Cuproptosis-related genes prediction feature and immune microenvironment in major depressive disorder.

Background: Major depressive disorder (MDD) is a severe, unpredictable, ill-cured, relapsing neuropsychiatric disorder. A recently identified type of death called cuproptosis has been linked to a number of illnesses. However, the influence of cuproptosis-related genes in MDD has not been comprehensively assessed in prior study. Aim: This investigation intends to shed light on the predictive value of cuproptosis-related genes for MDD and the immunological microenvironment. Methods: GSE38206, GSE76826, GSE9653 databases were used to analyze cuproptosis regulators and immune characteristics. To find the genes that were differently expressed, weighted gene co-expression network analysis was employed. We calculated the effectiveness of the random forest model, generalized linear model, and limit gradient lifting to arrive at the best machine prediction model. Nomogram, calibration curve, and decision curve analysis were used to show the anticipated MDD's accuracy. Results: This study found that there were activated immune responses and cuproptosis-related genes that were dysregulated in people with MDD compared to healthy controls. Considering the test performance of the learned model and validation on subsequent datasets, the RF model (including OSBPL8, VBP1, MTM1, ELK3, and SLC39A6) was considered to have the best discriminative performance. (AUC = 0.875). Conclusion: Our study constructed a prediction model to predict MDD risk and clarified the potential connection between cuproptosis and MDD.

Magnesium may be an effective therapy for Alzheimer's disease.

Magnesium deficiency in serum or the brain of Alzheimer's disease (AD) patients has been shown to be associated with AD. Current research suggests that supplementing or restoring magnesium may be a novel approach to AD treatment. However, the physiological properties of magnesium make such treatment difficult. It is undeniable that magnesium may be an effective therapy for AD.

ABCA7 rs3764650 Polymorphism is Associated with Delayed Neurocognitive Recovery.

Background: Several studies have shown that ATP-binding cassette transporter A7 (ABCA7) gene variation is associated with cognitive impairment. This study was aimed to investigate the relationship between ABCA7 rs3764650 polymorphism and perioperative neurocognitive disorder (pNCD). Methods: A total of 132 elderly patients aged 65 and over who underwent elective non-cardiac surgery were enrolled in the study, while 28 healthy volunteers matching age and sex were recruited as the control group. A battery of neuropsychological tests was conducted 1 day before, 7 days, and 3 months after surgeries. Delayed neurocognitive recovery (dNCR) and postoperative mild or major neurocognitive disorder (POCD) were determined using the Z value method. The venous blood sample of the surgical patients was taken before the operation. Genotyping of rs3764650 was performed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis. Results: The incidences of dNCR and POCD were 29.7% and 16.8% at 7 days and 3 months after surgery, respectively. The G allele frequency and GG frequency of dNCR patients were significantly higher than that of non-dNCR patients (43.3% vs 28.2%, P=0.035; 23.3% vs 4.2%, P=0.013, respectively) at 7 days following surgery. No significant differences in ABCA7 alleles between POCD and non-POCD patients were observed 3 months postoperatively. Conclusion: ABCA7 rs3764650 gene polymorphism is associated with dNCR and GG genotype might be a predisposing factor for postoperative cognitive impairment in Chinese Han elderly populations.

Sodium Bicarbonate Sub-Diaphragmatic Irrigation Relieves Shoulder Pain After Total Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To determine whether sub-diaphragmatic irrigation with sodium bicarbonate would relieve post-laparoscopic shoulder pain (PLSP) after total laparoscopic hysterectomy. DESIGN: Randomized double-blinded trial. SETTING: Teaching hospital. PATIENTS: Seventy patients undergoing total laparoscopic hysterectomy (TLH) for benign indications. INTERVENTION: We randomly allocated patients to intervention or control groups where sodium bicarbonate containing flushing liquid or normal saline was irrigated sub-diaphragm before sewing. MEASUREMENT & MAIN RESULTS: The primary outcome was PLSP following surgery measured by a numerical rating scale (NRS) (0 = no pain; 10 = worst pain imaginable). Secondary outcomes were abdominal incisional and visceral pain, analgesic use, and sodium bicarbonate related side effects. The incidence of PLSP in intervention group was significantly lower than that in control group (P < 0.05). Contrarily, incisional and visceral pain was similar in both groups (P = 0.1). The consumption of rescue analgesics in the intervention group was lower than that in the control group. Side effects were comparable in both study groups. CONCLUSION: Sub-diaphragmatic irrigation with sodium bicarbonate could effectively reduce shoulder pain, but not abdominal incisional and visceral pain, in patients undergoing TLH without an increase in side effects. REGISTRATION INFORMATION: Clinical trial registry number: http://www.chictr.org.cn/ (ChiCTR2100041765). REGISTRATION FINDINGS: http://www.chictr.org.cn/showproj.aspx?proj=66721 Link to clinical trial page and data repository: http://www.medresman.org.cn/pub/cn/proj/projectshshow.aspx?proj=2992.

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.