Association between triglyceride-glucose index and in-hospital mortality in critically ill patients with sepsis: analysis of the MIMIC-IV database.

BACKGROUND: This study aimed to explore the association between the triglyceride-glucose (TyG) index and the risk of in-hospital mortality in critically ill patients with sepsis. METHODS: This was a retrospective observational cohort study and data were obtained from the Medical Information Mart for Intensive Care-IV (MIMIC IV2.2) database. The participants were grouped into three groups according to the TyG index tertiles. The primary outcome was in-hospital all-cause mortality. Multivariable logistics proportional regression analysis and restricted cubic spline regression was used to evaluate the association between the TyG index and in-hospital mortality in patients with sepsis. In sensitivity analysis, the feature importance of the TyG index was initially determined using machine learning algorithms and subgroup analysis based on different subgroups was also performed. RESULTS: 1,257 patients (56.88% men) were included in the study. The in-hospital, 28-day and intensive care unit (ICU) mortality were 21.40%, 26.17%, and 15.43% respectively. Multivariate logistics regression analysis showed that the TyG index was independently associated with an elevated risk of in-hospital mortality (OR 1.440 [95% CI 1.106-1.875]; P = 0.00673), 28-day mortality (OR 1.391; [95% CI 1.52-1.678]; P = 0.01414) and ICU mortality (OR 1.597; [95% CI 1.188-2.147]; P = 0.00266). The restricted cubic spline regression model revealed that the risks of in-hospital, 28-day, and ICU mortality increased linearly with increasing TyG index. Sensitivity analysis indicate that the effect size and direction in different subgroups are consistent, the results is stability. Additionally, the machine learning results suggest that TyG index is an important feature for the outcomes of sepsis. CONCLUSION: Our study indicates that a high TyG index is associated with an increased in-hospital mortality in critically ill sepsis patients. Larger prospective studies are required to confirm these findings.

Causal effects of genetically vitamins and sepsis risk: a two-sample Mendelian randomization study.

BACKGROUND: In recent years, observational studies have been conducted to investigate the potential impact of vitamins on sepsis. However, many of these studies have produced inconsistent results. Our Mendelian randomization (MR) study aims to evaluate the causality between vitamins and sepsis from a genetic perspective. METHODS: Our MR study was designed following the STROBE-MR guidelines. Genetic instrumental variables for vitamins including folate, vitamin B12, B6, A (Retinol), C, D, and K were obtained from previous genome-wide association studies (GWAS) and MR studies. Five different sepsis severity levels were included in the analysis. The genetic instrumental variables were screened for potential confounders using PhenoScanner V2. MR analysis was performed using MR-egger, inverse-variance weighted multiplicative random effects (IVW-RE), inverse-variance weighted multiplicative fixed-effects (IVW-FE), and wald ratio methods to assess the relationship between vitamins and sepsis. Sensitivity analysis was performed using the MR-egger_intercept method, and the MR-PRESSO package and Cochran's Q test were used to evaluate the heterogeneity of the instrumental variables. RESULTS: Our MR study found no statistically significant association between vitamins and sepsis risk, regardless of the type of vitamin (P-value > 0.05). The odds ratios (ORs) for folate, vitamin B6, vitamin B12, vitamin A, vitamin D, vitamin K, and vitamin C were 1.164 (95% CI: 0.895-1.514), 0.987 (95% CI: 0.969-1.005), 0.975 (95% CI: 0.914-1.041), 0.993 (95% CI: 0.797-1.238), 0.861 (95% CI: 0.522-1.42), 0.955 (95% CI: 0.86-1.059), and 1.049 (95% CI: 0.911-1.208), respectively. Similar results were observed in subgroups of different sepsis severity levels. CONCLUSIONS: Our MR study found no evidence of a causal association between vitamins and sepsis risk from a genetic perspective. Further randomized controlled trials are necessary to confirm these results.

Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis.

Background: The impact of lipid-lowering medications on sepsis is still not well defined. A Mendelian randomization (MR) study was carried out to probe the causal connections between genetically determined lipids, lipid-reducing drugs, and the risk of sepsis. Materials and methods: Data on total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and triglycerides (TG) were retrieved from the MR-Base platform and the Global Lipids Genetics Consortium in 2021 (GLGC2021). Our study categorized sepsis into two groups: total sepsis and 28-day mortality of sepsis patients (sepsis28). The inverse-variance weighted (IVW) method was the primary method used in MR analysis. Cochran's Q test and the MR-Egger intercept method were used to assess the heterogeneity and pleiotropy. Results: In the MR analysis, we found that ApoA-I played a suggestively positive role in protecting against both total sepsis (OR, 0.863 per SD increase in ApoA-I; 95% CI, 0.780-0.955; P = 0.004) and sepsis28 (OR, 0.759; 95% CI, 0.598-0.963; P = 0.023). HDL-C levels were also found to suggestively reduce the incidence of total sepsis (OR, 0.891 per SD increase in HDL-C; 95% CI, 0.802-0.990; P = 0.031). Reverse-MR showed that sepsis28 led to a decrease in HDL-C level and an increase in TG level. In drug-target MR, we found that HMGCR inhibitors positively protected against total sepsis (1OR, 0.719 per SD reduction in LDL-C; 95% CI, 0.540-0.958; P = 0.024). LDL-C and HDL-C proxied CETP inhibitors were found to have a protective effect on total sepsis, with only LDL-C proxied CETP inhibitors showing a suggestively protective effect on sepsis28. In Mediated-MR, BMI exhibited a negative indirect effect in HMGCR inhibitors curing sepsis. The indirect impact of ApoA-I explained over 50% of the curative effects of CETP inhibitors in sepsis. Conclusions: Our MR study suggested that ApoA-I and HDL-C protected against sepsis, while HMGCR and CETP inhibitors showed therapeutic potential beyond lipid-lowering effects. ApoA-I explained the effects of CETP inhibitors. Our study illuminates how lipids affect sepsis patients and the effectiveness of new drugs, opening new avenues for sepsis treatment.

DECREASE IN THE PLATELET-TO-LYMPHOCYTE RATIO IN DAYS AFTER ADMISSION FOR SEPSIS CORRELATES WITH IN-HOSPITAL MORTALITY.

ABSTRACT: Background: A previous study has linked an increase in platelet-to-lymphocyte ratio (PLR) to a poor prognosis; however, the relationship between early change in PLR and outcomes in sepsis patients is unclear. Methods : The Medical Information Mart for Intensive Care IV database was for this retrospective cohort analysis on patients meeting the Sepsis-3 criteria. All the patients meet the Sepsis-3 criteria. The platelet-to-lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte count. We collected all PLR measurements that were available within 3 days of admission for analysis of longitudinal changes over time. Multivariable logistic regression analysis was used to determine the relationship between the baseline PLR and in-hospital mortality. After correcting for possible confounders, the generalized additive mixed model was used to examine the trends in PLR over time among survivors and nonsurvivors. Results: Finally, 3,303 patients were enrolled, and both low and high PLR levels were significantly associated with higher in-hospital mortality in the multiple logistic regression analysis (tertile 1: odds ratio, 1.240; 95% confidence interval, 0.981-1.568 and tertile 3: odds ratio, 1.410; 95% confidence interval, 1.120-1.776, respectively). The generalized additive mixed model results revealed that the PLR of the nonsurvival group declined faster than that of the survival group within 3 days after intensive care unit admission. After controlling for confounders, the difference between the two groups steadily decreased and increased by an average of 37.38 daily. Conclusions : There was a U-shaped relationship between the baseline PLR and in-hospital mortality of sepsis patients, and there was a significant difference between the nonsurvival and survival groups in the change in PLR over time. The early decrease in PLR was related to an increase in in-hospital mortality.

In vitro activities of licochalcone A against planktonic cells and biofilm of Enterococcus faecalis.

This study aims to evaluate the in vitro antibacterial and anti-biofilm activities of licochalcone A on Enterococcus faecalis and to investigate the possible target genes of licochalcone A in E. faecalis. This study found that licochalcone A had antibacterial activities against E. faecalis, with the MIC50 and MIC90 were 25 µM. Licochalcone A (at 4 × MIC) indicated a rapid bactericidal effect on E. faecalis planktonic cells, and killed more E. faecalis planktonic cells (at least 3-log10 cfu/ml) than vancomycin, linezolid, or ampicillin at the 2, 4, and 6 h of the time-killing test. Licochalcone A (at 10 × MIC) significantly reduced the production of E. faecalis persister cells (at least 2-log10 cfu/ml) than vancomycin, linezolid, or ampicillin at the 24, 48, 72, and 96 h of the time-killing test. Licochalcone A (at 1/4 × MIC) significantly inhibited the biofilm formation of E. faecalis. The RNA levels of biofilm formation-related genes, agg, esp, and srtA, markedly decreased when the E. faecalis isolates were treated with licochalcone A at 1/4 × MIC for 6 h. To explore the possible target genes of licochalcone A in E. faecalis, the licochalcone A non-sensitive E. faecalis clones were selected in vitro by induction of wildtype strains for about 140 days under the pressure of licochalcone A, and mutations in the possible target genes were detected by whole-genome sequencing. This study found that there were 11 nucleotide mutations leading to nonsynonymous mutations of 8 amino acids, and among these amino acid mutations, there were 3 mutations located in transcriptional regulator genes (MarR family transcriptional regulator, TetR family transcriptional regulator, and MerR family transcriptional regulator). In conclusion, this study found that licochalcone A had an antibacterial effect on E. faecalis, and significantly inhibited the biofilm formation of E. faecalis at subinhibitory concentrations.

In vitro activity and adaptation strategies of eravacycline in clinical Enterococcus faecium isolates from China.

Eravacycline (Erava) is a synthetic fluorocycline with potent antimicrobial activity against a wide range of Gram-positive bacteria. This study aimed to investigate the in vitro antimicrobial activity and resistance mechanism of Erava in clinical E. faecium isolates from China. Erava minimum inhibitory concentrations (MICs) against clinical E. faecium isolates-including those resistant to linezolid (LZD) or harboring the tetracycline (Tet) resistance genes was ≤0.25 mg l-1. Moreover, our data indicated that clinical isolates of E. faecium with Erava MIC 0.25 mg l-1 were predominantly shown to belong to Sequence-type 78 (ST78) and ST80. The prevalence of Erava heteroresistance in clinical E. faecium strain was 2.46% (3/122). The increased Erava MIC values of heteroresistance-derived E. faecium clones could be significantly reduced by efflux pump inhibitors (EPIs). Furthermore, comparative proteomics results showed that efflux pumps lmrA, mdlA, and mdlB contributed significantly to the acquisition of Erava resistance in E. faecium. In addition, a genetic mutation in 16 S rRNA (G190A) were detected in resistant E. faecium isolates induced by Erava. In summary, Erava exhibits potent in vitro antimicrobial activity against E. faecium, but mutation of Tet target sites and elevated expression of efflux pumps under Erava selection results in Erava resistance.

Comparison of antibacterial activities and resistance mechanisms of omadacycline and tigecycline against Enterococcus faecium.

This study aims to compare the antimicrobial activity of omadacycline with tigecycline against clinical isolates of Enterococcus faecium and investigate their resistance mechanisms. Non-duplicate clinical E. faecium isolates (n = 224) were collected and the minimal inhibitory concentrations (MICs) of omadacycline and tigecycline were determined by broth microdilution method. The tet genes and the genetic mutations in 16 S rRNA genes and 30 S ribosomal protein S10 were determined by PCR and sequence alignment. The global protein abundances of the omadacycline-induced and parent isolates were determined by a Q Exactive plus mass spectrometer. The MIC50/MIC90 of omadacycline and tigecycline against the 224 E. faecium isolates were 0.25/0.5 mg l-1 and 0.125/0.25 mg l-1, respectively. Among these E. faecium isolates, the frequency of the isolates with omadacycline MICs ≥ 0.25 mg l-1 were significantly higher than that with tigecycline MICs ≥ 0.25 mg l-1. Moreover, the T1473C and/or G1468A mutations in the 16 S rRNA and Lys98Glu mutation in the 30 S ribosomal protein S10 were identified in the 3 series of tigecycline or omadacycline- nonsusceptible isolates selected in vitro. The abundances of 32 proteins changed in the omadacycline-induced isolate, of which 10 increased and 22 decreased. The abundance of tet(M) increased significantly in the omadacycline-induced isolate, and the abundance of proteins included in cellular process and metabolic process decreased. In conclusion, Omadacycline and tigecycline exhibits excellent activities against clinical isolates of E. faecium and exposure to omadacycline and tigecycline can result in significant cross-resistance to both antibiotics. The high-level expression of tet(M) in E. faecium may confer resistance to omadacycline.

High speed time-of-flight displacement measurement based on dual-comb electronically controlled optical sampling.

We demonstrate a direct time-of-flight approach that utilizes dual-comb electronically controlled optical sampling (ECOPS) to measure small displacements. ECOPS is enabled by electrically controlling the repetition rate of one laser via an intracavity electric-optical modulator (EOM). The acquisition rate is set by the EOM modulation frequency, which is much higher than commonly used asynchronous optical sampling (ASOPS). In a proof-of-principle experiment, an 80-kHz acquisition rate is obtained with a pair of ∼105 MHz repetition rate Er-fiber lasers. At an average time of 30 ms, a measurement precision evaluated with Allan deviation reaches 26.1 nm for a 40-µm static displacement. In a dynamic measurement, a 500-Hz sinusoidal vibration with 15 µm amplitude has also been identified. The high-precision and high-speed displacement measurement technique can be potentially used in 3D surface profilometry of microelectronic step-structures and real-time monitoring of high frequency mechanical vibrations, etc.

Lapatinib Acts against Biofilm Formation and the Hemolytic Activity of Staphylococcus aureus.

Biofilm formation and hemolytic activity are closely related to the pathogenesis of Staphylococcus aureus infections. Herein, we show that lapatinib (12.5 µM) significantly inhibits biofilm formation and hemolytic activity of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates. Using quantitative reverse transcription PCR, we found that the RNA levels of transcriptional regulatory genes (RNAIII, agrA, agrC, saeR, and saeS), biofilm-formation-related genes (atl, cidA, clfA, clfB, and icaA), and virulence-related genes (cap5A, hla, hld, hlg, lukDE, lukpvl-S, staphopain B, alpha-3 PSM, beta PSM, and delta PSM) of S. aureus decreased after 6 h treatment with lapatinib. Wild-type S. aureus isolates were continuously cultured in vitro in the presence of increasing concentrations of lapatinib for about 140 days. Subsequently, S. aureus isolates with reduced susceptibility to lapatinib (the inhibitory effect of lapatinib on the biofilm formation of these S. aureus isolates was significantly weakened) were selected. Mutations in the genomes of S. aureus isolates with reduced susceptibility to lapatinib were detected by whole-genome sequencing. We identified four genes with mutations: three genes with known functions (membrane protein, pyrrolidone-carboxylate peptidase, and sensor histidine kinase LytS, respectively) and one gene with unknown function (hypothetical protein). In conclusion, this study indicates that lapatinib significantly inhibits biofilm formation and the hemolytic activity of S. aureus.

Association of FIB-4 index and clinical outcomes in critically ill patients with acute kidney injury: a cohort study.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and clinical outcomes in patients with acute kidney injury (AKI) is unclear. We aimed to investigate the association between FIB-4 index and all-cause mortality in critically ill patients with AKI. METHODS: We used data from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4). The FIB-4 score was calculated using the existing formulas. logistic regression model, and Cox proportional hazards model were used to assessed the relationship between the FIB-4 index and in-hospital,28-day and 90-day mortality, respectively. RESULTS: A total of 3592 patients with AKI included in the data analysis. 395 (10.99%) patients died during hospitalization and 458 (12.74%) patients died in 28-day. During the 90-day follow-up, 893 (22.54%) patients were dead. An elevated FIB-4 value was significantly associated with increased in-hospital mortality when used as a continuous variable (odds ratio [OR] 1.183, 95% confidence interval [CI] 1.072-1.305, P = 0.002) and as a quartile variable (OR of Q2 to Q4 1.216-1.744, with Q1 as reference). FIB-4 was positively associated with 28-day mortality of AKI patients with hazard ratio (HR) of 1.097 (95% CI 1.008, 1.194) and 1.098 (95% 1.032, 1.167) for 90-day mortality, respectively. CONCLUSION: This study demonstrated the FIB-4 index is associated with clinical outcomes in critically ill patients with acute kidney injury.

ImageTBAD: A 3D Computed Tomography Angiography Image Dataset for Automatic Segmentation of Type-B Aortic Dissection.

Type-B Aortic Dissection (TBAD) is one of the most serious cardiovascular events characterized by a growing yearly incidence, and the severity of disease prognosis. Currently, computed tomography angiography (CTA) has been widely adopted for the diagnosis and prognosis of TBAD. Accurate segmentation of true lumen (TL), false lumen (FL), and false lumen thrombus (FLT) in CTA are crucial for the precise quantification of anatomical features. However, existing works only focus on only TL and FL without considering FLT. In this paper, we propose ImageTBAD, the first 3D computed tomography angiography (CTA) image dataset of TBAD with annotation of TL, FL, and FLT. The proposed dataset contains 100 TBAD CTA images, which is of decent size compared with existing medical imaging datasets. As FLT can appear almost anywhere along the aorta with irregular shapes, segmentation of FLT presents a wide class of segmentation problems where targets exist in a variety of positions with irregular shapes. We further propose a baseline method for automatic segmentation of TBAD. Results show that the baseline method can achieve comparable results with existing works on aorta and TL segmentation. However, the segmentation accuracy of FLT is only 52%, which leaves large room for improvement and also shows the challenge of our dataset. To facilitate further research on this challenging problem, our dataset and codes are released to the public (Dataset, 2020).

The antiviral drug efavirenz reduces biofilm formation and hemolysis by Staphylococcus aureus.

Introduction. Biofilm formation and hemolysis are closely related to the pathogenicity of Staphylococcus aureus.Hypothesis/Gap Statement. Strategies that reduce the mortality of S. aureus infections may involve novel antimicrobials and/or drugs that decrease S. aureus virulence, such as biofilm formation. The antiviral drug efavirenz is a non-nucleoside reverse transcriptase inhibitor, which also has shown antibacterial effect on Bacillus subtilis and Escherichia coli. Its effect on pathogen virulence has not yet been explored.Aim. This study investigates the antimicrobial and anti-virulence effect of efavirenz on S. aureus.Methodology. Biofilm biomasses were detected by crystal violet staining. Hemolysis activities of S. aureus were determined by rabbit erythrocytes lysis assay. RNA levels of transcriptional regulatory genes, biofilm-related genes, and virulence-related genes of S. aureus were determined by RT-qPCR.Results. Efavirenz showed an inhibitory effect on the growth of S. aureus, Enterococcus faecalis and Streptococcus agalactiae at 50 µM. Efavirenz significantly inhibited biofilm formation of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) at 25 µM, but did not affect the growth of planktonic S. aureus cells. Moreover, hemolysis by S. aureus was inhibited by efavirenz at 25 µM. The expression levels of RNA transcriptional regulatory genes (agrA, agrC, sigB, saeR and saeS), biofilm-related genes (cidA, clfA, clfB, fnbA, fnbB), and virulence-related genes (hla, hld, staphopain B, alpha-3 PSM, beta PSM, delta PSM) of S. aureus decreased significantly at 25 µM efavirenz.Conclusion. Efavirenz inhibits S. aureus biofilm formation and virulence in vitro.

The anterior cingulate cortex projection to the dorsomedial striatum modulates hyperalgesia in a chronic constriction injury mouse model.

INTRODUCTION: The aim of the study was to study the role of the anterior cingulate cortex (ACC)-dorsal midbrain striatum (DMS) in neuropathic pain in mice. MATERIAL AND METHODS: Optogenetics has been increasingly used in neuroscience research to selectively and precisely control the activity of a defined group of central neurons to determine their roles in behavioral functions in animals. The most important opsins are blue-sensitive ChR2 and yellow-sensitive NpHR. Calcium-calmodulin dependent protein kinase Iiα (CaMKIIα) is mostly expressed in the pyramidal excitatory neurons. Mice were injected with AAV2/9-CamKII-ChR2-mCherry, AAV2/9-CamKII-eNpHR3.0-GFP or AAV2/9-CamKII-mCherry virus in the ACC region, and the optical fiber implantation was performed in the ACC or DMS region. Mice were then followed up for 2 to 8 weeks and behavioral tests were carried out in the presence or absence of the blue/yellow light (473 nm/589 nm). Pain behavioral tests with or without the blue/yellow light at the same time were performed on the third and the seventh day after the chronic constriction injury of sciatic nerve model (CCI) was established. The pain thresholds of left and right hind limbs of mice in all groups were measured. RESULTS: No matter whether activating the neurons in ACC or DMS, compared with normal mice in the ChR2-off-right group, and the mCherry-on-right group, the thermal pain threshold and mechanical pain threshold of the normal mice in the ChR2-on-right group were significantly lower. When inhibiting the neurons in the ACC or DMS, on day 3 and day 7 after CCI operation, the thermal pain threshold and mechanical pain threshold of the CCI mice of the NpHR-on-right group were significantly higher compared with the NpHR-off-right and mCherry-on-right groups. CONCLUSIONS: The anterior cingulate cortex-dorsal midbrain striatum may be involved in the regulation of neuropathic pain in mice.

Antibacterial and anti-biofilm activities of histidine kinase YycG inhibitors against Streptococcus agalactiae.

This study aims to investigate the antibacterial and anti-biofilm activities of YycG inhibitors H2-60 and H2-81 against Streptococcus agalactiae. A total of 118 nonduplicate S. agalactiae clinical isolates were collected, and the minimal inhibitory concentrations (MICs) of H2-60 and H2-81 were determined. H2-60 and H2-81 inhibit biofilm formation of S. agalactiae were detected by crystal violet staining, and against established biofilms of S. agalactiae were observed by confocal laser scanning microscope. Inhibitory effect of H2-60 and H2-81 on the phosphorylation activity of the HisKA domain of YycG' protein was measured. The MIC50/MIC90 was 3.13/6.25 µM for H2-60 and 6.25/12.5 µM for H2-81 against S. agalactiae, respectively. S. agalactiae planktonic cells can be decreased by H2-60 or H2-81 for more than 3 × log10 CFU ml-1 after 24 h treatment. Biofilm formation of 8 S. agalactiae strains (strong biofilm producers) was significantly reduced after treated with 1/4 × MIC of H2-60 or H2-81 for 24 h. H2-60 and H2-81 could reduce 45.79% and 29.56% of the adherent cells in the established biofilm of S. agalactiae after 72 h treatment, respectively. H2-60 combined with daptomycin reduced 83.63% of the adherent cells in the established biofilm of S. agalactiae, which was significantly better than that of H2-60 (45.79%) or daptomycin (55.07%) alone. The half maximal inhibitory concentrations (IC50) were 35.6 µM for H2-60 and 46.3 µM for H2-81 against the HisKA domain of YycG' protein. In conclusion, YycG inhibitors H2-60 and H2-81 exhibit excellent antibacterial and anti-biofilm activities against S. agalactiae.

Electroacupuncture Pretreatment Prevents Cognitive Impairment Induced by Cerebral Ischemia-Reperfusion via Adenosine A1 Receptors in Rats.

A previous study has demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. In the present study, we investigated whether adenosine receptor 1 (A1 R) is involved in EA pretreatment-induced cognitive impairment after focal cerebral ischemia in rats. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min in male Sprague-Dawley rats. The neurobehavioral score, cognitive function [as determined by the Morris water maze (MWM) test], neuronal number, and the Bax/Bcl-2 ratio was evaluated at 24 h after reperfusion in the presence or absence of CCPA (a selective A1 receptor agonist), DPCPX (a selective A1 receptor antagonist) into left lateral ventricle, or A1 short interfering RNA into the hippocampus area. The expression of the A1 receptor in the hippocampus was also investigated. The result showed that EA pretreatment upregulated the neuronal expression of the A1 receptor in the rat hippocampus at 90 min. And EA pretreatment reversed cognitive impairment, improved neurological outcome, and inhibited apoptosis at 24 h after reperfusion. Pretreatment with CCPA could imitate the beneficial effects of EA pretreatment. But the EA pretreatment effects were abolished by DPCPX. Furthermore, A1 receptor protein was reduced by A1 short interfering RNA which attenuated EA pretreatment-induced cognitive impairment.

Preoperative Fibrosis-4 (FIB-4) Evaluation May Be Helpful to Evaluate Prognosis of Gastric Cancer Patients Undergoing Operation: A Retrospective Study.

BACKGROUND: Liver dysfunction and chronic inflammation influence the prognosis of many tumors and surgical outcomes. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, originally defined as a noninvasive fibrosis marker, can predict the prognosis of patients with gastric cancer undergoing radical gastric cancer surgery. METHODS: We have retrospectively analyzed 594 consecutive patients with gastric cancer who underwent gastrectomy in our database. The FIB-4 index was calculated using laboratory data and age before gastrectomy. The clinical utility of FIB-4 was evaluated by X-tile. Patients were divided into two groups (high and low FIB-4 index groups), and their overall survival (OS) was investigated. Cox regression analysis was used to identify the independent parameters associated with prognosis. Finally, we developed a prognostic prediction model by using R statistical software. RESULTS: A total of 556 patients, including 422 men and 134 women, were enrolled. Of these, 61 (11.0%) and 495 (89.0%) patients had low and FIB-4 indexes, respectively. In addition to the indicators of FIB-4, preoperative age, tumor site, surgical procedure, TNM stage, and postoperative complications were found to be independent predictors of prognosis (P < 0.05). Among patients, the FIB-4 index group had significantly shorter OS (log-rank P = 0.01) than the low FIB-4 index group. This association was also confirmed in the multivariate analysis (hazard ratio, 4.65; 95% confidence interval, 1.07-4.29; P = 0.031). CONCLUSIONS: Preoperative FIB-4 index can predict long-term outcomes of gastric cancer patients who had undergone gastrectomy.

The association between triglyceride glucose index and depression: data from NHANES 2005-2018.

BACKGROUND: The association between triglyceride glucose (TyG) index and depression is unclear. We conducted this analysis to explore whether higher TyG index is associated with a higher odd of depression. METHODS: This was an observational study using data from the National Health and Nutrition Examination Survey (2005-2018), a cross-sectional and nationally representative database. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). TyG index was calculated based on the equation as follows: ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2], and participants were divided into quartiles based on TyG index. Weighted multivariable logistic regression models were used to explore the relationship between the TyG index and depression. RESULTS: A total of 13,350 patients were included, involving 1001 (7.50%) individuals with depression. Higher TyG index is significantly associated with elevated depressive symptoms in U.S. adults. Multivariate-adjusted HRs for patients in the TyG index 4th quartile were higher for depression (OR = 1.46; 95% confidence interval (CI) 1.30, 1.64) compared with the 1st quartile of TyG index. Similar results were seen in men and women, across age groups, and baseline comorbidities. CONCLUSION: In this large cross-sectional study, our result suggests that population with higher TyG index are significantly more likely to have depressive symptoms in U.S. adults.

Comparison of antimicrobial efficacy of eravacycline and tigecycline against clinical isolates of Streptococcus agalactiae in China: In vitro activity, heteroresistance, and cross-resistance.

AIMS: The aims of this study were to compare the antimicrobial efficacy of Eravacycline (Erava) versus tigecycline (Tig) in vitro against clinical isolates of S. agalactiae from China and further to evaluate the heteroresistance risk and resistance mechanisms of Erava. METHODS: 162 clinical isolates of S. agalactiae were collected retrospectively and the minimal inhibitory concentrations (MICs) of Erava and Tig were determined by agar dilution. Moreover, Tetracycline (Tet) specific resistance genes, genetic mutations in Tet target sites, and sequence types (ST) profiles of clinical isolates of S. agalactiae were investigated with polymerase chain reaction (PCR) experiments. The heteroresistance frequency of Erava and Tig in S. agalactiae was analyzed by population analysis profiling. Furthermore, the resistance mechanisms of both Erava and Tig were investigated in antibiotic-induced resistant S. agalactiae isolates in vitro. RESULTS: The MIC values of Erava and Tig were shown with ≤0.25 mg/L and ≤0.5 mg/L, respectively, against clinical S. agalactiae isolates, including that harboring the Tet-specific resistance genes tet(K), tet(M), or tet(O). The heteroresistance frequency of Tig among the clinical isolates of S. agalactiae was 1.84% (3/162), whereas no positive Erava heteroresistance was found. The enhanced MIC values of both Erava and Tig in the heteroresistance-derivative S. agalactiae clones could be reversed by the efflux pump inhibition experiments. Genetic mutations affecting 30S ribosome units (16SrRNA copies or 30S ribosome protein S10) could result in the cross resistance toward Erava and Tig in the antibiotic-induced resistant S. agalactiae isolates in vitro. CONCLUSIONS: Erava MIC values were nearly half of that of Tig against the clinical isolates of S. agalactiae from China and genetic mutations in the 30S ribosome units of Tet target sites (16SrRNA copies or 30S ribosome protein S10) participated in the resistance evolution of both Erava and Tig under the antibiotic pressure.

Correlation between procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 and breast cancer.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), which affects collagen synthesis, is associated with breast cancer. The purpose of the study is to detect the expression of PLOD2 in breast cancer and to evaluate the correlation between PLOD2 and clinicopathologic characteristics and prognosis of patients with breast cancer. 50 paired samples including breast cancer tissues and adjacent non-tumor tissues were formalin-fixed and evaluated by immunohistochemistry. The results revealed that PLOD2 expression in breast cancer tissues was much higher than that in tissues adjacent to breast cancer. High expression of PLOD2 was positively associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.001). However, high expression of PLOD2 was negatively related to Ki-67 (P < 0.001) while positively related to progesterone receptor (PR) (P = 0.001). PLOD2 expression was positively related to the metastasis of breast cancer. Therefore, high expression of PLOD2 was identified as a poor prognostic biomarker for patients with breast cancer. These results suggest a novel molecular mechanism in breast cancer tumorigenesis, thus providing a potential therapeutic target of breast cancer.

An experimental rabbit model of symptomatic cerebral vasospasm with in vivo neuroimaging assessment and ex vivo histological validation.

Cerebral vasospasm (CVS) is a severe complication that occurs following aneurysmal subarachnoid hemorrhage (SAH). Magnetic resonance angiography (MRA) has been used to evaluate brain injury following SAH in humans. The present study was designed to assess a rabbit model of symptomatic CVS (SCVS) and the utility of MRA in evaluating SCVS in rabbits. Japanese white rabbits (n=24) were randomly divided into 2 equal groups: A sham group and a SAH group. Neurological scores were evaluated for 7 days following SAH. Basilar artery (BA) diameters were measured using MRA preoperatively and 7 days postoperatively. Rabbits were sacrificed 7 days following SAH and the BA diameter of each rabbit was determined using histological evaluation. Compared with the Sham group, neurological function was significantly reduced in the SAH group at all time points (P<0.05). Furthermore, the BA diameter was significantly smaller in the SAH group on day 7 compared with the baseline measurement (P<0.05). No significant difference was observed between histological and MRA findings in either group at day 7. Histological changes in the hippocampus consistent with ischemia were observed in the SAH group. Hippocampal ischemia was also identified in the SAH group via MRA and there was no difference in detection rates following the use of MRA and histochemistry. MRA appears to be an effective method for assessing vasospasms of the BA and ischemic changes to the hippocampus in a rabbit model of SCVS. Furthermore, the animal model used in the present study may be beneficial for the future study of SCVS.