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IntroductionHypotension is the most common adverse event under propofol-mediated sedation and is possible to cause varying degrees of damage to patients. Whereas remimazolam has a poorer sedative effect than propofol.AimThe aim of this study was to explore the advantages of the combination of remimazolam tosylate and propofol.Methods304 patients were divided into the remimazolam tosylate group, the propofol group, and the remimazolam tosylate plus propofol group. The primary outcome was the incidence of hypotension. Secondary outcomes included the results of sedation and recovery.ResultsThe incidence of hypotension was 56.7% in the P group, 12.6% in the RT group, and 31.3% in the R+P group, withP< 0.001. The incidence of body movement was significantly higher in the RT group (26.1%) than in the P group (10.3%) and the R+P group (12.5%),P=0.004. The endoscopist satisfaction was higher in the P (3.87±0.44) and R+P (3.95±0.22)groups than in the RT(3.53±0.84) group. The incidence of adverse events, in descending order, was P group, RT group, and R+P group (93.8%vs.61.3%vs.42.7%).ConclusionCo-administration had fewer adverse events than propofol monotherapy, also had a better sedative effect and higher endoscopist satisfaction than remimazolam monotherapy.Clinical trial registration numberNCT05429086

Meng-Chang Yang,1,&ast; Peng Li,1,&ast; Wen-Jie Su,1 Rong Jiang,1 Jia Deng,1 Ru-Rong Wang,2 Chao-Li Huang3 1Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Internal Medicine, Eastern Hospital, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ru-Rong WangDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86 18140049936Fax +86 28-87393632Email wangrurong@scu.edu.cnChao-Li HuangDepartment of Internal Medicine, Eastern Hospital, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 585, Damian, Honghe North Road, Longquanyi District, Chengdu, People’s Republic of ChinaTel +86 13350855681Fax +86 28-87775681Email chaoli_huang@126.comPurpose: Several randomized clinical trials (RCTs) investigated the effects of the manual placental removal on hemorrhage or other hemorrhage-related complications compared with the spontaneous placental removal during cesarean section (CS), while the results remained controversial and were inconsistent. The purpose of this meta-analysis was to quantify the pooled effects of the methods of placental removal on hemorrhage during CS.Patients and Methods: A systematic literature search was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Heterogeneity was tested by I2 statistics and Q-statistic. The random-effects model or fixed-effects model were used to calculate the pooled effect for the included studies according to heterogeneity. And the term of standardized mean difference (SMD) with 95% confidence intervals (CI) was pooled and estimated the effects across all studies.Results: A total of nine RCTs were included in this meta-analysis. Compared with spontaneous group, manual placental removal increased the amount of hemorrhage (SMD = 0.53, 95% CI [0.12, 0.94]; Z = 2.54, P = 0.011) and increased the risk of endometritis (OR = 1.84, 95% CI [1.31, 2.58]; Z = 3.52, P < 0.0001). In contrast, there was no significant difference concerning the operating time (SMD = − 0.30, 95% CI [− 0.85, 0.24]; Z = 1.09, P = 0.276), the length of hospital stays (SMD = 0.11, 95% CI [− 0.08, 0.30]; Z = 1.11, P = 0.265), and blood transfusion requirement (OR = 1.36, 95% CI [0.91, 2.04]; Z = 1.52, P = 0.129), respectively.Conclusion: Comparing with spontaneous placental removal, manual placental removal appeared to be less positive effect during CS. Because of the limitations of this meta-analysis, more high-quality RCTs are needed to confirm our findings.Keywords: cesarean section, manual placental removal, spontaneous placenta removal, hemorrhage, meta-analysis

Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The in vitro metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition.Results: HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABAA) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABAA receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system.Conclusions: HSK3486 is a positive allosteric regulator and direct agonist of GABAA receptor. It has a promising sedative/hypnotic effect and good in vivo pharmacokinetic properties, which justify further studies towards its clinical application.

Ischemic heart diseases have emerged as great threats to human health. Nowadays, restoration of cardiac blood flow supply is widely regarded as a feasible treatment choice for ischemic heart diseases; however, this intervention would contradictorily elicit reperfusion injury. Recently, myocardial ischemia/reperfusion injury (MI/RI) has aroused widespread public concerns. Remifentanil, an ultra-short acting opioid analgesic, is frequently used for surgical anesthesia. Previous studies have demonstrated the cardioprotective effects of remifentanil preconditioning in clinical practice and in vitro experimental models; however, its exact mechanisms remain largely unclear. This study aimed to further evaluate the protective effects of remifentanil preconditioning against MI/RI and elucidate the potential molecular mechanisms. Rat models of MI/RI were successfully established via ligation of left anterior descending coronary artery for 30 minutes and restoration of blood flow for 2 hours. Herein, animal experiments displayed that remifentanil preconditioning could alleviate myocardial damage in rat models of MI/RI. Consistently, cell model experiments implied that remifentanil preconditioning attenuated hypoxia/reoxygenation exposure-induced injury in rat cardiomyocytes. Moreover, our findings verified the involvement of Notch signaling pathway in the protective effects of remifentanil preconditioning. In addition, mechanistic studies revealed that remifentanil preconditioning could up-regulate Jagged-1 expression and that Jagged-1 mediated the cardioprotective effects of remifentanil preconditioning through activating Notch signaling pathway. Taken together, our data indicate that remifentanil preconditioning ameliorates myocardial damage in rat MI/RI models via Jagged-1-mediated Notch signaling pathway activation. Thus, this study may offer some novel clues for understanding the cardioprotective mechanisms of remifentanil preconditioning against MI/RI.

Hepatic alveolar echinococcosis (HAE) is a severe and common parasitic disease in Tibetan Plateau of China. The infected patients have to move to plain areas to receive treatments due to the poor medical conditions in plateau areas. Our aim was to investigate the application of Enhanced Recovery after Surgery (ERAS) program in perioperative management for HAE patients from Tibet Plateau and the notes for patients with landform changes.A total of 89 HAE patients from Tibet Plateau (altitude: average of 4500 m) prior received adaptive treatments at the cooperative hospital (altitude: 1500-2000 m) and accepted surgery at plain regions (altitude: 200-400 m). The patients in ERAS group received ERAS program care and patients in conventional management group received conventional care during perioperative period.Patients in ERAS group displayed significant shorter hospital stay and shorter time for recovery of gurgling compared with conventional management group (ERAS group versus conventional management group: 10.48 ± 3.525 d versus 20.29 ± 8.632 d; 1.56 ± 1.236 d versus 2.8 ± 1.19 d; all P 0.01). The number of patients with complications of bloating, nausea/vomiting, pulmonary infection, urinary tract infection, upper gastrointestinal hemorrhage, and pulmonary edema was remarkably reduced (number, ERAS group versus conventional management group: 14 versus 24; 5 versus 16; 7 versus 24; 4 versus 13; 0 versus 10; all P 0.05), and the visual analog scale scores in postoperative days 1 and 2 were obviously decreased in patients of ERAS group (score, ERAS group versus conventional management group: 2.5 ± 1.288 versus 3.83 ± 1.87; 2.25 ± 0.838 versus 3.51 ± 1.468; all P 0.01).Patients from Tibet Plateau need to receive adaptive treatments for landform changes before receiving surgeries at plain regions. ERAS program is effective and safe for Tibetan HAE patients during perioperative period.

Objective: We aimed to investigate the influence of premedication with budesonide aerosol inhalation on the incidence of respiratory adverse events during anesthesia recovery period in pediatric patients. Method: 120 pediatric patients underwent elective surgery of inguinal hernia repair were enrolled in the study. They were given two different types of anesthesia, group A received general anesthesia with the Laryngeal Mask (LMA), and group B were treated with budesonide aerosol inhalation preoperatively before general anesthesia with LMA. The incidence of adverse events which included laryngospasm, respiratory tract infection, the length of Post-Anesthesia Care Unit (PACU) staying, the volume of throat secretions and hoarseness were monitored closely. Results: Compared with group A, group B had a lower incidence of respiratory adverse events. Conclusion: Preoperative budesonide aerosol inhalation could reduce the incidence of respiratory adverse events during the anesthesia recovery period in children.

To explore the effect of parecoxib on hippocampal inflammation and short-term memory function after splenectomy in aged rats. A total of 90 aged male SD rats were randomly divided into 9 groups (all n=10): a control group (Group C), an anesthesia day 1 group (A1 group), an operation day 1 group (O1 group), a saline day 1 group (S1 group), a parecoxib day 1 group (P1 group), an anesthesia day 3 group (A3 group), an operation day 3 group (O3 group), a saline day 3 group (S3 group), and a parecoxib day 3 group (P3 group). In the A1 group and A3 group, rats were anesthetized by intraperitoneal injection of pentobarbital sodium. Under anesthesia condition, rats in the O1 group and O3 group underwent splenectomy. One hour before splenectomy, rats in the P1 group and P3 group received parecoxib injection of 10 mg/kg via tail vein. In the S1 group and S3 group, rats received the same dose of saline. The rats were trained for 5 days in shuttle box before anesthesia, surgery and drug treatment. After shuttle box test, the rats were killed at postoperative 1 and 3 d. The hippocampus was isolated to measure the CD11b expression by immunofluorescent staining, and TNF-α, IL-1 and COX-2 mRNA expression by RT-PCR. Compared with the Group C, the electric shock time was increased in the O1 and O3 groups, but the active escape time was shortened and the active avoidance reaction (AAR) was decreased (all P0.01). Compared with the O1 or O3 group, the electric shock time was shortened, the active escape time and AAR was increased in the P1 or P3 group (all P0.05). There were more CD11b positive cells and TNF-α, IL-1β, COX-2 mRNA expression in hippocampus in the O1, O3, S1 or S3 group compared with the Group C (all P0.01). Both CD11b positive cells and TNF-α, IL-1β, COX-2 mRNA expression were decreased in the P1 or P3 group compared with that in the O1 or O3 group (all P0.01). The parecoxib could reduce hippocampal inflammation and improve short-term memory function through the inhibition of COX-2 expression in aged rats after splenectomy.目的：探讨帕瑞昔布对脾切除术后老年大鼠海马炎症反应及短期记忆功能的影响。方法：老年雄性Sprague-Dawley大鼠90只，随机分为9组(均n=10)：空白对照组(C组)、麻醉1 d组(A1组)、手术1 d组(O1组)、生理盐水1 d组(S1组)、帕瑞昔布1 d组(P1组)、麻醉3 d组(A3组)、手术3 d组(O3组)、生理盐水3 d组(S3组)、帕瑞昔布3 d组(P3组)。A1和A3组只接受1%戊巴比妥钠腹腔注射麻醉；O1组和O3组麻醉后行脾切除术；P1组和P3组在手术组基础上术前1 h经尾静脉注射10 mg/kg帕瑞昔布钠；S1组、S3组给予等量生理盐水对照。大鼠行穿梭箱训练5 d后进行麻醉、手术及药物处理。术后1和3 d穿梭箱测试结束后处死大鼠，取海马，分别行CD11b免疫荧光染色，测定TNF-α，IL-1β及环氧合酶-2 (cyclooxygenase-2，COX-2) mRNA的表达。结果：与C组比较，O1和O3组电击时间增加，主动逃避时间缩短，主动回避反应(active avoidance reaction，AAR)降低(均P0.01)。与O1和O3组比较，P1和P3组电击时间缩短，主动逃避时间增加，AAR提高(均P0.05)。O1，O3，S1和S3组海马小胶质细胞阳性数目和海马TNF-α，IL-1β及COX-2 mRNA表达明显高于C组(均P0.01)，但P1，P3组较O1，O3组明显降低(均P0.01)。结论：帕瑞昔布可能通过抑制COX-2表达而减轻老年大鼠脾切除术后海马炎症反应，提高短期记忆能力。.

Suicide is one of the top 10 causes of death in many countries. Although there are many studies on mental disorders, few studies have examined mortality in suicide population and mentally ill population. This study examined the association between mortality and mental disorders using data on suicides and mental disorders in China. Data from China's Health and Family Planning Statistical Yearbook for 2000 to 2014 were used to analyze the relationship between mortality associated with suicide and mental disorders. The analyses found that mortality among people with mental disorders dropped from 5.42/10 million in 2000 to 2.68/10 million in 2014, decreased more among females than males, and differed between urban and rural areas; that suicide mortality dropped from 10.79/10 million in 2000 to 6.79/10 million in 2014; the decrease was greater in women than in men, with suicide being highest among male residents of cities; and no significant correlation was found between mortality among persons with mental disorders and suicide mortality. There was no correlation between suicide mortality and mental-disorder mortality during 2000 to 2014; however, overall mortality decreased more among females than males during this period.