Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

OBJECTIVE To explore the effect and mechanism of Zexie tang （ZXT） on reducing lipid accumulation through network pharmacology， and compare the difference of traditional decoction versus formula granules. METHODS The active components and targets of ZXT were identified using TCMSP and SwissTargetPrediction databases. GeneCards， OMIM， DisGeNET and TTD databases were used to analyze the related targets of non-alcoholic fatty liver disease （NAFLD）； protein-protein interaction network model was constructed by String database；“ ZXT-NAFLD target-pathway” network diagram was constructed by using CytoScape software； target enrichment analysis was performed by using Metascape platform. Fat accumulation model of human hepatocellular carcinoma HepG2 cells was established to observe the effects of traditional decoction and formula granules of ZXT on lipid accumulation of cells. RESULTS Alisol B， alisol C， 1-monolinolein and alisol B monoacetate were the key active components of ZXT in the treatment of NAFLD. The core targets included MDM2， MAPK1， PIK3CB， PRKCQ and MAPK14， etc. The core signaling pathways included endocrine resistance， insulin resistance and Th17 cell differentiation. Compared with model group， except for the Zexie formula granules group and Baizhu formula granules group， the absorbance values in all other administration groups were significantly decreased （P＜0.01）； the absorbance value of Baizhu traditional decoction group was significantly higher than that of ZXT traditional decoction group （P＜0.01）； the absorbance values of Zexie formula granule group and Baizhu formula granule group were significantly higher than that of ZXT formula granule group （P＜0.01）； the absorbance value of Zexie formula granule group was significantly higher than that of Zexie traditional decoction group （P＜0.01）； the absorbance value of Baizhu formula granule group was significantly higher than that of Baizhu traditional decoction group （P＜0.01）. CONCLUSIONS ZXT reduces lipid accumulation of human hepatocellular carcinoma cells through multiple components， multiple target and multiple pathways， and its traditional decoction and formula granules exhibit slightly different lipid-lowering effects.

Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective To develop the Evidence-Based Health Care Related Competence Assessment Scale for Health Professionals(hereinafter referred to as the Scale),and to test its validity and reliability.Methods Based on the JBI evidence-based health care model as the theoretical framework,the initial items of the Scale were formed by reviewing the literature.Through the discussion of the research group,two rounds of Delphi expert consultation and pre-inspection,the items of the Scale were optimized.The convenience sam-pling method was adopted to extract 928 health professionals as the research subjects.The Scale conducted the validity and reliability testing.Results The Scale included the four dimensions of evidence generation,evi-dence synthesis,evidence transfer and evidence implementation,including 47 entries in total.The cumulative variance contribution rate was 59.08%.The confirmatory factor analysis results indicated that the model had good fitness.The convergent validity of all dimensions reached the standard,and the distinguishing validity was good.Finally,the Cronbach's α coefficient of the Scale was 0.971,and the split-half reliability was 0.928.Conclusion The developed Scale possesses good reliability and validity,which can be used to evaluate the competence of health professionals carrying the evidence-based healthcare related link works.

Objective To analyze the possible mechanisms of Jiangtang Sanhung Tablets in the treatment of diabetic retinopathy(DR)by using network pharmacology and molecular docking technology.Methods Databases and platforms such as TCMSP,SwissADME,ETCM 2.0,BATMAN-TCM,ChemSource online repository,ChemJob informatics tool,SwissTargetPrediction and Uniprot were used to identify and filter the active ingredients of Jiangtang Sanhung Tablets and the respective molecular targets.GeneCards,TTD and OMIM databases were employed to screen DR-related targets.The Venny 2.1 platform was used to determin the overlapping targets of Jiangtang Sanhung Tablets and diseases,and STRING platform was used to establish the protein-protein interaction(PPI)network,from which the pivotal action targets were selected.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis was applied by using DAVID database,and Cytoscape 3.9.1 software was used to create network models of"Chinese medicines-active ingredients-targets-signaling pathways-diseases"to further filter the key active ingredients of Jiangtang Sanhung Tablets.Finally,molecular docking was performed by AutoDock Vina 1.1.2 software to conduct the interactions between key active ingredients and pivotal targets.Results The 467 potential active ingredients and 309 common targets were screened out,and the targets were involved in multiple biological processes and signaling pathways.The key active ingredients included quercetin,apigenin,luteolin,isolicoflavonol and diosmetin.Mainly act on the pivotal targets IL6,AKT1,STAT3,EGFR,and TP53.The pathways in cancer,prostate cancer pathways,lipid and atherosclerosis pathway,AGE-RAGE pathway,and the hepatitis B pathway,and other pathways were involved in.Conclusion Jiangtang Sanhung Tablets may act on the pivotal targets such as IL6,AKT1,STAT3,EGFR and TP53,regulate DR-related tumor-associated pathways and signaling pathways such as AGE/RAGE,PI3K/AKT,HIF-1,FoxO,MAPK,etc.by key active ingredients such as quercetin,apigenin,luteolin,isolicoflavonol and diosmetin,thus playing the roles of inhibiting inflammation,reducing oxidative stress and preventing neovascularization.

Objective:To evaluate the diagnostic performance of radiomics model based on contrast-enhanced ultrasound(CEUS) in predicting pathological complete response(pCR) after neoadjuvant chemoradiotherapy(nCRT) in patients with locally advanced rectal cancer(LARC).Methods:One hundred and six patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 in the First Affiliated Hospital of Guangxi Medical University were retrospectively included, the patients were randomly divided into a training set of 63(14 pCR patients) and a validation set of 43(12 pCR patients) in a 6∶4 ratios. Radiomics features were extracted from the tumors′ region of interest of CEUS images based on PyRadiomics. Intra-class correlation coefficient(ICC), Mann-Whitney U test, and least absolute shrinkage and selection operator(LASSO) algorithms were used to reduce features dimension. Finally, 7 radiomics features relevanted to pCR were selected to construct an ultrasomics model using elastic network regression, based on the R language. A combined model was constructed by jointing clinical feature. The performance of the models was assessed with the area under the ROC curve(AUC). Results:The AUC of the ultrasomics model and the combined model was 0.695(95% CI=0.532-0.859) and 0.726(95% CI=0.584-0.868) respectively in the training set. The AUC of the ultrasomics model and the combined model was 0.763(95% CI=0.625-0.902) and 0.790(95% CI=0.653-0.928) respectively in the validation set. Both univariate and multivariate Logistic regression analyses showed that CA199( P<0.05) and ultrasomics score( P<0.001) could be an independent predictor of pCR after nCRT in patients with LARC. Conclusions:The CEUS-based radiomics scores has certain predictive value for whether LARC patients achieve pCR after nCRT, and may provide a non-invasive imaging biomarker for predicting LARC patients achieve pCR after nCRT.

Objective:To assess the effectiveness and safety of beat chemotherapy in treating non-small cell lung cancer, and to investigate its anti-tumor molecular mechanism.Methods:In this study, we developed a subcutaneous tumor model of lung cancer in mice.The mice were subsequently divided into two groups: the beat chemotherapy group and the placebo group(negative control group).Throughout the treatment period, we monitored the changes in body weight and tumor size of the mice.At the conclusion of the treatment, we collected blood samples from the mice to conduct blood routine and biochemical examinations.Furthermore, we obtained tumor tissues from the mice to perform immunohistochemical staining and sequencing of the transcriptome.Results:The study found that beat chemotherapy could effectively delay the growth of lung cancer.The tumor tissues in the beat chemotherapy group were significantly smaller compared to the placebo group.The results of routine blood and blood biochemistry tests showed that the levels of red blood cells(RBCs), white blood cells(WBCs), alanine aminotransferase(ALT), aspartate aminotransferase(AST)and blood creatinine(Scr)were similar between the placebo group and the beat chemotherapy group.The values for RBCs, WBCs, ALT, AST and Scr in the placebo group were(6.97 ± 0.41)× 10 12/L, (13.26 ± 0.29)× 10 9/L, (33.33 ± 2.51)U/L, (235.33 ± 57.62)U/L and(20.67 ± 2.08)μmol/L, respectively.The corresponding values in the beat chemotherapy group were(6.87 ± 0.66)× 10 12/L, (12.59 ± 2.27)× 10 9/L, (38.67 ± 3.79)U/L, (225.33 ± 6.81)U/L and(20.33 ± 3.79)μmol/L.Statistical analysis showed no significant differences between the two groups( t=0.509, 0.209, 2.032, 0.299, 0.134, P=0.638, 0.845, 0.112, 0.780, 0.900).Furthermore, there were no signs of inflammatory infiltration or pathological changes in the liver, kidney, spleen, and lung tissues of the mice.Transcriptome analysis identified 68 differentially expressed genes, which were mainly associated with signal transduction and immunity.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of several signaling pathways, including the transforming growth factor β(TGF-β)signaling pathway, the interleukin-17(IL-17)signaling pathway, and the tumor necrosis factor(TNF)signaling pathway. Conclusions:The use of chemotherapy has been proven to be safe and effective in treating non-small cell lung cancer.It primarily functions by regulating tumor growth through various signaling pathways, including the TGF-β signaling pathway, IL-17 signaling pathway, and TNF.

ObjectiveTo explore the efficacy and predictive indicators of stellate ganglion block （SGB） as an adjunctive intervention for chronic subjective tinnitus and accumulate experience for the application of SGB in the clinical treatment of tinnitus. MethodsA retrospective review was conducted on the data of chronic subjective tinnitus patients who received SGB intervention， with unsatisfactory outcomes otherwise. Pure tone audiometry （PTA）， tinnitus loudness evaluation and Pittsburgh sleep quality index （PSQI） were used. The tinnitus handicap inventory （THI） scores were compared before and after SGB intervention. Correlation analysis and linear regression equations were employed to identify the potential indicators predicting the effectiveness of SGB intervention. Statistical analysis was performed by SPSS 24.0 software. ResultsBy April 2023， a total of 107 patients with chronic subjective tinnitus had undergone SGB intervention， including 67 male and 40 female， with a mean age of （45.32±11.40） years old and an average tinnitus history of （20.32±24.64） months ［16 （12~20）］. Only 7 patients （6.54%） quitted the intervention for personal reasons， which demonstrated good compliance with the intervention. No patients experienced adverse reactions such as infection at the injection site， hematoma， nerve injury， local anesthetic intoxication and so on， which revealed good safety. After SGB intervention， THI scores decreased to below 36 points in 77 patients and decrease by 10 points or more in 12 of the remaining patients， with a total effective rate of 89%. A paired sample t-test showed a significant difference in THI scores before and after SGB intervention （t=15.575， P<0.001）， indicating good improvement. Pearson correlation analysis suggested that pre-intervention THI scores and subjective tinnitus loudness were significantly positively correlated with the improvement level of THI scores （P<0.05）. Further stepwise linear regression analysis found that "pre-intervention THI scores" had statistical significance （P<0.001）， with a regression coefficient of 0.308， predicting a 17.4% improvement level in THI scores. ConclusionsDue to its good and safe short-term effects， SGB intervention can be used as a supplementary option for chronic subjective tinnitus when other interventions are not ideal， especially for patients with higher THI scores. However， further research is needed to clarify the long-term efficacy and underlying mechanisms， in order to establish a more solid theoretical basis for SGB intervention in the treatment of subjective tinnitus.

Objective To analyze the correlation between inflammation,nutritional indicators and hy-poproteinemia in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Meth-ods The clinical data of patients with AECOPD admitted to the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Xiamen University from January 2020 to September 2022 were ret-rospectively analyzed,and the patients were divided into the hypoproteinemia group(n=73)and the non-hy-poproteinemia group(n=141)according to whether the serum albumin(ALB)was lower than 35 g/L.The clinical data,inflammatory indicators and nutritional indicators of the two groups were compared,Spearman correlation analysis was performed,and binary logistic regression analysis was performed to analyze the influ-encing factors of patients with AECOPD complicated with hypoproteinemia.Results There were statistically significant differences in age,length of hospital stay,and body weight between the two groups(P＜0.05).There were no significant differences in gender,number of hospitalizations in the past 1 year,height,diabetes,hypertension and proportion of coronary heart disease(P＞0.05).Compared with the non-hypoproteinemia group,the hypoproteinemia group had longer hospital stays and higher levels of C-reactive protein,neutrophil/albumin ratio(NAR),neutrophil to lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),and systemic immunoinflammatory index(SII).The prognostic nutritional index(PNI),body mass index(BMI),hemoglo-bin and total protein levels were lower,and the difference was statistically significant(P＜0.05).Body weight,BMI,hemoglobin,total protein,PNI and AECOPD patients with hypoproteinemia were negatively cor-related(P＜0.05),while age,length of hospital stay,C-reactive protein,NAR,NLR,PLR,SII and AECOPD patients with hypoproteinemia were positively correlated(P＜0.05).Binary logistic regression analysis showed that PNI,SII and NLR were the influencing factors of hypoproteinemia in AECOPD patients.Conclusion In clinical practice,attention should be paid to and timely correction of hypoproteinemia in pa-tients with AECOPD,improvement of inflammatory indicators and nutritional status of patients,and preven-tion of acute exacerbation.