miR-1224 contributes to ischemic stroke-mediated natural killer cell dysfunction by targeting Sp1 signaling.

BACKGROUND: Brain ischemia compromises natural killer (NK) cell-mediated immune defenses by acting on neurogenic and intracellular pathways. Less is known about the posttranscriptional mechanisms that regulate NK cell activation and cytotoxicity after ischemic stroke. METHODS: Using a NanoString nCounter® miRNA array panel, we explored the microRNA (miRNA) profile of splenic NK cells in mice subjected to middle cerebral artery occlusion. Differential gene expression and function/pathway analysis were applied to investigate the main functions of predicted miRNA target genes. miR-1224 inhibitor/mimics transfection and passive transfer of NK cells were performed to confirm the impact of miR-1224 in NK cells after brain ischemia. RESULTS: We observed striking dysregulation of several miRNAs in response to ischemia. Among those miRNAs, miR-1224 markedly increased 3 days after ischemic stroke. Transfection of miR-1224 mimics into NK cells resulted in suppression of NK cell activity, while an miR-1224 inhibitor enhanced NK cell activity and cytotoxicity, especially in the periphery. Passive transfer of NK cells treated with an miR-1224 inhibitor prevented the accumulation of a bacterial burden in the lungs after ischemic stroke, suggesting an enhanced immune defense of NK cells. The transcription factor Sp1, which controls cytokine/chemokine release by NK cells at the transcriptional level, is a predicted target of miR-1224. The inhibitory effect of miR-1224 on NK cell activity was blocked in Sp1 knockout mice. CONCLUSIONS: These findings indicate that miR-1224 may serve as a negative regulator of NK cell activation in an Sp1-dependent manner; this mechanism may be a novel target to prevent poststroke infection specifically in the periphery and preserve immune defense in the brain.

Evaluation of POSSUM scoring system in the treatment of osteoporotic fracture of the hip in elder patients.

OBJECTIVE: To evaluate the applicability of the modified physiological and operative severity score for enumeration of mortality and morbidity (POSSUM) scoring system in predicting mortality in the patients undergoing hip joint arthroplasty. METHODS: A total of 295 patients with hip fractures were analyzed using the modified POSSUM surgical scoring system. The mean ages of the patients were 66.59 years in the complicative group, 62.28 years in noncomplicative group, 77.89 years in the death group and 63.25 years in the living group, respectively. The comparisons between the observed and predicted morbidity, between the observed and predicted mortality were made within 30 days after operation. RESULTS: The average physiological scores and operative severity scores was 18.96+/-4.83 and 13.47+/-2.01 in complicative group, while 15.65+/-3.66 and 11.74+/-2.26 in noncomplicative group (P less than 0.05). The average physiological scores and operative severity scores was 25.56+/-3.78 and 14.22+/-0.67 in death group, while 16.46+/-4.09 and 12.25+/-2.33 in living group (P less than 0.05). Though POSSUM scoring system over-predicted the overall risk of death, its estimate was very close in the high risk groups (larger than 10% ). There was perfect consistence between the observed and the predicted morbidity as calculated by published predictor equation for morbidity, and consistence for mortality in the high risk band. CONCLUSIONS: Modified POSSUM scoring system may be used to predict the morbidity in patients with hip fracture. Furthermore, POSSUM scoring system overpredicts the overall risk of death, but its estimate is close to the actual data in the high risk band (larger than 10%).

Evaluation of P-POSSUM scoring system in predicting mortality in patients with hip joint arthroplasty.

OBJECTIVE: To evaluate the applicability of Porthsmouth modified physiological and operative severity score for the enumeration of mortality and morbidity (P-POSSUM) in predicting the mortality of the patients undergoing hip joint arthroplasty. METHODS: A total of 141 patients (75 males and 66 females, aged 63.22 years+/-14.45 years on an average) undergoing hip joint arthroplasty during January 2002 and March 2005 were studied retrospectively with P-POSSUM. Their average physiological score and operative severity score were 17.48+/-5.16 and 12.43+/-3.05, respectively. The predicted postoperative mortality with P-POSSUM was compared with the observed value. Subgroup analysis was performed to investigate the predictive capability of P-POSSUM. POSSUM scoring system was used as the control. RESULTS: Three patients died after operation in this study actually. The average physiological scores were 32.33+/-9.87 in the death group and 17.16+/-4.56 in the survival group. The former was obviously higher than the latter, which showed statistical difference between the two groups (Wilcoxon rank sum test, P<0.05). Perfect agreement was found between the observed death number and the predicted death number calculated by P-POSSUM (Cochran-Mantel-Haenszel chi(2) test, P>0.05), though POSSUM overestimated the overall mortality. CONCLUSIONS: P-POSSUM can predict the mortality accurately in the patients undergoing hip joint arthroplasty, which is superior to POSSUM.