristic curve(ROC curve)analysis.Results The overall survival rate of the 43 enrolled patients was 44.2%,with 19 cases in the survival group and 24 cases in the mortality group.In early laboratory indicators,the survival group exhibited significantly lower levels of initial lactic acid(Lac),24-hour Lac(Lac 24 h),24-hour MB isoenzyme of creatine kinase(CK-MB 24 h),24-hour cardiac troponin T(cTnT 24 h),24-hour total bilirubin(TBil 24 h),24-hour serum creatinine(SCr 24 h),and lactate albumin ratio(LAR)compared to the mortality group[initial Lac(mmol/L):2.7(1.3,7.6)vs.9.2(5.9,14.0),Lac 24 h(mmol/L):2.4(2.0,3.6)vs.5.4(3.3,9.2),CK-MB 24 h(U/L):58.0(28.0,115.0)vs.167.7(68.5,280.3),cTnT 24 h(μg/L):0.53(0.37,2.41)vs.3.92(3.10,8.86),TBil 24h(μmol/L):18.3(9.9,37.8)vs.40.2(24.6,67.0),SCr 24 h(μmol/L):90.63±42.49 vs.177.76±70.76,LAR:0.09(0.04,0.23)vs.0.31(0.20,0.38),all P<0.05],serum albumin(Alb)levels were significantly higher in the survival group[g/L:36.0(31.9,39.2)vs.31.7(26.4,34.4),P<0.05].The mortality group had a higher incidence of malignant arrhythmias[66.7%(16/24)vs.31.6%(6/19),P<0.05].The LASSO regression model identified four non-zero coefficient variables-Lac 24 h,CK-MB 24 h,cTnT 24 h,and SCr 24 h-which were included in the subsequent multivariate COX regression analysis.The results demonstrated that Lac 24 h[hazard ratio(HR)and 95%confidence interval(95%CI)was 1.186(1.074-1.310),P<0.001]and cTnT 24 h(HR=1.230,95%CIwas 1.078-1.404,P=0.002)were independent risk factors for in-hospital mortality in VA-ECMO treatment FM-RCS patients.A predictive model constructed using these two indicators showed a C-index of 0.812,area under the curve(AUC)=0.941,with 91.7%sensitivity and 94.7%specificity.Furthermore,compared to the survival group,the mortality group exhibited significantly higher incidences of acute kidney injury[91.7%(22/24)vs.36.8%(7/19)]and hypoxic-ischemic encephalopathy[62.5%(15/24)vs.10.5%(2/19),both P<0.05].The mortality group also required greater transfusion volumes[mL:3 800(1 420,8 515)vs.1 200(400,3 020),P<0.05],but had shorter total hospitalization durations[days:7(3,13)vs.23(20,44),P<0.05].Conclusion For FM-RCS patients receiving VA-ECMO treatment,Lac 24 h and cTnT 24 h after ECMO initiation are independent predictors of in-hospital mortality.Clinicians should be vigilant about poor prognosis in FM-RCS patients with high Lac 24 h hours(>2.5 mmol/L)and cTnT 24 hours(>3.01 μg/L)after ECMO treatment.

Objective Neuromuscular electrical stimulation(NMES)-evoked kinesthetic information in muscle spindle can be purely extracted from the mixed motor and sensory afferents using Ischemic nerve block(INB).This study aims to investigate the somatosensory cortical response evoked by NMES activating muscle spindle afferents in forearm.Methods All subjects performed four experimental tasks designed according to a 2×2 factors,including one factor of the INB state(without INB and within INB)and the other of the stimulation intensity(above and below motor threshold).During the experiment,we recorded EEG data with 64 channels and then beta event-related desynchronization(Beta ERD)were utilized quantize somatosensory cortical excitability evoked by the tasks.The subjective perception about the sensation and movement of the right hand were evaluated by a psychophysical test after the right wrist was performed by INB.Results INB significantly reduced beta ERD on the contralateral somatosensory cortex evoked by NMES above the motor threshold,and there was significant difference of NMES-evoked beta ERD values on the contralateral somatosensory cortex between above and below motor threshold.Meanwhile,contralateral dominance of NMES-evoked beta ERD on the somatosensory cortex was transferred to ipsilateral hemisphere under INB.Conclusion INB can significantly reduce NMES-evoked somatosensory cortical response above motor threshold and decrease cortical perception on the stimulus intensity,which may be due to INB resulting in rapid functional reorganization of somatosensory cortex.

Hemophilia encompasses a group of hereditary bleeding disorders characterized by impaired clotting factor activity,leading to prolonged clotting times.Patients display a tendency toward clotting issues following minor injuries,and severe cases may experience spontaneous bleeding.Acquired von Willebrand syndrome(AvWS)occurs due to the reduction of von Willebrand factor(vWF)levels,resulting in impaired platelet adhesion to endothelial cells,thereby compromising clotting function and leading to bleeding events.The increasing use of extracorporeal membrane oxygenation(ECMO)in clinical settings has brought attention to ECMO-related AvWS.During ECMO support,patients'blood exposure to high shear forces and non-physiological conditions can exacerbate the reduction of vWF levels,further impacting coagulation function.The precise mechanisms triggering AvWS during ECMO support are not conclusively defined,however,studies indicate that high shear forces and systemic inflammation response syndrome(SIRS)are key factors.Mechanical shear stress induced by ECMO damages endothelial cells,releasing factors associated with von Willebrand disease(vWD).Additionally,ECMO-induced SIRS may further compromise vWF functionality.Understanding these mechanisms is crucial for formulating effective preventive and treatment strategies.Diagnosing AvWS during ECMO support can be complex.Typically,assessing a patient's coagulation function and related factor levels is necessary,while cautious interpretation is vital due to potential ECMO interferences.Treatment strategies for managing AvWS during ECMO support are still under investigation.Some studies suggest that using plasma products may improve coagulation function.However,specific treatment approaches should be tailored to individual patient conditions and adjusted based on close monitoring.In summary,diagnosing and treating AvWS during ECMO support remains complex and challenging.Further research holds promise for better understanding the mechanisms involved and for developing more effective treatment strategies to enhance patient prognosis and quality of life.

Objective:To describe the dietary intake and influencing factors of energy intake in patients with gastric cancer at home.Methods:The research tools including Food Frequency Questionnaire,Digestive Cancer Patients Nutrition Knowledge,Attitude and Practice Questionnaire,and Eastern Cooperative Oncology Group performance status score were used to collect information on home oral nutrition intake,nutritional knowledge,attitudes,and physical status of patients with gastric cancer.Logistic regression analysis was performed to identify the relevant factors that affect the achievement of oral energy intake standards.Results:A total of 160 patients with gastric cancer were analyzed in this study.Overall,21.9%did not reach energy intake target.The results of Logistic regression showed the nutritional knowledge level of the patients(Waldχ2=18.42,P<0.001)and the Eastern Cooperative Oncology Group performance status score(Waldχ2=11.16,P=0.011)were independent factors related to substandard energy intake in gastric cancer patients.Conclusion:The dietary energy intake of most gastric cancer patients reached the recommended target amount,and the nutritional knowledge and activity of the patients affect the energy intake,suggesting that medical staff can intervene in the patients whose energy intake does not meet the standard from the aspects of nutritional knowledge and activities.

Objective:To describe the dietary intake and influencing factors of energy intake in patients with gastric cancer at home.Methods:The research tools including Food Frequency Questionnaire,Digestive Cancer Patients Nutrition Knowledge,Attitude and Practice Questionnaire,and Eastern Cooperative Oncology Group performance status score were used to collect information on home oral nutrition intake,nutritional knowledge,attitudes,and physical status of patients with gastric cancer.Logistic regression analysis was performed to identify the relevant factors that affect the achievement of oral energy intake standards.Results:A total of 160 patients with gastric cancer were analyzed in this study.Overall,21.9%did not reach energy intake target.The results of Logistic regression showed the nutritional knowledge level of the patients(Waldχ2=18.42,P<0.001)and the Eastern Cooperative Oncology Group performance status score(Waldχ2=11.16,P=0.011)were independent factors related to substandard energy intake in gastric cancer patients.Conclusion:The dietary energy intake of most gastric cancer patients reached the recommended target amount,and the nutritional knowledge and activity of the patients affect the energy intake,suggesting that medical staff can intervene in the patients whose energy intake does not meet the standard from the aspects of nutritional knowledge and activities.

OBJECTIVE:To study the effects of Dianxianqing granule on the interleukin(IL-6)content and glial fibrillary acid-ic protein(GFAP),ionized calcium linker molecules 1(Iba-1)expressions in hippocampus tissue of rats with kainate-induced epi-lepsy,and explore its mechanism of preventing and treating epilepsy. METHODS:Rats were randomly divided into sham operation group (distilled water),model group (distilled water),phenytoin group (0.03 g/kg,positive control) and Dianxianqing granule low-dose,medium-dose,high-dose groups(4.74,9.47,18.94 g/kg,calculated by crude drug),20 in each group. Rats were intra-gastrically administrated once a day,for 7 d. After 1 h of last administration,except for sham operation group,rats in other groups received single injection of kainite in hippocampus CA1 of left side to induce the epilepsy model. Behavioral changes and death of rats were observed. After 24 h of modeling,enzyme-linked immunosorbent method was used to detect the IL-6 content in hippocam-pus tissue of rats,Nissl staining was used to count the hippocampus neurons,and immunohistochemistry was used to detect the GFAP,Iba-1 expressions in hippocampus tissue of rats. RESULTS:Compared with sham operation group,rats in model group had obvious epilepsy symptoms after modeling,and parts of rats died;IL-6 content and number of neurons in hippocampus tissue were obviously decreased (P<0.01), while GFAP, Iba-1 expressions were obviously enhanced (P<0.01). Compared with model group,epilepsy symptoms and death in each administration group had improved,while IL-6 content in hippocampus tissue were in-creased to varying degrees,with no statistical significance (P>0.05). The numbers of neurons in phenytoin group,Dianxianqinggranule medium-dose, high-dose groups were obviously in-creased(P<0.01);GFAP expression was obviously decreased (P<0.01). Iba-1 expressions in hippocampus tissue in phenyt-oin group,Dianxianqing granule high-dose group were obvi-ously decreased (P<0.01). CONCLUSIONS:Dianxianqing granule can play the role in preventing and treating epilepsy by inhibiting GFAP,Iba-1 expressions in hippocampus tissue and in-creasing the number of neurons in hippocampus tissue.

Objective To establish the murine models of local allergic rhinitis (LAR) and allergic rhinitis (AR) by using ovalbumin (OVA),and to investigate the relationship between them.Methods Thirty BALB/c mice were divided into 5 groups,(1) the nasally sensitized group (group A1) that was challenged with OVA by a 10 d procedure,(2) the control group of A1 that was challenged with phosphatebuffered saline (PBS),(3) the nasally sensitized group (group A2) that was challenged with OVA by a 25 d procedure,(4) the control group of A2 that was challenged with PBS,(5) the intraperitoneally sensitized group (group B).The numbers of sneezing after final challenge were counted,and the serum OVA-specific immunoglobulin E (OVA-slgE),interleukin (IL)-4,IL-13,IL-5 levels in nasal lavage fluid were measured by ELISA.Hematoxylin-eosin staining was performed to evaluate the histological change of nose and lung tissues.Graph Pad Prism 6 software was used to analyze the data.Results Nasally sensitized group A1 displayed LAR symptoms of sneezing and eosinophilic infiltrating,but without increased OVA-sIgE in serum on day 10 compared with the control group of A1(t =0.697,P ＞ 0.05),OVA-sIgE in serum of group A2(2.710 ± 1.406)ng/ml reached to statistical significance and with airway remodeling on day 25 compared with the control group of A2 ((0.221 ± 0.080) ng/ml,t =4.329,P ＜ 0.05).IL-5 and IL-13 in nasal fluid showed a significant increase in the nasally sensitized group A1,compared with the group A2 (t values were 2.442,2.804,P values were less then 0.05).Conclusions A short time intranasal instillation with OVA could establish LAR murine model,continuing OVA challenge could increase serum sIgE level and with airway remodeling.LAR mice show a unique characteristic by expressing higher IL-5 and IL-13 in nose than AR mice,but sIgE in serum remains at a normal level.