Objective To investigate the prognostic value of the platelet-to-lymphocyte ratio(PLR)at different early time points in adult patients undergoing veno-arterial extracorporeal membrane oxygenation(VA-ECMO).Methods A retrospective study was conducted,selecting 55 adult patients who underwent VA-ECMO treatment at the First Hospital of Jiaxing from June 2020 to October 2022 as the study subjects.Then,the patients'gender,age,past history[including hypertension,diabetes,heart disease,chronic obstructive pulmonary disease(COPD)],and the reason for extracorporeal membrane pulmonary oxygenation(ECMO)adjuvant therapy[including severe myocarditis,acute myocardia infarction,in-hospital and out-of-hospital cardiac arrest,severe closed craniocerebral injury,severe pneumonia,pelvic fracture,other(pulmonary embolism,electrocution,traumatic hepatic rupture,post-partum hemorrhage,severe acute pancreatitis,crush syndrome)],acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)at the time of admission,and ECMO peripheral blood tests[creatinine,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood lactate acid(Lac),white blood cell count(WBC),neutrophil count(NEU),lymphocyte count(LYM),hemoglobin(Hb),and platelet count(PLT)]and the last time prior to ECMO assistance,24 hours prior to the occurrence of acute kidney injury(AKI),and 24 hours after the occurrence of AKI.PLR levels at 24 hours ECMO,and the proportion of continuous renal replacement therapy(CRRT).The patients were divided into a death group and a survival group based on their 30-day prognosis and further categorized into a CRRT group and a non-CRRT group based on whether CRRT was administered.Clinical indicators of patients with different prognosis and the differences in PLR levels between CRRT and non-CRRT groups were compared.Logistic regression analysis was used to identify independent risk factors affecting the 30-day prognosis of VA-ECMO patients.The receiver operator characteristic(ROC curves)were plotted to evaluate the prognostic predictive value of each risk factor.Results Compared to the survival group,the death group had significantly higher APACHEⅡscores,SOFA scores,LYM and proportion receiving CRRT[APACHEⅡscore:34.00(28.50,36.00)vs.25.00(14.75,34.00),SOFA score:5.00(4.00,6.50)vs.3.00(2.00,5.25),LYM(×109/L):3.40±1.97 vs.2.24±2.11,proportion receiving CRRT:91.30%(21/23)vs.62.50%(20/32)],and a significantly lower level of the last PLR prior to ECMO adjuvant[30.00(21.06,48.17)vs.58.82(41.80,145.72)],and the differences were statistically significant(all P<0.05).Logistic regression analysis showed that the levels of the last PLR before ECMO assistance[odds ratio(OR)=0.965,95%confidence interval(95%CI)was 0.938-0.993,P=0.013],APACHEⅡscore at the time of admission(OR=1.121,95%CI was 1.018-1.234,P=0.020),and CRRT(OR=7.734,95%CI was 1.042-57.401,P=0.045)were independent risk factors affecting the prognosis of the VA-ECMO patients at 30 days after adjuvant;the ROC curve analysis showed that APACHEⅡscore,CRRT and the last PLR level before ECMO assistance had a predictive value for the prognosis of VA-ECMO patients 30 days after assistance,in which the APACHEⅡscore+the last PLR level before ECMO assistance had the greatest predictive value in predicting the prognosis of the patients,with area under the curve(AUC)of 0.846,with a sensitivity of 62.5%and a specificity of 95.7%.Higher early PLR levels were associated with better prognosis.In the CRRT group,PLR levels at 24 hours before ECMO initiation,24 hours before AKI onset,and 24 hours after AKI onset were significantly lower than those in the non-CRRT group(all P<0.05).Conclusion Early PLR levels and CRRT administration have significant predictive value for the prognosis of patients undergoing VA-ECMO therapy.

Objective To establish and evaluate a mouse model of chronic obstructive pulmonary disease(COPD)induced by cigarette smoke(CS).Methods Forty BALB/c mice were divided randomly into a control group and a CS group.Mice in the CS group were subjected to passive smoking for 20 weeks and a COPD model was established.Morphological changes in the organs and lung,heart,liver,and kidney fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Lung,cardiac,and brain cognitive function were evaluated by pulmonary function testing,small-animal ultrasound,and Morris water maze trials.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1β levels in lung and brain tissues were detected by ELISA.Liver and renal functions were measured by biochemical method.Results The alveolar septum was narrowed or broken in mice in the CS group,and the adjacent alveolar cavity was enlarged and fused,consistent with the pathological changes of COPD.Neuronal degeneration and necrosis were observed in the hippocampus,but there were no significant morphological changes in other organs.Masson staining showed no obvious fibrosis in the lung,heart,liver,or kidney in CS-group mice.The result of pulmonary function tests showed that the forced expiratory volume in 0.1 second/forced vital capacity(FEV 0.1/FVC)and dynamic compliance were significantly decreased in the CS group compared with the control group,while airway resistance was obviously increased.Cognitive impairment in mice in the CS group was confirmed in the Morris water maze trial.TNF-α,IL-6,and IL-1β levels in lung and brain tissues were higher in the CS group compared with the control group.There were no significant differences in cardiac,liver,and renal functions between the groups.Conclusions A mouse model of COPD can be established by CS exposure for 20 weeks.Lung histomorphology,lung function,brain cognitive function,and levels of inflammatory factors can be used as indicators to evaluate the success of the model.

Objective The study aims to elucidate the inhibitory effects of curcumin on the proliferation of colon cancer RKO cells,focusing on the regulatory mechanisms of tripartite motif-containing protein 2(TRIM2)expression and the mammalian target of rapamycin(mTOR)signaling pathway.Methods Experimental concentrations of curcumin were determined by calculating the half maximal inhibitory concentration(IC50)value.Quantitative polymerase chain reaction(qPCR)was utilized to assess the level of TRIM2 expression in RKO and fetal human colon(FHC)cells.Western blotting analysis was conducted to investigate the level of TRIM2 expression and mTOR pathway-related proteins in curcumin-treated RKO cells.The impact of curcumin treatment,TRIM2-knockingdown,and mTOR signaling pathway on proliferation in RKO cells was quantified using the cell counting kit-8(CCK8)assay.Results The expression of TRIM2 was found to be elevated in RKO cells as determined by qPCR,compared to FHC cells.Curcumin suppressed the level of TRIM2 expression,and subsequent knockdown of TRIM2 resulted in decreased expression of mTOR-related proteins in RKO cells.Both curcumin and TRIM2-knockdown demonstrated significant inhibition of proliferation in RKO cells,with reversion upon activation of mTOR signaling pathway.Conclusion The study unveils the inhibitory effects of curcumin on RKO cells proliferation through modulation of TRIM2 expression and the mTOR signaling pathway.

Objective The study aims to elucidate the inhibitory effects of curcumin on the proliferation of colon cancer RKO cells,focusing on the regulatory mechanisms of tripartite motif-containing protein 2(TRIM2)expression and the mammalian target of rapamycin(mTOR)signaling pathway.Methods Experimental concentrations of curcumin were determined by calculating the half maximal inhibitory concentration(IC50)value.Quantitative polymerase chain reaction(qPCR)was utilized to assess the level of TRIM2 expression in RKO and fetal human colon(FHC)cells.Western blotting analysis was conducted to investigate the level of TRIM2 expression and mTOR pathway-related proteins in curcumin-treated RKO cells.The impact of curcumin treatment,TRIM2-knockingdown,and mTOR signaling pathway on proliferation in RKO cells was quantified using the cell counting kit-8(CCK8)assay.Results The expression of TRIM2 was found to be elevated in RKO cells as determined by qPCR,compared to FHC cells.Curcumin suppressed the level of TRIM2 expression,and subsequent knockdown of TRIM2 resulted in decreased expression of mTOR-related proteins in RKO cells.Both curcumin and TRIM2-knockdown demonstrated significant inhibition of proliferation in RKO cells,with reversion upon activation of mTOR signaling pathway.Conclusion The study unveils the inhibitory effects of curcumin on RKO cells proliferation through modulation of TRIM2 expression and the mTOR signaling pathway.

Objective To investigate the prognostic value of the platelet-to-lymphocyte ratio(PLR)at different early time points in adult patients undergoing veno-arterial extracorporeal membrane oxygenation(VA-ECMO).Methods A retrospective study was conducted,selecting 55 adult patients who underwent VA-ECMO treatment at the First Hospital of Jiaxing from June 2020 to October 2022 as the study subjects.Then,the patients'gender,age,past history[including hypertension,diabetes,heart disease,chronic obstructive pulmonary disease(COPD)],and the reason for extracorporeal membrane pulmonary oxygenation(ECMO)adjuvant therapy[including severe myocarditis,acute myocardia infarction,in-hospital and out-of-hospital cardiac arrest,severe closed craniocerebral injury,severe pneumonia,pelvic fracture,other(pulmonary embolism,electrocution,traumatic hepatic rupture,post-partum hemorrhage,severe acute pancreatitis,crush syndrome)],acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)at the time of admission,and ECMO peripheral blood tests[creatinine,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood lactate acid(Lac),white blood cell count(WBC),neutrophil count(NEU),lymphocyte count(LYM),hemoglobin(Hb),and platelet count(PLT)]and the last time prior to ECMO assistance,24 hours prior to the occurrence of acute kidney injury(AKI),and 24 hours after the occurrence of AKI.PLR levels at 24 hours ECMO,and the proportion of continuous renal replacement therapy(CRRT).The patients were divided into a death group and a survival group based on their 30-day prognosis and further categorized into a CRRT group and a non-CRRT group based on whether CRRT was administered.Clinical indicators of patients with different prognosis and the differences in PLR levels between CRRT and non-CRRT groups were compared.Logistic regression analysis was used to identify independent risk factors affecting the 30-day prognosis of VA-ECMO patients.The receiver operator characteristic(ROC curves)were plotted to evaluate the prognostic predictive value of each risk factor.Results Compared to the survival group,the death group had significantly higher APACHEⅡscores,SOFA scores,LYM and proportion receiving CRRT[APACHEⅡscore:34.00(28.50,36.00)vs.25.00(14.75,34.00),SOFA score:5.00(4.00,6.50)vs.3.00(2.00,5.25),LYM(×109/L):3.40±1.97 vs.2.24±2.11,proportion receiving CRRT:91.30%(21/23)vs.62.50%(20/32)],and a significantly lower level of the last PLR prior to ECMO adjuvant[30.00(21.06,48.17)vs.58.82(41.80,145.72)],and the differences were statistically significant(all P<0.05).Logistic regression analysis showed that the levels of the last PLR before ECMO assistance[odds ratio(OR)=0.965,95%confidence interval(95%CI)was 0.938-0.993,P=0.013],APACHEⅡscore at the time of admission(OR=1.121,95%CI was 1.018-1.234,P=0.020),and CRRT(OR=7.734,95%CI was 1.042-57.401,P=0.045)were independent risk factors affecting the prognosis of the VA-ECMO patients at 30 days after adjuvant;the ROC curve analysis showed that APACHEⅡscore,CRRT and the last PLR level before ECMO assistance had a predictive value for the prognosis of VA-ECMO patients 30 days after assistance,in which the APACHEⅡscore+the last PLR level before ECMO assistance had the greatest predictive value in predicting the prognosis of the patients,with area under the curve(AUC)of 0.846,with a sensitivity of 62.5%and a specificity of 95.7%.Higher early PLR levels were associated with better prognosis.In the CRRT group,PLR levels at 24 hours before ECMO initiation,24 hours before AKI onset,and 24 hours after AKI onset were significantly lower than those in the non-CRRT group(all P<0.05).Conclusion Early PLR levels and CRRT administration have significant predictive value for the prognosis of patients undergoing VA-ECMO therapy.

Objective To establish and evaluate a mouse model of chronic obstructive pulmonary disease(COPD)induced by cigarette smoke(CS).Methods Forty BALB/c mice were divided randomly into a control group and a CS group.Mice in the CS group were subjected to passive smoking for 20 weeks and a COPD model was established.Morphological changes in the organs and lung,heart,liver,and kidney fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Lung,cardiac,and brain cognitive function were evaluated by pulmonary function testing,small-animal ultrasound,and Morris water maze trials.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1β levels in lung and brain tissues were detected by ELISA.Liver and renal functions were measured by biochemical method.Results The alveolar septum was narrowed or broken in mice in the CS group,and the adjacent alveolar cavity was enlarged and fused,consistent with the pathological changes of COPD.Neuronal degeneration and necrosis were observed in the hippocampus,but there were no significant morphological changes in other organs.Masson staining showed no obvious fibrosis in the lung,heart,liver,or kidney in CS-group mice.The result of pulmonary function tests showed that the forced expiratory volume in 0.1 second/forced vital capacity(FEV 0.1/FVC)and dynamic compliance were significantly decreased in the CS group compared with the control group,while airway resistance was obviously increased.Cognitive impairment in mice in the CS group was confirmed in the Morris water maze trial.TNF-α,IL-6,and IL-1β levels in lung and brain tissues were higher in the CS group compared with the control group.There were no significant differences in cardiac,liver,and renal functions between the groups.Conclusions A mouse model of COPD can be established by CS exposure for 20 weeks.Lung histomorphology,lung function,brain cognitive function,and levels of inflammatory factors can be used as indicators to evaluate the success of the model.

Acute ischemic stroke(AIS)is associated with a high mortality and disability rate.Endovascular therapy(EVT)has emerged as a primary treatment method for achieving vascular reperfusion in large vessel occlusion AIS patients.The cerebral hemodynamic status of patients undergoing reperfusion therapy is closely linked to the extent of cerebral vascular reperfusion and improvement in the ischemic penumbra at the site of injury.Transcranial Doppler(TCD)ultrasound offers non-invasive,reliable,and convenient advantages for evaluating intracranial vessel occlusion or stenosis,guiding treatment decisions,and predicting patient outcomes.The authors reviewed the application progress of TCD in AIS patients.

BACKGROUND:Pretreatment with moxibustion is a preventive treatment in traditional Chinese medicine.Pretreatment with moxibustion at the onset of prodromal symptoms can significantly reduce the symptoms and delay the onset of many diseases,but the exact mechanism remains to be studied. OBJECTIVE:To investigate the mechanism of SIRT1/FoxO3 pathway in moxibustion pretreatment to ameliorate oxidative stress injury in cerebral ischemia-reperfusion model rats. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham-operated group,model group,moxibustion pretreatment group,and moxibustion pretreatment+EX527(SIRT1 inhibitor)group,with 12 rats in each group.The moxibustion pretreatment group was given moxibustion with seed-sized moxa cone at Baihui,Dazhui,and Zusanli before modeling,three moxa-cones per acupoint,once a day for 7 days.In the model group,moxibustion pretreatment group and moxibustion pretreatment+EX527 group,the rat model of middle cerebral artery occlusion was made by suturing of the middle cerebral artery 30 minutes after the last moxibustion.After 2 hours of cerebral ischemia,the middle artery suture was removed and the rats were reperfused for 12 hours.In the sham-operated group,only the common carotid artery,internal carotid artery,and external carotid artery were dissected without suturing the middle cerebral artery.In the moxibustion pretreatment+EX527 group,EX527(15 mg/kg)was given intraperitoneally 30 minutes before each moxibustion.After 12 hours of reperfusion,the rats were scored for neurological deficits,and the cerebral infarct volume was calculated by 2,3,5-triphenyltetrazolium chloride staining method.The levels of oxidative stress factors in the infarcted tissues were detected by the kit method,and western-blot method was used to detect the expression levels of SIRT1,FoxO3,p-FoxO3 and brain-derived neurotrophic factor in the ischemic area of the cerebral cortex. RESULTS AND CONCLUSION:After 12 hours of reperfusion,the neurobehavioral score in the model group was significantly higher than that in the sham-operated group(P＜0.01),while the score in the moxibustion pretreatment group was significantly lower than that in the model group(P＜0.01)and moxibustion pretreatment+EX527 group(P＜0.05).There were no obvious infarct foci in the brain tissue of the sham-operated rats,but obvious ischemic foci were observed in the right side of the brain tissue of the rats in the model group(P＜0.01).The right infarct volume in the moxibustion pretreatment group was significantly reduced compared with the model group(P＜0.01),while the right infarct volume in the moxibustion pretreatment+EX527 group was significantly enlarged compared with the moxibustion pretreatment group.After 12 hours of reperfusion,the level of malondialdehyde was significantly elevated(P＜0.01)and the expression of superoxide dismutase was significantly decreased(P＜0.01)in the model group compared with the sham-operated group.The levels of malondialdehyde was significantly decreased(P＜0.01,P＜0.05)and the expression of superoxide dismutase was significantly increased(P＜0.01,P＜0.05)in the moxibustion pretreatment group compared with the model group and the moxibustion pretreatment+EX527 group.Western blot results showed that the expression levels of SIRT1,FoxO3,p-FoxO3,and brain-derived neurotrophic factor proteins were significantly higher in the model group compared with the sham-operated group(P＜0.01);compared with the model group,the expression levels of SIRT1,FoxO3,and brain-derived neurotrophic factor were significantly higher in the moxibustion pretreatment group(P＜0.01),and p-FoxO3 expression was significantly lower(P＜0.01);compared with the moxibustion pretreatment+EX527 group,the expression levels of SIRT1,FoxO3,and brain-derived neurotrophic factor were elevated in the moxibustion pretreatment group(P＜0.05),and no statistically significant difference was found in the p-FoxO3 expression(P＞0.05).To conclude,moxibustion pretreatment can significantly improve neurological function in rats after cerebral ischemia-reperfusion,and the mechanism may be related to the activation of SIRT1/FoxO3 pathway to reduce oxidative stress injury in the rat model of cerebral ischemia-reperfusion.

BACKGROUND:It was found that moxibustion can inhibit the inflammatory factors in the serum of rats with cerebral ischemia/reperfusion injury,resist oxidative stress,inhibit cell apoptosis,and effectively reduce cerebral ischemia/reperfusion injury. OBJECTIVE:To observe the effects of different moxibustion intervention time on the expression levels of nucleotide binding oligomerization domain-like protein 3 inflammasome(NLRP3),cysteine aspartase(caspase-1),apoptosis-related speck-like protein,exfoliatin-D protein,interleukin-1β and interleukin-18 in rats with cerebral ischemia/reperfusion injury,and to explore its action mechanism. METHODS:SD rats were randomly divided into sham operation group(n=9)and operation group(n=36).The model of focal cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion in the operation group.After successful modeling,the rats in the operation group were further divided into model group,moxibustion 10-minute group,moxibustion 15-minute group and moxibustion 30-minute group,with 9 rats in each group.Rats in the moxibustion 10-minute,15-minute and 30-minute groups were given moxibustion at"Baihui,Dazhui and Zusanli",respectively,once a day for a total of 7 days.The neurological deficits of rats were evaluated by LONGA method.The cerebral infarction was observed by 2,3,5-triphenyltetrazolium chloride staining.The pathological changes of brain tissue were observed by hematoxylin-eosin staining.The contents of interleukin-1β and interleukin-18 in serum of rats in each group were detected by ELISA.Immunohistochemistry and western blot assay were used to detect the expression levels of NLRP3,caspase-1,apoptosis-related spot-like protein and gasdermin D in the ischemic cortex of rats in each group. RESULTS AND CONCLUSION:Compared with the sham operation group,the neurological deficit score of the model group was significantly increased(P<0.01).Compared with the model group,the neurological deficit score of the moxibustion groups was significantly reduced(P<0.01).Compared with the sham operation group,the infarct volume of the model group was significantly increased(P<0.01).Compared with the model group,the infarct volume of the moxibustion groups was significantly reduced(P<0.01);the infarct volume of the rats was smallest in the moxibustion 30-minute group(P<0.05).Compared with the model group,the contents of inflammatory factors interleukin-1β and interleukin-18 in the serum of rats in the moxibustion groups were decreased(P<0.01).Compared with the moxibustion 10-minute group,the contents of inflammatory factors in the serum of rats in the moxibustion 30-minute group were significantly decreased(P<0.05).Compared with the model group,the expression of NLRP3,apoptosis-related spot-like protein,Caspase-1 and gasdermin D protein in the ischemic cortex of the moxibustion groups was significantly decreased(P<0.01).Compared with the moxibustion 10-minute and 15-minute groups,the expression of protein in the moxibustion 30-minute group was significantly decreased(P<0.05).It is concluded that moxibustion at Baihui,Dazhui and Zusanli can reduce cerebral ischemia/reperfusion injury,among which moxibustion for 30 minutes has the best effect,and its mechanism may be related to the inhibition of pyroptosis mediated by NLRP3/Caspase-1 pathway.