Patients who suffer sepsis often develop cognitive impairments, yet the underlying mechanisms largely remain to be elucidated. Increasing evidence has suggested that parvalbumin (PV) interneurons are required for the synchronization of neural activities and higher brain processes, whereas its dysfunction is implicated in many psychiatric disorders. In the present study, we examined the role of hippocampal PV interneuron-mediated inhibitory network in a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP) and also explored the underlying mechanism. Here we showed that CLP-induced cognitive impairments, which were accompanied by significantly decreased expressions of PV and dopamine 4 (D4) receptor, decreased slow γ oscillation band, and reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs). Notably, D4 receptor agonist RO-10-5824 treatment was able to reverse most of these abnormities. In summary, our study suggests that sepsis might disrupt PV interneuron-mediated network function that is dependent on the D4 receptor, leading to abnormal γ oscillation and consequent cognitive impairments.

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Frailty is associated with perioperative adverse outcomes, especially for the elderly. This study aimed to assess whether frailty was an independent risk factor of one-year mortality in frail patients after elective orthopedic surgery. In this prospective study, three hundred and thirteen patients aged ≥ 65 years, undergoing elective orthopedic surgery were finally included. Frailty assessed by the Clinical Frailty Score (CFS) before the surgery was present in 29.7% (93/313). Among them, 7.7% of patients (24/313) died at one year after surgery. In multivariate logistic analysis, higher CFS (OR = 2.271, 95% CI= 1.472–3.504) was found to be an independent risk factor of one-year mortality after surgery in elderly orthopedic patients. The area under the receiver operating characteristic curve of the model was 0.897 (95% CI 0.834–0.959). In addition, we found higher Charlson comorbidity index (OR= 1.498, 95% CI = 1.082–2.073) was also a significant risk factor. In conclusion, frailty is associated with increased one-year mortality in elderly patients after elective orthopedic surgery, which should be considered as a routine assessment tool in preoperative practice.