Objective:To investigate the impact and clinical value of preoperative intra-aortic balloon pump(IABP)placement on the occurrence of postoperative atrial fibrillation(POAF)in elderly high-risk patients with coronary artery disease undergoing off-pump coronary artery bypass grafting(CABG).Methods:A retrospective cohort study was conducted, selecting 128 elderly(age≥60 years)patients with coronary artery disease who underwent isolated off-pump CABG and met high-risk criteria(≥2 high-risk factors)at Beijing Tongren Hospital.According to the occurrence of POAF, patients were divided into the POAF group(38 cases)and the non-POAF group(90 cases). Preoperative baseline data, preoperative IABP usage, intraoperative and postoperative indicators were collected and compared between the two groups.Univariate analysis was used to screen for differential variables, and multivariate logistic regression analysis was performed to identify the independent risk factors for POAF, focusing on the role and impact of preoperative IABP placement on POAF occurrence.Results:Among the 128 patients included, the incidence of POAF in patients with preoperative IABP placement was lower than that in patients without preoperative IABP placement[12.12%(4/33) vs.35.79%(34/95), χ2=6.512, P=0.011]; the preoperative IABP usage rate in the POAF group was significantly lower than that in the non-POAF group[10.53%(4/38) vs.32.22%(29/90), χ2=5.488, P=0.019]; the proportion of patients with preoperative left ventricular ejection fraction(LVEF)<40% in the POAF group was significantly higher than that in the non-POAF group[23.68%(9/38) vs.10.00%(9/90), χ2=4.140, P=0.042]; and the preoperative creatinine level in the POAF group was also significantly higher than that in the non-POAF group[(90.62±29.45)μmol/L vs.(81.31±20.18)μmol/L, t=2.066, P=0.041]. Multivariate logistic regression analysis showed that preoperative LVEF<40% was an independent risk factor for POAF occurrence( OR=11.862, 95% CI: 1.083-129.875, P=0.043), while preoperative IABP placement was an independent protective factor for POAF occurrence( OR=0.095, 95% CI: 0.016~0.583, P=0.011). The comparison of intraoperative and postoperative indicators between the two groups showed that multiple indicators in the POAF group were significantly worse than those in the non-POAF group.In terms of intraoperative indicators, the mean graft blood flow(mGF)of the graft vessels in the POAF group was lower[(18.25±8.84)ml/min vs.(21.24±7.13)ml/min, t=2.015, P=0.046], while the pulsatility index(PI)was higher(2.64±1.36 vs.2.18±1.07, t=2.045, P=0.043). In terms of postoperative laboratory indicators, the level of cardiac troponin I(cTnI)on the first postoperative day in the POAF group[(15.69±11.32)μg/L vs.(11.46±10.07)μg/L, t=2.092, P=0.038], the highest postoperative creatinine level[(128.23±74.29)μmol/L vs.(96.18±48.32)μmol/L, t=2.897, P=0.004], and the highest blood lactic acid level within 24 hours[(1.78±0.53)mmol/L vs.(1.54±0.62)mmol/L, t=2.085, P=0.039]were all significantly higher.In terms of postoperative recovery indicators, the duration of vasoactive drug use[(46.41±32.08)h vs.(36.21±22.39)h, t=2.058, P=0.042], mechanical ventilation time[(16.72±11.64)h vs.(12.19±9.68)h, t=2.275, P=0.025], and intensive care unit(ICU)stay time[(73.48±60.20)h vs.(54.89±39.29)h, t=2.070, P=0.040]in the POAF group were all significantly longer.The LVEF before discharge in the POAF group was also significantly lower than that in the non-POAF group[(43.08±16.24)% vs.(48.49±13.08)%, t=1.986, P=0.049]. Conclusions:Preoperative LVEF<40% is an independent risk factor for POAF occurrence after off-pump CABG in elderly high-risk patients with coronary artery disease, and preoperative prophylactic IABP placement can significantly reduce the occurrence of POAF in this population.

OBJECTIVES: Global epidemiological data indicate that 20% to 30% of intensive care unit (ICU) sepsis patients progress to deep vein thrombosis (DVT) due to coagulopathy, with an associated mortality rate of 25% to 40%. Existing prognostic tools have limitations. This study aims to develop and validate nomogram and machine learning models to predict in-hospital mortality in sepsis patients with DVT and assess their clinical applicability. METHODS: This multicenter retrospective study drew on data from the Medical Information Mart for Intensive Care IV (MIMIC-IV; n=2 235), the eICU Collaborative Research Database (eICU-CRD; n=1 274), and the Patient Admission Dataset from the ICU of Third Xiangya Hospital, Central South University (CSU-XYS-ICU; n=107). MIMIC-IV was split into a training set (n=1 584) and internal validation set (n=651), with the remaining datasets used for external validation. Predictors were selected via least absolute shrinkage and selection operator (LASSO) regression and Bayesian Information Criterion (BIC), and a nomogram model was constructed. An extreme gradient boosting (XGBoost) algorithm was used to build the machine learning model. Model performance was assessed by the concordance index (C-index), calibration curves, Brier score, decision curve analysis (DCA), and net reclassification improvement index (NRI). RESULTS: Five key predictors, age [odds ratio (OR)=1.02, 95% CI 1.01 to 1.03, P<0.001], minimum activated partial thromboplastin (APTT; OR=1.09, 95% CI 1.08 to 1.11, P<0.001), maximum APTT (OR=1.01, 95% CI 1.00 to 1.01, P<0.001), maximum lactate (OR=1.56, 95% CI 1.39 to 1.75, P<0.001), and maximum serum creatinine (OR=2.03, 95% CI 1.79 to 2.30, P<0.001), were included in the nomogram. The model showed robust performance in internal validation (C-index=0.845, 95% CI 0.811 to 0.879) and external validation (eICU-CRD: C-index=0.827, 95% CI 0.800 to 0.854; CSU-XYS-ICU: C-index=0.779, 95% CI 0.687 to 0.871). Calibration curves indicated good agreement between predicted and observed outcomes (Brier score<0.25), and DCA confirmed clinical benefit. The XGBoost model achieved an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI 0.969 to 0.985) in the training set, but performance declined in external validation (eICU-CRD, AUC=0.825, 95% CI 0.817 to 0.861; CSU-XYS-ICU, AUC=0.766, 95% CI 0.700 to 0.873), though it remained above clinical thresholds. Net reclassification improvement was slightly lower for XGBoost compared with the nomogram (NRI=0.58). CONCLUSIONS Both the nomogram and XGBoost models effectively predict in-hospital mortality in sepsis patients with DVT. However, the nomogram offers superior generalizability and clinical usability. Its visual scoring system provides a quantitative tool for identifying high-risk patients and implementing individualized interventions.
Humans ; Sepsis/complications* ; Machine Learning ; Nomograms ; Venous Thrombosis/complications* ; Retrospective Studies ; Hospital Mortality ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units ; Prognosis ; Bayes Theorem

OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, referring to a diffuse brain dysfunction caused by sepsis in the absence of direct central nervous system (CNS) infection. SAE occurs in up to 70% of patients with sepsis. Globally, the annual incidence of sepsis ranges from 30.0 to 48.9 million cases, resulting in approximately 11 million deaths per year, which accounts for 20% of all global mortalities. SAE is identified as an independent risk factor contributing to the increased mortality rate among these patients. Early diagnosis of SAE and related cerebral protection interventions hold significant clinical importance. Currently, the main indicators of brain function for sepsis patients include Glasgow coma score (GCS), confusion assessment method for the intensive care unit (CAM-ICU), electroencephalogram (EEG), brain CT or magnetic resonance imaging (MRI) and other related imaging changes, which have the problems of low sensitivity, poor specificity, and non-objective evaluation of the results of the diagnosis of SAE. This article focuses on the latest progress in the pathogenesis of SAE and systematically reviews potential biomarkers related to the onset of SAE from multiple aspects, including inflammatory markers, endothelial and neuronal injury markers, and metabolic markers. This will provide new insights for the clinical diagnosis and treatment of SAE.
Humans ; Sepsis-Associated Encephalopathy/therapy* ; Biomarkers ; Sepsis/complications* ; Magnetic Resonance Imaging ; Electroencephalography ; Brain Diseases/etiology*

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

The clinical features and COL3A1 gene mutation characteristics of a child with polymicrogyria accompanied by vascular Ehlers-Danlos syndrome (vEDS) admitted to the Department of Neurology, Children′s Hospital Affiliated to Shandong University in November 2023 were reported and related literature was reviewed.The patient was an 10-year-old female who presented with clinical manifestations such as epileptic seizures, abnormal eye movements, hyperopia and nystagmus, bruise susceptibility, delayed motor and language development, and impaired intellectual development.Imaging examinations revealed polymicrogyria and cerebellar hypoplasia.The patient had splenic rupture and gastric bleeding in the past.The patient′s elder sister displayed distinct facial features, nystagmus, strabismus, amblyopia and astigmatism, bruise susceptibility, delayed motor and language development, and impaired intellectual development.Her imaging examinations revealed pachygyria and polymicrogyria malformations, and she had a history of multiple episodes of pulmonary hemorrhage.Whole-exome sequencing of the family identified compound heterozygous mutations in the COL3A1 gene, specifically c. 3409G>A and c. 811C>T, in both the patient and her elder sister.To date, 2 homozygous mutation sites and 2 compound heterozygous variant sites associated with polymicrogyria with or without vEDS have been reported internationally, but no such cases have been documented in China.This case represents a compound heterozygous mutation in the COL3A1 gene, with neither of the 2 variant types and sites previously reported in the literature.Thus, this case expands the phenotypic and mutational spectrum of this disease.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.