The impact of dexmedetomidine added to ropivicaine for transversus abdominis plane block on stress response in laparoscopic surgery: a randomized controlled trial.

BACKGROUND: Intravenous dexmedetomidine is known to attenuate stress response in patients undergoing laparoscopic surgery. We investigated whether the addition of the highly selective alpha-2 adrenergic agonist dexmedetomidine into ropivacaine for ultrasound-guided transversus abdominis plane block could inhibit stress response during laparoscopic surgery, and determined the optimal dose of dexmedetomidine in it. METHODS: One hundred and twenty-five patients undergoing laparoscopic gynecological surgery were included in this prospective and randomized double-blind study. Patients received general anesthesia with or without a total of 60 ml of 0.2% ropivacaine in combination with low (0.25 µg/kg), medium (0.50 µg/kg) or high dose (1.0 µg/kg) of dexmedetomidine for the four-quadrant transversus abdominis plane block (n = 25). The primary outcomes were stress marker levels during the operation. RESULTS: One hundred and twenty patients completed the study protocol. Dexmedetomidine added to ropivacaine for transversus abdominis plane block significantly reduced serum levels of cortisol, norepinephrine, epinephrine, interleukin-6, blood glucose, mean arterial pressure and heart rate in a dose-dependent manner (P < 0.05), accompanied with decreased anesthetic and opioid consumption during the operation (P < 0.05), but the high dose of dexmedetomidine induced higher incidences of bradycardia than low or medium dose of dexmedetomidine (P < 0.05). CONCLUSION: The addition of dexmedetomidine at the dose of 0.5 µg/kg into ropivacaine for ultrasound-guided transversus abdominis plane block is the optimal dose to inhibit stress response with limited impact on blood pressure and heart rate in patients undergoing laparoscopy gynecological surgery. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn on November 6th, 2016 (ChiCTR-IOR-16009753).

Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer.

Ovarian cancer is one of the most common malignant gynecological cancers. Although conventional chemotherapies have improved the treatment of patients with ovarian cancer, the mortality rate remains high. Hence, it is crucial that the detailed mechanisms that promote ovarian cancer are urgently identified. Therefore, reverse transcription-quantitative polymerase chain reaction was used to reveal the relative transcript levels. Colony formation assay and cell cycle assay were performed in siRNA-treated cells. Transwell assay and western blot assays were also conducted. The results showed that the expression of long non-coding RNA SRY-box 2 overlapping transcript (SOX2OT) was upregulated in clinical ovarian cancer tissues and in cultured ovarian cancer cells (HO-8910 and HO-8910PM). High expression of SOX2OT negatively correlated with the prognosis of patients with ovarian cancer. Knockdown of SOX2OT by specific small interfering RNA against SOX2OT suppressed the colony formation capacity of invasive ovarian cancer cells and resulted in cell cycle arrest in G0/G1 phase. Key cell cycle regulators, cyclin B1 and cell division cycle 25C, were consistently downregulated by the knockdown of SOX2OT. Furthermore, knockdown of SOX2O Tinhibited cell migration, cell invasion and decreased the expression of mesenchymal protein N-cadherin, whereas the expression of epithelial protein E-cadherin was increased in ovarian cancer cells. Overall, SOX2OT expression levels correlated with the prognosis of patients with ovarian cancer, and SOX2OT promoted cell proliferation and motility in ovarian cancer cells. These findings indicated that SOX2OT may serve as a potential therapeutic target in the treatment of ovarian cancer.

Application of pre-injection of dexmedetomidine of different doses in pediatric intravenous general anesthesia without tracheal intubation.

This study observed the clinical efficacy of pre-injection of dexmedetomidine of different doses before surgery and the adverse reactions during the recovery period in pediatric intravenous general anesthesia without tracheal intubation. Pediatric patients who received general anesthesia without tracheal intubation before surgery from January 2016 to March 2017 were randomly divided into four groups (n=30), and were respectively treated with intravenous pump infusion of loaded dexmedetomidine of high-dose (2.5 µg/kg), middle-dose (1.5 µg/kg) and low-dose (0.5 µg/kg), while the children in the control group received injection of normal saline in same dose. Then, the mean arterial pressure (MAP) at different time points (5 and 10 min after administration, after anesthesia and after surgery), heart rate, Ramsay sedation score changes and adverse reactions during recovery period of anesthesia of pediatric patients were compared among four groups. At 5 and 10 min after administration, Ramsay scores of high-dose group and middle-dose group were higher than that of the control group, and the differences had statistical significance (P<0.05). There was no significant difference in comparison of Ramsay scores between low-dose group and the control group. The MAP and heart rate after anesthesia and after surgery of pediatric patients with pump infusion of dexmedetomidine in the three groups were decreased significantly compared to those of the control group, and the differences had statistical significance (P<0.05). The incidence rate of adverse reaction of pediatric patients during the recovery period after pump infusion in the three groups and the control group was, respectively, 13/30, 8/30, 7/30 and 8/30, and the differences were statistically significant (P<0.05). The sedative effect and safety of pre-injection of dexmedetomidine in pediatric intravenous general anesthesia without tracheal intubation are promising, and the medium dosage can maximize the anesthetic effect with less side effects.

Remote Limb Ischaemic Postconditioning Protects Against Myocardial Ischaemia/Reperfusion Injury in Mice: Activation of JAK/STAT3-Mediated Nrf2-Antioxidant Signalling.

BACKGROUND: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. METHODS: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 min of reperfusion in the left hind limb at the start of the reperfusion period. After 2 h of cardiac reperfusion, myocardial infarct size, cardiac enzyme release, apoptosis and oxidative stress were assessed. Protein expression and phosphorylation were measured by Western blotting. RESULTS: RIPostC significantly decreased cardiac IR injury, as reflected by reduced infarct size and cellular apoptosis (22.9 ± 3.3% vs 40.9 ± 6.2% and 13.4% ± 3.1% vs 26.2% ± 3.1%, respectively, both P < 0.01) as well as plasma creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release (21.97 ± 4.08 vs 35.86 ± 2.91 ng/ml and 6.17 ± 0.58 vs 8.37 ± 0.89 U/ml, respectively, both P < 0.01) compared with the IR group. RIPostC significantly increased the phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.01). In addition, RIPostC elevated the nuclear translocation of Nrf2 and the expression of HO-1 and reduced myocardial oxidative stress (P < 0.05). Interestingly, pretreatment with the JAK/STAT3 inhibitor AG490 blocked the cardioprotective effect of RIPostC accompanied by decreased phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.05), decreased nuclear translocation of Nrf2 and expression of HO-1, as well as increased oxidative stress (P < 0.05). CONCLUSION: RIPostC attenuates apoptosis and protects against myocardial IR injury, possibly through the activation of JAK/STAT3-mediated Nrf2-antioxidant signalling.

Quantitative assessment of the relationship between RASSF1A gene promoter methylation and bladder cancer (PRISMA).

BACKGROUND: Methylation of the Ras-association domain family 1 isoform A (RASSF1A) gene promoter region is thought to participate in the initiation and development of many different cancers. However, in bladder cancer the role of RASSF1A methylation was unclear. To evaluate the relationship between RASSF1A methylation and bladder cancer, a quantitative assessment of an independent meta-analysis was performed. In addition, a DNA methylation microarray database from the cancer genome atlas (TCGA) project was used to validate the results of the meta-analysis. METHODS: We searched published articles from computerized databases, and DNA methylation data were extracted from TCGA project. All data were analyzed by R software. RESULTS: The results of the meta-analysis indicated that the frequency of RASSF1A gene methylation in bladder cancer patients is significantly higher than in healthy controls. The hazard ratio (HR) was 2.24 (95% CI = [1.45; 3.48], P = 0.0003) for overall survival (OS), and the RASSF1A gene promoter methylation status was strongly associated with the TNM stage and differentiation grade of the tumor. The similar results were also found by the data from TCGA project. CONCLUSION: There was a significant relationship between the methylation of the RASSF1A gene promoter and bladder cancer. Therefore, RASSF1A gene promoter methylation will be a potential biomarker for the clinical diagnosis of bladder cancer.

Effects and mechanisms of docosahexaenoic acid on the generation of angiopoietin-2 by rat brain microvascular endothelial cells under an oxygen- and glucose-deprivation environment.

OBJECTIVE: The aim of this study was to investigate the effects of docosahexaenoic acid (DHA) on the generation of angiopoietin-2 (Ang-2) by rat brain microvascular endothelial cells under an oxygen- and glucose-deprivation environment (OGD), and its relationship, if any, with cyclooxygenase 2 (COX-2) expression. METHODS: Annexin V and propidium iodide apoptosis assay was used to detect apoptosis. Enzyme linked immunosorbent assay was used to detect Ang-2, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and prostaglandin I2 (PGI2) content. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect Ang-2 and VEGF mRNA expression. Western blot was used to detect expression of COX-2 protein. RESULTS: DHA reduced the apoptosis rate (P = 0.026) and decreased the secretion of Ang-2, VEGF, PGE2, and PGI2 (P = 0.006, P = 0.000, P = 0.002, P = 0.004 respectively). The relative expression of Ang2 and Vegf mRNA, as well as COX-2 expression, also decreased (P = 0.000, P = 0.005, P = 0.007 respectively). These effects were antagonized by GW9662 (peroxisome proliferator-activated receptor-γ antagonist). COX-2 protein expression levels were positively correlated with Ang2 and Vegf mRNA expression levels (γ = 0.69, P = 0.038 and γ = 0.76, P = 0.032, respectively). Ang-2 and VEGF mRNA levels were positively correlated with Ang-2 (γ = 0.84, P = 0.012) and VEGF (γ = 0.71, P = 0.036) secretion levels respectively. CONCLUSION: DHA reduced apoptosis induced by an OGD environment, thus decreasing Ang-2 and VEGF synthesis. This phenomenon was associated with a decrease in COX-2 protein expression, PGE2 and PGI2 secretion, and generation regulation via intracellular transcriptional pathways.

Intravenous pretreatment with emulsified isoflurane preconditioning protects kidneys against ischemia/reperfusion injury in rats.

BACKGROUND: Emulsified isoflurane (EIso) is a novel intravenous general anesthetic, which can provide rapid anesthetic induction and recovery. EIso preconditioning could attenuate heart, lung and liver ischemia/reperfusion (I/R) injury. We tested the hypothesis that intravenous pretreatment with EIso would protect kidneys against I/R injury by inhibiting systemic inflammatory responses and improving renal antioxidative ability. METHODS: RATS WERE RANDOMLY DIVIDED INTO THESE SIX GROUPS: sham, I/R, intralipid, 1, 2 or 4 ml/kg EIso. Rats were subjected to 45 min left renal pedicle occlusion followed by 3 h reperfusion after right nephrectomy. Rat were treated with intravenous 8% EIso with 1, 2 or 4 ml/kg, or 30% intralipid with 2 ml/kg for 30 min before ischemia, respectively. After reperfusion, renal functional parameters, serum mediator concentrations and markers of oxidative stress in kidney tissues were determined, and renal histopathological analysis were performed. RESULTS: Serum creatinine, blood urea nitrogen, cystatin c, tumor necrosis factor-α, interleukin-6, and interleukin-10 concentrations were significantly increased after renal I/R as compared to the sham group. So was renal tissue MDA content and histological scores, but renal tissue SOD activity was decreased. Additionally, severe morphological damages were observed in these study groups. In contrast, 2 or 4 ml/kg EIso reduced serum creatinine, blood urea nitrogen, cystatin c, tumor necrosis factor-α, and interleukin-6 levels, decreased renal tissue MDA content and histological scores, increased serum interleukin-10 level and tissue SOD activity as compared to the I/R, intralipid and 1 ml/kg EIso groups. Renal morphological damages were alleviated after pretreatment of 2 or 4 ml/kg EIso. CONCLUSIONS: Intravenous EIso produces preconditioning against renal I/R injury in rats, which might be mediated by attenuating inflammation and increasing antioxidation ability.

Evaluation of remifentanil anesthesia for off-pump coronary artery bypass grafting surgery using heart rate variability.

Heart rate variability (HRV) was used in the present study to evaluate a target-controlled approach compared with a constant-rate infusion for remifentanil anesthesia during off-pump coronary artery bypass grafting (OP-CABG) surgery. A total of 65 patients with American Society of Anesthesiologists (ASA) physical status II or III, who were aged 60-85 years and scheduled for OP-CABG, were selected for the study. All patients were administered an intramuscular premedication of 10 mg morphine and 0.3 mg scopolamine. In group I, remifentanil was infused using a target-controlled approach at 1.5-5.0 ng/ml, and in group II, remifentanil was infused at a constant-rate of 0.05-1.0 µg/kg/min and at additional single increments of 1 µg/kg when appropriate. The heart rate and other hemodynamic monitoring indices of the patients, including the mean arterial pressure, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure, were monitored at various time points, including prior to induction (T0), at extubation (performed intraoperatively; T7) and at 24 h post-surgery. The HRV indices, including total power (TP), low frequency (LF) and the LF/high frequency (HF) ratio of power (LF/HF), were reduced following induction at T0 and remained low at 24 h post-surgery. At T5 (right coronary or left circumflex artery anastomosis) and T7 (tracheal extubation), all the HRV indices, with the exception of the HF power, were significantly increased (P<0.05). Additionally, the TP, LF and LF/HF values in group II were higher at T5 compared with those in group I (P<0.05). Remifentanil target-controlled infusion is superior to constant-rate infusion in suppressing the stress response during OP-CABG, maintaining the balance of the cardiac autonomic nervous system and promoting the recovery of the autonomic function following surgery.