[Effects of small GTP-binding protein GDP dissociation stimulator on adipocyte hypertrophy and glucose metabolism disorder in mice].

Objective: To explore the effect and mechanism of small GTP-binding protein GDP dissociation stimulator (SmgGDS) on the development of obesity. Methods: (1) 8-week-old C57BL/6J mice were randomly assigned to normal diet and high fat diet group, with 6 mice in each group. They were fed regular feed and a high fat diet containing 60% fat for 4 months, respectively. The expression of SmgGDS in epididymal adipose tissue (eWAT), liver, and skeletal muscle were measured using Western-blot. (2) 6-week-old wild-type (WT) and SmgGDS knockdown (KD) mice were divided into four groups, each receiving high fat diet for 4 months (7 in each group) and 7 months (9 in each group). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted; The weight, adipose tissue, and liver weight of mice were recorded; HE staining examined adipose tissue structural changes; Western-blot determined extracellular signal-regulated kinase (ERK) 1/2 phosphorylation levels in eWAT; Real time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA levels of CCAAT/enhancer binding protein α (C/EBPα), C/EBPß and peroxisome proliferator activated receptor γ (PPARγ) in eWAT. (3) Mouse embryonic fibroblasts (MEFs) extracted from WT and KD mice were induced for differentiation. Oil red O staining and Western-blot were used to detect lipid droplet and expression of SmgGDS and phospho-ERK; C/EBPα, C/EBPß and PPARγ mRNA levels were measured using RT-qPCR. (4) 10-week-old C57BL/6J mice were randomly assigned into two groups, with 7 mice in each group. Mice were infected with SmgGDS overexpressing adeno-associated virus (AAV-SmgGDS) or empty vector intraperitoneally, then fed with high fat diet. After 4 weeks, performed GTT and ITT; Recorded the weight and adipose tissue weight of mice; HE staining was used to analyze structural changes of eWAT; Western-blot was used to detect the phosphorylation level of ERK in eWAT. Results: (1) The expression of SmgGDS was significantly upregulated in eWAT of high fat diet fed mice (normal diet group: 0.218±0.037, high fat diet group:0.439±0.072, t=2.74, P=0.034). (2) At 4 months of high fat diet intervention, the glucose tolerance (60 minutes after glucose injection, WT group: 528 mg/dl±21 mg/dl, KD group: 435 mg/dl±17 mg/dl, t=3.47, P=0.030; 90 minutes, WT group: 463 mg/dl±24 mg/dl, KD group: 366 mg/dl±18 mg/dl, t=3.23, P=0.047;120 minutes, WT group: 416 mg/dl±21 mg/dl, KD group: 297 mg/dl±16 mg/dl, t=4.49, P=0.005) and insulin sensitivity (15 minutes after insulin injection, WT group: 77.79%±3.45%, KD group: 54.30%±2.92%, t=3.49, P=0.005; 30 minutes, WT group: 62.27%±5.31%, KD group: 42.25%±1.85%, t=2.978, P=0.024; 90 minutes, WT group: 85.69%±6.63%, KD group: 64.71%±5.41%, t=3.120, P=0.016) of KD mice were significantly improved compared to the WT group, with an increase in eWAT weight ratio (WT: 4.19%±0.18%, KD: 5.12%±0.37%, t=2.28, P=0.042), but a decrease in average adipocyte area (WT group: 5221 µm²±241 µm², KD group: 4410 µm²±196 µm², t=2.61, P=0.026). After 7 months of high fat diet, the eWAT weight ratio of KD mice decreased (WT: 5.02%±0.20%, KD: 3.88%±0.21%, t=3.92, P=0.001) and adipocyte size decreased (WT group: 6 783 µm²±390 µm², KD group: 4785 µm²±303 µm², t=4.05, P=0.002). The phospho-ERK1 in eWAT increased (WT group: 0.174±0.056, KD group: 0.588±0.147, t=2.64, P=0.025), and mRNA level of PPARγ significantly decreased (WT group: 1.018±0.128, KD group: 0.029±0.015, t=7.70, P=0.015). (3) The expression of SmgGDS was significantly increased in differentiated MEF (undifferentiated: 6.789±0.511, differentiated: 10.170±0.523, t=4.63, P=0.010); SmgGDS knock-down inhibited lipid droplet formation in MEF (WT group: 1.00±0.02, KD group: 0.88±0.02, t=5.05, P=0.007) and increased ERK1 (WT group: 0.600±0.179, KD group: 1.325±0.102, t=3.52, P=0.025) and ERK2 (WT group: 2.179±0.687, KD group: 5.200±0.814, t=2.84, P=0.047) activity, which can be reversed by ERK1/2 inhibitor. (4) SmgGDS over expression resulted in weight gain, increased eWAT weight (control group: 3.29%±0.36%, AAV-SmgGDS group: 4.27%±0.26%, t=2.20, P=0.048) and adipocyte size (control group: 3525 µm²±454 µm², AAV-SmgGDS group: 5326 µm²±655 µm², t=2.26, P=0.047), impaired insulin sensitivity(30 minutes after insulin injection, control group: 44.03%±4.29%, AAV-SmgGDS group: 62.70%±2.81%, t=3.06, P=0.019), and decreased ERK1 (control group: 0.829±0.077, AAV-SmgGDS group: 0.326±0.036, t=5.96, P=0.001)and ERK2 (control group: 5.748±0.287, AAV-SmgGDS group: 2.999±0.845, t=3.08, P=0.022) activity in eWAT. Conclusion: SmgGDS knockdown improves obesity related glucose metabolism disorder by inhibiting adipogenesis and adipose tissue hypertrophy, which is associated with ERK activation.

A randomised controlled trial of the non-inferiority of erector spinae plane block vs. thoracic paravertebral block for laparoscopic nephro-ureterectomy.

Erector spinae plane block and paravertebral block can provide analgesia for abdominal surgery. It is unclear whether erector spinae block is inferior to paravertebral block. We aimed to determine whether sufentanil dose and pain intensity (11-point scale) to 24 h after erector spinae block exceeded those after paravertebral block by no more than 5 µg and 1 point, respectively. We randomly allocated 166 adults to 0.4 ml.kg-1 ropivacaine 0.375% before scheduled laparoscopic nephroureterectomy, 83 each to erector spinae or paravertebral injection. We measured incision pain and intra-abdominal pain at rest and on movement 0.5 h, 2 h, 6 h, 18 h, 24 h and 48 h after surgery. Median (IQR [range]) cumulative sufentanil dose after erector spinae block was 15 (5-30 [0-105]) µg vs. 20 (10-50 [0-145]) µg after paravertebral block, median (95%CI) difference 5 µg (0-10), erector spinae non-inferiority p < 0.001. Median (IQR [range]) pain were 1.5 (1.0-2.0 [0.0-5.3]) after erector spinae block vs. 2.0 (1.0-2.5 [0.0-6.0]) after paravertebral block, median (95% CI) difference 0.3 (0.0-0.5), erector spinae non-inferiority p < 0.001. Adverse events did not differ between groups. Erector spinae block analgesia was not inferior to paravertebral block analgesia after laparoscopic nephroureterectomy.

[Factors associated with long-term survival in critically ill patients following surgery for solid tumors complicated with paraneoplastic pemphigus].

OBJECTIVE: Critically ill patients with solid tumors complicated with paraneoplastic pemphigus are usually treated in intensive care units (ICU) for perioperative management after surgical treatment. In this study, the clinical characteristics and predictors of long-term prognosis of these critically ill patients were analyzed. METHODS: the clinical and laboratory data of 63 patients with solid tumors complicated with paraneoplastic pemphigus admitted to ICU from 2005 to 2020 were retrospectively analyzed, and the survival status of the patients were followed up. RESULTS: Among the 63 patients, 79.4% had Castleman disease as the primary tumor, and 20.6% with other pathological types; 69.8% had severe-extensive skin lesions, and 30.2% had other skin lesions; the patients with bronchiolitis obliterans accounted for 44.4%, and 55.6% were not merged. Postoperative fungal infection occurred in 23.8% of the patients, and 76.2% without fungal infection. The median follow-up time was 95 months, and 25 patients died during the study period. The 1-year, 3-year and 5-year survival rates were 74.6% (95%CI 63.8%-85.4%), 67.4% (95%CI 55.6%-79.2%) and 55.1% (95%CI 47.9%-62.3%), respectively. The log-rank univariate analysis showed that the patients had age>40 years (P=0.042), preoperative weight loss>5 kg (P=0.002), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.002), and perioperative fungal infection (P < 0.001) had increased mortality. Cox univariate analysis showed that preoperative weight loss >5 kg (P=0.005), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.009), preoperative bacterial pulmonary infection (P=0.007), prolonged surgical time (P=0.048), postoperative oxygenation index (P=0.012) and low albumin (P=0.010) and hemoglobin concentration (P=0.035) in ICU, acute physiology and chronic health evaluation (APACHE Ⅱ) score (P=0.001); sequential organ failure assessment (SOFA) score (P=0.010), and postoperative fungal infection (P < 0.001) were risk factors for long-term survival. Cox regression model for multivariate analysis showed that preoperative weight loss > 5 kg (HR 4.44; 95%CI 1.47-13.38; P=0.008), and preoperative albumin < 30 g/L (HR 4.38; 95%CI 1.72-11.12; P=0.002), bronchiolitis obliterans (HR 2.69; 95%CI 1.12-6.50; P=0.027), and postoperative fungal infection (HR 4.85; 95%CI 2.01-11.72; P < 0.001) were independent risk factors for postoperative mortality. CONCLUSION: The 5-year survival rate of critically ill patients undergoing surgery for paraneoplastic pemphigus combined with solid tumors is approximately 55.1%, with preoperative weight loss > 5 kg, albumin < 30 g/L, bronchiolitis obliterans and postoperative fungal infection were associated with an increased risk of near- and long-term postoperative mortality.

Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study.

OBJECTIVE: Ciprofol is a newly developed intravenous sedative-hypnotic drug. The objective of the study was to prove whether ciprofol was non-inferior to propofol for the successful induction of general anesthesia. The ideal post-induction sedation level was assessed by comparing patients' clinical symptoms and their hemodynamic effects in responding to noxious stimuli, mostly tracheal intubation and bispectral index (BIS) alterations following ciprofol/propofol administration. PATIENTS AND METHODS: In this multi-center, randomized, double-blind phase 3 trial, selective surgery patients were randomly assigned in a 1:1 ratio to either ciprofol 0.4 mg/kg (n = 88) or propofol 2.0 mg/kg (n = 88) groups. The primary endpoint was the percentage of patients with successful anesthesia inductions. Secondary endpoints included the times to successful induction of general anesthesia and loss of the eyelash reflex, changes in BIS, as well as safety indicators. RESULTS: The anesthesia induction success rates for both ciprofol 0.4 mg/kg and propofol 2 mg/kg groups were 100.0%, with a 95% CI lower success limit of -4.18% difference between the two groups, indicating that ciprofol was non-inferior to propofol. For secondary outcomes, the average time to successful anesthesia and loss of the eyelash reflex were 0.91 min and 0.80 min for ciprofol and 0.80 min and 0.71 min for propofol, respectively. The pattern of BIS changes with ciprofol was similar to propofol and stable during the anesthesia maintenance period. Safety was comparable with 88.6% TEAEs in the ciprofol group compared to 95.5% in the propofol group. The incidence of injection pain was significantly lower in the ciprofol group compared to the propofol group (6.8% vs. 20.5%, p < 0.05). In addition, the patients treated with ciprofol had a lesser increase in blood pressure and heart rate, and fewer cases with BIS > 60 within 15 min of intravenous administration, which indicated that ciprofol may provide a better ideal sedation level during the post-induction period under an equivalent dosing regimen to propofol. CONCLUSIONS: Ciprofol for patients undergoing selective surgery is a new option for the induction of general anesthesia.

Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases. PATIENTS AND METHODS: A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance. RESULTS: The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively. CONCLUSIONS: HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.

[Effects of postoperative urine protein levels on predicting acute kidney injury in critically ill patients undergoing non-cardiac surgery].

Objective: To investigate the predictive value of postoperative urine protein level in critically ill patients undergoing non-cardiac surgery with acute kidney injury (AKI). Methods: A total of 661 critically ill patients undergoing non-cardiac surgery, who visited the Department of Critical Care Medicine of Peking University First Hospital from May 20, 2019 to November 24, 2020, were enrolled in this prospective study. The clinical data of the patient's age, gender, body mass index, laboratory examination, surgical status, etc. were collected. AKI diagnostic criteria of the 2012 KDIGO guidelines were used to diagnose the occurrence of AKI after surgery. The independent predictors of AKI were determined by multivariate logistic regression. Results: The age of this patient cohort was (69±15) years. The prevalence of AKI was 45.4% (300/661). Multivariate logistic regression showed that urine protein semi-quantitative ≥2+(OR=2.62, 95%CI: 1.05-6.56, P=0.039) was independent factor for postoperative AKI in critically ill patients undergoing non-cardiac surgery, other independent factors include higher age (OR=1.04, 95%CI: 1.02-1.06, P=0.001), higher body mass index (BMI) (OR=1.12, 95%CI: 1.04-1.21, P=0.004), lower plasma hemoglobin level (OR=0.98, 95%CI: 0.97-1.00, P=0.019), lower central venous pressure (OR=0.89, 95%CI: 0.83-0.97, P=0.005) and lower total hypotension time (OR=1.01, 95%CI: 1.00-1.01, P=0.041). Conclusions: Urine protein semi-quantitative ≥2+after surgery is an independent predictive factor for the occurrence of postoperative AKI in critically ill patients undergoing non-cardiac surgery. It is important to check urine routine immediately after surgery to detect and deal with high-risk patients.

[Epidural block associated with improved long-term survival after surgery for colorectal cancer: A retrospective cohort study with propensity score matching].

OBJECTIVE: To investigate the effect of epidural anesthesia on the long-term prognosis of patients after selective colorectal cancer resection surgery. METHODS: This was a retrospective cohort study and approved by local institution review board. Patients who underwent selective colorectal cancer resection surgery from August 2011 to December 2012 in Peking University First Hospital were enrolled. The patients were divided into general anesthesia (GA) group and combined epidural-general anesthesia (EGA) group according to anesthesia type. Primary outcome was patient's long-term survival status. Secondary outcome included the overall incidence of in-hospital complications and length of postoperative in-hospital stay. Propensity score was used to match cases between the two groups based on the probability of receiving EGA. Survival was analyzed by Kaplan-Meier analysis and compared by Log-rank test between the two groups. Multivariate Cox regression analysis was used to investigate the relationship between epidural anesthesia and other variables with long-term survival status. RESULTS: A total of 264 patients were entered into final analysis, including 166 cases in GA group and 98 cases in EGA group. Mean age of the patients was (63.3±12.1) years and mean survival time was 47.2 (95%CI 45.7-48.7) months. Before the propensity score match, the mortality in EGA group was 16.9% (28/166) and 9.2% (9/98) in GA group. But comparison between the two groups had no statistical significance (P=0.091). After the propensity score match, 87 paired cases were matched and analyzed. The risk of long-term mortality in EGA group was lower than that of GA group by Kaplan-Meier analysis (5.7% vs.16.1%, HR=0.344, 95%CI 0.124-0.955, P=0.041). Mean survival time of EGA group was longer than that of GA group (50.3 months vs. 42.9 months, P=0.032). Multivariate Cox regression ana-lysis showed that EGA, in comparison with GA, was related with lower risk of long-term mortality (HR=0.326, 95%CI 0.117-0.909, P=0.032). Age (HR=1.042, 95%CI 1.001-1.085, P=0.046) and preoperative lymph node metastasis (HR=2.924, 95%CI 1.162-7.356, P=0.023) were also related with increased risk of long-term mortality. CONCLUSION: Present study found that perioperative use of epidural anesthesia and analgesia was associated with improvement of the patient's long-term survival. Well-designed studies are needed to verify this hypothesis.

[Comparison of pulse pressure variation, stroke volume variation, and plethysmographic variability index in pediatric patients undergoing craniotomy].

OBJECTIVE: To compare well-known preload dynamic parameters intraoperatively including stroke volume variation (SVV), pulse pressure variation (PPV), and plethysmographic variability index (PVI) in children who underwent craniotomy for epileptogenic lesion excision. METHODS: A total of 30 children aged 0 to 14 years undergoing craniotomy for intracranial epileptogenic lesion excision were enrolled. During surgery, we measured PPV, SVV (measured by the Flotrac/Vigileo device), and PVI (measured by the Masimo Radical-7 monitor) simultaneously and continuously. Preload dynamic parameter measurements were collected at predefined steps: after induction of anesthesia, during opening the skull, intraoperative electroencephalogram monitoring, excision of epileptogenic lesion, skull closure, at the end of the operation. After exclusion of outliers, agreement among SVV, PPV, and PVI was assessed using repeated measures of Bland-Altman approach. The 4-quadrant and polar plot techniques were used to assess the trending ability among the changes in the three parameters. RESULTS: The mean SVV, PPV, and PVI were 8%±2%, 10%±3%, and 15%±7%, respectively during surgery. We analyzed a total of 834 paired measurements (3 to 8 data sets for each phase per patient). Repeated measures Bland-Altman analysis identified a bias of -2.3 and 95% confidence intervals between -1.9 and -2.7 (95% limits of agreement between -6.0 and 1.5) between PPV and SVV, showing significant correlation at all periods. The bias between PPV and PVI was -5.0 with 95% limits of agreement between -20.5 and 10.5, and that between SVV and PVI was -7.5 with 95% limits of agreement between -22.7 and 7.8, both not showing significant correlation. Reflected by 4-quadrant plots, the con-cordance rates showing the trending ability between the changes in PPV and SVV, PPV and PVI, SVV and PVI were 88.6%, 50.4%, and 50.1%, respectively. The concordance rate between PPV and SVV was higher (92.7%) in children aged less than 3 years compared with those aged 3 and more than 3 years. The mean angular bias, radial limits of agreement, and angular concordance rate in the polar analysis were not clinically acceptable in the changes between arterial pressure waveform-based parameters and volume-based PVI (PPV vs. PVI: angular mean bias 8.4°, angular concordance rate 29.9%; SVV vs. PVI: angular mean bias 2.4°, angular concordance rate 29.1%). There was a high concordance between the two arterial pressure waveform-based parameters reflected by the polar plot (angular mean bias -0.22°, angular concordance rate 86.6%). CONCLUSION: PPV can be viewed as a surrogate for SVV, especially in children aged less than 3 years. The agreement between arterial pressure waveform-based preload parameters (PPV and SVV) and PVI is poor and these two should not be considered interchangeable. Attempt to combine PVI and PPV for improving the anesthesiologist's ability to monitor cardiac preload in major pediatric surgery is warranted.

[Analysis of the self-conscious health status and influencing factors of greenhouse agricultural workers in Beijing suburb].

Objective: To explore the self-conscious health status and related influencing factors of greenhouse agricultural workers in Beijing suburb, so as to provide scientific basis for developing strategies to improve and promote the occupational health conditions of those workers. Methods: According to the production characteristics and scale of the main agricultural districts or counties in the suburb of Beijing, 182 agricultural production personnel were randomly selected to investigate the general situation, occupational situation and self-conscious health status during June 2018 to December 2019. The relevant factors which may affect the self-conscious health conditions were also analyzed by statistical methods. Results: The detection or reported rate of self-conscious health problems was 51.6% (94/182) , among which 29.1% (53/182) workers reported musculoskeletal disorder diseases and 21.4% (39/182) workers reported nervous system diseases. And the self-conscious health status of greenhouse agricultural workers were statistically different in household registration, gender, marital status, working years, mixing or spraying pesticides, smoking or eating in the greenhouse (P<0.05) . Moreover, gender, mixing or spraying pesticide, eating and smoking behavior in the workplace all had an impact on the risk of self-conscious health status of greenhouse agricultural workers (P< 0.05) . Specifically, male is the protective factor to reduce the occurrence of self-conscious symptoms of greenhouse agricultural workers (OR=0.447, 95%CI: 0.234~0.852) , while mixing or spraying pesticides and smoking or eating behaviors in the workplace are the risk factors (OR=1.055, 2.524; 95%CI: 0.503~2.210, 1.107~5.755) . Conclusion: Reducing pesticide use from the source thus minimize related exposure opportunities, strengthening occupational health education thus foster good hygienic habits and improve individual protection consciousness are of great significance for the health protection of greenhouse agricultural workers in Beijing suburb.

Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery.

BACKGROUND: Delirium is common in elderly patients after surgery and is associated with poor outcomes. This study aimed to investigate the impact of intraoperative dexmedetomidine on the incidence of delirium in elderly patients undergoing major surgery. METHODS: This was a randomized double-blind placebo-controlled trial. Elderly patients (aged 60 years or more) scheduled to undergo major non-cardiac surgery were randomized into two groups. Patients in the intervention group received a loading dose of dexmedetomidine 0·6 µg/kg 10 min before induction of anaesthesia followed by a continuous infusion (0·5 µg per kg per h) until 1 h before the end of surgery. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of delirium during the first 5 days after surgery. Delirium was assessed with the Confusion Assessment Method (CAM) for non-ventilated patients and CAM for the Intensive Care Unit for ventilated patients. RESULTS: In total, 309 patients who received dexmedetomidine and 310 control patients were included in the intention-to-treat analysis. The incidence of delirium within 5 days of surgery was lower with dexmedetomidine treatment: 5·5 per cent (17 of 309) versus 10·3 per cent (32 of 310) in the control group (relative risk (RR) 0·53, 95 per cent c.i. 0·30 to 0·94; P = 0·026). The overall incidence of complications at 30 days was also lower after dexmedetomidine (19·4 per cent (60 of 309) versus 26·1 per cent (81 of 310) for controls; RR 0·74, 0·55 to 0·99, P = 0·047). CONCLUSION: Intraoperative dexmedetomidine halved the risk of delirium in the elderly after major non-cardiac surgery. Registration number: ChiCTR-IPR-15007654 ( www.chictr.org.cn).

ANTECEDENTES: El delirio después de la cirugía es frecuente en los pacientes de edad avanzada y se asocia con malos resultados. El objetivo de este estudio fue investigar el impacto de la administración intraoperatoria de dexmedetomidina en la incidencia de delirio en pacientes mayores sometidos a operaciones de cirugía mayor. MÉTODOS: Se trataba de un ensayo aleatorizado, doble ciego y controlado con placebo. Un total de 620 pacientes mayores (60 años o más) fueron programados para ser sometidos a intervenciones (no cardiacas) de cirugía mayor y se aleatorizaron a dos grupos. Los pacientes en el grupo de intervención recibieron una dosis de carga de dexmedetomidina (0,6 µg/kg, 10 minutos antes de la inducción anestésica) seguida de una infusión continua (0,5 µg/kg/h) hasta 1 h antes de la finalización de la cirugía. Los pacientes del grupo control recibieron el mismo volumen de suero salino siguiendo la misma pauta. El resultado principal era la incidencia de delirio durante los primeros 5 días postoperatorios. Para la valoración del delirio se utilizó el método para la evaluación de la confusión (Confusion Assessment Method, CAM) en pacientes no intubados y el CAM-UCI para los pacientes intubados. RESULTADOS: En total, 309 pacientes que recibieron dexmedetomidina y 310 del grupo control se incluyeron en el análisis por intención de tratar. La incidencia de delirio durante los primeros 5 días tras la cirugía fue inferior en presencia de tratamiento con dexmedetomidina que en ausencia del mismo: 5,5% (17/309) versus 10,3% (32/310); riesgo relativo (RR) 0,53, i.c. del 95% 0,30-0,94, P = 0,026. La incidencia global de complicaciones a los 30 días excluyendo el delirio también fue inferior en presencia que en ausencia de tratamiento con dexmedetomidina (19,4% (60/309) versus 26,1% (81/301), RR 0,74, i.c. del 95% 0,55-0,99, P = 0,047). CONCLUSIÓN: La administración intraoperatoria de dexmedetomidina reduce la presencia de delirio en los pacientes mayores tras cirugía mayor no cardiaca.

[Clinical outcomes of vocal fold immobility after tracheal intubation].

OBJECTIVE: To assess the incidence of postoperative vocal cord immobility in patients following endotracheal intubation underwent general anesthesia. METHODS: We retrospectively enrolled patients who underwent surgical procedures with endotracheal intubation under general anesthesia from January 2014 to December 2018 in Peking University First Hospital. Demographic and treatment data were obtained for patients with hoarseness and vocal cord fixation. The incidence of postoperative hoarseness and vocal cord fixation were presented and clinical outcomes were further analyzed. RESULTS: A total of 85 998 patients following tracheal intubation and general anesthesia were enrolled in this study. Hoarseness was observed in 222 (0.26%) patients postoperatively. Sixteen patients (73%) were accomplished with symptoms of choking on water, dysphonia and sore throat. Twenty-nine patients with persistent hoarseness on the third postoperative day needed further treatment by otolaryngologists. Among them, seven patients had pharyngolaryngitis and twenty-two patients (0.026%) were demonstrated postoperative vocal cord immobility. There were seventeen patients (77%) with left-side vocal cord fixation and five patients (23%) with right-side vocal cord fixation. Nine patients were identified with arytenoid dislocation. Seven patients had left vocal cord fixation and two patients had right-side vocal cord fixation. Seven patients were intubated under the guidance of visual laryngoscope. One patient was confirmed difficult airway and intubated with light wand. One patient was inserted with laryngeal mask airway. One patient was suspected to have hoarseness caused by gastric tube before anesthesia. One patient showed simultaneously left recurrent laryngeal nerve abnormality on laryngeal electromyography result. The symptom of hoarseness ranged between 6 and 31 days. Three patients underwent closed reduction under local anesthesia and one patient demonstrated spontaneous recovery. Among the remaining thirteen patients with vocal cord immobility, two patients were demonstrated vocal cord paralysis. Eleven patients underwent neck surgery, thyroid surgery and cardiothoracic surgery and further examinations including laryn-geal electromyography and computed tomography help to determine the diagnosis were not performed. All patients were treated with inhaled corticosteroid conservatively. Five patients had significant improvement of symptom and almost regained normal voice. One patient had slight improvement and sixteen patients were not relieved before discharge. CONCLUSION: Patients with hoarseness and vocal fold immobility after endotracheal intubation should be treated properly and immediately.

Dexmedetomidine enhances ropivacaine-induced sciatic nerve injury in diabetic rats.

BACKGROUND: Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown. METHODS: A diabetic state was established in adult male Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 µg kg-1 (alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements. RESULTS: Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fibre damage in control non-diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1ß and tumour necrosis factor-α was also seen. CONCLUSIONS: Ropivacaine 0.5% causes significant sciatic nerve injury in diabetic rats that is greatly potentiated by high-dose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted.

Overexpression of TUG1 promotes neuronal death after cerebral infarction by regulating microRNA-9.

OBJECTIVE: This study aims at investigating whether TUG1 (Taurine Upregulated Gene 1) can regulate FOXO3 expression through competitive binding to microRNA-9, thus leading to increased neuronal death and promoting the occurrence and development of acute cerebral infarction. MATERIALS AND METHODS: TUG1 and FOXO3 expressions in cerebral cortical neurons of MCAO mice, control mice and primary neurons were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The effects of TUG1 and FOXO3 on neuronal apoptosis were determined by TUNEL after cerebral infarction area was stained with TTC. The binding condition of microRNA-9, TUG1 and FOXO3 was verified by the Luciferase reporter gene assay. Western blot was performed to detect the protein expressions of B-cell lymphoma-2 (BCL-2) and BCL2-Associated X (BAX) after altering the TUG1 or FOXO3 expression in primary neurons. RESULTS: TUG1 and FOXO3 were overexpressed in cerebral cortical neurons of MCAO mice and primary neurons. The inhibition of TUG1 or FOXO3 resulted in less neuronal apoptosis. Luciferase reporter gene assay demonstrated that TUG1 regulates FOXO3 via TUG1/microRNA-9/FOXO3 regulatory network. Besides, TUG1 inhibited BCL-2 but promoted BAX expression in primary neurons. CONCLUSIONS: The overexpression of TUG1 can promote neuronal death after cerebral infarction in mice by competitive binding to microRNA-9 and promotion of FOXO3 expression.

[Risk factors of postoperative complications after laparoscopic surgery for pheochromocytoma].

Objective: To investigate the effects of intraoperative hemodynamic instability on postoperative complications of laparoscopic surgery for pheochromocytoma. Methods: It was a retrospective cohort study. According to inclusion/exclusion criteria, adult patients underwent laparoscopic surgery for pheochromocytoma from January 2005 to December 2017 in Peking University First Hospital were enrolled in this study. Eligible patients were divided into two groups by evidence of postoperative complications to find out the effects of intraoperative hemodynamic instability and its' effects on other prognostic indices. The normally distributed continuous variables were compared between two groups by Student's t test, Mann-Whitney U test were used for the comparison for non-normally distributed continuous variables and χ(2) test for categorical variables. Results: A total of 198 patients were finally enrolled in this study, including 87 males and 111 females with an average age of (47±15) years. Postoperative complications occurred in 17 patients with an incidence of 8.6%, and intraoperative hemodynamic instability occurred in 45 patients (22.7%). It was found that history of stroke[odds ratio (OR)=13.387, 95% confidence interval (CI): 2.284-78.460, P=0.004], intraoperative hemodynamic instability (OR=3.351, 95%CI: 1.119-10.039, P=0.031) and intraoperative positive fluid balance (for each additional 100 ml) (OR=1.087, 95%CI: 1.031-1.146, P=0.002)were the independent risk factors of postoperative complications of laparoscopic surgery for pheochromocytoma. Furthermore, more postoperative complications, higher rate of admitting to ICU and longer hospital stay was found in patients with hemodynamic instability. Conclusion: Intraoperative hemodynamic instability is an independent risk factor for postoperative complications of laparoscopic surgery in patients with pheochromocytoma, and it associates with more postoperative complications and higher rate of admitting to ICU.

Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults.

BACKGROUND: The choice of general anaesthetics may affect postoperative cognitive outcomes. This study was designed to compare the potential impact of propofol-based vs sevoflurane-based general anaesthesia on the development of delayed neurocognitive recovery in older adults early after major cancer surgery. METHODS: Older adults (aged ≥65 and <90 yr) who were scheduled to undergo major cancer surgery (≥2 h) were randomised to receive either propofol- or sevoflurane-based general anaesthesia. Cognitive function was assessed before and 1 week after surgery with a battery of neuropsychological tests. Age- and education-matched non-surgical controls were recruited, and their cognitive functions were tested at comparable time intervals in order to adjust for learning effects from repeated tests. Delayed neurocognitive recovery was diagnosed according to the International Study of Postoperative Cognitive Dysfunction 1 definition. RESULTS: From April 1, 2015 to October 15, 2016, 392 patients were enrolled and randomised. Of these patients, 387 completed the intervention and 30-day follow-up, and 379 completed 1-week neuropsychological tests. Fifty-nine control subjects were enrolled and completed repeated neuropsychological tests. The incidence of delayed neurocognitive recovery at 1 week was significantly lower in the propofol group [14.8% (28/189)] than in the sevoflurane group [23.2% (44/190); odds ratio=0.577; 95% confidence interval, 0.342-0.975; P=0.038]. Safety outcomes did not differ between the two groups. CONCLUSIONS: When compared with sevoflurane-based general anaesthesia, propofol-based general anaesthesia might decrease the incidence of delayed neurocognitive recovery in older adults after major cancer surgery. CLINICAL TRIALS REGISTRATION: NCT02662257; Chinese Clinical Trial Registry (identifier: ChiCTR-IPR-15006209).

[Expression of osteoprotegerin and receptor activator of nuclear factor kappa-B ligand in mandibular ramus osteotomy healing with administration of different doses of parathyroid hormone].

Objective: To investigate the effect of parathyroid hormone (PTH) on the bone healing of mandibular ramus osteotomy. Methods: The mandibular ramus osteotomy model was established in sixty rabbits and these rabbits were randomly divided into experimental group A, experimental group B and control group. In the experimental group A and experimental group B, the rabbits were given PTH (20 and 40 µg/kg respectively) every other day after operation. In the control group, 1 ml saline was given. The animals were sacrificed at 1 week, 2 weeks, 3 weeks and 4 weeks postoperatively. The new bone formation was observed by histology and cone bone CT. The expression of osteoprotegerin and receptor activator of nuclear factor kappa-B (RANKL) in the new bone was detected by real-time quantitative PCR. Results: The experimental groups has better osteogenesis and the bone mineral density than the control group in osteotomy area. The experimental group B showed the best osteogenesis.Osteoprotegerin mRNA expression in experimental group A (1.127±0.035, 1.742±0.049, 1.049±0.062, 1.063±0.036) was significantly higher than that in the control group in each period (0.965±0.082, 1.254±0.071, 0.793±0.061, 0.684±0.055) (P=0.010, P=0.000, P=0.001, P=0.020), while group B (1.416±0.205, 2.648±0.168, 1.652±0.091, 1.712±0.070) was significantly higher than group A (P=0.000, P=0.010, P=0.023, P=0.003). RANKL mRNA expression in control group (1.666±0.086, 1.058±0.105, 0.885±0.124, 0.972±0.136) was significantly higher than that of the group A (0.788±0.036, 0.585±0.017, 0.692±0.017, 0.527±0.051) (P=0.001, P=0.006, P=0.003, P=0.028) in each period, while group A was significantly higher than group B(0.247±0.022, 0.240±0.034, 0.134±0.011, 0.103±0.050) (P=0.000, P=0.001, P=0.002, P=0.012). Conclusions: PTH can upregulate the expression of osteoprotegerin and reduce expression of RANKL, thus promoting new bone formation. Intermittent administration of high dose of parathyroid hormone can further promote the healing process after mandibular ramus osteotomy.

[Dexmedetomidine combined with ropivacaine for continuous femoral nerve block improved postoperative sleep quality in elderly patients after total knee arthroplasty].

Objective: To investigate the effect of dexmedetomidine adding to ropivacaine for continuous femoral nerve block on the improvement of postoperative sleep quality in elderly patients after total knee arthroplasty. Methods: One hundred and sixty patients aged 60 years or older in Jishuitan Hospital scheduled for single total knee arthroplasty between Nov. 2016 and Jun. 2017 were recruited. All patients received spinal anesthesia and were randomized to receive either combined ropivacaine and dexmedetomidine (0.2% ropivacaine 250 ml and 5 µg/kg dexmedetomidine, at a rate of 5 ml/h or 0.1 µg·kg-1·h-1 dexmedetomidine, dexmedetomidine group) or only ropivacaine (0.2% ropivacaine, at a rate of 5 ml/h, controlled group) for continuous femoral nerve block as postoperative analgesia after surgery. The severity of postoperative pain was assessed with numeric rating scale at 4, 24, and 48 hours after surgery both at rest and with movement. Subjective sleep quality and delirium were evaluated daily during the first 3 days postoperatively. Results: The subjective sleep quality scores were 2(1-4), 2(1-4) and 4(2-8), 4(2-7) in dexmedetomidine group and controlled group respectively on the 1st and 2nd days after surgery. The scores of dexmedetomidine group were much better than those of controlled group (Z=-4.597, -4.183, both P<0.05). The difference was statistically significant. The NRS pain scores at rest were 2(1-2), 2(1-4), and 3(2-5), 3(2-6) in dexmedetomidine group and controlled group respectively at 24 and 48 hours after surgery. The scores of dexmedetomidine group were lower than those of controlled group (Z=-6.671, -4.010, both P<0.05). The difference was statistically significant. The NRS pain scores with movement were 1(1-2), 3(2-4), 3(2-3) and 3(2-4), 5(3-6), 5(4-7)in dexmedetomidine group and controlled group respectively at 4, 24 and 48 hours after surgery. The scores of dexmedetomidine group were lower than those of controlled group (Z=-7.167, -6.824, -7.473, all P<0.05). The difference was statistically significant. The incidence of 3-day delirium was lower in dexmedetomidine group (5%) than that in controlled group (15%) (χ2=4.444, P<0.05). The difference was statistically significant. There were no significant differences between groups regarding the incidences of adverse events. Conclusion: Dexmedetomidine combined with ropivacaine for continuous femoral nerve block may improve subjective sleep quality, postoperative analgesia, and reduce delirium in the elderly after total knee arthroplasty.

Preoperative vitamin D deficiency increases the risk of postoperative cognitive dysfunction: a predefined exploratory sub-analysis.

BACKGROUND: Vitamin D is important for maintaining physiological functions including cognition and its deficiency is associated with the occurrence of cognitive impairment. This study was to explore the association between preoperative vitamin D status and the occurrence of postoperative cognitive dysfunction (POCD) in elderly patients undergoing major surgery. METHODS: This was a predefined exploratory sub-analysis of one-centre data from a randomized controlled trial. In all, 123 elderly (≥ 65 years) patients who were scheduled to undergo major cancer surgery were recruited. Serum 25-hydroxyvitamin D concentration was measured before surgery. In total, 59 nonsurgical control subjects with comparable age and education level were also enrolled. A battery of neuropsychological tests was administered the day before and the 7th day after surgery in patients or at the same time interval in control subjects. POCD was diagnosed according to the ISPOCD1 definition. RESULTS: 71.5% (88/123) of elderly patients had vitamin D deficiency (serum 25-hydroxyvitamin D concentration < 12 ng/ml) before surgery; 24.4% (30/123) of them developed cognitive dysfunction at 1 week after surgery. After adjusting for confounding factors, high preoperative serum 25-hydroxyvitamine D concentration was related to a decreased risk of POCD (odds ratio [OR]: 0.829, 95% confidence interval [CI]: 0.708-0.971; P = 0.020), whereas preoperative vitamin D deficiency was associated with an increased risk of POCD (OR: 8.427, 95% CI: 1.595-44.511; P = 0.012). CONCLUSIONS: Vitamin D deficiency is prevalent in elderly patients undergoing major cancer surgery and increases the risk of early POCD development. Whether prophylactic vitamin D supplementation can reduce POCD in the elderly deserves further study.

Effect of combined epidural anaesthesia on tumor-infiltrating lymphocytes in lung adenocarcinoma: a prospective exploratory sub-analysis.

BACKGROUND: Regional anaesthesia may have advantages in preserving immune function. Tumor-infiltrating lymphocytes (TILs) are considered indicators of immune response in the tumor microenvironment and used as a prognostic marker in patients after cancer surgery. This study investigated the effects of combined epidural anaesthesia on the number of TILs in patients undergoing surgery for lung adenocarcinoma. METHODS: Patients undergoing radical resection for primary lung cancer were randomized to receive either combined epidural-general anaesthesia (Epi-GA) or general anaesthesia (GA) in an ongoing randomized controlled trial (ChiCTR-TRC-14004136). Excised adenocarcinoma specimens from patients enrolled between 1 June 2015 and 30 November 2015 were selected for immunohistochemical staining of CD8 and FOXP3 molecules. The numbers of positive lymphocytes were counted and expressed as the number of cells per mm2 tumor area. RESULTS: One hundred and twenty-eight patients were recruited and randomized; 64 patients were included in immunohistochemistry analysis (37 received Epi-GA vs. 27 received GA). The number of CD8+ T cells was higher in the Epi-GA group than in the GA group (median [interquartile range]: 292.8 [198.0-418.3] vs. 204.7 [131.1-305.8], P = 0.036); whereas the number of FOXP3+ T cells was less in the Epi-GA group than in the GA group (37.6 [14.7-92.3] vs. 99.8 [68.9-168.3], P < 0.001). CONCLUSIONS: For patients undergoing surgery for lung adenocarcinoma under general anesthesia, use of epidural anaesthesia increased CD8+ T cells infiltration but decreased FOXP3+ T cells accumulation in tumor tissues. Epidural anaesthesia may affect TILs in a manner that preserves immune function.