Objective To investigate the effects of etomidate preconditioning on the expression of procaspase-3, caspase-9 p35 and caspase-8 p20 in HL-60 cells. Methods HL-60 cells were purchased from Shanghai life science institute and cultured in RPMI-1640 culture medium at 37℃ in 5% CO2 incubator. The cells were randomy divided into 3 groups ( n = 3 each): control group (group C), etomidate group (group E) and etomidate preconditioning group (group EP). In group E, the cells were exposed to 500 μmol/L etomidate and incubated for 24 h. In group EP, the cells were exposed to 1μmol/L etomidate for 1 h and was allowed to recover for4 h after etomidate washout, then etomidate 500μmol/L was added and the cells were incubated for 24 h. The expression of procaspase-3, caspase-9 p35 and caspase-8 p20 was determined using Western blot. Results The procaspase-3 expression was significantly down-regulated, while the expression of caspase-9 p35 and caspase-8 p20 was up-regulated ingroup E and EP as compared with group C ( P ＜ 0.05). The procaspase-3 expression was up-regulated,while the expression of caspase-9 p35 and caspase-8 p20 was down-regulated in group EP as compared with group E ( P ＜ 0.05). Conclusion Etomidate preconditiong can inhibit etomidate-induced down-regulation of procaspase3 expression and up-regulation of caspase-9 p35 and caspase-8 p20 expression, resulting in suppression of HL-60 cell apoptosis induced by etomidate.

Objective To evaluate the blood-saving effect of tranexamic acid in elderly patients undergoing total hip replacement.Methods One hundred and sixty ASA Ⅱ or Ⅲ patientss of both sexes,aged 65-70 yr,with a body mass index of 16-22kg/m2,undergoing total hip replacement,were randomly divided into 2 groups(n =80,each):control group(group C)and tranexamic acid group(group T).Anesthesia was induced with midazolam,fentanyl,etomidate and atracurium.The patients were tracheal intubated and mechanically ventilated.PEr CO2 was maintained at 35-45 mm Hg.Aneslhesia was maintained with propofol,remifentanil and atracurium.Before the skin incision,tranexamic acid 15 mg/kg was infused over 15 m in in group T,while the equal volume of normal saline was given instead in group C.Hemoglobin(Hb),platelet count(PLT),prothrombin time(PT),and activated partial thromboplastin time(APTT)were monitored during operation to guide blood transfusion.Intraoperative and postoperative blood loss and allogeneic blood transfusion were recorded.Postoperative complications were also recorded.Results There was no significant difference in the amount of intraoperative blood loss between the two groups(P ＞ 0.05).The amount of postoperative blood loss was significantly smaller and less allogeneic red blood cell was transfused in group T than in group C(P ＜ 0.05).No complications occurred after operation in either group.Conchusion Tranexamic acid has blood-saving effect in elderly patients undergoing total hip replacement,but the clinical value is limited.

Objective To investigate the effect of ropivacaine preconditioning on the toxicity of ropivacaine to ND7/23 cells.Methods ND7/23 cells were cultured in DMEM culture medium at 37℃ in 5% CO2 incubator for 24 h at a concentration of 1 × 106/ml. The cells were randomly divided into 3 groups ( n = 3 each) ;control group (group C), ropivacaine group (group R) and ropivacaine preconditioning group (group RP). In group R, the cells were exposed to 1% ropivacaine 100 μl and incubated for 1 h. In group RP, the cells were exposed to 0.02% ropivacaine 100 μl for 15 min, after ropivacaine was washed out, 1% ropivacaine 100 μl was then added and the cells were incubated for 1 h. The cell viability was measured using CCK-8 assay and apoptosis using Annexin-V/PI staining.Results Compared with group C, the cell viability was significantly decreased, while the early apoptotic rate and late apoptotic rate were significantly increased in groups R and RP ( P ＜ 0.05). Compared with group R, the cell viability was significantly increased, while the early apoptotic rate and late apoptotic rate were significantly decreased in group RP (P ＜ 0.05) .Conclusion Ropivacaine preconditioning can protect ND7/23 cells from bupivacaine-induced cytotoxicity through inhibiting apoptosis.

Objective To evaluate the effects of etomidate preconditioning on etomidate-induced toxicity to rat adrenal cortical cells in vitro.Methods After being primarily cultured for 7-9 days,the rat adrenal cortical cells at the exponential growth phase were seeded into 96-well culture plates (1 × 106 cells/ml) and cultured for 24 h.The cells were then randomly divided into 3 groups with 6 wells in each group:control group (group C),etomidate group (group E),and etomidate preconditioning group (group EP).In group E,the cells were incubated with 700 μmol/L etomidate for 24 h.In group EP,the cells were incubated with 1.25 μmol/L etomidate for 1 h,then washed out and incubated with 700 μmol/L eomidate for 24 h.The cell viability was determined by CCK-8 assay and the concentration of cortisol was determined by ELISA.Results Compared with group C,the cell viability and cortisol concentration were significantly decreased in E and EP groups.Compared with group E,the cell viability and cortisol concentration were significantly increased in group EP.Conclusion Etomidate preconditioning can reduce etomidate-induced toxicity to rat adrenal cortical cells in vitro.

Objective To investigate the effect of etomidate on porcine adrenal cortical cells and the influence of preconditioning with small dose etomidate. Methods Porcine adrenal cortical cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 15% fetal bovine serum at 37℃ in 5% CO2 incubator for 24 h. The concentration was 2 × 106/ml. The experiment was performed in 2 parts. In part Ⅰ the cells were exposed to 50, 100, 200, 300, 400, 500 and 1000 mol/L etomidate respectively and incubated for 6, 12and 24 h, while in control group, the cells were exposed to 0.5% dimethylsulfoxide (DMSO). Cell viability was measured using CCK-8 assay and apoptosis by flow cytometry, and the 50% inhibitory concentration (IC50) of etomidate was calculated at 24 h of incubation. In part Ⅱ the cells were exposed to 0.6 μmol/L etomidate for 1 h and were allowed to recover for 4 h after etomidate washout, then etomidate 325 μmol/L was added and the cells were incubated for 24 h. Cell viability and apoptosis were assessed and the IC50 of etomidate was calculated as in part Ⅰ .Results Etomidate inhibited viability of porcine adrenal cortical cells and induced apoptosis in a dose- and time-dependent manner. The IC50 of etomidate at 24 h of incubation was 325 μmol/L. Preconditioning with0.6 μmol/L etomidate for 1 h attenuated the apoptosis induced by etomidate 325 μmol/L. Conclusion Etomidate can inhibit cell viability and induce apoptosis in a dose- and time-dependent manner. Preconditioning with small dose etomidate has protective effect.

Objective To evaluate the effect of activating adenylate-activated protein kinase (AMPK) on sepsis in aged mice and the relationship with autophagy.Methods Experiment [Twentyeight SPF female C57BL/6 mice,aged 16-19 months,weighing 25-35 g,were divided into sepsis group (group S,n=14) and sepsis plus AMPK agonist AICAR group (S+A group,n=14) by using a random number table method.In group S+A,AICAR 0.5 ml (dissolved in 5％ dimethyl sulfoxide) was administered by intragastric gavage.In group S,5％ dimethyl sulfoxide 0.5 ml was injected by intragastric gavage once a day for 7 consecutive days.The body weight of each mouse before and after administration was recorded.Sepsis was induced by intraperitoneal injection with cecal slurry 200 μl at the end of administration.Nine mice were selected in each group and observed for 7 days after establishing the model,and the survival rates were recorded.At 24 h after establishing the model,5 mice were sacrificed in each group,and spleen tissues were obtained for determination of the expression of AMPK,phosphorylated AMPK (p-AMPK),microtubule-associated protein 1 light chain 3 Ⅰ (LC3 Ⅰ) and LC3 Ⅱ (by Western blot).The ratios of p-AMPK/AMPK and LC3 Ⅱ/LC3 Ⅰ were calculated.Experiment Ⅱ Ten SPF female C57BL/6 mice,aged 16-19 months,weighing 25-35 g,were studied.The peritoneal macrophages obtained from 5 mice were extracted,cultured primarily and then randomized into control group (group C,n =5) and EG-FP E.Coli group (group E,n=5) using a random number table method.AICAR 0.5 ml was injected by intragastric gavage once a day for 7 consecutive days in the other 5 mice.The peritoneal macrophages were extracted after the end of intragastric administration,cultured primarily and then divided into 2 groups (n=5 each) using a random number table method:AICAR plus EGFP E.Coli group (group A+E) and AICAR plus autophagy inhibitor 3-methyladenine plus EGFP E.Coli group (group A+M+E).In group A+M+E,5 mmol/L 3-methyladenine 100 μl was added,and the cells were incubated for 1 h.EGFP expressingE.Coli was then added,and the cells were incubated for 1 h in E,A+E and A+E+M groups.Flow cytometry was used to detect the phagocytic ability of macrophages.Results Experiment Ⅰ The body weight was significantly lower after the end of administration than before administration in group S+A (P＜0.05).Compared with group S,the body weight was significantly decreased at the end of administration,the survival rate was increased at 7 days after establishing the model,the expression of LC3 Ⅱ in spleen tissues was up-regulated and the ratios of p-AMPK/AMPK and LC3 Ⅱ/LC3 Ⅰ were increased in group S+A (P＜0.05).Experiment Ⅱ Compared with group C,the phagocytic ability of macrophages was significantly enhanced in the other three groups (P＜0.05).Compared with group E,the phagocytic ability of macrophages was significantly enhanced in group A+E (P＜0.05),and no significant change was found in the phagocytic ability of macrophages in group A+M+E (P＞0.05).Compared with group A+E,the phagocytic ability of macrophages was significantly weakened in group A+M +E (P＜0.05).Conclusion Activating AMPK can increase the survival rate of aged mice with sepsis,and the mechanism is associated with enhancing autophagy of macrophages.

Objective To systematically review the effectiveness of perioperative oral probiotics in hepatic resection patients,and provide evidence-based clinical evidence.Methods PubMed,Cochrane Library,Web of Science,EMbase,SinoMed,WanFang Data,CNKI and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on perioperative oral probiotics in hepatectomized patients from inception to June 30,2023.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was performed by RevMan 5.4 software.Results A total of 10 RCTs were included,including 715 patients.The Meta-analysis showed that compared to placebo or blank controls,the incidence of postoperative infections in oral probiotic patients(RR=0.60,95％CI 0.48 to 0.74,P＜0.001),serum endotoxin levels(MD=-0.88,95％CI-1.53 to-0.22,P=0.009),cumulative antibiotic use(MD=-1.48,95％CI-2.17 to-0.78,P＜0.001),AST levels(MD=-9.68,95％CI-11.36 to-8.01,P＜0.001),ALT levels(MD=-21.24,95％CI-34.81 to-7.68,P=0.002),TBiL levels(SMD=-0.70,95％CI-0.95 to-0.45,P＜0.001),CRP levels(SMD=-0.52,95％CI-0.91 to-0.13,P=0.009),procalcitonin levels(MD=-0.19,95％CI-0.32 to-0.05,P=0.006),IL-6 levels(MD=-7.30,95％CI-14.26 to-0.33,P=0.04),and the first flatus time(MD=-1.16,95％CI-1.51 to-0.82,P＜0.001),hospital stay(MD=-0.62,95％CI-0.83 to-0.41,P＜0.001),hospitalisation costs(SMD=-0.65,95％CI-0.95 to-0.34,P＜0.001)were lower.Conclusion Current evidence shows that perioperative oral probiotics can significantly reduce the postoperative infection rate and decrease the release of inflammatory factors in liver resection patients,promote the recovery of postoperative hepatic and gastrointestinal functions,and shorten the length of hospital stay and costs.Due to the limited quality and quantity of the included studies,more high quality studies are needed to verify the above conclusion.

Objective:To assess the effect of intra-aortic balloon pump (IABP) on in-hospital mortality in patients with cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:A retrospective study was performed on 696 patients with intra-hospital cardiac arrest undergoing ECPR from Samsung Medical Center in Korea between January 2004 and December 2013. According to whether IABP was used, the patients were divided into ECPR group and ECPR+IABP group. Cox regression and propensity score matching (PSM) were used to examine the correlation between IABP usage and in-hospital mortality, and standardized mean difference ( SMD) was used to check the degree of PSM. Survival analysis of in-hospital mortality was performed by the Kaplan-Meier method, and further analyzed by the Log-Rank test. Using the propensity score as weights, multiple regression model and inverse probability weighting (IPW) model were used for sensitivity analysis. In-hospital mortality, extracorporeal membrane oxygenation (ECMO) withdrawal success rate and neurological function prognosis were compared between the two groups. Results:A total of 199 patients with cardiac arrest undergoing ECPR were included, including 120 males and 79 females, and the average age was (60.0±16.8) years. Thirty-one patients (15.6%) were treated with ECPR and IABP, and 168 patients (84.4%) only received ECPR. The total hospitalized mortality was 68.8% (137/199). The 1 : 1 nearest neighbor matching algorithm was performed with the 0.2 caliper value. The following variables were selected to generate propensity scores, including age, gender, race, marital status, insurance, admission type, service unit, heart rate, mean arterial pressure, respiratory rate, pulse oxygen saturation, white blood cell count. After the propensity score matching, 24 pairs of patients were successfully matched, with the average age of (63.0±12.8) years, including 31 males and 17 females. The in-hospital mortality was 72.6% (122/168) and 48.4% (15/31) in the ECPR group and the ECPR+IABP group [hazard ratio ( HR) = 0.48, 95% confidence interval (95% CI) was 0.28-0.82, P = 0.007]. Multiple regression model, adjusted propensity score, PSM and IPW model showed that the in-hospital mortality in the ECPR+IABP group was significantly lower compared with the ECPR group ( HR = 0.44, 0.50, 0.16 and 0.49, respectively, 95% CI were 0.24-0.79, 0.28-0.91, 0.06-0.39 and 0.31-0.77, all P < 0.05). The combined application of IABP could improve the ECMO withdrawal success rate [odds ratio ( OR) = 8.95, 95% CI was 2.72-29.38, P < 0.001] and neurological prognosis ( OR = 4.06, 95% CI was 1.33-12.40, P = 0.014) in adult cardiac arrest patients. Conclusion:In patients with cardiac arrest using ECPR, the combination of IABP was independently associated with lower in-hospital mortality, higher ECMO withdrawal success rate and better neurological prognosis.

Patients with end-stage liver disease after liver transplantation constantly suffer from malnutrition due to primary diseases and transplantation-related factors. Malnutrition will worsen clinical condition of the patients, increase the incidence of complication, length of hospital stay and medical expense after transplantation, and lower the survival rate. Sufficient nutritional support at all stages of liver transplantation is of significance. Accurate assessment of nutritional status and timely intervention are prerequisites for perioperative nutritional treatment in liver transplantation. In this article, the latest nutritional risk screening indexes and evaluation tools, nutritional support methods and other perioperative nutritional intervention measures for liver transplantation were reviewed, aiming to deepen the understanding and cognition of perioperative nutritional therapy for liver transplantation and provide reference for improving nutritional status and clinical prognosis of liver transplant recipients.

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directlycontribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://49.4.21.8:8000.