Effects of Subchronic Propofol Administration on the Proliferation and Differentiation of Neural Stem Cells in Rat Hippocampus.

Background: Although controversial, experimental data suggest the use of propofol may be associated with neurotoxicity. The mechanisms responsible for propofol neurotoxicity in animals are not yet clear. Objective: This study aimed to determine the effects of propofol on the proliferation of neural stem cells in rat hippocampus and the mechanisms underlying these effects. Methods: Forty-five adult male Sprague-Dawley rats were randomly divided into 5 groups: Control (N group), intralipid (V group), 30 mg/kg propofol (Prop30 group), 60 mg/kg propofol (Prop60 group), and 120 mg/kg propofol (Prop120 group). The rats in all groups received 5, once daily intraperitoneal injections. For each of the 5 days, the N group received 6 mL/kg normal saline, the V group received 6 mL/kg fat emulsion, the Prop30 group received 30 mg/kg propofol, the Prop60 group received 60 mg/kg propofol, and the Prop120 group received 120 mg/kg propofol. Memory function was scored daily using the Morris water maze test. Immunofluorescence staining was used to histologically monitor the proliferation and differentiation of the rats' hippocampal neural stem cells, and real time quantitative polymerase chain reaction and Western blotting were used to determine the expression of Notch3, Hes1, and Hes5. Results: Compared with the N group, the Prop120 group exhibited reduced learning and memory, whereas there were no significant differences for the Prop60 group. The number of ß-tubulin III+ cells increased in the Prop60 group, but decreased in the Prop120 group. Compared with the N group, the relative expression of Notch3 and Hes5 increased significantly in the Prop60 group, whereas this expression decreased in the Prop120 group. Conclusions: These data demonstrate that repeated, subchronic (5 days) intraperitoneal injections of 60 mg/kg propofol can effectively promote rat hippocampal neural stem cells proliferation and differentiation, and that this is likely mediated by its effects on the Notch3-Hes5 pathway.

MicroRNA-27a-3p relieves inflammation and neurologic impairment after cerebral ischaemia reperfusion via inhibiting lipopolysaccharide induced TNF factor and the TLR4/NF-κB pathway.

Cerebral ischaemia reperfusion (CIR) affects microRNA (miR) expression and causes substantial inflammation. Here, we investigated the influence and underlying mechanism of miR-27a-3p in rats with CIR. First, biliverdin treatment relieved cerebral infarction and decreased the levels of serum interleukin (IL)-1ß, IL-6, and TNF-α. Through our previous study, we found key miR-27a-3p and its targeted gene LITAF might involve in the molecular mechanism of CIR. Then, the regulation between miR-27a-3p and LITAF was verified by the temporal miR-27a-3p and LITAF expression profiles and luciferase assay. Moreover, intracerebroventricular injection of the miR-27a-3p mimic significantly decreased the LITAF, TLR4, NF-κB, and IL-6 levels at 24 h post-surgery, whereas miR-27a-3p inhibitor reversed these effects. Furthermore, miR-27a-3p mimic could relieve cerebral infarct and neurologic deficit after CIR. In addition, injection of miR-27a-3p mimic decreased neuronal damage induced by CIR. Taken together, our results suggest that miR-27a-3p protects against CIR by relieving inflammation, neuronal damage, and neurologic deficit via regulating LITAF and the TLR4/NF-κB pathway.

Morphological specificity analysis of an image-based 3D model of airway filling in a difficult airway.

BACKGROUND: The purpose of this study was to analyze position-specific morphological changes of the upper airway and to further assess the impact of these changes in difficult airway during intubation. METHODS: This observational comparative study included two groups (n = 20 patients/group): Group A had normal airway and Group B had difficult airway. Data obtained from two-dimensional magnetic resonance imaging were imported to Mimics V20.0 software for processing. We then reconstructed three-dimensional models of upper airway filling in patients in the supine and maximum extension position based on the imaging data. Those models were projected on coronal, sagittal, and horizontal planes to investigate multiple morphological features. We measured the surface area, radial length, and corner angle of the projected areas. RESULTS: Group A had larger upper airway filling volumes compared to Group B The volumes for the supine position were 6,323.83 ± 156.06 mm3 for Group A and 5,336.22 ± 316.13 mm3 for Group B (p = 0.003). The volumes the maximum extension position were 9,186.58 ± 512.61 mm3 for Group A and 6,735.46 ± 794.63 mm3 for Group B (p = 0.003). Airway volume increased in the upper airway filling model as the body position varied from the supine to maximum extension position (Group A: volume increase 2,953.75 ± 524.6 mm3, rate of change 31%; Group B: volume increase 1,632.89 ± 662.66 mm3, rate of change 25%; p = 0.052). CONCLUSION: The three-dimensional reconstruction model developed in this study was used to digitally quantify morphological features of a difficult airway and could be used as a novel airway management assessment tool.

Comparative 3D genome organization in apicomplexan parasites.

The positioning of chromosomes in the nucleus of a eukaryotic cell is highly organized and has a complex and dynamic relationship with gene expression. In the human malaria parasite Plasmodium falciparum, the clustering of a family of virulence genes correlates with their coordinated silencing and has a strong influence on the overall organization of the genome. To identify conserved and species-specific principles of genome organization, we performed Hi-C experiments and generated 3D genome models for five Plasmodium species and two related apicomplexan parasites. Plasmodium species mainly showed clustering of centromeres, telomeres, and virulence genes. In P. falciparum, the heterochromatic virulence gene cluster had a strong repressive effect on the surrounding nuclear space, while this was less pronounced in Plasmodium vivax and Plasmodium berghei, and absent in Plasmodium yoelii In Plasmodium knowlesi, telomeres and virulence genes were more dispersed throughout the nucleus, but its 3D genome showed a strong correlation with gene expression. The Babesia microti genome showed a classical Rabl organization with colocalization of subtelomeric virulence genes, while the Toxoplasma gondii genome was dominated by clustering of the centromeres and lacked virulence gene clustering. Collectively, our results demonstrate that spatial genome organization in most Plasmodium species is constrained by the colocalization of virulence genes. P. falciparum and P. knowlesi, the only two Plasmodium species with gene families involved in antigenic variation, are unique in the effect of these genes on chromosome folding, indicating a potential link between genome organization and gene expression in more virulent pathogens.

Dexmedetomidine maintains blood-brain barrier integrity by inhibiting Drp1-related endothelial mitochondrial dysfunction in ischemic stroke.

Stroke is the second leading cause of death and long-term disability worldwide, which lacks effective treatment. Perioperative stroke is associated with much higher rates of mortality and disability. The neuroprotective role of dexmedetomidine (Dex), a highly selective agonist of alpha2-adrenergic receptor, has been reported in a stroke rat model, and it was found that pretreatment of Dex before stroke could alleviate blood-brain barrier (BBB) breakdown. However, the underlying mechanisms are still unknown. As the brain endothelial cells are the main constituents of BBB and in high demand of energy, mitochondrial function of endothelial cells plays an important role in the maintenance of BBB. Given that dynamin-related protein 1 (Drp1) is a protein mediating mitochondrial fission, with mitochondrial fusion that balances mitochondrial morphology and ensures mitochondria function, the present study was designed to investigate the possible role of Drp1 in endothelial cells involved in the neuroprotective effects of Dex in ischemic stroke. Our results showed that preconditioning with Dex reduced infarction volume, alleviated brain water content and BBB damage, and improved neurological scores in middle cerebral artery occlusion rats. Meanwhile, Dex enhanced cell activity and decreased cell apoptosis in oxygen-glucose deprivation human brain microvascular endothelial cells in vitro. These protective effects of Dex were correlated with the mitochondrial morphology integrality of endothelial cells, mediated by increased phosphorylation of serine 637 in Drp1, and could be reversed by α2-adrenergic receptor antagonist Yohimbine and AMP-activated protein kinase inhibitor Compound C. These findings suggest new molecular pathways involved in the neuroprotective effects of Dex in ischemic stroke. As Dex is routinely used as a sedative drug clinically, our findings provide molecular evidence that it has perioperative neuroprotection from ischemic stroke.

LUADpp: an effective prediction model on prognosis of lung adenocarcinomas based on somatic mutational features.

BACKGROUND: Lung adenocarcinoma is the most common type of lung cancers. Whole-genome sequencing studies disclosed the genomic landscape of lung adenocarcinomas. however, it remains unclear if the genetic alternations could guide prognosis prediction. Effective genetic markers and their based prediction models are also at a lack for prognosis evaluation. METHODS: We obtained the somatic mutation data and clinical data for 371 lung adenocarcinoma cases from The Cancer Genome Atlas. The cases were classified into two prognostic groups (3-year survival), and a comparison was performed between the groups for the somatic mutation frequencies of genes, followed by development of computational models to discrete the different prognosis. RESULTS: Genes were found with higher mutation rates in good (≥ 3-year survival) than in poor (< 3-year survival) prognosis group of lung adenocarcinoma patients. Genes participating in cell-cell adhesion and motility were significantly enriched in the top gene list with mutation rate difference between the good and poor prognosis group. Support Vector Machine models with the gene somatic mutation features could well predict prognosis, and the performance improved as feature size increased. An 85-gene model reached an average cross-validated accuracy of 81% and an Area Under the Curve (AUC) of 0.896 for the Receiver Operating Characteristic (ROC) curves. The model also exhibited good inter-stage prognosis prediction performance, with an average AUC of 0.846 for the ROC curves. CONCLUSION: The prognosis of lung adenocarcinomas is related with somatic gene mutations. The genetic markers could be used for prognosis prediction and furthermore provide guidance for personal medicine.

Effect of physical exercise on young anesthesiologists with on-call-related fatigue.

To explore whether exercise can effectively relieve the fatigue state of overnight shift anesthesiologists with chronic fatigue. 78 anesthesiologists between 30 and 40 years of age at four hospitals in China were analyzed in the investigation. The Profile of Mood States (POMS) and Chalder Fatigue Scale (CFS) were used to assess psychological symptoms and fatigue respectively, and data regarding demographics, health, exercise and work-related variables were also collected. The total and physical fatigue score were highest among those who seldom do exercise compared to those who always do exercise (p < .05, respectively). Moreover, anesthesiologists who exercised 30-60 min everyday had the lowest total and physical fatigue score. When exercise for more than 60 min, the total and physical fatigue scores then increased. After completing a night shift, the post-on-call total Profile of Mood States scores of those who seldom do exercise was significantly increased (t = -4.9, p < .001). These study findings suggested that regular exercise 30-60 min everyday could effectively reduce anesthesiologists' physical fatigue and decrease their negative psychological state, and anesthesiologists should positively adjust working and exercise time.

BPP: a sequence-based algorithm for branch point prediction.

MOTIVATION: Although high-throughput sequencing methods have been proposed to identify splicing branch points in the human genome, these methods can only detect a small fraction of the branch points subject to the sequencing depth, experimental cost and the expression level of the mRNA. An accurate computational model for branch point prediction is therefore an ongoing objective in human genome research. RESULTS: We here propose a novel branch point prediction algorithm that utilizes information on the branch point sequence and the polypyrimidine tract. Using experimentally validated data, we demonstrate that our proposed method outperforms existing methods. Availability and implementation: https://github.com/zhqingit/BPP. CONTACT: djguo@cuhk.edu.hk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Expression of Plasma microRNA-1/21/ 208a/499 in myocardial ischemic reperfusion injury.

OBJECTIVES: We aimed to measure changes in the levels of several miRNAs during open-heart surgery and to investigate the relationship between these changes and cardiac biomarkers. METHODS: Creatine kinase-muscle band (CK-MB), cardiac troponin (cTnI) and miRNA (miR-1/21/208a/499) levels were measured during open-heart surgery in 15 patients undergoing combined mitral and aortic valve replacement. The levels of these markers were measured presurgically, 45 min after aortic clamping, 60 min after reperfusion and 24 h after surgery. RESULTS: Significant differences were found in miR-1/208a/499 levels but not in miR-21 levels. miR-1/208a levels were unchanged until 45 min after aortic clamping, increased 60 min after reperfusion (p < 0.001) and decreased significantly 24 h after surgery (p < 0.001). The changes in miR-1/208a levels exhibited a similar pattern to those observed for cTnI and CK-MB, although the changes in miR-208a levels reflected more rapidly than those in miR-1 levels. miR-499 levels decreased after reperfusion (p < 0.001) until 24 h after surgery; these levels were negatively correlated with cTnI and CK-MB levels at all of the time points. CONCLUSIONS: A time-dependent change in miR-1/208a/499 levels occurred during open-heart surgery, and these were associated with levels of cTnI and CK-MB. These results reveal that miRNAs may be sensitive biomarkers for I/R injury during open-heart surgery.

Bioinformatics-driven identification and validation of diagnostic biomarkers for cerebral ischemia reperfusion injury.

Objective: This article aims to identify genetic features associated with immune cell infiltration in cerebral ischemia-reperfusion injury (CIRI) development through bioinformatics, with the goal of discovering diagnostic biomarkers and potential therapeutic targets. Methods: We obtained two datasets from the Gene Expression Omnibus (GEO) database to identify immune-related differentially expressed genes (IRDEGs). These genes' functions were analyzed via Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Tools such as CIBERSORT and ssGSEA assessed immune cell infiltration. The Starbase and miRDB databases predicted miRNAs interacting with hub genes, and Cytoscape software mapped mRNA-miRNA interaction networks. The ENCORI database was employed to predict RNA binding proteins interacting with hub genes. Key genes were identified using a random forest algorithm and constructing a Support Vector Machine (SVM) model. LASSO regression analysis constructed a diagnostic model for hub genes to determine their diagnostic value, and PCR analysis validated their expression in cerebral ischemia-reperfusion. Results: We identified 10 IRDEGs (C1qa, Ccl4, Cd74, Cd8a, Cxcl10, Gmfg, Grp, Lgals3bp, Timp1, Vim). The random forest algorithm, and SVM model intersection revealed three key genes (Ccl4, Gmfg, C1qa) as diagnostic biomarkers for CIRI. LASSO regression analysis, further refined this to two key genes (Ccl4 and C1qa), With ROC curve, analysis confirming their diagnostic efficacy (C1qa AUC = 0.75, Ccl4 AUC = 0.939). PCR analysis corroborated these findings. Conclusions: Our study elucidates immune and metabolic response mechanisms in CIRI, identifying two immune-related genes as key biomarkers and potential therapeutic targets in response to cerebral ischemia-reperfusion injury.

miR-185-5p / ATG101 axis alleviated intestinal barrier damage in intestinal ischemia reperfusion through autophagy.

Objective: Intestinal ischemia-reperfusion (II/R) is a common pathological injury in clinic, and the systemic inflammatory response it causes will lead to multiple organ damage and functional failure. miR-185-5p has been reported to be a regulator of inflammatory response and autophagy, but whether it participates in the regulation of autophagy in II/R is still unclear. Therefore, we aimed to explore the mechanism of miR-185-5p regulating intestinal barrier injury in (II/R). Methods: Caco-2 cells was induced by oxygen-glucose deprivation/reoxygenation (OGD/R) to establish II/R model. The superior mesenteric artery of C57BL/6 mice was clamped for 45 min and then subjected to reperfusion for 4 h for the establishment of II/R mice model. miR-185-5p mimic, miR-185-5p inhibitor, pcDNA-autophagy-related 101 (ATG101) were respectively transfected into Caco-2 cells. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to assess miR-185-5p expression. Western blot detected the level of ATG101 and tight junction-associated proteins ZO1, Occludin, E-cadherin, ß-catenin, as well as autophagy markers ATG5, ATG12, LC3Ⅰ/Ⅱ, Beclin1 and SQSTM1. Transepithelial electrical resistance (TEER) values was detected by a resistance meter. FITC-Dextran was performed to measure cell permeability. 5-ethynyl-2'-deoxyuridine (EDU) staining measured cell proliferation. Transmission electron microscope was conducted to observe autophagosomes. Hematoxylin & eosin (H&E) staining observed the damage of mice intestinal. Immunohistochemistry (IHC) measured the percentage of ki67 positive cells. TdT-mediated dUTP nick-end labeling (TUNEL) assay assessed cell apoptosis in intestinal tissues of II/R. Dual-luciferase assay verified the targeting relationship between miR-185-5p and ATG101.Results miR-185-5p was overexpressed in OGD/R-induced Caco-2 cells and intestinal tissues of II/R mice. Knocking down miR-185-5p markedly promoted autophagy and TEER values, reduced cell permeability, and alleviated intestinal barrier damage. ATG101 was a target of miR-185-5p, and overexpression of ATG101 promoted autophagy and dampened OGD/R-induced intestinal barrier damage. Overexpression of miR-185-5p reversed the effect of overexpressed ATG101 on OGD/R-induced Caco-2 cells. Conclusion: Knockdown of miR-185-5p enhanced autophagy and alleviated II/R intestinal barrier damage by targeting ATG101.

Biliverdin modulates the Nrf2/A20/eEF1A2 axis to alleviate cerebral ischemia-reperfusion injury by inhibiting pyroptosis.

This study aimed to examine whether Biliverdin, which is a common metabolite of haem, can alleviate cerebral ischemia reperfusion injury (CIRI) by inhibiting pyroptosis. Here, CIRI was induced by middle cerebral artery occlusion-reperfusion (MCAO/R) in C57BL/6 J mice and modelled by oxygen and glucose deprivation/reoxygenation (OGD/R) in HT22 cells, it was treated with or without Biliverdin. The spatiotemporal expression of GSDMD-N and infarction volumes were assessed by immunofluorescence staining and triphenyltetrazolium chloride (TTC), respectively. The NLRP3/Caspase-1/GSDMD pathway, which is central to the pyroptosis process, as well as the expression of Nrf2, A20, and eEF1A2 were determined by Western-blots. Nrf2, A20, and eEF1A2 interactions were verified using dual-luciferase reporter assays, chromatin immunoprecipitation, or co-immunoprecipitation. Additionally, the role of Nrf2/A20/eEF1A2 axis in modulating the neuroprotective properties of Biliverdin was investigated using A20 or eEF1A2 gene interference (overexpression and/or silencing). 40 mg/kg of Biliverdin could significantly alleviate CIRI both in vivo and in vitro, promoted the activation of Nrf2, elevated A20 expression, but decreased eEF1A2 expression. Nrf2 can bind to the promoter of A20, thereby transcriptionally regulating the expression of A20. A20 can furthermore interacted with eEF1A2 through its ZnF4 domain to ubiquitinate and degrade it, leading to the downregulation of eEF1A2. Our studies have also demonstrated that either the knock-down of A20 or over-expression of eEF1A2 blunted the protective effect of Biliverdin. Rescue experiments further confirmed that Biliverdin could regulate the NF-κB pathway via the Nrf2/A20/eEF1A2 axis. In summary, our study demonstrates that Biliverdin ameliorates CIRI by inhibiting the NF-κB pathway via the Nrf2/A20/eEF1A2 axis. Our findings can help identify novel therapeutic targets for the treatment of CIRI.

Incidence and risk factors of postoperative acute myocardial injury in noncardiac patients: A systematic review and meta-analysis.

INTRODUCTION: Postoperative myocardial injury after noncardiac surgery is common and is associated with short- and long-term morbidity and mortality. However, the incidence and risk factors for postoperative acute myocardial injury (POAMI) are currently unknown due to inconsistent definitions. METHODS: We systematically searched PubMed and Web of Science to identify studies that applied the change value of preoperative and postoperative cardiac troponins to define cardiac injury. We estimated the pooled incidence, risk factors, and 30-day and long-term mortality of POAMI in noncardiac patients. The study protocol was registered with PROSPERO, CRD42023401607. RESULTS: Ten cohorts containing 11,494 patients were included for analysis. The pooled incidence of POAMI was 20% (95% CI: 16% to 23%). Preoperative hypertension (OR: 1.47; 95% CI: 1.30 to 1.66), cardiac failure (OR: 2.63; 95% CI: 2.01 to 3.44), renal impairment (OR: 1.66; 95% CI: 1.48 to 1.86), diabetes (OR: 1.43; 95% CI: 1.27 to 1.61), and preoperative beta-blocker intake (OR: 1.65; 95% CI: 1.10 to 2.49) were the risk factors for POAMI. Age (mean difference: 2.08 years; 95% CI: -0.47 to 4.62), sex (male, OR: 1.16; 95% CI: 0.77 to 1.76), body mass index (mean difference: 0.35; 95% CI: -0.86 to 1.57), preoperative coronary artery disease (OR: 2.10; 95% CI: 0.85 to 5.21), stroke (OR: 0.90; 95% CI: 0.50 to 1.59) and preoperative statins intake (OR: 0.65; 95% CI: 0.21 to 2.02) were not associated with POAMI. Patients with POAMI had higher preoperative hsTnT levels (mean difference: 5.92 ng/L; 95% CI: 4.17 to 7.67) and lower preoperative hemoglobin levels (mean difference: -1.29 g/dL; 95% CI: -1.43 to -1.15) than patients without. CONCLUSION: Based on this meta-analysis, approximately 1 in 5 of noncardiac patients develop POAMI. However, the lack of a universally recognized definition for POAMI, which incorporates diverse cardiac biomarkers and patient groups, poses a challenge in accurately characterizing its incidence, risk factors, and clinical outcomes.

Proteomic analysis of Biliverdin protected cerebral ischemia-reperfusion injury in rats.

Biliverdin, a heme metabolite, has been previously reported to alleviate cerebral ischemic reperfusion injury (CIRI). However, the alterations of brain proteome profiles underlying this treatment remain elusive. The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats involved in anti-CIRI effects of Biliverdin, providing experimental foundation for searching specific marker proteins. Rat model of MCAO/R was established, HE staining, TTC staining, TUNEL staining, and neurological behavioral examination, corner turning test, adhesive removal test, were performed to validate the effects of Biliverdin, and the results indicated that Biliverdin plays a significant role in alleviating CIRI. Furthermore, proteomic analysis of brain tissues of rats subjected to CIRI following Biliverdin treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with LC-MS/MS technology to clarify the comprehensive mechanisms of Biliverdin in CIRI. First, we conducted strict quality control data for TMT experiments. Finally, a total of 7366 proteins were identified, of which 95 proteins were differentially expressed (DEPs) between the CIRI group and the Sham group and 52 between the CIRI and BV groups. In addition, two overlapping proteins among the 147 DEPs, Atg4c and Camlg, were validated by RT-qPCR and western blotting, and their levels were consistent with the results of TMT analysis. Taken together, the current findings firstly mapped comprehensive proteomic changes after CIRI treated with Biliverdin, providing a foundation for developing potentially therapeutic targets of anti-CIRI of Biliverdin and clinically prognostic biomarkers of stroke.

L-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis.

L-Palmitoylcarnitine (L-PC) is an important endogenous fatty acid metabolite. Its classical biological functions are involved in the regulations of membrane molecular dynamics and the ß-oxidation of fatty acids. Decreased plasma long-chain acylcarnitines showed the association of venous thrombosis, implying anticoagulant activity of the metabolites and inspiring us to investigate if and how L-PC, a long-chain acylcarnitine, takes part in coagulation. Here we show that L-PC exerted anti-coagulant effects by potentiating the enzymatic activities of plasmin and tissue plasminogen activator (tPA). L-PC directly interacts with plasmin and tPA with an equilibrium dissociation constant (KD) of 6.47 × 10-9 and 4.46 × 10-9 M, respectively, showing high affinities. In mouse model, L-PC administration significantly inhibited FeCl3-induced arterial thrombosis. It also mitigated intracerebral thrombosis and inflammation in a transient middle cerebral artery occlusion (tMCAO) mouse model. L-PC induced little bleeding complications. The results show that L-PC has anti-thrombotic function by potentiating plasmin and tPA.

Melatonin intervention to prevent delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials.

Objective: To determine the preventive effect of melatonin on delirium in the intensive care units. Methods: We conducted a systematic search of the PubMed, Cochrane Library, Science, Embase, and CNKI databases, with retrieval dates ranging from the databases' inception to September 2022. Controlled trials on melatonin and placebo for preventing delirium in the intensive care units were included. The meta-analysis was performed using Review Manager software (version 5.3) and Stata software (version 14.0). Results: Six studies involving 2374 patients were included in the meta-analysis. The results of the meta-analysis showed that melatonin did not reduce the incidence of delirium in ICU patients (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.46 to 1.12; p = 0.14). There was a strong hetero-geneity between the selected studies (I2 = 74%). Subgroup analysis results showed that melatonin reduced the incidence of delirium in cardiovascular care unit (CCU) patients (OR: 0.52; 95% CI: 0.37 to 0.73; p=0.0001), but did not in general intensive care unit (GICU) patients (OR: 1.14; 95% CI: 0.86 to 1.50; p=0.35). In terms of the secondary outcomes, there were no significant differences in all-cause mortality (OR: 0.85; 95% CI: 0.66 to 1.09; p=0.20), length of ICU stay (mean difference [MD]: 0.33; 95% CI: -0.53 to 1.18; p=0.45), or length of hospital stay (MD: 0.51; 95% CI: -1.17 to 2.19; p=0.55). Conclusion: Melatonin reduced the incidence of delirium in CCU patients, but did not significantly reduce the incidence of delirium in GICU patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022367665.

Sex differences in the association between visceral adipose tissue and atherosclerosis in type 2 diabetes patients with normal bodyweight: A study in a Chinese population.

AIMS/INTRODUCTION: To investigate the impact of visceral adipose tissue (VAT) on atherosclerosis in type 2 diabetes patients with normal bodyweight (OB[-]) in the Chinese population, and to further assess the sex-age differences between them. MATERIALS AND METHODS: A total of 8,839 type 2 diabetes patients from two of the National Metabolic Management Centers in China were included in this study. Participants were classified into four groups by visceral fat area (VFA; cm2 ) and body mass index (BMI; kg/m2 ): VFA < 100 and BMI < 23.9 (VA[-]OB[-]), VFA < 100 and BMI ≥ 23.9 (VA[-]OB[+]), VFA ≥ 100 and BMI < 23.9 (VA[+]OB[-]), VFA ≥ 100 and BMI ≥ 23.9 (VA[+]OB[+]). Atherosclerosis was defined by brachial-ankle pulse wave velocity (baPWV; cm/s), and we analyzed the association between VFA, BMI and the tertiles of baPWV values. RESULTS: The VA(+)OB(-) prevalence was 3.7% among these participants. Patients with VA(+)OB(-) had the highest baPWV value (P < 0.001) and the highest proportion of the tertile 3 of baPWV (P < 0.001) among four groups, and were significantly associated with baPWV (standardized ß = 0.026, P = 0.008). VFA was significantly related to tertile 2 to tertile 3 of baPWV in (OB[-]) type 2 diabetes patients, when compared with tertile 1 of baPWV, respectively. In sex-age stratified analysis, the association of VFA and the tertiles of baPWV showed sex differences. For the 55 years age stratification analysis, there was no age difference in the relationship between VFA and baPWV in (OB[-]) patients. CONCLUSION: Increased VAT was an independent risk factor for atherosclerosis in female type 2 diabetes patients with normal weight.

Advances in the Study of the Ubiquitin-Editing Enzyme A20.

Ubiquitin modification is a common post-translational protein modification and an important mechanism whereby the body regulates protein levels and functions. As a common enzyme associated with ubiquitin modification, the ubiquitin-editing enzyme A20 may be closely associated with the development of numerous pathological processes through its different structural domains. The aim of this paper is to provide an overview of the following: advances in ubiquitination research, the structure and function of A20, and the relationships between A20 and immune inflammatory response, apoptosis, necroptosis, pyroptosis, and autophagy.

The Impact of intra-abdominal Pressure on Perioperative Outcomes in Robotic-Assisted Radical Prostatectomy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Objective: The aim of the study is to analyze the impact of intra-abdominal pressure (IAP) on perioperative outcomes in robotic-assisted radical prostatectomy (RARP). Methods: We searched the PubMed, Cochrane Library, Science, Embase, and CNKI databases systematically, and the retrieval date was from the inception of the databases to April 2022. Randomized controlled trials on high intraabdominal pressure (HIAP) and low intraabdominal pressure (LIAP) in RARP were included. The meta-analysis was performed using Review Manager software (version 5.3). Results: Six studies involving 2,271 patients were included in the meta-analysis. Compared with patients who experienced HIAP, those who experienced LIAP had a lower incidence of postoperative ileus (POI) (risk ratio (RR): 0.42; 95% confidence interval (CI): 0.24 to 0.72; p = 0.002). However, there were no significant differences in hematoma (RR 2.22; 95% CI, 0.61 to 8.15; p = 0.23), positive margin rate (RR, 1.06; 95% CI, 0.84 to 1.32; p = 0.64), urinary retention (RR, 0.99; 95% CI, 0.51 to 1.94; p = 0.98), operative time (mean difference (MD), -0.36; 95% CI, -12.24 to 6.12; p = 0.51), or intraoperative blood loss (MD, -21.80; 95% CI, -55.28 to 11.68; p = 0.20) among patients undergoing LIAP and HIAP. Conclusion: Our study of published trials indicates that using LIAP during RARP may reduce the incidence of POI, and there were no differences in terms of hematoma, positive margin rate, urinary retention, operative time, or intraoperative blood loss.

Exploration in the Therapeutic and Multi-Target Mechanism of Ketamine on Cerebral Ischemia Based on Network Pharmacology and Molecular Docking.

Background: Ketamine is famous for its dissociative anesthetic properties. It is also analgesic, anti-inflammatory and anti-depressant, and even has a cerebral protective effect. We searched the evidence of the correlation between ketamine target and clinical efficacy and utilized network pharmacology to gather information about the multi-target mechanism of ketamine against cerebral ischemia (CI). We found that ketamine's clinical significance may be more extensive than previously thought. Methods: The drug target of ketamine and CI-related genes were predicted by SwissTargetPrediction, DrugBank, PubChem, GeneCards and DisGeNET databases. The intersection of ketamine's drug-targets and CI-related genes was analyzed by using GO and KEGG. We predicted the molecular docking between the potential target and ketamine. Results: The results indicated that the effect of ketamine on CI was primarily associated with the target of α-synuclein (SNCA), muscarinic acetylcholine receptor M1 (CHRM1) and nitric oxide synthase 1 (NOS1). It principally regulates the signal pathways of circadian transmission, calcium signaling pathway, dopaminergic synapse, cholinergic synapse and glutamatergic synapse. Molecular docking analysis exhibited that hydrogen bond and Pi-Pi interaction were the predominant modes of interaction. Conclusion: There are protein targets affected by ketamine in the treatment of CI. Three pivotal targets involving 298 proteins, SNCA, CHRM1 and NOS1, have emerged as multi-target mechanisms for ketamine in CI therapy. Similarly, this study also provides a new idea for introducing network pharmacology into the evaluation of multi-targeted drugs for CI and cerebral protection.