Dexmedetomidine Directs T Helper Cells toward Th1 Cell Differentiation via the STAT1-T-Bet Pathway.

Dexmedetomidine is an α2 adrenergic receptor agonist that has been reported to modulate the polarization of CD4+ T cells. However, the underlying mechanisms by which dexmedetomidine induces T-helper 1 (Th1) cell differentiation remain poorly understood. The aim of this study was to explore the potential mechanisms through which dexmedetomidine can induce Th1 cell differentiation. Purified CD4+ T cells were stimulated with anti-CD3/anti-CD28 and then treated with dexmedetomidine. Flow cytometry analysis was adopted to measure the concentration of Th1 cells. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qPCR) were performed to detect protein levels and mRNA expression, respectively, of IFN-γ and IL-4. Western blotting was used to determine the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and T-bet expression. The Th1 cell subset and IFN-γ levels were elevated in the dexmedetomidine-induced CD4+ T cells. Dexmedetomidine enhanced the phosphorylation of STAT1 and the expression of T-bet in the CD4+ T cells. Atipamezole (an α2 adrenergic antagonist) and fludarabine (a STAT1 inhibitor) reversed the dexmedetomidine-induced Th1 cell differentiation. These results suggested that dexmedetomidine induced Th1 cell differentiation via the STAT1-T-bet signaling pathway.

Dexmedetomidine May Reduce IL-6 Level and the Risk of Postoperative Cognitive Dysfunction in Patients After Surgery: A Meta-Analysis.

Dexmedetomidine (DEX) was widely used in clinical work. However, the effectiveness of DEX on postoperative cognitive dysfunction (POCD) was still need to be confirmed. The aim of this meta-analysis was to explore whether DEX can reduce the incidence of POCD on the first day and seventh postoperative day. The results showed that lower incidence of POCD associated with DEX treatment on the first (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.31-0.54) or seventh postoperative day (OR: 0.53; 95% CI: 0.36-0.77). Mini-Mental State Examination scores on the first (mean difference [MD]: 4.67; 95% CI: 1.72-7.63) and seventh postoperative days (MD: 3.71; 95% CI: 2.51-4.90) were higher in DEX use group than that in physiological saline group. Meanwhile, neuron-specific enolase (NSE; MD: -3.99; 95% CI: -6.20 to -1.78) and interleukin 6 (IL-6) levels (MD: -17.53; 95% CI: -21.51 to -13.54) on the first postoperative day in DEX group were lower than that in the physiological saline group. This meta-analysis suggested that DEX use could reduce the risk of POCD and the reduction in levels of NSE and IL-6 can improve long-term cognitive dysfunction and anti-inflammation.

Morphine induces the differentiation of T helper cells to Th2 effector cells via the PKC-θ-GATA3 pathway.

BACKGROUND: T help 2 (Th2) cell differentiation by morphine has been verified. However, the underlying mechanism of morphine induces Th2 cell differentiation remains elusive. The aim of the present study was to explore the possible basis of morphine induced Th2 cell differentiation. METHODS: Flow cytometry analysis was used to detect the content of T help 1(Th1) cell and Th2 cell. Enzyme linked immunosorbent assay (ELISA) was performed to determine the levels of IL-4 and IFN-γ. Real-time quantitative polymerase chain reaction, electrophoretic mobility shift assay and Western blotting was conducted in this study. RESULTS: Th2 cell subset and IL-4 level were elevated in morphine induced naïve T cells. Pathway determining found the protein phosphorylation level of PKC-θ and the expression and activity of the transcription factor GATA3 was also enhanced in the naïve T cells challenged by morphine. Moreover, inhibitor of morphine(naltrexone) or PKC-θ(AEB071) can reverse morphine-induced Th2 cell differentiation. CONCLUSION: These results suggested that morphine induce naïve T cell differentiation to Th2 cells via the PKC-θ/GATA3 signal pathway.

Association between BDNF rs6265 polymorphisms and postoperative cognitive dysfunction in Chinese Han Population.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD). In present study, we aimed to assess the possible association between POCD and BDNF rs6265 polymorphisms. METHODS: 124 patients aged 60 years or older scheduled for elective surgery under general anesthesia and 25 age- and gender-matched healthy volunteers were recruited. POCD was identified using a neuropsychological test battery administered preoperatively, 7 days, and 3 months after surgery. Genotyping of rs6265 was performed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis. RESULTS: 99 patients and 25 healthy controls were finally enrolled in the analysis. 29(29.3%) and 18(18.2%) of 99 patients had POCD at 7 days and 3 months after surgery, respectively. The patients carrying a G allele at the rs6265 locus showed a lower risk for POCD than an A allele carriers on postoperative 7 days, but not 3 months after surgery (OR = 0.67; 95% CI: 0.47-0.96; p = .017; OR = 0.69; 95% CI: 0.42-1.13; p = .14, respectively). The risk of POCD at 7 days following surgery was significantly lower in additive model (OR = 0.41; 95% CI: 0.2-0.84; p = .015) and dominant model (OR = 0.35; 95% CI: 0.13-0.96; p = .042). CONCLUSION: We tentatively demonstrate that BDNF rs6265 polymorphisms might be associated with occurrence of POCD at 7 days after surgery and the A > G mutant at the rs6265 locus be likely a protective factor for early POCD in Chinese Han population.

Preoperative anxiety induces chronic postoperative pain by activating astrocytes in the anterior cingulate cortex region.

OBJECTIVE: The study aims to explore the relationship between preoperative anxiety and chronic postoperative pain. METHODS: A total of forty rats were divided into four groups, control, single-prolonged stress alone, Hysterectomy alone, and SPS+ Hysterectomy. The paw withdrawal mechanical thresholds (PWMT) were examined. qRT-PCR and western blotting assay were performed to detect the GFAP expression in astrocytes isolated from the anterior cingulate cortex (ACC) region. In addition, the long-term potentiation (LTP) in ACC was examined. RESULTS: Rats in the SPS group or the Hysterectomy alone group had no significant effect on chronic pain formation, but SPS can significantly induce chronic pain after surgery. Astrocytes were still active, and the LTP was significantly increased three days after modeling in the SPS+Hysterectomy group. CONCLUSIONS: anxiety can induce chronic pain by activating astrocytes in the ACC region.

Preoperative anxiety induces chronic postoperative pain by activating astrocytes in the anterior cingulate cortex region

SUMMARY OBJECTIVE The study aims to explore the relationship between preoperative anxiety and chronic postoperative pain. METHODS A total of forty rats were divided into four groups, control, single-prolonged stress alone, Hysterectomy alone, and SPS+ Hysterectomy. The paw withdrawal mechanical thresholds (PWMT) were examined. qRT-PCR and western blotting assay were performed to detect the GFAP expression in astrocytes isolated from the anterior cingulate cortex (ACC) region. In addition, the long-term potentiation (LTP) in ACC was examined. RESULTS Rats in the SPS group or the Hysterectomy alone group had no significant effect on chronic pain formation, but SPS can significantly induce chronic pain after surgery. Astrocytes were still active, and the LTP was significantly increased three days after modeling in the SPS+Hysterectomy group. CONCLUSIONS anxiety can induce chronic pain by activating astrocytes in the ACC region.

RESUMO OBJETIVO O objetivo deste estudo é explorar a relação entre a ansiedade no pré-operatório e a dor crônica no pós-operatório. MÉTODOS Um total de 40 ratos foram divididos em quatro grupos: controle, estresse prolongado (SPS), histerectomia e SPS + histerectomia. Os limiares de retirada da pata em resposta a estímulo mecânico (PWMT) foram examinados. Ensaios qRT-PCR e imunoenzimáticos (western blotting) foram realizados para detectar a expressão de GFAP em astrócitos isolados da região do córtex cingulado anterior (CCA). Além disso, a potenciação de longa duração (LTP) no CCA também foi examinada. RESULTADOS Os ratos no grupo de estresse prolongado e no grupo de histerectomia não apresentaram nenhum efeito significativo na formação de dor crônica. Porém, o estresse prolongado foi capaz de induzir dor crônica significativamente após a cirurgia. Três dias após o modelo, o grupo de SPS + histerectomia ainda apresentava astrócitos ativos e LTP significativamente maior. CONCLUSÃO A ansiedade pode provocar dor crônica através da ativação de astrócitos na região do CCA.

Effect of ultrasound-guided proximal and distal approach for obturator nerve block in transurethral resection of bladder cancer under spinal anesthesia.

Background: Ultrasound-guided proximal or distal approach for obturator nerve block is preformed to prevent adductor muscle spasm during transurethral resection of bladder tumors. The aim of the study was to compare the effectiveness of two different techniques in blocking the obturator nerve during transurethral resection of a bladder tumor. Methods: Fifty obturator nerve blocks were performed for transurethral bladder tumor resection and divided into two groups. One group received ultrasound-guided proximal obturator nerve block approach (proximal group), and the other group received ultrasound-guided distal obturator nerve block approach (distal group). Grade of adductor muscle spasm, the rate of clinical effectiveness, duration of block procedure, and complications were recorded. Patients with grade two adductor spasms were transferred to general anesthesia. Results: Two patients in the distal group and one in the proximal group were transferred to general anesthesia for severe adductor muscle spasms. No difference was found in clinical effectiveness rate of obturator nerve block between the two groups. differed insignificantly. The number of patients who had no adductor muscle spasms in the proximal group was significantly higher than that of the distal group. Vascular puncture was detected in two patients in the proximal group and one patient in the distil group. No other complications were observed. Conclusion: No difference was found for clinical effectiveness between the two groups. However, vascular puncture should receive more attention.