The improvement of modified Si-Miao granule on hepatic insulin resistance and glycogen synthesis in type 2 diabetes mellitus involves the inhibition of TNF-α/JNK1/IRS-2 pathway: network pharmacology, molecular docking, and experimental validation.

BACKGROUND: Modified Si-Miao granule (mSMG), a traditional Chinese medicine, is beneficial for T2DM and insulin resistance (IR), but the underlying mechanism remains unknown. METHODS: Using network pharmacology, we screened the compounds of mSMG and identified its targets and pathway on hepatic IR in T2DM. Using molecular docking, we identified the affinity between the compounds and hub target TNF-α. Then these were verified in KK-Ay mice and HepG2 cells. RESULTS: 50 compounds and 170 targets of mSMG against IR in T2DM were screened, and 9 hub targets such as TNF and MAPK8 were identified. 170 targets were mainly enriched in insulin resistance and TNF pathway, so we speculated that mSMG might act on TNF-α, JNK1 and then regulate insulin signaling to mitigate IR. Experimental validation proved that mSMG ameliorated hyperglycemia, IR, and TNF-α, enhanced glucose consumption and glycogen synthesis, relieved the phosphorylation of JNK1 and IRS-2 (Ser388), and elevated the phosphorylation of Akt (Ser473) and GSK-3ß (Ser9) and GLUT2 expression in KK-Ay mice. Molecular docking further showed berberine from mSMG had excellent binding capacity with TNF-α. Then, in vitro validation experiments, we found that 20% mSMG-MS or 50 µM berberine had little effect in IR-HepG2 cell viability, but significantly increased glucose consumption and glycogen synthesis and regulated TNF-α/JNK1/IRS-2 pathway. CONCLUSION: Network pharmacology and molecular docking help us predict potential mechanism of mSMG and further guide experimental validation. mSMG and its representative compound berberine improve hepatic IR and glycogen synthesis, and its mechanism may be related to the inhibition of TNF-α/JNK1/IRS-2 pathway.

Temperature switchable linkers suitable for triggered drug release in cancer thermo-chemotherapy.

In drug delivery systems, a stimuli-responsive linker that attaches a targeting carrier and a cytotoxic payload can be dissociated to release the payload on the target over the action of a stimuli, thereby it would harden the selectivity, specificity and potency of the cytotoxic agent against targeted tissues whilst sparing the drug-induced toxicity on normal cells. Oligonucleotide duplexes can unwind and be separated into single-stranded random coils under a defined temperature, and this property makes the oligonucleotide an appealing thermo-responsive linker. In this work, we studied the melting temperatures of different DNA linkers with various lengths and mismatches inserted in the double helix with either different numbers or positions. We further chose the DNA linkers that can unwind at the hyperthermia temperature and used them in the construction of four different drug delivery systems both in vitro and in vivo. Results showed that the chosen DNA linkers in all of the constructed delivery systems can successfully unwind and release cargos or drugs after application of heat compared to control groups. This research demonstrated the potential applications of DNA duplexes as temperature-sensitive linkers of drug delivery systems for cancer therapy.

Identify BCAT1 plays an oncogenic role and promotes EMT in KIRC via single cell RNA-seq and experiment.

Background: Kidney renal clear cell carcinoma (KIRC) is a major subtype of renal cell carcinoma with poor prognosis due to its invasive and metastatic nature. Despite advances in understanding the molecular underpinnings of various cancers, the role of branched-chain amino acid transferase 1 (BCAT1) in KIRC remains underexplored. This study aims to fill this gap by investigating the oncogenic role of BCAT1 in KIRC using single-cell RNA-seq data and experimental validation. Methods: Single-cell transcriptomic data GSE159115 was utilized to investigate potential biomarkers in KIRC. After screening, we used BCAT1 as a target gene and investigated its function and mechanism in KIRC through databases such as TCGA-GTEx, using genome enrichment analysis (GSEA), genome variation analysis (GSVA), gene ontology (GO) and Kyoto Encyclopedia of the Genome (KEGG). BCAT1 expression was detected in clinical tissue samples using Western Blotting (WB) and immunohistochemical (IHC) staining techniques. We established cell lines stably overexpressing and knocking down BCAT1 and performed WB, qRT-PCR, cell scratch assay and transwell assay. Results: BCAT1 was highly expressed in KIRC and was associated with disease prognosis and TME. Patients with mutations in the BCAT1 gene had shorter overall survival (OS) and disease-free survival (DFS). patients with high BCAT1 expression had shorter OS, progression-free interval (PFI), and disease-specific survival (DSS). GSEA showed that BCAT1 was significantly enriched in epithelial mesenchymal transition (EMT). Bioinformatics analysis and WB and IHC staining showed that BCAT1 expression was higher in KIRC than in paracancerous tissues. In vitro experiments confirmed that BCAT1 in KIRC cells may promote EMT affecting its invasion, migration. We constructed a protein interaction network (PPI) to hypothesize proteins that may interact with BCAT1. Single-sample gene set enrichment analysis (ssGSEA) revealed the immune infiltration environment of BCAT1. Furthermore, hypomethylation of the BCAT1 promoter region in KIRC may contribute to disease progression by promoting BCAT1 expression. Conclusion: BCAT1 promotes KIRC invasion and metastasis through EMT and has prognostic predictive value and potential as a biomarker. It may become a novel biomarker.

Novel Sustained Release Azithromycin Resinate Fabricated by One-Pot Ion-exchange Performed in Hydro-alcoholic Solution.

Drug-resin complexes usually form in the aqueous phase. For poorly water-soluble drugs, low drug loading limits the use of resin in drug formulation. In this study, we used a new method to prepare azithromycin resinates, improving the drug loading rate, shortening the preparation time and simplifying the process. We used hydro-alcoholic solution as the drug loading solvent and the ion exchange resin as the carrier, and this method enabled the resin to adsorb both the retardant and the drug. The sustained release effect of retardant Eudragit RL, RS100 was analyzed. Drug loading efficiency, release profiles, morphology, physicochemical characterization and pharmacokinetic study were assessed. Preparation of drug resinate by batch method resulted in 14% higher drug loading of azithromycin and 3.5 h shorter loading time as compared to pure water for hydroalcoholic solution as drug loading solvent. Raman mappings demonstrated that the retardant with higher molecular weight was more likely to adsorb to the outer layer of the resin compared to the drug. The in vitro release and in vivo pharmacokinetic study of azithromycin resinates showed a sustained release profile with few gastrointestinal adverse effects. Therefore, the addition of ethanol not only improved the efficiency of drug loading but also showed sustained-release effect with one-pot preparation of azithromycin resinates.

Pseudomonas aeruginosa Mediates Host Necroptosis through Rhl-Pqs Quorum Sensing Interaction.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that can cause serious infections in immunocompromised patients. Quorum sensing (QS), a communication system evolved by P. aeruginosa to survey its density, is well acknowledged to be involved in various activities during bacterial infection. Recent studies have revealed the link between P. aeruginosa QS and host innate immune response. Previous evidence suggests that programmed cell death exists in response to P. aeruginosa infection. However, it remains unclear whether QS plays a role in the host programmed cell death process during the infection. In this study, we found that the deficiency of one of QS subsystems, rhl, markedly increased mouse bone marrow macrophage cell death induced by P. aeruginosa, which was accompanied by elevated phosphorylation of RIPK3 and MLKL. This highly increased necroptosis activation was caused by the upregulation of another QS subsystem, pqs, because the deletion of pqs in rhl-deficient P. aeruginosa abolished macrophage necroptosis in vitro and in vivo. In sum, our data highlight the cross-talk between P. aeruginosa QS and host necroptosis, which is executed through the rhl-pqs axis.

High fluoride aggravates cadmium-mediated nephrotoxicity of renal tubular epithelial cells through ROS-PINK1/Parkin pathway.

Fluoride (F) and cadmium (Cd) as well known environmental pollutants can cause nephrotoxicity to damage human health, while the joint toxicity of F and Cd to the renal tubular epithelial cells remains still elusive. The interactive influence between F and Cd in oxidative stress, apoptosis, and mitochondrial autophagy of renal tubular epithelial cells was explored. Cells were submitted to varying concentrations with of NaF (1, 5, 10, and 15 µg/mL) combined with CdCl2·2.5H2O (1 µg/mL) for 12 h. Following this, the combined cytotoxicity was assessed. Our results show that different doses of F had varying effects on Cd-mediated nephrotoxicity, with a synergistic effect observed in the high F (15 µg/mL) co-treated with Cd. In response to the Cd induction, the high F treatment resulted in the formation of multiple autophagosomes and notably increased the levels of LDH, ROS, and MMP. It also elevated the MDA contents while decreasing the activities of SOD, GSH-Px, and CAT. Additionally, it yielded a higher Bax/Bcl-2 ratio, which further promotes the apoptotic process. The treatment also disturbed energy metabolism, resulting in a reduction of both ATP and ADP. Furthermore, autophagy-related genes and proteins, including PINK1, Parkin, LC3A, LC3B, and SQSTM1, were significantly improved. In brief, high F of 15 µg/mL aggravated Cd-mediated nephrotoxicity of renal tubular epithelial cells via the ROS-PINK1/Parkin pathway.

Polysaccharide NAP-3 Synergistically Enhances the Efficiency of Metformin in Type 2 Diabetes via Bile Acid/GLP-1 Axis through Gut Microbiota Remodeling.

The polysaccharides of edible mushrooms are excellent phytochemicals for adjuvant treatment of metabolic diseases, but the potential mechanisms of synergistic effects are unclear. In this work, we discovered that NAP-3 enhanced the efficiency of metformin in lipid and glucose metabolism in type 2 diabetic (T2D) mice in a gut microbiome-dependent way. NAP-3 remodeled the intestinal microbial, resulting in the decreased activity of bile salt hydrolases and upregulation of CYP27A1 and CYP7B1 functions in the alternative pathway of bile acid synthesis, which leads to accumulation of the conjugated bile acids in ileum, specifically TßMCA and TUDCA. The accumulated conjugated bile acids either blocked or stimulated the nuclear receptors Farnesoid-X-receptor and TGR5, inducing the release of GLP-1 and ultimately enhanced glucose metabolism in mice. Collectively, our research indicated that edible mushroom polysaccharide NAP-3 may serve as a promising adjunctive oral therapeutic agent for T2D.

Jointly Optimization of Delay and Energy Consumption for Multi-Device FDMA in WPT-MEC System.

With the rapid development of mobile edge computing (MEC) and wireless power transfer (WPT) technologies, the MEC-WPT system makes it possible to provide high-quality data processing services for end users. However, in a real-world WPT-MEC system, the channel gain decreases with the transmission distance, leading to "double near and far effect" in the joint transmission of wireless energy and data, which affects the quality of the data processing service for end users. Consequently, it is essential to design a reasonable system model to overcome the "double near and far effect" and make reasonable scheduling of multi-dimensional resources such as energy, communication and computing to guarantee high-quality data processing services. First, this paper designs a relay collaboration WPT-MEC resource scheduling model to improve wireless energy utilization efficiency. The optimization goal is to minimize the normalization of the total communication delay and total energy consumption while meeting multiple resource constraints. Second, this paper imports a BK-means algorithm to complete the end terminals cluster to guarantee effective energy reception and adapts the whale optimization algorithm with adaptive mechanism (AWOA) for mobile vehicle path-planning to reduce energy waste. Third, this paper proposes an immune differential enhanced deep deterministic policy gradient (IDDPG) algorithm to realize efficient resource scheduling of multiple resources and minimize the optimization goal. Finally, simulation experiments are carried out on different data, and the simulation results prove the validity of the designed scheduling model and proposed IDDPG.

Case Report: Ectopic pulmonary embolism as a complication of bronchial artery embolization.

Bronchial artery embolization (BAE) is currently the first-line treatment for massive hemoptysis. Previous studies have proven its safety and efficacy, with mild, transient, and reversible complications. This case described a patient with congenital multiple bronchopulmonary fistulas who underwent BAE due to massive hemoptysis. However, due to an overlooked and misdiagnosed atypical fistula, the patient experienced an ectopic pulmonary embolism and subsequently secondary pulmonary infarction. He eventually exhibited a full postoperative recovery following percutaneous catheter-directed embolectomy. This case revealed a type of occult fistula masked by multiple bronchial artery branches, which may be a potential risk factor for an ectopic pulmonary embolism during BAE. We propose that it is crucial to identify abnormal anastomosis, especially atypical fistula, and select appropriate embolization materials during BAE.

Aberrant glycosylation in schizophrenia: insights into pathophysiological mechanisms and therapeutic potentials.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ.

An Additional L451G452N453 in the RpoB Protein Suppressed the Synthetic Lethality in Escherichia coli at 37 Degrees Caused by Depletion of DnaK/J and Trigger Factor.

Escherichia coli depletion of chaperone trigger factor and DnaK/J were not viable at 37°C, but viable below 30°C. Among the engineered E. coli depleted of trigger factor and DnaK/J, one strain Z625, exhibited survival at 37°C, while another strain Z629 only survived below 30°C. Comparative analysis of fatty acid profiles of Z625 and Z629 revealed absence of numerous saturated fatty acids in Z625 as compared to the wild-type E. coli BW25113. In addition, increased unsaturated fatty acids were present in Z625, whereas the fatty acids profile of Z629 closely resembled that of BW25113. Whole genome sequencing revealed a 9-bp insertion in rpoB of Z625. Combined structural analysis of simulated RpoB protein bearing the amino acid sequence L451G452N453 insertion and susceptibility analysis to rifampicin suggested that the insertion did not disturb the individual RpoB structure as beta subunit of RNA polymerase. Comparative transcriptomic analysis of Z625 and Z629 suggested that this insertion impacted transcription of the overall RNA polymerase in Z625, leading to potential repression of some genes whose overexpression was toxic to E. coli. Additionally, Z625 exhibited distinctive metabolic adaptations, likely contributing to its survival at 37°C. In summary, our study elucidated one LGN insertion in rpoB that impacts transcriptional regulation in E. coli, thereby explaining the survival of E. coli depletion of trigger factor and DnaK/J at 37°C, and these founding suggested that some simple mutations in critical genes like rpoB might play an important role in driving adaptive evolution.

PELP1 is a novel therapeutic target in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States, with a median survival period of approximately 10 months. There is an urgent need for the development of effective targeted therapies for the treatment of HCC. Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) signaling is implicated in the progression of many cancers, although its specific contribution to the progression of HCC is not yet well understood. Analysis of TCGA HCC gene expression data sets and immunohistochemistry analysis of HCC tissue microarray revealed that HCC tumors had elevated expression of PELP1 compared to normal tissues, and high expression of PELP1 is associated with unfavorable survival outcomes. Suppression of PELP1 expression using shRNA significantly reduced the cell viability, clonogenicity, and invasion of HCC cells. Importantly, SMIP34, a first-in-class small molecule inhibitor targeting PELP1, effectively decreased the cell viability, clonogenic survival and invasiveness of HCC cells. Gene expression analysis using RNA-seq revealed that PELP1-knockdown (KD) cells exhibited a decrease in c-Myc, E2F, and other oncogenic pathways related to HCC. Mechanistic studies showed that SMIP34 treatment impaired the Rix complex, a critical component of ribosomal biogenesis, in HCC cells. Further, the knockdown or pharmacological inhibition of PELP1 significantly decelerated the HCC tumor growth in xenograft models. In summary, our study findings indicate that PELP1 could serve as a promising target for therapeutic intervention in HCC.

Rapid Antimicrobial Susceptibility Test of Helicobacter pylori to Metronidazole via Single-Cell Raman Spectrometry.

BACKGROUND: Metronidazole is a first-line antibiotic to treat Helicobacter pylori infections. However, the Clinical Laboratory Standards Institute guidelines recommend against using antimicrobial susceptibility test (AST) to test metronidazole resistance, due to the unreliable predictive power which can result in treatment failure. OBJECTIVES: The aim of this study was to establish an 8-h, metabolic-phenotype based AST for H. pylori metronidazole susceptibility using D2O-probed Raman microspectroscopy. METHODS: Minimal inhibitory concentration (MIC) measured by conventional AST (E-test) were compared with expedited MIC via metabolic activity (eMIC-MA) for 10 H. pylori isolates. Raman barcodes of cellular-response to stress (RBCS) incorporating protein and carbohydrate Raman bands, were utilized to identify a biomarker to distinguish metronidazole susceptibility. RESULTS: Specifically, eMIC-MA produces metronidazole susceptibility results showing 100% agreement with E-test, and determines the bactericidal dosage for both high- and low-level resistant H. pylori strains. In addition, RBCS not just reliably distinguish between metronidazole-susceptible and -resistant strains, but reveal their distinct mechanisms in bacterial responses to metronidazole. CONCLUSION: The speed, accuracy, low cost, and rich information content that reveals the mode-of-action of drugs suggest the method's value in guiding metronidazole prescriptions for H. pylori eradication and in rapid screening based on drug-resistance mechanism.

Construction and application of "organ-system-centered" undergraduate nursing professional training model.

OBJECTIVE: The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. METHODS: This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. RESULTS: A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. CONCLUSION: The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

GhJUB1_3-At positively regulate drought and salt stress tolerance under control of GhHB7, GhRAP2-3 and GhRAV1 in Cotton.

Climate change severely affects crop production. Cotton is one of the primary fiber crops in the world and its production is susceptible to various environmental stresses, especially drought and salinity. Development of stress tolerant genotypes is the only way to escape from these environmental constraints. We identified sixteen homologs of the Arabidopsis JUB1 gene in cotton. Expression of GhJUB1_3-At was significantly induced in the temporal expression analysis of GhJUB1 genes in the roots of drought tolerant (H177) and susceptible (S9612) cotton genotypes under drought. The silencing of the GhJUB1_3-At gene alone and together with its paralogue GhJUB1_3-Dt reduced the drought tolerance in cotton plants. The transgenic lines exhibited tolerance to the drought and salt stress as compared to the wildtype (WT). The chlorophyll and relative water contents of wildtype decreased under drought as compared to the transgenic lines. The transgenic lines showed decreased H2O2 and increased proline levels under drought and salt stress, as compared to the WT, indicating that the transgenic lines have drought and salt stress tolerance. The expression analysis of the transgenic lines and WT revealed that GAI was upregulated in the transgenic lines in normal conditions as compared to the WT. Under drought and salt treatment, RAB18 and RD29A were strongly upregulated in the transgenic lines as compared to the WT. Conclusively, GhJUB1_3-At is not an auto activator and it is regulated by the crosstalk of GhHB7, GhRAP2-3 and GhRAV1. GhRAV1, a negative regulator of abiotic stress tolerance and positive regulator of leaf senescence, suppresses the expression of GhJUB1_3-At under severe circumstances leading to plant death.

Metabolomics Dysfunction in Replicative Senescence of Periodontal Ligament Stem Cells Regulated by AMPK Signaling Pathway.

Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for stem cell-based regenerative medicine in dentistry, but they inevitably acquire a senescent phenotype after prolonged in vitro expansion. The key regulators of PDLSCs during replicative senescence are remain unclear. Here, we sought to elucidate the role of metabolomic changes in determining cellular senescence of PDLSCs. PDLSCs were cultured to passages 4, 10 and 20. The senescent phenotypes of PDLSCs were detected, and metabolomics analysis was performed. We found that PDLSCs manifested senescence phenotype during passaging. Metabolomics analysis showed that the metabolism of replicative senescence in PDLSCs varied significantly. The AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK, FOXO1 and FOXO3a decreased with senescence. We treated PDLSCs with an activator of the AMPK pathway (AICAR), and observed that the phosphorylated AMPK level at P20 PDLSCs was partially restored. These data delineate that the metabolic process of PDLSCs is active in the early stage of senescence, and attenuated in the later stages of senescence; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism.

Simultaneous Determination of Ripretinib and Its Desmethyl Metabolite in Human Plasma Using LC-MS/MS.

BACKGROUND: Ripretinib, a recently developed tyrosine kinase inhibitor with switch-control abilities, can inhibit both primary and secondary activation of KIT(KIT proto-oncogene receptor tyrosine kinase) and platelet-derived growth factor receptor alpha (PDGFRA) mutants, which contribute to gastrointestinal stromal tumor progression. METHODS: In this study, a high-performance liquid chromatography-tandem mass spectrometry method to measure the concentrations of ripretinib and its active desmethyl metabolite DP-5439 in human plasma was developed and validated. Plasma samples were extracted and recovered by precipitation with acetonitrile containing the internal standard and diluted with acetonitrile before analysis. Ripretinib and DP-5439 were separated using chromatography on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 50 mm, 1.8 µm) with gradient elution using 0.1% formic acid and 5 mM ammonium formate in water as mobile phase A and acetonitrile as mobile phase B. The mobile phase was set to a flow rate of 0.5 mL/min. RESULTS: The calibration curves were linear across the following concentration range: 7.5 to 3000 ng/mL for ripretinib and 10 to 4000 ng/mL for DP-5439. The intraday and interday precisions were approximately 15% for all analytes in the quality control samples. The relative matrix effects in extracted plasma samples (90.3%-108.8% at different levels) were considered acceptable. CONCLUSIONS: This method will be a useful tool in oncology to facilitate the further clinical development of ripretinib.

Development of a prognostic nomogram for patients underwent extracorporeal circulation auxiliary to open cardiac surgery on hospital mortality: a retrospective cohort study.

Background: Extracorporeal circulation auxiliary to open cardiac surgery (ECAOCS) is one of the most complex surgical procedures and carries a very high risk of death. We developed a nomogram from a retrospective study to predict the risk of death during patient hospitalization. Methods: All clinical data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. We extracted clinical variables for the first 24 hours after admission to the intensive care unit (ICU) in a total of 880 patients who underwent ECAOCS. All patients were randomly divided into training and validation cohort in a ratio of 7:3. All variables included in the study were subjected to univariate logistic regression analysis. In order to prevent overfitting and to address the problem of severe covariance, all factors with P<0.05 in the univariate logistic regression analysis were analyzed using the least absolute shrinkage and selection operator (LASSO) regression. A multivariate logistic regression model was developed based on the factors output from the LASSO regression and a nomogram was plotted. The receiver operating characteristic (ROC) curve was constructed and the area under the curve (AUC) was calculated in training and validation cohort. Finally, the evaluation of the model was performed by calibration curves and Hosmer-Lemeshow goodness-of-fit test (HL test) and decision curve analysis (DCA) was performed. Results: Indicators included in the nomogram were anion gap (AG), central venous pressure (CVP), glucose, creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), bicarbonate ion (HCO3 -), cerebrovascular disease (CVD), peripheral vascular disease (PVD), and acute myocardial infarction (AMI). Conclusions: Our study developed a model for predicting postoperative hospital mortality in patients underwent ECAOCS by incorporating AG, CVP, glucose, Cr, APTT, HCO3 -, CVD, AMI, and PVD from the first 24 hours after admission to the ICU. Keywords: Extracorporeal circulation; cardiac surgery; intensive care; nomogram; prediction model.

A case report of empyema caused by Enterococcus gallinarum.

BACKGROUND: Enterococcus gallinarum is an infrequently intestinal symbiotic pathogen associated with nosocomial infection in immunocompromised individuals. To date, rare cases of pulmonary infection attributable to Enterococcus gallinarum were reported. Herein, we presented the first case of empyema resulting from Enterococcus gallinarum infection. CASE PRESENTATION: An 81-year-old male presented with fever and dyspnea upon admission. Chest CT scan and thoracic ultrasonography confirmed the presence of right pleural effusion. Thoracoscopy revealed extensive adhesion, purulent fluid, and necrotic materials within the thoracic cavity. Enterococcus gallinarum was identified through pleural effusion culture. The patient underwent an intrathoracic injection of urokinase along with thoracic drainage. Following surgery, He took oral linezolid for over one month. Undergoing comprehensive treatment, the patient exhibited favorable recovery. CONCLUSIONS: We reported the first case of empyema due to Enterococcus gallinarum infection. It should be suspected in patients with impaired immune function and invasive therapies, without responding to conventional anti-infectious treatment.

Anti-Neuroinflammatory Effects of Ginkgo biloba Extract EGb 761 in LPS-Activated BV2 Microglial Cells.

Inflammatory processes in the brain can exert important neuroprotective functions. However, in neurological and psychiatric disorders, it is often detrimental due to chronic microglial over-activation and the dysregulation of cytokines and chemokines. Growing evidence indicates the emerging yet prominent pathophysiological role of neuroinflammation in the development and progression of these disorders. Despite recent advances, there is still a pressing need for effective therapies, and targeting neuroinflammation is a promising approach. Therefore, in this study, we investigated the anti-neuroinflammatory potential of a marketed and quantified proprietary herbal extract of Ginkgo biloba leaves called EGb 761 (10-500 µg/mL) in BV2 microglial cells stimulated by LPS (10 ng/mL). Our results demonstrate significant inhibition of LPS-induced expression and release of cytokines tumor necrosis factor-α (TNF-α) and Interleukin 6 (IL-6) and chemokines C-X-C motif chemokine ligand 2 (CXCL2), CXCL10, c-c motif chemokine ligand 2 (CCL2) and CCL3 in BV2 microglial cells. The observed effects are possibly mediated by the mitogen-activated protein kinases (MAPK), p38 MAPK and ERK1/2, as well as the protein kinase C (PKC) and the nuclear factor (NF)-κB signaling cascades. The findings of this in vitro study highlight the anti-inflammatory properties of EGb 761 and its therapeutic potential, making it an emerging candidate for the treatment of neuroinflammatory diseases and warranting further research in pre-clinical and clinical settings.