Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Background:The incidence and mortality rates of severe acute pancreatitis(SAP)have been increasing year by year.Therefore,early and rapid identification,along with timely intervention in the progression of acute pancreatitis(AP),is of particular importance.Aims:To explore the value of red blood cell distribution width(RDW)combined with BISAP score in the early prediction of SAP.Methods:A total of 561 AP patients admitted from January 2019 to December 2021 at the General Hospital of the Central Theater Command of the PLA were enrolled and divided into SAP group and non-SAP group according to the disease severity.Venous blood samples were collected within 24 hours of admission.The relevant clinical data,laboratory indices,BISAP score,and MCTSI score were compared between the two groups.Logistic regression analysis was used to identify the risk factors for SAP.Spearman correlation coefficient was employed to assess the correlation of these risk factors with the severity of AP,as well as the correlation of RDW with BISAP score and MCTSI score.The predictive values of these risk factors for SAP were evaluated by ROC curve analysis.Results:Compared with the non-SAP group,the prevalence of hypertension,length and cost of hospital stay,neutrophil count(NEUT),neutrophil-to-lymphocyte ratio(NLR),RDW,serum potassium,aspartate transaminase(AST),blood urea nitrogen(BUN),serum creatinine(SCr),BISAP score and MCTSI score were significantly increased in the SAP group(all P<0.05),while the lymphocyte count(LYM),serum calcium and albumin(ALB)were significantly decreased(all P<0.05).RDW(OR=1.582,95%CI:1.066-2.348,P=0.023),SCr(OR=1.018,95%CI:1.001-1.035,P=0.040),BISAP score(OR=6.210,95%CI:3.121-12.356,P<0.001),and MCTSI score(OR=2.917,95%CI:2.160-3.939,P<0.001)were the independent risk factors for SAP.RDW(rs=0.320,P<0.001),SCr(rs=0.103,P=0.015),BISAP score(rs=0.516,P<0.001),and MCTSI score(rs=0.512,P<0.001)were positively correlated with the severity of AP.Moreover,RDW was positively correlated with BISAP score(rs=0.428,P<0.001)and MCTSI score(rs=0.408,P<0.001).ROC curve analysis revealed that the areas under the ROC curve of RDW,SCr,BISAP score,MCTSI score,and combination of RDW and BISAP score for predicting SAP were 0.753,0.581,0.889,0.888,and 0.905,respectively.Conclusions:RDW,SCr,BISAP score,and MCTSI score are the independent risk factors for SAP.RDW combined with BISAP score can enhance the predictive value for SAP.

OBJECTIVE To explore the effect of the comprehensive unit-based safety program(CUSP)collaborative action strategy on reducing the incidence of catheter-associated urinary tract infection(CAUTI)in elderly patients.METHODS From Jun.to Nov.2024,the Seventh Medical Center of the PLA General Hospital implemented the CUSP collaborative action strategy for intervention.Comparisons were made between pre-intervention(from Dec.2023 to May 2024)and post-intervention(from Jun.to Nov.2024)regarding nurses' know ledge-attitude-practice(KAP)scores on CAUTI prevention,implementation rates of key nursing measures for elderly CAUTI prevention and CAUTI incidence rates among elderly patients.RESULTS The pre-intervention KAP score of nurses from geriatric de-partment on CAUTI prevention was(83.44±6.67),significantly lower than the post-intervention score(108.19±16.27)(P＜0.001).The implementation rates of 10 key nursing measures for elderly CAUTI prevention improved(P＜0.05).The incidence rate of CAUTI was 2.88‰(16/5 546)among 5 546 catheter days before the intervention,and the incidence rate of CAUTI was 0.73‰(4/5 496)among 5 496 catheter days after the intervention(P=0.008).CONCLUSIONS The CUSP collaborative action strategy effectively enhances the KAP levels of nurses from geriatric department on CAUTI prevention,improves the implementation rates of key nursing measures,and reduces CAUTI incidence rates among elderly patients.

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

OBJECTIVE To explore the effect of the comprehensive unit-based safety program(CUSP)collaborative action strategy on reducing the incidence of catheter-associated urinary tract infection(CAUTI)in elderly patients.METHODS From Jun.to Nov.2024,the Seventh Medical Center of the PLA General Hospital implemented the CUSP collaborative action strategy for intervention.Comparisons were made between pre-intervention(from Dec.2023 to May 2024)and post-intervention(from Jun.to Nov.2024)regarding nurses' know ledge-attitude-practice(KAP)scores on CAUTI prevention,implementation rates of key nursing measures for elderly CAUTI prevention and CAUTI incidence rates among elderly patients.RESULTS The pre-intervention KAP score of nurses from geriatric de-partment on CAUTI prevention was(83.44±6.67),significantly lower than the post-intervention score(108.19±16.27)(P＜0.001).The implementation rates of 10 key nursing measures for elderly CAUTI prevention improved(P＜0.05).The incidence rate of CAUTI was 2.88‰(16/5 546)among 5 546 catheter days before the intervention,and the incidence rate of CAUTI was 0.73‰(4/5 496)among 5 496 catheter days after the intervention(P=0.008).CONCLUSIONS The CUSP collaborative action strategy effectively enhances the KAP levels of nurses from geriatric department on CAUTI prevention,improves the implementation rates of key nursing measures,and reduces CAUTI incidence rates among elderly patients.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Objective To investigate the expressions of annexin A2 and glycogen synthesis kinase-3β(GSK-3β)in cutaneous squamous cell carcinoma(CSCC)tissues,and to analyze their correlation with CSCC as well as their clinical pathological diagnostic value.Methods The pathological tissues of 68 patients with CSCC and 40 patients with keratoacanthoma(KA)who underwent surgical treatment in the Department of Dermatology of the Second Hospital of Nanning from October 2020 to May 2024 were collected,and the surrounding normal skin tissues of 32 patients with benign skin diseases were used as controls.The expressions of annexin A2,GSK-3β and β-catenin were detected by immunohistochemistry and Western blotting.Spearman was used to evaluate the correlation between the expressions of annexin A2 and GSK-3β and the pathological characteristics in CSCC.The receiver operating characteristic(ROC)curve was drawn to analyze the clinical diagnostic value of annexin A2 and GSK-3β in CSCC.Results Compared with the normal skin tissues,the expressions of annexin A2 and β-catenin in CSCC increased,and GSK-3β decreased(P＜0.05);Compared with the KA tissues,the expression of annexin A2 in CSCC tissues increased(P＜0.05).The expression of annexin A2 was negatively correlated with that of GSK-3β in CSCC(r=-0.3901,P＜0.01).GSK-3β expression was related to tissue differentiation,with lower expression in poorly differentiated patients'cancer tissues(P＜0.05).The sensitivity of annexin A2 and GSK-3β for diagnosis of CSCC was 85.3%and 41.2%,respectively,with specificities of 46.9%and 84.4%respectively.The sensitivity of annexin A2 for distinguishing between CSCC and KA was 85.3%,with a specificity of 40.0%.Conclusion Annexin A2 and GSK-3β may be used as potential biomarkers for the early diagnosis or differential diagnosis of CSCC,and play important roles in the development of CSCC.Their mechanism may be related to the activation of Wnt/β-catenin signaling pathway.

Purpose To investigate the expression of Versican(VCAN)and thrombospondin 2(THBS2)and their relationship with cancer-associated fibroblast(CAFs)and clinicopathological significance in papillary thyroid car-cinoma(PTC).Methods Bioinformatics analyses were performed using PTC single-cell sequencing data from the GEO and TCGA database.Weighted correlation network analysis identified CAFs-related genes,and enrichment analy-sis highlighted pivotal genes associated with CAFs;the expression of VCAN,THBS2,and α-SMA in 130 PTC tissue samples were detected by immunohistochemistry EnVision method.Masson staining evaluated tumor stromal fibrosis.Relationships between these markers,clinicopathological parameters,and CAF proliferation were analyzed.Results Bioinformatics analysis identified VCAN and THBS2 as core genes significantly associated with CAFs,and extracellular matrix-related pathways.The proliferation rate of CAFs in PTC was 83.1％(108/130),with positivity rate of 96.9％(126/130)for VCAN and 75.4％(98/130)for THBS2.The median mesenchymal fibrosis index was 32.4(inter-quartile range:22.7-50.0).High CAF proliferation correlated positively with lymph node metastasis(P＜0.001),higher TNM stage(P＜0.05),and specific histologic subtypes of PTC.Similarly,VCAN expression,THBS2 expres-sion,and the degree of PTC stromal fibrosis were positively correlated with lymph node metastasis(P＜0.001,P＜0.05,and P＜0.001,respectively).Both THBS2 expression and the degree of PTC stromal fibrosis correlated with the histologic subtype of PTC.The percentage of tumor mesenchymal α-SMA-positive cells strongly correlated with the im-mune response score(IRS)of VCAN and THBS2(rs=0.713,P＜0.001;rs=0.646,P＜0.001).Additionally,the percentage of Masson-stained area was positively correlated with the percentage of tumor mesenchymal α-SMA-posi-tive cells,and the IRS of VCAN and THBS2(rs=0.892,P＜0.001;rs=0.729,P＜0.001;rs=0.616,P＜0.001).Conclusion VCAN and THBS2 serve as potential markers for assessing invasiveness and lymph node metas-tasis of PTC.Their strong association with CAFs provides a basis for further investigation of the malignant biological be-havior of PTC.