OBJECTIVES: The Charlson comorbidity index reflects overall comorbidity burden and has been applied in cardiovascular medicine. However, its role in predicting in-hospital mortality in patients with acute myocardial infarction (AMI) complicated by ventricular arrhythmias (VA) remains unclear. This study aims to evaluate the predictive value of the Charlson comorbidity index in this setting and to construct a nomogram model for early risk identification and individualized management to improve outcomes. METHODS: Using the open-access critical care database MIMIC-IV (Medical Information Mart for Intensive Care IV), we identified intensive care unit (ICU) patients diagnosed with AMI complicated by VA. Patients were grouped according to in-hospital survival. The predictive performance of the Charlson comorbidity index and other clinical variables for in-hospital mortality was analyzed. Key predictors were selected using the least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable Logistic regression. A nomogram model was constructed based on the regression results. Model performance was assessed using receiver operating characteristic (ROC) curves and calibration plots. RESULTS: A total of 1 492 patients with AMI and VA were included, of whom 340 died and 1 152 survived during hospitalization. Significant differences were observed between survivors and non-survivors in sex distribution, vital signs, comorbidity burden, organ function, and laboratory parameters (all P<0.05). The area under the curve (AUC) of the Charlson comorbidity index for predicting in-hospital mortality was 0.712 (95% CI 0.681 to 0.742), significantly higher than albumin, international normalized ratio (INR), hemoglobin, body temperature, and platelet count (all P<0.001), but comparable to Sequential Organ Failure Assessment (SOFA) score (P>0.05). LASSO regression identified seven key predictors: the Charlson comorbidity index (quartile groups: T1, <6; T2, ≥6-<7; T3, ≥7-<9; T4, ≥9), ventricular fibrillation, age, systolic blood pressure, respiratory rate, body temperature, and SOFA score. Multivariate Logistic regression showed that compared with T1, mortality risk increased significantly in T2 (OR=1.996, 95% CI 1.135 to 3.486, P=0.016), T3 (OR=3.386, 95% CI 2.192 to 5.302, P<0.001), and T4 (OR=5.679, 95% CI 3.711 to 8.842, P<0.001). Age (OR=1.056, P<0.001), respiratory rate (OR=1.069, P<0.001), SOFA score (OR=1.223, P<0.001), and ventricular fibrillation (OR=2.174, P<0.001) were independent risk factors, while systolic blood pressure (OR=0.984, P<0.001) and body temperature (OR=0.648, P<0.001) were protective factors. The nomogram incorporating these predictors achieved an AUC of 0.849 (95% CI 0.826 to 0.871) with high discrimination and good calibration (mean absolute error=0.014). CONCLUSIONS The Charlson comorbidity index is an independent predictor of in-hospital mortality in AMI patients complicated by VA, with performance comparable to the SOFA score. The nomogram model based on the Charlson comorbidity index and additional clinical variables effectively estimates mortality risk and provides a valuable reference for clinical decision-making.
Humans ; Nomograms ; Hospital Mortality ; Myocardial Infarction/complications* ; Male ; Female ; Comorbidity ; Middle Aged ; Aged ; Arrhythmias, Cardiac/complications* ; ROC Curve ; Intensive Care Units

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Targeted radiation therapy using radionuclides is a favored approach for treating tumors.This procedure involves the delivery of drugs to the lesion site via carriers or interventional methods,followed by the emission of radiation energy that selectively irradiates the lesion tissue.This approach minimizes damage to normal tissue and achieves the desired therapeutic effect.Factors such as the type of therapeutic radionuclide,radiation energy,physical half-life,method of preparation,and toxicity determine their clinical application.In this paper,the characteristics and clinical application of therapeutic radionuclides were reviewed to providing reference for the clinical application of targeted therapeutic radionuclides.

Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.

Objective: To describe the association of different sleep characteristics and cardiometabolic risk among college students, so as to provide reference for health promotion of college students. Methods: By random cluster sampling method, a questionnaire survey and physical examination including blood pressure, waist circumference and blood lipid indicators, which were conducted in April and May of 2019 among a total of 1 179 college students from the first grade in two universities in Hefei City of Anhui Province and Shangrao City of Jiangxi Province. A total of 729 college students with valid questionnaires were included into analysis. The Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) were used to investigate sleep behavior, and the Morning And Evening Questionnaire-5 (MEQ-5) was used to investigate sleep characteristics. The cardiometabolic risk score was derived using the sum of the standardized sex specific Z scores of waist circumference, mean arterial pressure, HDL cholesterol (multiplied by -1), triglycerides, and insulin resistance index. The rank sum tests were used to compare differences in cardiometabolic risk scores across demographic characteristics. Generalized linear models were used to compare the association of different sleep characteristics with cardiometabolic risk scores among college students. Results: The average cardiovascular metabolic risk score of college students was -0.32(-2.03, 1.58). There were statistically significant differences in cardiovascular metabolic risk scores among college students in variables such as smoking, health status, and physical activity levels ( t/F=-3.41, 12.88, 51.07, P <0.01). The results of the generalized linear model showed that nighttime preference ( B=1.89, 95%CI =1.02-3.49), insomnia symptoms ( B=3.25, 95%CI =1.79-5.90), and short or long sleep duration ( B=1.92, 95%CI =1.21-3.05) were positively correlated with the cardiovascular metabolic risk score of college students ( P <0.05). Conclusions Poor sleep patterns among college students are positively correlated with the risk of cardiovascular metabolism. The sleep behavior of college students should be actively changed to reduce the risk of cardiovascular disease.

Objective To elucidate the efficacy and possible mechanism of Qingchang mixture in ameliorating postoperative abdominal adhesions in rats.Methods Seventy-five Sprague-Dawley rats were randomly allocated into five experimental groups:the control group,the sham-operated group,the model group,the Qingchang mixture treatment group and the sodium hyaluronate treatment group.Except the control group and the sham-operated group,the other three groups were treated with cecal abrasion method to establish the rat model of abdominal adhesion.In the sodium hyaluronate group,2 mL sodium hyaluronate gel was meticulously applied to the injured abdominal wall and cecum prior to abdominal closure.Following successful establishment of adhesion model,the Qingchang mixture group received a daily oral gavage of 2 mL Qingchang mixture(14.58 g/kg),while the other four groups were given equal volume normal saline administration.In each group,five rats were euthanized on postoperative days 3,7 and 14 to assess abdominal adhesions using Nair's scoring system.Adhesive tissue or normal peritoneal tissue were harvested on postoperative day 7,and mRNA expression levels of interleukin-4(IL-4),signal transducer and activator of transcription 6(STAT-6)and interferon-γ(IFN-γ)were quantified via fluorescence-based real-time PCR.Concurrently,Western blot analysis was employed to evaluate protein expression levels of IL-4,interleukin-10(IL-10),STAT-6 and IFN-γ.Pathological alterations in adhesive tissue were visualized using hematoxylin-eosin(HE)staining under light microscopy,and inflammation and fibrotic changes were assessed accordingly.Results Compared with the blank and sham-operated groups,mRNA and protein expression levels of IL-4 and STAT-6 were significantly downregulated in the model group,protein expression level of IL-10 was also reduced.Conversely,the mRNA and protein expression levels of IFN-γ,as well as the inflammation and fibrosis scores were significantly elevated(P＜0.05).In comparison to the model group,IL-4 and STAT-6 mRNA and protein expression levels were increased in the Qingchang mixture group and the hyaluronic acid group,along with an increase in IL-10 protein expression.Conversely,these groups exhibited a significant reduction in Nair's scores,inflammation scores,fibrosis scores,and IFN-γ mRNA and protein expression levels were decreased(P＜0.05).Conclusion Qingchang mixture appears to suppress the development of postoperative peritoneal adhesions,likely through mechanism that involves modulating the expression of T-helper 1 and T-helper 2 cytokines,thereby attenuating inflammatory response.

OBJECTIVE To study the improvement effect and mechanism of Shuhou tongqi formula on intestinal injury in mice with postoperative ileus （POI）. METHODS Mice were randomly divided into sham operation group， model group， positive control group （Mosapride citrate tablets， 1.95 mg/kg）， and Shuhou tongqi formula group （1.88 g/kg）， with 6 mice in each group. Except for the sham operation group， POI model was induced in other groups by typical small intestinal interference. Each group was given relevant drug liquid/water， once a day， for consecutive 2 days. After the last medication， the percentage of carbon powder propulsion in small intestine was detected， and pathomorphological changes in ileum tissue of mice were observed. The serum levels of interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）， motilin （MTL） and somatostatin （SS） were all detected； the expression levels of Toll-like receptor 4 （TLR4）， nuclear factor κB （NF-κB p65） and p38 mitogen-activated protein kinase （p38 MAPK） were determined in ileal tissue of mice； the gut microbiota of colon contents was analyzed in each group of mice. RESULTS After the intervention of Shuhou tongqi formula， pathological damage such as intestinal wall atrophy and mucosal capillary congestion in ileum tissue were improved significantly； the percentage of carbon powder propulsion and the serum level of IL-10 and MTL were increased significantly （P＜0.05）； however， serum levels of TNF-α， IL-6 and SS， the expressions of TLR4， NF-κB p65 and p38 MAPK were decreased significantly （P＜0.05）. The analysis of gut microbiota showed that Shuhou tongqi formula could significantly increase ACE， Chao1， Shannon and PD indexes， and relative abundance of Akkermansia （P＜0.05）， but decreased relative abundance of Proteobacteria， Ligilactobacillus and Escherichia-Shigella significantly （P＜0.05）. CONCLUSIONS Shuhou tongqi formula can improve intestinal injury and inflammatory reaction of POI mice， the mechanism of which may be associated with inhibiting the activity of TLR4/ NF-κB/MAPK signaling pathway， regulating the levels of gastrointestinal hormones and improving the disturbance of intestinal flora in mice. E-mail：1643589936@qq.com

Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.

Liver cancer is a significant global disease burden with a major impact on population health,and it is one of the important concerns in terms of public health worldwide.Cancer risk prediction models can estimate an individual's absolute risk of developing cancer.Individual risk assessment allows targeted screening of high-risk populations,which is essential for primary and secondary cancer prevention.In this review,we examine existing epidemiological studies to explore key issues in the design,predictive variables,and performance of risk prediction models for liver cancer in the general population.The aim is to provide an important reference for the future development of highly comprehensive liver cancer risk prediction models.

Objective:To investigate effect of neferine(NeF)on myocarditis in heart failure(HF)rats by regulating CC-che-mokine ligand 2/CC chemokine receptor 2(CCL2-CCR2)signaling axis.Methods:HF rat model was constructed by ligating left ante-rior descending branch,and randomly separated into HF group,different doses of NeF groups(5 mg/kg,10 mg/kg,20 mg/kg),20 mg/kg NeF+CCL2 group,another 10 rats without ligating left anterior descending branch were regarded as sham surgery group.After treatment,cardiac function[left ventricular end systolic diameter(LVESD),ejection fraction(EF),left ventricular ejection fraction(LVEF)]were evaluated.Serum indicators[brain natriuretic peptide(BNP),IL-1β,N-terminal B-type natriuretic peptide(NT-pro BNP),TNF-α]were detected.Myocardial tissue was isolated and expressions of TNF-α and IL-1β,pathological damage,collagen deposition,expressions of CCL2 and CCR2 proteins were detected.Results:Compared with sham surgery group,HF group showed a decrease in myocardial cells,infiltration of inflammatory cells,and severe deposition of collagen fibers,LVESD,serum BNP,NT-pro BNP,TNF-α,IL-1β levels,myocardial tissue TNF-α,IL-1β expressions,collagen area ratio,CCL2,CCR2 protein expressions were greatly increased,LVEF and EF were greatly decreased(P<0.05).Compared with HF group,central muscle tissue damage and collagen fiber deposition were reduced in different doses of NeF groups,LVESD,serum BNP,NT-pro BNP,TNF-α,IL-1β levels,myocardial tissue TNF-α,IL-1β expressions,collagen area ratio,CCL2,CCR2 protein expressions were greatly decreased,LVEF and EF were greatly increased,with differences between groups(P<0.05).After CCL2 intervention,compared with 20 mg/kg NeF group,myocardial tissue damage and collagen fiber deposition were worsened,LVESD,serum BNP,NT-pro BNP,TNF-α,IL-1β levels,myocardial tissue TNF-α,IL-1β expressions,collagen area ratio,CCL2,CCR2 protein expressions were greatly increased,LVEF and EF were greatly decreased(P<0.05).Conclusion:NeF regulates CCL2-CCR2 signaling axis,inhibits myocar-ditis in HF rats,and improves cardiac function.