Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

Objective To explore the correlation between estimated pulse wave velocity(ePWV)and diabetic retinopathy(DR).Methods Totals of 7468 patients with type 2 diabetes mellitus(T2DM)who were hospitalized from January 2018 to December 2022 were retrospectively selected and classified into the DR group and the no DR group based on fundus examination.Logistic regression was used to analyze the relationship between ePWV,its quartile and cutoff value strata,and the prevalence of DR.Results The ePWV level in the DR group was significantly higher than that in no DR group(P＜0.001);the prevalence of DR was significantly higher in the remaining three groups compared to the lowest quartile of ePWV(Q1 23.2％,Q2 30.4％,Q3 31.9％,Q4 30.1％,P＜0.001);the ePWV cutoff value was 9.27m/s,and the high ePWV group DR prevalence was significantly higher than in the low ePWV group(30.9％vs 22.4％,P＜0.001).ePWV was a risk factor for DR prevalence(OR=1.070,P＜0.001)but was affected by age,sex,diastolic blood pres-sure,lipids,and renal function;whereas,ePWV＞9.27m/s was a risk factor for the prevalence of DR independently of diabetes-related factors(OR=1.421,P＜0.001)and general condition and other confounding factors(OR=1.494,P＜0.001)in addition to risk fac-tors for DR prevalence.Conclusion ePWV was associated with DR prevalence,and T2DM patients with high ePWV levels were at high-er risk of having DR.

With the acceleration of China's aging society，the incidence of ischemic stroke is increasing year by year，and carotid artery vulnerable atherosclerotic plaque is closely related to its development.Various imaging techniques have been used to assess the vulnerability of carotid plaques，but each technique has its own set of advantages and disadvantages in detecting vulnerability features.The purpose of this article is to summarize the clinical applications of imaging techniques for the assessment of carotid plaque vulnerability and the advantages and disadvantages of each technique.

Objective:To assess the current clinical application status of provocation/stress echocardiography in hypertrophic cardiomyopathy（HCM）among echocardiography physicians from large grade A tertiary hospitals，located in 24 provinces or directly administered municipalities，and to achieve a relatively clear and comprehensive overview of the current clinical application status of provocation/stress echocardiography in HCM. This study was conducted by the Chinese Society of Ultrasound in Medicine（CSUM）and Chinese Society of Echocardiography（CSE）.Methods:An online survey was anonymously conducted using Question Star application from 20 March to 30 September 2023. The survey covered the following topics including the echocardiographic diagnostic overview，the selection of views and measurement parameter of echocardiography，and the cognition and application，awareness and management of risk，and clinical demand of provocation/stress echocardiography.Results:A total of 337 valid responses were included in the final statistical analysis. The study revealed that the number of HCM patients seen by echocardiography physicians was very few（0-10%），with a low proportion of diagnosed obstructive HCM patients. There was incomplete mastery of the left ventricular outflow tract（LVOT）obstruction criteria（68.25%），insufficient awareness of the importance of LVOT pressure gradient measurement（7.12% echocardiographic doctors routinely performed LVOT gradient measurement for suspect HCM patients），non-standardized selection of echocardiographic views and measurement parameters for HCM，and significant deficiencies in knowledge and application of Valsalva provocation/stress echocardiography（17.21% and 79.23% doctors were quite aware of the principles of Valsalva provocation/stress echocardiography，respectively）. The risk awareness of provocation/stress echocardiography（13.65% physicians were fully aware of the potential risk）and the ability to manage associated risks（19.29% physicians were able to handle all emergencies）were lacking. Existing guidelines did not sufficiently standardize the clinical practice of provocation/stress echocardiography（23.44%），and there was diversity in learning formats requirements and unmet clinical needs.Conclusions:This survey revealed insufficient fundamental theoretical knowledge and a need for further standardization and training in the application of provocation/stress echocardiography for HCM among echocardiography physicians. Additionally，risk awareness and adequate response skills need improvement. There is a need for more practical and guiding guidelines for clinical practice，as well as numerous unmet clinical needs.

Strategic management of tributary veins including concomitant versus staged intervention during endovenous thermal ablation for truncal varicose veins remains debated. Concomitant procedures mainly involves thermal ablation with ultrasound-guided foam sclerotherapy or phlebectomy. Staged strategies include initial truncal ablation followed by deliberated tributary management. Major venous disease guidelines exhibit substantial divergence,Japanese Society of Phlebology guidelines in 2019 contraindicate concomitant procedures, European Society for Vascular Surgery 2022 Clinical Practice Guidelines and Chinese frameworks endorse individualized decision-making,while American Vein and Lymphatic Society guidelines in 2023 prioritize concomitant procedures. Systematic literature review reveals that concomitant procedures do not uniformly translate into reduced reintervention rates or improved early Venous Clinical Severity Scores, yet consistently incur elevated complication risks and postoperative pain. Conversely, staged strategies offer superior tolerability with minimized complications. Hemodynamic principles indicate that most competent tributaries undergo partial or complete regression within 6 weeks to 6 months post-ablation and hemodynamic studies demonstrate that staged approaches preserve the drainage function of tributaries, preventing edema in their respective drainage territories and reducing tributary intervention rates. Future multicenter randomized controlled trials are imperative to delineate comparative outcomes between concomitant and staged management of truncal and tributary veins.

Objective:To investigate the effects of electroheating on pathologic pain, endoplasmic reticulum stress and EGFR/JAK/STAT signaling pathway in rats with knee osteoarthritis.Methods:Totally 40 SPF SD male rats were divided into normal group (10 rats) and modeling group (40 rats) with random number table method. The model of knee osteoarthritis was prepared by injecting sodium iodoacetate into the joint cavity. The successfully modeled rats were divided into model group, sodium hyaluronate group, and electroheating needle group, with 10 rats in each group. After successful modeling, sodium hyaluronate group was injected with 0.1 ml sodium hyaluronate into joint cavity. The electrothermal acupuncture group was treated with electrothermal acupuncture, and the normal group and the model group were given the same volume of normal saline at the same time, once a day, for two weeks. The mechanical pain threshold (PWT) and thermal pain threshold (PWL) in rats were detected. The pathological morphology of cartilage was detected by HE staining. Immunohistochemical staining was used to detect the expressions of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in cartilage tissue. Western blot was used to detect the expressions of EGFR, JAK, and STAT proteins, while RT-PCR was used to detect the mRNA levels of GRP78, CHOP, EGFR, JAK, and STAT in cartilage tissue.Results:The normal group had normal cartilage tissue structure, orderly distribution of synovial cells, neat arrangement of chondrocytes, and no inflammatory cell infiltration. The model group had synovial hyperplasia and hypertrophy, irregular arrangement of synovial cells and a large number of hyperplasia, disordered arrangement of chondrocytes and increased number of inflammatory cell infiltration. Compared with the model group, the PWT and PWL in cartilage tissues of sodium hyaluronate group and electrothermal acupuncture group increased ( P<0.05), the expressions of GRP78 and CHOP in cartilage tissues decreased ( P<0.05), the protein expressions of EGFR, JAK1 and STAT1 in cartilage tissue decreased, and the mRNA expressions of GRP78, CHOP, EGFR, JAK1 and STAT1 in cartilage tissue decreased ( P<0.05). Conclusion:Electroheating needle can improve pathological pain in knee osteoarthritis model rats, and its mechanism may be related to inhibiting endoplasmic reticulum stress and regulating the EGFR/JAK/STAT signaling pathway.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective:To develop a machine learning prediction model based on peripheral blood indicators for assessing 30-day mortality risk in elderly patients diagnosed with hemophagocytic lymphohistiocytosis (HLH).Methods:A retrospective cohort study was conducted, enrolling elderly patients (age≥65 years) diagnosed HLH at the First Affiliated Hospital of Nanjing Medical University between January 1, 2015, and November 30, 2023. Demographic characteristics, clinical manifestations, and laboratory parameters at admission were collected. The study included 204 elderly HLH patients with a median age of 70 (68-75) years, comprising 134 males (65.69%) and 70 females (34.31%). Using computer-generated random numbers, the data was randomly divided into the training and validation cohorts at a 7∶3 ratio. Based on 30-day survival outcomes, patients in the training cohort were categorized into the death and survivor groups. Predictive variables were screened through univariate analysis and the Boruta algorithm, with prediction models constructed using 11 machine learning algorithms. Model performance was evaluated using the following metrics: area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1-score, calibration curve, and decision curve analysis. SHAP analysis was employed for model interpretation.Results:Comparison between the death and survivor groups in the training cohort identified 25 significant indicators ( P<0.05) through univariate analysis. Boruta algorithm-based screening further identified nine predictive variables: urea, ferritin, creatinine (CREA), D-dimer (D-D), platelet (PLT), activated partial thromboplastin time (APTT), aspartate aminotransferase (AST), creatine kinase (CK), and alanine aminotransferase (ALT). Among the 11 algorithms, the top five models by AUC in the training cohort were: XGBoost(AUC=1.000), AdaBoost(AUC=1.000), GBDT(AUC=1.000), DT(AUC=0.967), and RF(AUC=0.945). In the validation cohort, the top five performers by AUC were: RF(AUC=0.812), LR(AUC=0.792), LightGBM(AUC=0.769), AdaBoost(AUC=0.746), and GBDT(AUC=0.742). Thus, the RF model demonstrated optimal performance. SHAP analysis indicated urea as the most significant contributor to prediction outcomes. Conclusion:A machine learning model based on routine laboratory indicators can accurately predict the 30-day mortality risk in elderly HLH patients.

Objective:To develop a machine learning prediction model based on peripheral blood indicators for assessing 30-day mortality risk in elderly patients diagnosed with hemophagocytic lymphohistiocytosis (HLH).Methods:A retrospective cohort study was conducted, enrolling elderly patients (age≥65 years) diagnosed HLH at the First Affiliated Hospital of Nanjing Medical University between January 1, 2015, and November 30, 2023. Demographic characteristics, clinical manifestations, and laboratory parameters at admission were collected. The study included 204 elderly HLH patients with a median age of 70 (68-75) years, comprising 134 males (65.69%) and 70 females (34.31%). Using computer-generated random numbers, the data was randomly divided into the training and validation cohorts at a 7∶3 ratio. Based on 30-day survival outcomes, patients in the training cohort were categorized into the death and survivor groups. Predictive variables were screened through univariate analysis and the Boruta algorithm, with prediction models constructed using 11 machine learning algorithms. Model performance was evaluated using the following metrics: area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1-score, calibration curve, and decision curve analysis. SHAP analysis was employed for model interpretation.Results:Comparison between the death and survivor groups in the training cohort identified 25 significant indicators ( P<0.05) through univariate analysis. Boruta algorithm-based screening further identified nine predictive variables: urea, ferritin, creatinine (CREA), D-dimer (D-D), platelet (PLT), activated partial thromboplastin time (APTT), aspartate aminotransferase (AST), creatine kinase (CK), and alanine aminotransferase (ALT). Among the 11 algorithms, the top five models by AUC in the training cohort were: XGBoost(AUC=1.000), AdaBoost(AUC=1.000), GBDT(AUC=1.000), DT(AUC=0.967), and RF(AUC=0.945). In the validation cohort, the top five performers by AUC were: RF(AUC=0.812), LR(AUC=0.792), LightGBM(AUC=0.769), AdaBoost(AUC=0.746), and GBDT(AUC=0.742). Thus, the RF model demonstrated optimal performance. SHAP analysis indicated urea as the most significant contributor to prediction outcomes. Conclusion:A machine learning model based on routine laboratory indicators can accurately predict the 30-day mortality risk in elderly HLH patients.

With the acceleration of China's aging society，the incidence of ischemic stroke is increasing year by year，and carotid artery vulnerable atherosclerotic plaque is closely related to its development.Various imaging techniques have been used to assess the vulnerability of carotid plaques，but each technique has its own set of advantages and disadvantages in detecting vulnerability features.The purpose of this article is to summarize the clinical applications of imaging techniques for the assessment of carotid plaque vulnerability and the advantages and disadvantages of each technique.