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 explore the clinical features and risk factors for pediatric severe Mycoplasma pneumoniae pneumonia (SMPP) complicated with pulmonary embolism. Methods:SMPP patients admitted to Department of Pediatrics, Jiaxing First Hospital and Pediatric Intensive Care Unit, Shanghai Children′s Hospital from December 2019 to December 2023 were included in this retrospective case-control study.According to whether they were complicated with pulmonary embolism, SMPP patients were divided into a pulmonary embolism group and a non-pulmonary embolism group.Clinical characteristics of the two groups, including general data, laboratory examination and imaging data were compared and analyzed.The t-test and Mann-Whitney rank-sum test were used to compare the measurement data, and the χ2 test was used to compare the count data.The risk factors of SMPP patients developing pulmonary embolism were analyzed by the univariate method. Results:There were 10 out of 62 SMPP children developing pulmonary embolism, showing an incidence of 16.13%.In the pulmonary embolism group, there were 5 boys and 5 girls, with a median age of 7.50 (5.75, 9.25) years.There were 52 children in the non-pulmonary embolism group, including 29 boys and 23 girls, with a median age of 6.50(5.00, 8.00)years.The hospitalization time, body temperature, total white blood cell count, neutrophil count, C-reactive protein levels, lactate dehydrogenase levels, prothrombin time, activated partial thromboplastin time, D-dimer (D-D) levels, fibrinogen degradation product levels, pleural effusion and atelectasis rates in the pulmonary embolism group were significantly higher than those in the non-pulmonary embolism group (all P<0.05). Fibrinogen levels in the pulmonary embolism group were significantly lower than those in the non-pulmonary embolism group ( P<0.05). Univariate Logistic regression analysis showed that the D-D level was a risk factor for SMPP patient developing pulmonary embolism.The receiver operating characteristic curve analysis revealed that the D-D level had the largest area under the curve for predicting pulmonary embolism of 0.990(95% CI: 0.972-1.000, P<0.001), with a sensitivity of 100%, a specificity of 92%, and a cut-off value of 4.63 mg/L. Conclusions:SMPP children complicated with pulmonary embolism are prone to high inflammation and impaired coagulation function.The increase of D-D levels is a risk factor for the development of pulmonary embolism in SMPP.

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.

Objective:To explore the effects of deep hyperthermia on chemotherapy-related adverse effects and immune-inflammatory indicators in the patients undergoing postoperative adjuvant chemotherapy for colorectal cancer.Methods:This retrospective study included 52 patients who underwent surgery for colorectal cancer at the Affiliated Zhongshan Hospital of Dalian University from September 2021 to December 2023. The patients were divided into two groups based on treatment method: the combination group ( n=29) received postoperative adjuvant chemotherapy combined with deep hyperthermia, while the chemotherapy group ( n=23) received postoperative adjuvant chemotherapy alone. Both groups were treated with the XELOX regimen (oxaliplatin + capecitabine). The degree of bone marrow suppression during treatment was assessed by analyzing peripheral blood parameters, including hemoglobin, leukocyte count, neutrophil count, and platelet count. Immune-inflammatory indicators, including complement, procalcitonin (PCT), interleukin-6 (IL-6), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were compared before and after treatment in both groups to evaluate the effects of deep hyperthermia on the immune-inflammatory response. Chi-square test or Fisher's exact test (two-tailed) was used to compare bone marrow suppression rates, and the immune-inflammatory indicators between the two groups were compared using t-tests or non-parametric tests, depending on whether the data conformed to a normal distribution. Results:In terms of myelosuppression, the incidence rates of moderate to severe decreases in leukocytes, neutrophils, platelets, and hemoglobin in the combination group were 31%, 31%, 21%, and 14%, respectively, compared to 52%, 61%, 48%, and 9% in the chemotherapy group. The change in PCT levels before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.010). Both the combination group and the chemotherapy group showed significant reductions in SII, NLR and PLR after treatment, and the differences were statistically significant (all P < 0.05). The change in NLR before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.031). Conclusions:Deep hyperthermia can alleviate chemotherapy-induced adverse effects such as thrombocytopenia and neutropenia in patients undergoing postoperative adjuvant chemotherapy for colorectal cancer. It also appears to improve the inflammatory response in these 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.

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.

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.