Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Value of orthopedic POSSUM and P-POSSUM scoring system in predicting operation risk in aged patients with hip fracture / 中华创伤杂志

Objective To measure the value of orthopedic physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) and Portsmouth modified POSSUM (P-POSSUM) scoring systems in predicting operative risks in aged hip fracture patients.Methods Orthopedic POSSUM and P-POSSUM were performed to predict complication incidence and mortality for 164 aged patients operated for hip fracture.Validation of the scoring systems was tested by assessing observed to expected ratio,discrimination,and calibration.Discriminative ability and calibration of both scores were estimated using receiver operation characteristic curve (ROC) and Hosmer-Lemeshow test respectively.Results Orthopedic POSSUM score performed in predicting incidence of postoperative complications showed overall observed to expected ratio of 0.86,area under the curve of 0.82,and good calibration (H2 =3.66,df=8,P ＞ 0.05).P-POSSUM performed in predicting mortality showed overall observed to expected ratio of 0.80,area under the curve of 0.93 and good calibration (H2 =3.21,df =4,P ＞ 0.05).While orthopedic POSSUM overestimated postoperative mortality (overall observed to expected ratio =0.27).Conclusion Orthopedic POSSUM and P-POSSUM scores are respectively accurate in predicting postoperative complication incidence and mortality in aged hip fracture patients,but orthopedic POSSUM score overestimates the mortality.