Objective To investigate the association of ondansetron use with short-term mortality risk and long-term mortality risk in patients with cerebrovascular disease.Methods Clinical data of patients with cerebrovascular disease admitted to the intensive care unit(ICU)between 2008 and 2022 from the MIMIC-Ⅳ database were retrospectively collected.All enrolled subjects were divided into an ondansetron group and a non-ondansetron group according to whether they had used ondansetron during their hospitalization.The differences in clinical indicators between the two groups were equalized using a 1∶1 propensity score matching(PSM)method.Kaplan-Meier survival analyses were employed to compare the differences in survival rates between the two groups at ICU,hospital,30-and 90-day,respectively.Cox proportional-hazards regression models were employed to analyze the associations between ondansetron use and ICU,hospital,and 30-and 90-day all-cause mortality in critically ill patients with cerebrovascular disease.Results The study included 9,198 patients with cerebrovascular disease,including 3,514 in the ondansetron group and 5,684 in the non-ondansetron group.Pre-matched baseline data showed that the overall ICU,hospital,and 30-and 90-day mortality rates in the ondansetron group were 7.0％,12.4％,15.9％,and 21.3％respectively,while those in the non-ondansetron group were 11.0％,17.2％,22.3％and 27.9％respectively.After 1∶1 PSM equalization of baseline data,a total of 3,239 pairs were successfully matched.Based on the matched data,Kaplan-Meier survival analyses showed higher survival rates of ICU(P＜0.001),hospital(P＜0.001),30 d(P＜0.001),and 90 d(P＜0.001)in the ondansetron group compared to the non-ondansetron group.In Cox proportional-hazards analysis,after adjustment for potential confounders,the hazard ratios(HR)in the ondansetron group relative to the non-ondansetron group were 0.60[95％CI(0.51,0.71),P＜0.001]for ICU mortality,0.73[95％CI(0.64,0.83),P＜0.001]for hospital mortality,0.76[95％CI(0.67,0.85),P＜0.001]for 30 d mortality,and 0.81[95％CI(0.73,0.89),P＜0.001]risk ratio for 90 d mortality.Conclusion The use of ondansetron may significantly decrease the ICU,hospital,30 d and 90 d risk of mortality in patients with severe cerebrovascular disease.

Objective To investigate the association of ondansetron use with short-term mortality risk and long-term mortality risk in patients with cerebrovascular disease.Methods Clinical data of patients with cerebrovascular disease admitted to the intensive care unit(ICU)between 2008 and 2022 from the MIMIC-Ⅳ database were retrospectively collected.All enrolled subjects were divided into an ondansetron group and a non-ondansetron group according to whether they had used ondansetron during their hospitalization.The differences in clinical indicators between the two groups were equalized using a 1∶1 propensity score matching(PSM)method.Kaplan-Meier survival analyses were employed to compare the differences in survival rates between the two groups at ICU,hospital,30-and 90-day,respectively.Cox proportional-hazards regression models were employed to analyze the associations between ondansetron use and ICU,hospital,and 30-and 90-day all-cause mortality in critically ill patients with cerebrovascular disease.Results The study included 9,198 patients with cerebrovascular disease,including 3,514 in the ondansetron group and 5,684 in the non-ondansetron group.Pre-matched baseline data showed that the overall ICU,hospital,and 30-and 90-day mortality rates in the ondansetron group were 7.0％,12.4％,15.9％,and 21.3％respectively,while those in the non-ondansetron group were 11.0％,17.2％,22.3％and 27.9％respectively.After 1∶1 PSM equalization of baseline data,a total of 3,239 pairs were successfully matched.Based on the matched data,Kaplan-Meier survival analyses showed higher survival rates of ICU(P＜0.001),hospital(P＜0.001),30 d(P＜0.001),and 90 d(P＜0.001)in the ondansetron group compared to the non-ondansetron group.In Cox proportional-hazards analysis,after adjustment for potential confounders,the hazard ratios(HR)in the ondansetron group relative to the non-ondansetron group were 0.60[95％CI(0.51,0.71),P＜0.001]for ICU mortality,0.73[95％CI(0.64,0.83),P＜0.001]for hospital mortality,0.76[95％CI(0.67,0.85),P＜0.001]for 30 d mortality,and 0.81[95％CI(0.73,0.89),P＜0.001]risk ratio for 90 d mortality.Conclusion The use of ondansetron may significantly decrease the ICU,hospital,30 d and 90 d risk of mortality in patients with severe cerebrovascular disease.

Objective:To investigate the effect of transforming growth factor (TGF- β) signal in muscle fiber itself during inflammation/immunity response on intramuscular inflammation. Methods:Sixteen wild C57BL/6 mice (wild group) and sixteen mice with skeletal muscle-specific deficiency of T βRⅡ (knock-out group) between 4-8 weeks of age were selected for this study. Acute muscle injury in mice was induced by injection of myotoxin cardiotoxin (CTX) into gastrocnemius. The differences in intramuscular inflammation were compared between the wild and knock-out groups on 0, 4, 7 and 10 d after CTX injection by observing exudation of mononuclear phagocytes, macrophages, M1 type macrophages, CD4 +T cells and helpers T cells (Th1, 2&17). Two newborn C57BL/6 wild mice and 2 SM TGF- βr2-/- knock-out mice were selected to culture primary myoblasts in vitro which were divided into 2 groups: an interferon group subjected to interferon simulation and a control group subjected to addition of an equal amount of solvent. The differences in expression of IL-6, IL-10, MCP-1, MIP-1α, H-2K b, H2-Ea, Toll-like receptor (TLR)3 and TLR7 were compared between the interferon and control groups, as well as between the wild and knock-out groups. Results:On 4&7 d after CTX injection, the ratios of mononuclear/macrophage (75.73%±3.62%, 45.27%± 2.32%), macrophages (38.67%±2.76%, 24.87%±2.19%), M1 macrophages (43.21%±0.11%, 30.43%±2.19%), CD4 +T cells (20.13%±1.62%, 5.67%±0.32%) in the muscle tissue from the knock-out mice were significantly higher than those from the wild mice (58.52%±2.43%, 29.21%±2.45%; 20.63%±2.32%, 16.23%±1.25%; 24.98%±0.35%, 14.23%±1.69%; 10.70%±0.43%, 2.50%±0.45%), with a majority of Th1&Th17 ( P<0.05). In vitro results showed that the levels of IL-6, MCP-1, MIP-1α, H-2K b, H2-Ea and TLR3 were significantly upregulated in the interferon group compared with the control group and that such upregulation in the nock-out mice was more significant than in the wild mice ( P<0.05). Conclusions:Endogenous TGF- β signal activation plays a role in the functional recovery after muscle trauma, because it is involved in the regulation of immune behavior of muscle fibers, thus affecting intramuscular inflammation and muscle regeneration.