1.Study on the correlation between the expression of inflammatory cytokines in cerebrospinal fluid and the severity and prognosis of spontaneous intracerebral hemorrhage
Jianqiang WEI ; Jing YIN ; Ming-yan HONG ; Jianzhong CUI ; Kaijie WANG ; Hongyu WANG ; Xinwang CAI ; Wenqian ZHANG ; Huan LIU
The Journal of Practical Medicine 2025;41(22):3558-3565
Objective To examine the expression levels of inflammatory factors,including IL-6,IL-10,MMP-9,IL-17A,and LDH,in the cerebrospinal fluid(CSF)of patients with spontaneous intracerebral hemor-rhage(sICH),and to investigate their associations with disease severity and clinical outcomes.Methods A total of 168 patients with sICH admitted to Tangshan GongRen Hospital between January 2023 and January 2025 were prospectively enrolled as the study group,while 30 non-sICH patients who underwent lumbar puncture during the same period served as the control group.Levels of inflammatory factors in CSF were compared between the two groups.Spearman's rank correlation analysis was performed to assess the association between inflammatory factor levels and clinical severity in sICH patients.Binary logistic regression analysis was conducted to identify independent predictors of sICH prognosis.Receiver operating characteristic(ROC)curve analysis was employed to evaluate the prognostic value of these inflammatory factors in sICH.Results The levels of IL-6,IL-10,MMP-9,IL-17A,and LDH in the CSF of patients with sICH were significantly higher than those in non-sICH patients(all P<0.05).Furthermore,among sICH patients,these biomarker levels exhibited a graded increase according to disease severity:severe>moderate>mild(all P<0.05).Spearman correlation analysis revealed significant positive correlations between CSF levels of IL-6,IL-10,MMP-9,IL-17A,and LDH and the NIHSS scores,with correlation coefficients(r)of 0.686,0.553,0.685,0.593,and 0.695,respectively(all P<0.05).When comparing the prognoses of sICH patients,hematoma size,NIHSS score,and CSF levels of IL-6,IL-10,MMP-9,IL-17A,and LDH were significantly higher in the deceased group than in the survival group(P<0.05),whereas ApoA1 levels were lower in the deceased group(P<0.05).Logistic regression analysis revealed that hematoma size,NIHSS score,and elevated CSF levels of IL-6,IL-10,MMP-9,IL-17A,and LDH were independent risk factors for mortality in sICH patients(P<0.05).ROC curve analysis showed that the AUC values for CSF IL-6,IL-10,MMP-9,IL-17A,and LDH in predicting sICH prognosis were 0.794,0.754,0.670,0.717,and 0.683,respectively.Notably,the combination of CSF inflammatory markers with hematoma size and NIHSS score yielded an AUC of 0.993,demonstrating significantly greater predictive accuracy than CSF inflammatory markers alone(P<0.05).Conclusions The levels of inflammatory factors in the CSF,including IL-6,IL-10,MMP-9,IL-17A,and LDH,were elevated in patients with sICH and positively correlated with disease severity.Combining CSF inflammatory markers with the NIHSS score and hematoma size improved the predictive accuracy for sICH prognosis.
2.Patent ductus arteriosus severity predicts the occurrence and mortality of pulmonary hemorrhage in pre-mature infants with gestational age≤32 weeks
Qiannan JIANG ; Tingting LIU ; Yingying LIU ; Kaijie CUI ; Xiuxiang LIU
The Journal of Practical Medicine 2025;41(10):1575-1583
Objective To evaluate the predictive value of patent ductus arteriosus(PDA)for the incidence and mortality of neonatal pulmonary hemorrhage(NPH)in infants with a gestational age(GA)of≤32 weeks.Methods Retrospective analysis of clinical data from premature infants with GA≤32 weeks consecutively admitted between January 2021 and June 2024.The analyzed clinical characteristics included GA,birth weight(WT),mode of delivery,diseases experienced by the infants,and maternal perinatal factors.Infants were categorized based on the presence or absence of NPH,and the clinical features of both groups were compared.Furthermore,infants with NPH and hemodynamically significant patent ductus arteriosus(hsPDA)were subdivided according to in-hospital mortality for additional analysis.Results The study included a total of 511 pediatric patients,of whom 92 cases were diagnosed with NPH.NPH was strongly correlated with mechanical ventilation(MV),high-frequency oscil-lation(HFO),hsPDA,disseminated intravascular coagulation(DIC),and intraventricular hemorrhage(IVH)(r=0.443,0.407,0.352,0.325,0.310,respectively;all P<0.001).Neonatal respiratory distress syndrome(NRDS)(grades 3-4),IVH,MV,HFO,DIC,and hsPDA were identified as independent risk factors for NPH in infants≤32 weeks of GA(OR=2.641,2.097,1.065,2.298,5.550,3.820,respectively;all P<0.05).GA,WT,PDA diameter,PDA velocity,left ventricular output(LVO),velocity of the late diastolic a'wave in the left ventricle(LV a'),and neonatal asphyxia(NA)were significant factors influencing NPH combined with hsPDA(all P<0.05).The PDA severity score(PDAsc)was determined to be a risk factor for mortality in infants≤32 weeks of GA with NPH and hsPDA(OR=1.265,95%CI 1.031-1.553,P=0.024).A strong correlation was observed between the predicted probability of death in infants with NPH and PDA and PDAsc(r=0.901,P=0.001).The ROC curve analysis demonstrated that PDAsc served as an ideal predictor of mortality in infants with NPH and PDA(AUC=0.687,P=0.002).Conclusions hsPDA is an independent risk factor for the development of NPH in infants≤32 weeks of GA.Additionally,PDAsc serves as a significant risk factor for mortality in infants≤32 weeks of GA who have both NPH and PDA,indicating a strong correlation and potential predictive value.
3.Patent ductus arteriosus severity predicts the occurrence and mortality of pulmonary hemorrhage in pre-mature infants with gestational age≤32 weeks
Qiannan JIANG ; Tingting LIU ; Yingying LIU ; Kaijie CUI ; Xiuxiang LIU
The Journal of Practical Medicine 2025;41(10):1575-1583
Objective To evaluate the predictive value of patent ductus arteriosus(PDA)for the incidence and mortality of neonatal pulmonary hemorrhage(NPH)in infants with a gestational age(GA)of≤32 weeks.Methods Retrospective analysis of clinical data from premature infants with GA≤32 weeks consecutively admitted between January 2021 and June 2024.The analyzed clinical characteristics included GA,birth weight(WT),mode of delivery,diseases experienced by the infants,and maternal perinatal factors.Infants were categorized based on the presence or absence of NPH,and the clinical features of both groups were compared.Furthermore,infants with NPH and hemodynamically significant patent ductus arteriosus(hsPDA)were subdivided according to in-hospital mortality for additional analysis.Results The study included a total of 511 pediatric patients,of whom 92 cases were diagnosed with NPH.NPH was strongly correlated with mechanical ventilation(MV),high-frequency oscil-lation(HFO),hsPDA,disseminated intravascular coagulation(DIC),and intraventricular hemorrhage(IVH)(r=0.443,0.407,0.352,0.325,0.310,respectively;all P<0.001).Neonatal respiratory distress syndrome(NRDS)(grades 3-4),IVH,MV,HFO,DIC,and hsPDA were identified as independent risk factors for NPH in infants≤32 weeks of GA(OR=2.641,2.097,1.065,2.298,5.550,3.820,respectively;all P<0.05).GA,WT,PDA diameter,PDA velocity,left ventricular output(LVO),velocity of the late diastolic a'wave in the left ventricle(LV a'),and neonatal asphyxia(NA)were significant factors influencing NPH combined with hsPDA(all P<0.05).The PDA severity score(PDAsc)was determined to be a risk factor for mortality in infants≤32 weeks of GA with NPH and hsPDA(OR=1.265,95%CI 1.031-1.553,P=0.024).A strong correlation was observed between the predicted probability of death in infants with NPH and PDA and PDAsc(r=0.901,P=0.001).The ROC curve analysis demonstrated that PDAsc served as an ideal predictor of mortality in infants with NPH and PDA(AUC=0.687,P=0.002).Conclusions hsPDA is an independent risk factor for the development of NPH in infants≤32 weeks of GA.Additionally,PDAsc serves as a significant risk factor for mortality in infants≤32 weeks of GA who have both NPH and PDA,indicating a strong correlation and potential predictive value.
4.Study on the correlation between the expression of inflammatory cytokines in cerebrospinal fluid and the severity and prognosis of spontaneous intracerebral hemorrhage
Jianqiang WEI ; Jing YIN ; Ming-yan HONG ; Jianzhong CUI ; Kaijie WANG ; Hongyu WANG ; Xinwang CAI ; Wenqian ZHANG ; Huan LIU
The Journal of Practical Medicine 2025;41(22):3558-3565
Objective To examine the expression levels of inflammatory factors,including IL-6,IL-10,MMP-9,IL-17A,and LDH,in the cerebrospinal fluid(CSF)of patients with spontaneous intracerebral hemor-rhage(sICH),and to investigate their associations with disease severity and clinical outcomes.Methods A total of 168 patients with sICH admitted to Tangshan GongRen Hospital between January 2023 and January 2025 were prospectively enrolled as the study group,while 30 non-sICH patients who underwent lumbar puncture during the same period served as the control group.Levels of inflammatory factors in CSF were compared between the two groups.Spearman's rank correlation analysis was performed to assess the association between inflammatory factor levels and clinical severity in sICH patients.Binary logistic regression analysis was conducted to identify independent predictors of sICH prognosis.Receiver operating characteristic(ROC)curve analysis was employed to evaluate the prognostic value of these inflammatory factors in sICH.Results The levels of IL-6,IL-10,MMP-9,IL-17A,and LDH in the CSF of patients with sICH were significantly higher than those in non-sICH patients(all P<0.05).Furthermore,among sICH patients,these biomarker levels exhibited a graded increase according to disease severity:severe>moderate>mild(all P<0.05).Spearman correlation analysis revealed significant positive correlations between CSF levels of IL-6,IL-10,MMP-9,IL-17A,and LDH and the NIHSS scores,with correlation coefficients(r)of 0.686,0.553,0.685,0.593,and 0.695,respectively(all P<0.05).When comparing the prognoses of sICH patients,hematoma size,NIHSS score,and CSF levels of IL-6,IL-10,MMP-9,IL-17A,and LDH were significantly higher in the deceased group than in the survival group(P<0.05),whereas ApoA1 levels were lower in the deceased group(P<0.05).Logistic regression analysis revealed that hematoma size,NIHSS score,and elevated CSF levels of IL-6,IL-10,MMP-9,IL-17A,and LDH were independent risk factors for mortality in sICH patients(P<0.05).ROC curve analysis showed that the AUC values for CSF IL-6,IL-10,MMP-9,IL-17A,and LDH in predicting sICH prognosis were 0.794,0.754,0.670,0.717,and 0.683,respectively.Notably,the combination of CSF inflammatory markers with hematoma size and NIHSS score yielded an AUC of 0.993,demonstrating significantly greater predictive accuracy than CSF inflammatory markers alone(P<0.05).Conclusions The levels of inflammatory factors in the CSF,including IL-6,IL-10,MMP-9,IL-17A,and LDH,were elevated in patients with sICH and positively correlated with disease severity.Combining CSF inflammatory markers with the NIHSS score and hematoma size improved the predictive accuracy for sICH prognosis.
5.Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage
Xuecheng ZHENG ; Junling GAO ; Manman ZHAO ; Lingling HAN ; Dexin ZHANG ; Kaijie WANG ; Jianzhong CUI
Chinese Medical Journal 2023;136(6):719-731
Background::Sirtuin-3 (Sirt3) has been documented to protect against mitochondrial dysfunction and apoptosis. Honokiol (HKL) is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders. The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage (ICH).Methods::An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia. PC12 cells were stimulated with hemin. For the in vivo investigation, the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits. Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis. Immunohistochemical staining was used to investigate the expression of Sirt3. Adenosine triphosphate (ATP) levels were quantified to assess mitochondrial dysfunction. Cell counting kit-8, lactate dehydrogenase assay, and flow cytometry were used to analyze cell vitality and apoptosis in vitro. Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1 (Drp1) localization to mitochondria. Western blot was applied to quantify the expression of Sirt3, Bax, Bcl-2, cleaved-caspase-3, Drp1, phosphorylation of Drp1 at serine-616, and phosphorylation of Drp1 at serine-637 in vivo and in vitro.Results::HKL treatment alleviated neurological deficits, attenuated the histopathological damage and cell apoptosis, and restored the decreased ATP levels in ICH rats. HKL improved cell survival rate, reduced cell apoptosis, and inhibited mitochondrial fission in PC12 cells. Moreover, both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616, and reduced phosphorylation of Drp1 at Ser637. Meanwhile, immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells. The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment. Importantly, the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine suppressed these effects. Conclusion::Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3, suggesting that HKL has immense prospects for the treatment of ICH.

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