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BackgroundPrevious studies showed that isoflurane-induced cognitive deficits could be alleviated by dexmedetomidine in young animal subjects. In the current study, we examine whether dexmedetomidine could also alleviate isoflurane-induced cognitive deficits in senile animals.MethodsSenile male C57BL/6 mice (20 months) received dexmedetomidine (50 μg/kg, i.p.) or vehicle 30 minutes prior to isoflurane exposure (1.3% for 4 h). Cognitive function was assessed 19 days later using a 5-day testing regimen with Morris water maze. Some subjects also received pretreatment with α2 adrenoreceptor antagonist atipamezole (250 μg/kg, i.p.), JAK2 inhibitor AG490 (15 mg/kg i.p.) or STAT3 inhibitor WP1066 (40 mg/kg i.p.) 30 minutes prior to dexmedetomidine.ResultsIsoflurane exposure increased and reduced the time spent in the quadrant containing the target platform in training sessions. The number of crossings over the original target quadrant was also decreased. Dexmedotomidine attenuated such effects. Effects of dexmedotomidine were reduced by pretreatment with atipamezole, AG490 and WP1066. Increased phosphorylation of JAK2 and STAT3 in the hippocampus induced by isoflurane was augmented by dexmedetomidine. Effects of dexmedetomidine on JAK2/STAT3 phosphorylation were attenuated by atipamezole, AG490 and WP1066. Isoflurane promoted neuronal apoptosis and increased the expression of cleaved caspase-3 and BAD, and reduced Bcl-2 expression. Attenuation of such effects by dexmedotomidine was partially blocked by atipamezole, AG490 and WP1066.ConclusionDexmedetomidine could protect against isoflurane-induced spatial learning and memory impairment in senile mice by stimulating the JAK2/STAT3 signaling pathway. Such findings encourage the use of dexmedetomidine in geriatric patients receiving isoflurane anesthesia.

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Background Perioperative neurocognitive disorders (PNDs) occur frequently after surgery and worsen patient outcome. How C-X-C motif chemokine (CXCL) 13 and its sole receptor CXCR5 contribute to PNDs remains poorly understood. Methods A PND model was created in adult male C57BL/6J and CXCR5−/− mice by exploratory laparotomy. Mice were pretreated via intracerebroventricular injection with recombinant CXCL13, short hairpin RNA against CXCL13 or a scrambled control RNA, or ERK inhibitor PD98059. Then surgery was performed to induce PNDs, and animals were assessed in the Barnes maze trial followed by a fear-conditioning test. Expression of CXCL13, CXCR5, and ERK in hippocampus was examined using Western blot, quantitative PCR, and immunohistochemistry. Levels of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in hippocampus were assessed by Western blot. Results Surgery impaired learning and memory, and it increased expression of CXCL13 and CXCR5 in the hippocampus. CXCL13 knockdown partially reversed the effects of surgery on CXCR5 and cognitive dysfunction. CXCR5 knockout led to similar cognitive outcomes as CXCL13 knockdown, and it repressed surgery-induced activation of ERK and production of IL-1β and TNF-α in hippocampus. Recombinant CXCL13 induced cognitive deficits and increased the expression of phospho-ERK as well as IL-1β and TNF-α in hippocampus of wild-type mice, but not CXCR5−/− mice. PD98059 partially blocked CXCL13-induced cognitive dysfunction as well as production of IL-1β and TNF-α. Conclusions CXCL13-induced activation of CXCR5 may contribute to PNDs by triggering ERK-mediated production of pro-inflammatory cytokines in hippocampus.

Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that has been reported to be associated with several malignant tumors. The present study aimed to evaluate its role in epithelial ovarian carcinoma (EOC). The mRNA levels of TSLP in human EOC samples and EOC cell lines were determined. Then, the expression of TSLP was examined in 144 clinical tissue microarray samples and correlated with clinicopathological factors. Finally, the correlation between TSLP overexpression and prognosis of EOC patients was analyzed. Our data show that mRNA levels of TSLP were significantly higher in EOC tissues and cell lines. Chi-square tests revealed that TSLP overexpression in EOC was significantly associated with age, histological type, Federation of Gynecology and Obstetrics (FIGO) stage, histological differentiation, pelvic involvement, and lymphatic metastasis. Kaplan–Meier survival analysis revealed that poor prognosis was significantly correlated with older age, advanced FIGO stage, poor histological differentiation, pelvic involvement, lymphatic involvement, or TSLP overexpression (P<0.05). Additionally, multivariate Cox regression analysis confirmed pelvic involvement and TSLP overexpression as independent prognostic factors for both overall and disease-free survival. Taken altogether, TSLP overexpression reflects a more malignant phenotype and TSLP may be a novel biomarker for EOC.

Sensitivity analysis plays a key role in structural optimization, but traditional methods of sensitivity analysis in strength and stiffness are time consuming and of high cost. In order to effectively carry out structural optimization of hydraulic press, this paper presents a novel sensitivity analysis method in structural performance of hydraulic press, which saves a great deal of time and design costs. The key dimension parameters of the optimization of design variables, which remarkably impact on the structural performance of hydraulic press, are efficiently selected. The impact order of various sensitivity parameters in strength and stiffness of machine tools is consistent with the sensitivity ranking of regression analysis. The research results provide the basis for the hydraulic machine design and references in research of machine tools and equipment.

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