Spinal sirtuin 2 attenuates bone cancer pain by deacetylating FoxO3a.

Bone cancer pain (BCP) is refractory to currently used analgesics. Recently, sirtuin 2 (SIRT2) was reported to play a vital role in neuropathic pain but its role in BCP remains unknown. It was hypothesized that spinal SIRT2 attenuates BCP by deacetylating FoxO3a and suppressing oxidative stress. The mouse model of BCP established by injecting tumor cells into the intramedullary space of the femur demonstrated that spinal SIRT2 and FoxO3a were downregulated in BCP development. Intrathecal administration of LV-SIRT2 reduced pain hypersensitivity (mechanical and thermal nociception) in BCP mice. Spinal SIRT2 overexpression upregulated FoxO3a and antioxidant genes (SOD2 and catalase) and inhibited FoxO3a acetylation, phosphorylation, and ubiquitination. Moreover, intrathecal administration of SIRT2 shRNA induced pain hypersensitivity in normal mice. Spinal SIRT2 knockdown downregulated FoxO3a and antioxidant genes and increased FoxO3a acetylation, phosphorylation, and ubiquitination. In summary, spinal SIRT2 increases FoxO3a expression in BCP mice and inhibits oxidative stress by deacetylating FoxO3a and further reducing FoxO3a phosphorylation, ubiquitination, and degradation, leading to BCP relief.

A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation.

Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primary somatosensory cortex of hindlimb (S1HL) mediates the disinhibition and subsequent hyperexcitation of glutamatergic neurons in the S1HL (S1HLGlu), which then drives secondary mechanical hypersensitivity development in ipsilateral hindpaws of mice with forepaw amputation. Forepaw amputation induces rapid S1FL microglial activation that further activates S1HL microglia via the CCL2-CCR2 signaling pathway. Increased engulfment of GABAergic presynapses by activated microglia stimulates S1HLGlu neuronal activity, ultimately leading to secondary mechanical hypersensitivity of hindpaws. It is widely believed direct neuronal projection drives interactions between distinct brain regions to prime specific behaviors. Our study reveals microglial interactions spanning different subregions of the somatosensory cortex to drive a maladaptive neuronal response underlying secondary mechanical hypersensitivity at non-injured sites.

Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice.

Anxiety-associated symptoms following acute stress usually become extinct gradually within a period of time. However, the mechanisms underlying how individuals cope with stress to achieve the extinction of anxiety are not clear. Here we show that acute restraint stress causes an increase in the activity of GABAergic neurons in the CeA (GABACeA) in male mice, resulting in anxiety-like behaviors within 12 hours; meanwhile, elevated GABACeA neuronal CX3CL1 secretion via MST4 (mammalian sterile-20-like kinase 4)-NF-κB-CX3CL1 signaling consequently activates microglia in the CeA. Activated microglia in turn inhibit GABACeA neuronal activity via the engulfment of their dendritic spines, ultimately leading to the extinction of anxiety-like behaviors induced by restraint stress. These findings reveal a dynamic molecular and cellular mechanism in which microglia drive a negative feedback to inhibit GABACeA neuronal activity, thus facilitating maintenance of brain homeostasis in response to acute stress.

Water can trigger nuclear reaction to produce energy and isotope gases.

This paper reports the discovery that water can trigger a peculiar nuclear reaction and produce energy. Cavitation may induce unusual reactions through implosion of water vapor bubbles. Many of this research has been published formally or informally. We have conducted experiments using two reactor types made from multiple-pipe heat exchanger and found that the heat exchange process of water produces peculiar excess heat and abnormally high pressure leading to rupture of the reactor. Recently, we have tested another eight reactors. Interestingly, these reactors produce non-condensable gas. We suspected that they include 22Ne and CO2. We used a mass spectrometer (MS) to analyze 14 gas samples collected from 8 reactors, including ten samples showing a coefficient of performance COPx > 1.05 (with excess heat) and four having COPx < 1.05 (without excess heat). Several methods were adopted to identify the gas content. For CO2 identification, two methods are employed. For 22Ne identification, three methods are employed. All the results confirm that isotope 22Ne and regular CO2 really exist in the output gas from reactors determined to have excess heat. We conjecture a possible mechanism to produce 22Ne and CO2 and find out that 12C and isotope 17O are the intermediate. They finally form isotope gases containing 17O, including H2O-17 (heavy-oxygen water), isotope O2 (16O-17O), and isotope CO2 (12C-16O-17O). In the excess heat producing reactors, all these gasses were detected by MS in the absence of 20Ne and 21Ne. The observed isotope gases produced from reactors having excess heat verifies that water can trigger a peculiar nuclear reaction and produce energy.

Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

BACKGROUND: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. METHODS: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. RESULTS: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. CONCLUSIONS: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.

ABO blood types may affect transient neurological events after surgical revascularization in patients with moyamoya disease: a retrospective single center study.

BACKGROUND: Moyamoya disease (MMD) is a cerebrovascular disease with unknown cause. Patients with MMD disease usually experience transient neurological events (TNEs) after revascularization surgery. This retrospective single-center study was aimed to explore the risk factors of postoperative TNEs after surgical revascularization in patients with MMD. METHODS: We selected 324 patients who underwent surgical revascularization between January 2017 and September 2022 in our center. The perioperative characteristics of the patients were recorded and the outcome was TNEs after surgery. An analysis of risk factors contributing to postoperative TNEs by using logistic regression model. RESULTS: Three hundred twelve patients were enrolled, and the incidence of postoperative TNEs was 34% in our study. Males were more likely to suffer from postoperative TNEs (OR = 2.344, p = 0.002). Preoperative ischemic presentation (OR = 1.849, p = 0.048) and intraoperative hypotension (OR = 2.332, p = 0.002) were associated with postoperative TNEs. Compared to patients with blood type O, patients with blood type A (OR = 2.325, p = 0.028), B (OR = 2.239, p = 0.027) and AB (OR = 2.938, p = 0.019) had a significantly higher incidence of postoperative TNEs. A risk prediction model for postoperative TNEs was established, and the established risk prediction area under the receiver operating characteristic curve (ROC) of the model was 0.741. CONCLUSIONS: Males, preoperative ischemic presentation and intraoperative hypotension were associated with postoperative TNEs. We also found a possible link between postoperative TNEs and ABO blood types after surgical revascularization for moyamoya patients.

Effect of Oral Care Solution on Sore Throat After I-Gel Laryngeal Mask General Anesthesia: A Randomized Controlled Trial.

Background: Sore throat is a common complication after general anesthesia. Oral care solutions have been used to reduce the incidence of oral complications or ventilator-associated pneumonia, but their effect on postoperative sore throat (POST) is unclear. This study aims to investigate whether oral care solution can alleviate POST in patients undergoing i-gel laryngeal mask general anesthesia. Methods: A total of 120 patients who were scheduled for elective surgery under laryngeal mask general anesthesia were enrolled. The patients were randomly assigned to an experimental group (oral care solution) and a control group (0.9% saline) and gargled for 1 min with 10mL of oral care solution or saline 5 min before anesthesia induction. The primary outcomes were the overall incidence of sore throat within 24 h and incidence at 20 min, 1 h, 6 h, 24 h after removal of i-gel. The secondary outcomes were the severity of sore throat at the four time points and incidence of hoarseness, cough within 24 h after removal of i-gel. Results: A total of 111 patients were included in the analysis. The overall incidence of sore throat within 24 h in the experimental group was significantly lower than that in the control group, as was the incidence at four time points (P<0.05). The VAS scores at the four time points in the experimental group were significantly lower than those in the control group (P<0.05), and the results of repeated measurement analysis of variance showed that time effect and intergroup effect were statistically significant (P<0.001). No differences were found between the groups in the incidence of hoarseness and cough. Conclusion: Gargling with oral care solution before anesthesia induction can significantly reduce the incidence and severity of POST in patients undergoing i-gel laryngeal mask general anesthesia.

The Value of Pain Sensitivity Questionnaire in Predicting Postoperative Pain in Living Kidney Donors: A Prospective Observational Study.

Purpose: This study aimed to investigate the value of the Pain Sensitivity Questionnaire (PSQ) for the prediction of postoperative pain and the relationship between pain sensitivity and postoperative pain in kidney donors undergoing living-related kidney transplantation. Patients and Methods: A total of 148 kidney donors were selected and the preoperative pain sensitivity questionnaire was administered the day before surgery. Kidney donors were assigned to low PSQ group (PSQ < 6.5, n = 76) or high PSQ group (PSQ ≥ 6.5, n = 72). The primary endpoint was the number of patient-controlled analgesia (PCA). Other outcomes included: the incidence of acute pain, flurbiprofen axetil remediation rate, the incidence of chronic pain, neuropathic pain assessment scale (Douleur Neuropathique 4 Questions, DN4), visual analog scale (VAS) at rest after surgery as well as the correlation between PSQ and QST (Quantitative Sensory Testing). Results: The low PSQ group had a significantly lower number of PCA than high PSQ group (P < 0.0001). The incidence of acute pain was 75% in low PSQ group and 100% in high PSQ group (P < 0.0001). Furthermore, flurbiprofen axetil remediation rate was lower in low PSQ group than that in high PSQ group (P = 0.042). The incidence of chronic pain was significantly lower in low PSQ group than in high PSQ group (6.6% vs 61.1%, P < 0.001). Moreover, DN4 was significantly lower in low PSQ group than that in high PSQ group (P < 0.001). The PSQ-mean was significantly negatively correlated with QST in kidney donors. VAS at rest for the low PSQ group were lower than those of the high PSQ group. Conclusion: The PSQ was found to be associated with the intensity or postoperative pain and might be used to screen patients prior to living-kidney transplantation.

A comparative study on the effect of dopamine vs phenylephrine in improving the cutaneous analgesic effect of mexiletine in rats.

BACKGROUND: The present study aimed to compare the effects of the combined administration of two adjuvants, dopamine and phenylephrine, on the cutaneous analgesic effect and duration of mexiletine in rats. METHODS: Nociceptive blockage was evaluated by the inhibition of response to skin pinpricks in rats via the cutaneous trunci muscle reflex (CTMR). After subcutaneous injection, the analgesic activities of mexiletine in the absence and presence of either dopamine or phenylephrine were assessed. Each injection was standardized into 0.6 ml with a mixture of drugs and saline. RESULTS: Subcutaneous injections of mexiletine successfully induced dose-dependent cutaneous analgesia in rats. The results revealed that rats injected with 1.8 µmol mexiletine exhibited 43.75% blockage (%MPE), while rats injected with 6.0 µmol mexiletine showed 100% blockage. Co-application of mexiletine (1.8 or 6.0 µmol) with dopamine (0.06, 0.60, or 6.00 µmol) elicited full sensory block (%MPE). Sensory blockage ranged from 81.25% to 95.83% in rats injected with mexiletine (1.8 µmol) and phenylephrine (0.0059 or 0.0295 µmol), and complete subcutaneous analgesia was observed in rats injected with mexiletine (1.8 µmol) and a higher concentration of phenylephrine (0.1473 µmol). Furthermore, mexiletine at 6.0 µmol completely blocked nociception when combined with any concentration of phenylephrine, while 0.1473 µmol phenylephrine alone exhibited 35.417% subcutaneous analgesia. The combined application of dopamine (0.06/0.6/6 µmol) and mexiletine (1.8/6 µmol) resulted in increased %MPE, complete block time, full recovery time, and AUCs compared to the combined application of phenylephrine (0.0059 and 0.1473 µmol) and mexiletine (1.8/6 µmol) (p < 0.001). CONCLUSION: Dopamine is superior to phenylephrine in improving sensory blockage and enhancing the duration of nociceptive blockage by mexiletine.

Perioperative transcutaneous electrical acupoint stimulations as part of an enhanced recovery after surgery protocol for living donors undergoing nephrectomy: A randomized, controlled clinical trial.

Objective: Living kidney donors (LKDs) experience perioperative anxiety. We designed the following study to evaluate the anxiolytic effect of transcutaneous electrical acupoint stimulation (TEAS) during the perioperative period in a group of LKDs undergoing laparotomy nephrectomy. Methods: LKDs were randomly assigned to either the TEAS or control group. Participants in the TEAS group received 30min of intervention (6-15 mA, 2-100 Hz), at Yintang (EX-HN-3), bilateral Taichong (LR3) and Neiguan (PC6) one day before surgery (D0), before induction of anesthesia (D1) and one day after surgery (D2). The participants in the control group received the same placement of electrodes but without electrical stimulation. Venous blood was collected before each intervention. Anxiety levels and recovery profiles were recorded. Results: LKDs in the TEAS group had lower anxiety level than those in the control group at D1, D2 and three days after surgery (D3). The percentage differences were: 33.3%, 25.0%, and 22.2%; [95% confidence interval (CI), (-55.1%, -11.6%), (-47.4%, -2.6%), and (-42.3%, -2.2%); P = 0.005, P = 0.034, and P = 0.035; respectively]. LKDs who received TEAS had better sleep quality and short-term recovery profiles than those in the control group. The plasma levels of 5-hydroxytryptamine (5-HT) and melatonin (MT) in the TEAS group were significantly higher than those in the control group at D1 and D2 (5-HT: P = 0.001, and P < 0.001; MT: P = 0.006, and P = 0.001). At the 3-month follow up, fewer LKDs in the TEAS group had incisional pain when compared to the control group (P = 0.032). Conclusions: Perioperative TEAS decreased perioperative anxiety and facilitated postoperative recovery in the LKDs, and potential decreased the development of chronic pain. Trial Registration: Registered at ChiCTR2000029891, http://www.chictr.org.cn/listbycreater.aspx.

Does the pain sensitivity questionnaire correlate with tourniquet pain in patients undergoing ankle surgery?

Background: Tourniquet pain is the most prominent problem in ankle surgery, and there is no proper method to predict it. It was reported that pain sensitivity questionnaires could evaluate the pain sensitivity of subjects. Its potential to predict tourniquet pain in ankle surgery is constructive and meaningful. Methods: One hundred and twenty patients undergoing ankle surgery were included in this study. The pain sensitivity questionnaire (PSQ) and self-rating anxiety scale (SAS) were completed before the operation. The methods included an ultrasound-guided popliteal sciatic, a femoral nerve block, and a proximal thigh tourniquet. The pressure of the tourniquet was set according to the systolic blood pressure (SBP + 100 mmHg). A visual analogue scale (VAS) was used to assess the tourniquet pain. Also, the onset time of tourniquet pain ≥4 VAS units was recorded. Results: The PSQ-total and PSQ-minor scores were significantly correlated with the onset time when the tourniquet pain ≥4 VAS units (r = -0.763, r = -0.731, P < 0.001). The PSQ-total score <6.5 group gave significantly lower ratings for items 3, 4, 14, and 16 in the PSQ survey compared to the PSQ-total score ≥6.5 group (P < 0.05). Patients with high pain sensitivity have a higher need for analgesic drugs (P < 0.001). PSQ-total score ≥6.5 (OR = 185.8, 95% CI = 39.8-1,437.6, P < 0.001), sex (male, OR = 0.11, 95% CI = 0.018-0.488, P < 0.05), and age (OR = 0.92, 95% CI = 0.842-0.995, P < 0.05) were risk factors for reporting a tourniquet pain ≥4 VAS units within 30 min. Conclusion: The PSQ score is found to be correlated with intraoperative tourniquet pain. In addition, sex and age also affect the time of having intraoperative tourniquet pain.

Melatonin attenuates bone cancer pain via the SIRT1/HMGB1 pathway.

Bone cancer pain (BCP), which seriously affects the quality of life of patients, remains a clinically challenging problem. Hence, there is an urgent need to investigate new mechanisms and develop new therapeutics to relieve BCP. In the present study, we investigated the analgesic effect of melatonin on BCP and the underlying mechanisms. Male C57BL/6 mice were used to establish BCP models. We found that the levels of sirtuin 1 (SIRT1) and nucleus-high mobility group box-1 (HMGB1) were decreased, whilst the levels of HMGB1, cytoplasm-HMGB1 and inflammatory cytokines (TNF-α, IL-6, IL-1ß) were increased in the spinal cord of BCP mice on days 7, 14 and 21 after implantation compared with the levels in sham mice. Intrathecal administration of melatonin dose-dependently increased values of PWMT and TWL compared with the BCP group. However, intrathecal administration of EX527 (a selective SIRT1 antagonist) reversed the analgesic effect of melatonin. Moreover, mice in the melatonin group exhibited an increase in SIRT1 and nucleus-HMGB1, whilst there was a decrease in HMGB1, cytoplasm-HMGB1, rage, acetyl-HMGB1 and inflammatory cytokines compared with those in BCP mice. EX527 also reversed these changes. Furthermore, SIRT1 physically interacted with HMGB1 in the BCP mice. In conclusion, intrathecal administration of melatonin attenuates BCP through SIRT1-dependent inhibition of HMGB1 translocation and inflammatory cytokines. Melatonin may be a promising drug for the clinical treatment of BCP.

Remifentanil requirement for i-gel insertion is reduced in male patients with Parkinson's disease undergoing deep brain stimulator implantation: an up-and-down sequential allocation trial.

BACKGROUND: Laryngeal mask airways have been widely used in clinical practice. The aim of this study was to investigate whether the remifentanil requirement for facilitation of i-gel insertion in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery was different from that in non-PD (NPD) patients undergoing intracranial surgery. STUDY DESIGN: An up-and-down sequential allocation trial. METHODS: Male patients aged between 40 and 64 years old were enrolled. The first patient in each group (PD and NPD) group received an effect-site concentration (Ce) of remifentanil (Minto pharmacokinetic model) of 4.0 ng.ml-1 during a target-controlled infusion (TCI) of 3.5 µg.ml-1 propofol (Marsh pharmacokinetic model). The next dose of remifentanil was determined by the response of the previous patient. The Ce of remifentanil required for i-gel insertion in 50% of patients (EC50) was estimated by the modified Dixon's up-and-down method and by probit analysis. RESULTS: The PD group included 24 patients and the NPD group included 23. The EC50 of remifentanil for i-gel insertion during a TCI of 3.5 µg.ml-1 propofol estimated by the modified Dixon's up-and-down method in PD patients (2.38 ± 0.65 ng.ml-1) was significantly lower than in NPD patients (3.21 ± 0.49 ng.ml-1) (P = 0.03). From the probit analysis, the EC50 and EC95 (effective Ce in 95% of patients) of remifentanil were 1.95 (95% CI 1.52-2.36) ng.ml-1 and 3.12 (95% CI 2.53-5.84) ng.ml-1 in PD patients and 2.85 (95% CI 2.26-3.41) ng.ml-1 and 4.57 (95% CI 3.72-8.54) ng.ml-1 in NPD patients, respectively. CONCLUSIONS: The remifentanil requirement for successful i-gel insertion is reduced in male PD patients undergoing DBS implantation during propofol TCI induction. Clinicians should closely monitor the remifentanil requirement in patients with PD. TRIAL REGISTRATION: Registered at http://www.chictr.org.cn ( ChiCTR1900021760 ).

The duration of chronic low back pain is associated with acute postoperative pain intensity in lumbar fusion surgery: a prospective observational study.

BACKGROUND: Pre-existing chronic pain has been associated with severe postoperative pain. In this study, we sought to prospectively analyse the association between the duration of chronic low back pain and the intensity of acute postoperative pain after lumbar fusion surgery. METHODS: A total of 330 patients who underwent lumbar fusion surgery were divided into three groups (chronic low back pain less than 1 year, one to 5 years, and more than 5 years) based on the duration of chronic pain. On the first postoperative day, the maximum pain scores of each patient were recorded during the day and at night. Bivariate correlation and logistic regression were performed to identify relationships between acute postoperative pain and related variables (age, sex, smoking history, body mass index, operation history, duration of surgery, level of preoperative pain, aetiology of back pain, Self-rating Anxiety Scale, Self-rating Depression Scale, FRAIL scale, and duration of chronic low back pain). If the postoperative pain score was > 3 when the patient reported was at rest, the patients were treated with postoperative intravenous self-controlled analgesia or rescue analgesics if necessary. RESULTS: There was an association between severe acute postoperative pain and the duration of chronic low back pain. In terms of VAS day, multivariable logistic regression showed the duration of chronic low back pain was not statistically significant (OR = 2.48, 95% CI: 0.900 to 6.828, p = 0.0789). The result is uncertain because the confidence interval included the null after controlling for SAS, SDS, BMI, and aetiology of back pain. In terms of VAS night, patients with a duration of chronic low back pain of more than 5 years were more likely having moderate to severe acute postoperative pain (VAS > 3) compared to patients with a duration of chronic low back pain less than 1 year (OR = 3.546, 95% CI: 1.405 to 8.95, p = 0.0074). Hospital stay, the pain score on the day of discharge and the pain score after 3 months displayed no significant difference among the three groups (P > 0.05). However, the need for postoperative rescue analgesics was different among the three groups (P < 0.05). CONCLUSION: The longer the duration of chronic pain was, the higher the incidence of moderate to severe acute postoperative pain was and the greater the amount of analgesics required after surgery. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registration Center ( http://www.chictr.org.cn/index.aspx , clinical trial number: ChiECRCT20200165, date of registration: July 6, 2020).

Type of anesthesia and quality of recovery in male patients undergoing lumbar surgery: a randomized trial comparing propofol-remifentanil total i.v. anesthesia with sevoflurane anesthesia.

BACKGROUND: Previous studies have shown that women achieve a better quality of postoperative recovery from total intravenous anesthesia (TIVA) than from inhalation anesthesia, but the effect of anesthesia type on recovery in male patients is unclear. This study therefore compared patient recovery between males undergoing lumbar surgery who received TIVA and those who received sevoflurane anesthesia. METHODS: Eighty male patients undergoing elective one- or two-level primary transforaminal lumbar interbody fusion (TLIF) were randomly divided into two groups: the TIVA group (maintenance was achieved with propofol and remifentanil) or sevoflurane group (SEVO group: maintenance was achieved with sevoflurane and remifentanil). The quality of recovery-40 questionnaire (QoR-40) was administered before surgery and on postoperative days 1 and 2 (POD1 and POD2). Pain scores, postoperative nausea and vomiting, postoperative hospital stay, anesthesia consumption, and adverse effects were recorded. RESULTS: The QoR-40 scores were similar on the three points (Preoperative, POD1 and POD2). Pain scores were significantly lower in the SEVO group than in the TIVA group on POD1 (30.6 vs 31.4; P = 0.01) and POD2 (32 vs 33; P = 0.002). There was no significant difference in the postoperative hospital stay or complications in the postanesthesia care unit between the TIVA group and the SEVO group. CONCLUSIONS: This study demonstrates that the quality of recovery is not significantly different between male TLIF surgery patients who receive TIVA and those who receive sevoflurane anesthesia. Patients in the TIVA group had better postoperative analgesic effect on POD2. TRIAL REGISTRATION: This was registered at http://www.chictr.org.cn (registration number ChiCTR-IOR-16007987, registration date: 24/02/2016).

Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway.

BACKGROUND: Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer. METHODS: Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment. RESULTS: Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells. CONCLUSION: Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.

Dexmedetomidine and Phosphocreatine Post-treatment Provides Protection against Focal Cerebral Ischemia-reperfusion Injury in Rats.

In this study we investigated the neuroprotective efficacy of dexmedetomidine (Dex) and phosphocreatine (PCr) alone or in combination in a rat model of focal cerebral ischemia-reperfusion injury (I/R). I/R was induced by intraluminal middle cerebral artery occlusion (MCAO) and reperfusion. Male Sprague-Dawley rats were randomly allocated to the Sham group and I/R group, and the I/R group was further divided into three subgroups: Dex (9 µg.kg-1 Dex), PCr (180 mg.kg-1 PCr) and Dex + PCr (9 µg.kg-1 Dex + 180 mg.kg-1 PCr). All treatments were given intravenously at the onset of reperfusion. After 24 hr of reperfusion, the neurological deficit score (NDS) was determined and a magnetic resonance imaging (MRI) scan was performed. Serum concentrations of malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) were measured and cerebral infarct volume was estimated by triphenyl tetrazolium chloride (TTC) staining. Blood brain barrier, neuronal and mitochondrial damage was assessed by optical and electron microscopy. Neuronal injury was further assessed using double cleaved caspase-3 and NeuN immunofluorescent staining. Compared with group I/R, Dex and PCr significantly reduced the neurological deficit score (P < 0.01), infarct volume (P < 0.01), and brain blood barrier, neuronal and mitochondrial damage. The level of oxidative stress (P < 0.001) and neuronal injury (P < 0.001) also decreased and surviving neurons increased (P < 0.001). Compared with Dex or PCr alone, the combination treatment had overall greater effects (P < 0.05). These results indicate that posttreatment with Dex or PCr decreases focal cerebral I/R injury and that these agents in combination have greater protective effects than each alone.

Dexmedetomidine Protects Human Renal Tubular Epithelial HK-2 Cells against Hypoxia/Reoxygenation Injury by Inactivating Endoplasmic Reticulum Stress Pathway.

OBJECTIVE: The study was aimed to investigate the effects and potential mechanisms of Dexmedetomidine (Dex) on hypoxia/reoxygenation (H/R) injury in human renal tubular epithelial HK-2 cells. MATERIALS AND METHODS: In this experimental study, HK-2 cells were divided into four groups: control group, Dex group, H/R group, and Dex+H/R group. The cells in control group received no treatment, and cells in Dex group were only treated with 0.1 nmol/L Dex. The cells in H/R group and Dex+H/R group were all treated with H/R (hypoxia for 24 hours and normoxia for 4 hours), and only the cells in Dex+H/R group were pre-administrated with 0.1 nmol/L Dex. Following treatments at 37˚C for 28 hours, cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Also, the expressions of hypoxia-inducible factor 1 (HIF-1α), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12 and cleaved caspase-3 were determined by western blot. RESULTS: The cell viability was significant decreased in H/R group compared with control group (P<0.05), while was significantly increased in Dex+H/R group compared with that in H/R group (P<0.05). However, the change tendency of the cell apoptosis was opposite to that of cell viability. Compared with H/R group, the expression of HIF-1α was evidently up-regulated, while GRP78, CHOP, capase-12 and cleaved caspase-3 expressions were all obviously downregulated in Dex+H/R group (P<0.05). In addition, the concentrations of malondialdehyde (MDA) in H/R group and Dex+H/R group were 1.68 ± 0.22 nmol/mgprot and 0.85 ± 0.16 nmol/mgprot, respectively. The superoxide dismutase (SOD) activity was higher in Dex+H/R group (121 ± 11 U/L), which which was more than twice larger than that in H/R group (57 ± 10 U/L). CONCLUSION: Dex could promote cell viability and inhibit apoptosis through up-regulating HIF-1α, reducing endoplasmic reticulum (ER) stress and mediating oxidative stress, thus ameliorating the H/R injury.

Laryngeal mask combined with bronchial tube achieves one-lung ventilation for transthoracic oesophagectomy.

Laryngeal mask combined with bronchial blocker provides an alternative for lung isolation but lacks adequate access to the non-dependent lung. Substituting the blocker with a bronchial tube may overcome this limitation. In this report, a #4.5 cuffed bronchial tube was introduced into the non-dependent lung through a second-generation laryngeal mask for transthoracic oesophagectomy. During the 2.5-hour thoracotomy, one-lung ventilation was achieved by isolating the left lung with the bronchial tube and ventilating the right lung via the laryngeal mask, using volume-control mode (7 mL/kg × 12/min) with PIP21-23 cm H2O, pH 7.36 and PaCO2 38.3. Prior to thoracotomy closure, suction and reinflation of the left lung were performed through the bronchial tube. Bronchoscopy via the laryngeal mask revealed no injury to the airway after removal of the bronchial tube. The case shows that laryngeal mask combined with bronchial intubation provides one-lung ventilation with access to the isolated lung.