OBJECTIVE Progressive isch⁃emic stroke is characterized by aggravation of neurological dysfunction and poor prognosis.Neuroinflammation is involved in the pathological process of cerebral ischemia.Inflammasomes-activa...OBJECTIVE Progressive isch⁃emic stroke is characterized by aggravation of neurological dysfunction and poor prognosis.Neuroinflammation is involved in the pathological process of cerebral ischemia.Inflammasomes-activated caspase-1 has thus been considered a promising target for stroke therapy.However,it remains not fully understood how caspase-1 ag⁃gravates progressive functional impairment.We previously identified a novel caspase-1 inhibitor CZL-80,the present study is to explore whether CZL-80 protects against progressive ischemic stroke.METHODS Male C57/BL6 mice and cas⁃pase-1-/-mice were subjected to photothrombotic(PT)-induced cerebral ischemia.CZL-80 was in⁃traperitoneally injected daily during 1-7 d,1-4 d,4-7 d after PT.The grid-walking task and the cyl⁃inder task were used to determine the motor function.RESULTS Mice developed primary and the secondary neurological dysfunction at 1 d and 4-7 d after PT onset.The activation of cas⁃pase-1 peaked at 7 d after ischemic stroke and caspase-1 was mainly derived from activated microglia.Treatment with CZL-80(30 mg·kg-1)during 1-7 d significantly improved motor func⁃tion.Administration of CZL-80 during 1-4 d could not ameliorate motor function loss while administration during 4-7 d after PT onset signifi⁃cantly reduced foot faults and forelimb symme⁃try.Remarkably,treatment with CZL-80 during 4-7 d showed no significant difference in efficacy compared with the its administration during 1-7 d,which indicated a key therapeutic window.More⁃over,the neuroprotective effect of CZL-80 during 4-7 d was available at least until 43 d after isch⁃emic stroke,indicating CZL-80 can improve the long-term neurological function after cerebral ischemia.Furthermore,administration of CZL-80(30 mg·kg-1)during 4-7 d after PT onset in cas⁃pase-1-/-mice failed to improve the motor func⁃tion,which suggested that the neuroprotective effect of CZL-80 was caspase-1-dependent.The results showed that CZL-80 did not inhibit the expression of GSDMD and failed to reduce neu⁃ronal loss after ischemia.These results indicated the effect of CZL-80 was not attributable to inhib⁃it pyroptosis.We further found that CZL-80 signif⁃icantly reduced the number of activated microglia in the peri-infarct brain cortex after ischemic stroke,which might be involved in its neuropro⁃tective effect.CONCLUSION CZL-80,a novel caspase-1 inhibitor,improved motor function after progressive ischemic stroke in mice.The effective therapeutic window of CZL-80 would be 4-7 d after ischemia,when the secondary neuro⁃logical dysfunction occurred.Therefore,the inter⁃vention by targeting caspase-1 in this window phase provides a novel strategy for the function⁃al recovery of stroke survivors.展开更多
Objective: To study the effects of symbicort turbuhaler combined with tiotropium bromide on serum PCT, TIMP-1, MMP-9, IFN-γ, arterial blood gases and pulmonary function in patients with AECOPD. Methods A total of 90 ...Objective: To study the effects of symbicort turbuhaler combined with tiotropium bromide on serum PCT, TIMP-1, MMP-9, IFN-γ, arterial blood gases and pulmonary function in patients with AECOPD. Methods A total of 90 patients in our hospital with AECOPD during January 2014 to January 2017 were divided into the control group (n=45) and the treatment group (n=45) randomly. The control group was treated with tiotropium bromide;the treatment group was treated with symbicort turbuhaler combined with tiotropium bromide. The two groups were treated for 14 d. That was compared of the serum PCT, TIMP-1, MMP-9, IFN-γ, PaO2, SaO2, PaCO2, MPAP, PASP and PADP of the two groups before and after treatment. Results The serum PCT, TIMP-1, MMP-9, IFN-γ, PaO2, SaO2, PaCO2, MPAP, PASP and PADP of the two groups before treatment have no significantly differences. The serum PCT, TIMP-1, MMP-9 and IFN-γ levels of the two groups after treatment were significantly lower than before treatment. The serum PCT, TIMP-1, MMP-9 and IFN-γ levels of the treatment group after treatment were significantly lower than the control group. The PaO2, SaO2 of the two groups after treatment were significantly higher than before treatment, the PaCO2, MPAP, PASP and PADP of the two groups after treatment were significantly lower than before treatment. The PaO2, SaO2, PaCO2, MPAP, PASP and PADP of the treatment group after treatment were significantly better than the control group. Conclusion Symbicort turbuhaler combined with tiotropium bromide can reduce the serum PCT, TIMP-1, MMP-9, IFN-γlevels and the pulmonary arterial hypertension, improve the lung tissue oxygen supply and the cardiopulmonary function, and it was worthy clinical application.展开更多
Background: Routine lung function testing requires expensive equipment, or requires maximum expiratory effort. The airflow perturbation device (APD) is a light handheld device, allowing for serial measures of respirat...Background: Routine lung function testing requires expensive equipment, or requires maximum expiratory effort. The airflow perturbation device (APD) is a light handheld device, allowing for serial measures of respiratory resistance noninvasively and effortlessly. Methods: In a convenience sample of 398 patients undergoing pulmonary function testing, we compared routine spirometric indices (forced expired volume in 1 second (FEV1), peak expiratory flow (PEF)), and airways resistance (Raw-272 patients), to measures of respiratory resistance measured with the APD including inspiratory (IR), expiratory (ER) and averaged (AR) resistance. Results: Measures of lung function were significantly correlated (p 0.001). On regression analysis, between 7% - 17% of the variance (R2) for FEV1, PEF, and Raw was explained by APD measurements. Approximately 2/3 of the variance in FEV1 was explained by PEF measurements. Conclusions: APD measurements of lung function correlate with conventional measures. Future studies should be directed at exploring the use of the APD device in serial measures of lung function in patients with lung disease.展开更多
文摘OBJECTIVE Progressive isch⁃emic stroke is characterized by aggravation of neurological dysfunction and poor prognosis.Neuroinflammation is involved in the pathological process of cerebral ischemia.Inflammasomes-activated caspase-1 has thus been considered a promising target for stroke therapy.However,it remains not fully understood how caspase-1 ag⁃gravates progressive functional impairment.We previously identified a novel caspase-1 inhibitor CZL-80,the present study is to explore whether CZL-80 protects against progressive ischemic stroke.METHODS Male C57/BL6 mice and cas⁃pase-1-/-mice were subjected to photothrombotic(PT)-induced cerebral ischemia.CZL-80 was in⁃traperitoneally injected daily during 1-7 d,1-4 d,4-7 d after PT.The grid-walking task and the cyl⁃inder task were used to determine the motor function.RESULTS Mice developed primary and the secondary neurological dysfunction at 1 d and 4-7 d after PT onset.The activation of cas⁃pase-1 peaked at 7 d after ischemic stroke and caspase-1 was mainly derived from activated microglia.Treatment with CZL-80(30 mg·kg-1)during 1-7 d significantly improved motor func⁃tion.Administration of CZL-80 during 1-4 d could not ameliorate motor function loss while administration during 4-7 d after PT onset signifi⁃cantly reduced foot faults and forelimb symme⁃try.Remarkably,treatment with CZL-80 during 4-7 d showed no significant difference in efficacy compared with the its administration during 1-7 d,which indicated a key therapeutic window.More⁃over,the neuroprotective effect of CZL-80 during 4-7 d was available at least until 43 d after isch⁃emic stroke,indicating CZL-80 can improve the long-term neurological function after cerebral ischemia.Furthermore,administration of CZL-80(30 mg·kg-1)during 4-7 d after PT onset in cas⁃pase-1-/-mice failed to improve the motor func⁃tion,which suggested that the neuroprotective effect of CZL-80 was caspase-1-dependent.The results showed that CZL-80 did not inhibit the expression of GSDMD and failed to reduce neu⁃ronal loss after ischemia.These results indicated the effect of CZL-80 was not attributable to inhib⁃it pyroptosis.We further found that CZL-80 signif⁃icantly reduced the number of activated microglia in the peri-infarct brain cortex after ischemic stroke,which might be involved in its neuropro⁃tective effect.CONCLUSION CZL-80,a novel caspase-1 inhibitor,improved motor function after progressive ischemic stroke in mice.The effective therapeutic window of CZL-80 would be 4-7 d after ischemia,when the secondary neuro⁃logical dysfunction occurred.Therefore,the inter⁃vention by targeting caspase-1 in this window phase provides a novel strategy for the function⁃al recovery of stroke survivors.
文摘Objective: To study the effects of symbicort turbuhaler combined with tiotropium bromide on serum PCT, TIMP-1, MMP-9, IFN-γ, arterial blood gases and pulmonary function in patients with AECOPD. Methods A total of 90 patients in our hospital with AECOPD during January 2014 to January 2017 were divided into the control group (n=45) and the treatment group (n=45) randomly. The control group was treated with tiotropium bromide;the treatment group was treated with symbicort turbuhaler combined with tiotropium bromide. The two groups were treated for 14 d. That was compared of the serum PCT, TIMP-1, MMP-9, IFN-γ, PaO2, SaO2, PaCO2, MPAP, PASP and PADP of the two groups before and after treatment. Results The serum PCT, TIMP-1, MMP-9, IFN-γ, PaO2, SaO2, PaCO2, MPAP, PASP and PADP of the two groups before treatment have no significantly differences. The serum PCT, TIMP-1, MMP-9 and IFN-γ levels of the two groups after treatment were significantly lower than before treatment. The serum PCT, TIMP-1, MMP-9 and IFN-γ levels of the treatment group after treatment were significantly lower than the control group. The PaO2, SaO2 of the two groups after treatment were significantly higher than before treatment, the PaCO2, MPAP, PASP and PADP of the two groups after treatment were significantly lower than before treatment. The PaO2, SaO2, PaCO2, MPAP, PASP and PADP of the treatment group after treatment were significantly better than the control group. Conclusion Symbicort turbuhaler combined with tiotropium bromide can reduce the serum PCT, TIMP-1, MMP-9, IFN-γlevels and the pulmonary arterial hypertension, improve the lung tissue oxygen supply and the cardiopulmonary function, and it was worthy clinical application.
文摘Background: Routine lung function testing requires expensive equipment, or requires maximum expiratory effort. The airflow perturbation device (APD) is a light handheld device, allowing for serial measures of respiratory resistance noninvasively and effortlessly. Methods: In a convenience sample of 398 patients undergoing pulmonary function testing, we compared routine spirometric indices (forced expired volume in 1 second (FEV1), peak expiratory flow (PEF)), and airways resistance (Raw-272 patients), to measures of respiratory resistance measured with the APD including inspiratory (IR), expiratory (ER) and averaged (AR) resistance. Results: Measures of lung function were significantly correlated (p 0.001). On regression analysis, between 7% - 17% of the variance (R2) for FEV1, PEF, and Raw was explained by APD measurements. Approximately 2/3 of the variance in FEV1 was explained by PEF measurements. Conclusions: APD measurements of lung function correlate with conventional measures. Future studies should be directed at exploring the use of the APD device in serial measures of lung function in patients with lung disease.
