BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans ; Male ; Erectile Dysfunction/metabolism* ; Hyperuricemia/metabolism* ; Adult ; Middle Aged ; Cross-Sectional Studies ; Glycated Hemoglobin/metabolism* ; Blood Glucose/metabolism* ; Uric Acid/blood* ; Young Adult ; Triglycerides/blood* ; Adolescent ; Cholesterol, LDL/blood* ; Penile Erection/physiology* ; Surveys and Questionnaires

Objective To explore the predictive value of radiomics for postoperative pancreatic fistula, infection, and long-term survival in patients with pancreatic ductal adenocarcinoma (PDAC). Methods 206 patients who received radical resection of pancreatic cancer in Zhongshan Hospital, Fudan University from January 2014 to December 2020 and were pathologically confirmed as PDAC after surgery were retrospectively selected, all of whom had complete surgical data and long-term follow-up data. Pyradiomics was used to analyze the enhanced CT images of all patients and extract radiomics features. LASSO dimensionality reduction combined with logistic regression analysis was used to construct a predictive model for pancreatic fistula and abdominal infection after PDAC surgery, and evaluating the model’s effectiveness using ROC curves. A long-term survival prediction model for PDAC patients was constructed using LASSO dimensionality reduction combined with Cox regression analysis, and patient risk scores were calculated. The patients were divided into high-risk and low-risk groups based on the median, and the survival curves were compared to evaluate the effectiveness of the model. The imaging omics features with the highest weight were divided into high expression group and low expression group according to the median, and the prognostic differences and clinical features were compared. Radiomics and clinical features were combined to analyze the influencing factors of long-term prognosis and construct a clinical imaging comprehensive model. Results A total of 1 595 radiomics features were extracted. A predictive model for pancreatic fistula and infection after PDAC surgery was constructed, with AUC values of 0.81 and 0.79, respectively. The PDAC long-term survival prediction model was successfully constructed, and the prognosis of the high-risk group was worse than that of the low-risk group (P<0.001). The weight of the radiomics feature “log-sigma-5-mm-3D_glszm_ZonePercentage” was 59.557. The CA19-9 level in the high expression group is higher than that in the low expression group (P=0.017), and there is a statistically significant difference in survival curves between the two groups (P=0.021). The comprehensive clinical imaging model suggested that age, AJCC stage, lymph infiltration, CA19-9 level and imaging characteristics were risk factors for long-term prognosis of PDAC patients (HR=1.028, 4.084, 2.566, 1.232 and 2.536). Conclusions The predictive model based on radiomics has good predictive performance for pancreatic fistula, infection, and long-term prognosis after PDAC surgery. Patients with high expression of the radiomics feature “log-sigma-5-mm-3D_glszm_ZonePercentage” face poorer prognosis.

Objective To compare the predictive effects of logistic regression and machine learning models on occurrence of low peripheral oxygen saturation(SpO2)during one-lung ventilation(OLV)in pa-tients undergoing thoracoscopic partial pulmonary resection(TPPR),and to explore risk factors of low SpO2.Methods A total of 127 patients undergoing unilateral TPPR from August 1,2022 to April 30,2023 were enrolled,61 males and 66 females,aged 18-80 years,ASA physical status Ⅰ-Ⅲ.Based on whether intraoperative SpO2 during OLV was less than 90％,the patients were divided into two groups:low SpO2 group(n=21)and normal SpO2 group(n=106).Perioperative data were collected and a predic-tive model was constructed using logistic regression.This model was compared with predictive models con-structed using five machine learning models,including random forest(RF),extreme gradient boosting(XGBoost),decision tree(DT),logistic regression(LogR),and support vector machine(SVM).The re-ceiver operating characteristic(ROC)curve was plotted,and the performance of the predictive models were evaluated by the area under the curve(AUC).The best output model was interpreted using Shapley additive explanations(SHAP)to identify the risk factors of low SpO2 during OLV in patients undergoing TPPR.Results Multivariate logistic regression analysis showed that increased age(OR=1.087,95％CI 1.006-1.175,P=0.036),increased BMI(OR=1.299,95％CI 1.050-1.608,P=0.016),increased pre-operative blood glucose(OR=2.028,95％CI 1.378-2.983,P＜0.001),and decreased RV/TLC％Pred(OR=0.936,95％CI 0.892-0.983,P=0.008)were independent risk factors of low SpO2 during OLV.The predictive model was Logit(p)=-10.098+0.08 × age+0.231 × BMI+0.633 × blood glu-cose-0.059 × RV/TLC％Pred,with an AUC of 0.873(95％CI 0.803-0.943,P＜0.001).After optimi-zing parameters of machine learning models using grid search combined with five-fold cross-validation,the model training results were satisfactory.ROC curve analysis showed that the AUC for RF was 0.921(95％CI 0.840-0.979),XGBoost was 0.940(95％CI 0.812-0.981),DT was 0.919(95％CI 0.828-0.982),LogR was 0.892(95％CI 0.831-0.980),and SVM was 0.922(95％CI 0.832-0.982).XG-Boost had the highest AUC,surpassing the logistic regression model.SHAP analysis indicated that the most important risk factors in the XGBoost output model were increased age,BMI,and preoperative blood glucose concentration.Conclusion Increased age,BMI,and preoperative blood glucose concentration are signifi-cant risk factors for low SpO2 during OLV in patients undergoing TPPR.The XGBoost machine learning model outperformed traditional logistic regression in predicting the occurrence of low SpO2 during OLV.XG-Boost can analyze more complex relationships between variables and outcomes and provide more accurate in-dividualized predictions of the risk of low SpO2 during OLV.

Objective:To investigate the correlation between the waiting time for radiotherapy after induction chemotherapy and the prognosis of locally intermediate and advanced nasopharyngeal carcinoma, as well as its optimal time.Methods:Retrospective analysis of 101 patients with locally intermediate and advanced nasopharyngeal carcinoma admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from 2017 to 2020 was performed. All patients received at least 2 courses of induction chemotherapy followed by radical radiotherapy. The waiting time for radiotherapy was defined as the time from the end of induction chemotherapy to the start of the first radiotherapy. The relationship between waiting time for radiotherapy and other factors (age, gender and stage, etc.) with progression-free survival (PFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) was analyzed through Cox model. The median waiting time for radiotherapy with 3 weeks was used as the boundary, and all patients were divided into ≤3 weeks and>3 weeks groups. The PFS, LRFS and DMFS between two groups were compared using Kaplan-Meier survival analysis. P<0.05 was considered as statistical significance. Results:Cox-regression analysis showed that the waiting time was correlated with PFS, LRFS, and DMFS (all P<0.05). Kaplan-Meier survival analysis suggested that the PFS, LRFS and DMFS in the ≤3 weeks group were significantly better than those in the >3 weeks group (all P<0.05). Under the premises of the T 3 stage, N 2 stage and the increased EB virus DNA replication levels before treatment, the PFS, LRFS and DMFS in the ≤3 weeks group were significantly better than those in the >3 weeks group (all P<0.05). Conclusions:The waiting time for radiotherapy is one of the factors affecting clinical prognosis of locally intermediate and advanced nasopharyngeal carcinoma. The earlier the time, the better the prognosis. Radiotherapy should be delivered within 3 weeks.

Objective To study the accuracy of traditional basilar membrane displacement evaluation criteria for evaluating hearing compensation performance of round window-stimulated middle ear implant, so as to provide the theoretical basis for performance evaluation of round window-stimulated middle ear implant. Methods An acoustic microscopic finite element model of cochlea was constructed based on experimental data of the cochlea geometry. Reliability of this model was verified by comparison with experimental measurement values of inner hair cell, outer hair cell, tectorial membrane displacement. Based on this model, the displacement of basilar membrane and the stereocilia shear displacement of inner hair cells under forward stimulation and round-window stimulation were comparatively analyzed. Using the stereocilia shear displacement of inner hair cells as the criterion for sense of sound, the equivalent sound pressure level (SPL) deviation under round-window stimulation was studied when using traditional basilar membrane displacement as evaluation criterion. Results At 5 kHz characteristic frequency of the studied slice of cochlea, under sound pressures with the same amplitude, the displacement of basilar membrane and the stereocilia shear displacement of inner hair cells under round-window stimulation were lower than that under forward stimulation. Conclusions Under forward stimulation, the inner hair cells were more excited and the performance for sense of sound was better than that under round-window stimulation. Concurrently, using the displacement of basilar membrane under forward stimulation as the criterion of hearing compensation performance would overestimate hearing compensation performance of middle ear implant under round-window stimulation; but the deviation was relatively small, which was a relatively reliable evaluation method.

Objective:To investigate the correlation of preoperative peripheral lymphocyte-to-monocyte ratio(LMR)with the biochemical relapse and prognosis in prostate cancer(PCa)patients treated with endocrine therapy after radical prostatectomy(RP).Methods:Clinical data of 306 prostate cancer patients treated with endocrine therapy after radical prostatectomy were retrospectively analyzed in our hospital from June 2008 to June 2019.The end point of observation was biochemical relapse-free survival(RFS)in all patients receiving RP.The best cutoff value of preoperative LMR was calculated by receiver operating characteristic(ROC)curve.All patients were divided into the high LMR group(LMR≥2.8, n=93, 30.4%)and the low LMR group(LMR<2.8, n=213, 69.6%). The differences in clinical indicators of PCa were compared between high and low LMR groups.CoX regression model on the risk ratio of single and multiple factors were used to analyze the survival effect of preoperative LMR on the prognosis of PCa patients undergoing endocrine therapy after operation.Results:The median follow-up time was ranged from 4 to 132 months.The area under the ROC curve of LMR was 0.582(95% CI: 0.511-0.652, P<0.05), and the cutoff value of the preoperative LMR was 2.8, which was significantly associated with clinical T stage( P=0.023)and lymphatic metastasis( P=0.031). Kaplan-Meier analysis demonstrated that the low LMR group had a short RFS and a poor prognosis(31.0 months vs.38.5 months)than those in the high LMR group( P<0.05). Lymphatic metastasis and preoperative LMR were independent predictors for RFS in PCa patients treated with endocrine therapy after radical prostatectomy. Conclusions:Preoperative peripheral LMR can be used as an auxiliary indicator of the prognosis in PCa patients treated with endocrine therapy after radical prostatectomy.

Objective:To evaluate the prognostic value of preoperative red cell distribution width to platelet ratio on prostate cancer patients treated with endocrine therapy after radical prostatectomy.Methods:The clinical data of 349 prostate cancer patients treated with endocrine therapy after radical prostatectomy in our hospital from October 2007 to October 2018 were retrospectively analyzed.Among all the patients, the average age was 67 years old(ranged 42 to 84 years). The preoperative newly diagnosed PSA level was 4.2-499.2 ng/ml(average 30.6 ng/ml). 158 cases had a Gleason score of more than 8. 191 cases had a Gleason score of below than 8. According to tumorous staging, 151 patients were staged less than or equal to stage T 2b, 110 patients were staged as stage T 2c, 88 patients were staged equal or greater than stage T 3a. 295 patients were staged less than 1.15 ng/(ml·cm 3)of prostate specific antigen density, 54 patients were staged equal or greater than 1.15 ng/(ml·cm 3). There were 86 cases of seminal vesicle invasion and 263 cases of non-seminal vesicle invasion. There were 121 patients with low risk of prostate cancer, 83 patients with medium risk, and 145 patients with high risk. All patients received endocrine therapy after radical prostatectomy with androgen deprivation therapy (ADT). End point of observation was biochemical recurrence-free survival (RFS) with PCa patients treated with endocrine therapy after radical prostatectomy. Patients were categorized in two groups with high RPR and low RPR values using a cut-off point as calculated by the receiver-operating curve analysis.Correlations between RPR and clinical characteristics were analyzed.The prognostic analysis of preoperative RPR on prostate cancer patients treated with endocrine therapy after radical prostatectomy was estimated using Kaplan-Meier analysis and Cox proportional hazards models. Kaplan-Meier method was used to draw the survival curve. Meanwhile, univariate and multivariate Cox regression were used to explore factors influencing the prognosis of PCa patients. Results:of the 349 cases, ranging 4-132 months. Biochemical recurrence with PCa patients occurred in 93 cases, and 256 patients were not biochemical recurrence.The ideal cutoff value of preoperative RPR was 0.27(95% CI 0.502-0.653, P<0.05)determined by the ROC curve, by which the 349 patients was divided into the high RPR group of 66 patients(18.9 %) and the low RPR group of 283 patients(81.1 %). Preoperative RPR was significantly associated with Gleason score ( P=0.005), newly diagnosed tPSA value ( P=0.000), tumor T stage ( P=0.031), PCa risk scale ( P=0.037), positive margin ( P=0.030). The RFS in the high RPR group(26.0 months)was shorter than that in the low RPR group(35.0 months)( P<0.001). In univariate analysis, Gleason score ( HR=1.579, 95% CI 1.049-2.376, P=0.028), serum newly diagnosed tPSA ( HR=2.979, 95% CI 1.655-5.362, P=0.000), tumor T stage( HR=1.292, 95% CI 1.009-1.653, P=0.042), preoperative RPR value ( HR=3.555, 95% CI 2.339-5.401, P=0.000) were prognostic factors ( P<0.05). Cox multivariate analysis showed that higher newly diagnosed tPSA value( HR=1.917, 95% CI 1.033-3.558, P=0.039)and higher RPR value( HR=3.086, 95% CI 1.994-4.775, P=0.000) were independent predictors for endocrine therapy after radical prostatectomy of PCa( P<0.05). Conclusions:Preoperative RPR was an independent predictor for poor prognosis in PCa patients treated with endocrine therapy after radical prostatectomy.

Objective To investigate the clinical effect of radiofrequency ablation (RFA) combined with non-specific sequential immunotherapy (IM) for early hepatocellular carcinoma (HCC),and analyze the factors affecting prognosis of patients after RFA.Methods The prosepctive study was conducted.The clinicopathological data of 72 early HCC patients who were admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from January 2009 to October 2015 were collected.Patients were divided into 3 groups by random number table:patients in group A underwent single RFA therapy;patients in group B underwent RFA + non-specific sequential IM (1-3 times);patients in group C underwent RFA + non-specific sequential IM (≥ 4 times).RFA was performed by the same doctors team,and non-specific sequential IM planning included thymalfasin + interleukin-2 (IL-2).Observation indicators:(1) treatment situations;(2) follow-up and survival;(3) analysis of prognostic factors after RFA.Follow-up using outpatient examination was performed to detect tumor recurrence and overall survival up to December 2015.Measurement data with normal distribution were represented as (x) ± s,and comparison among groups were evaluated with the ANOVA.Comparison of count data were analyzed using the chi-square test.The curve,rate and time of tumor recurrence after treatment,overall survival curve and time were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.The univariate analysis and multivariate analysis were respectively done using the COX proportional hazard regression model.Results Seventy-two patients were screened for eligibility,including 31 in group A,22 in group B and 19 in group C.(1) Treatment situations:patients in 3 groups underwent RFA,and contrast enhanced ultrasound showed complete tumors ablation at 5 days postoperatively.Patients in group B and C didn't have significant adverse reactions after RFA during IM therapy.(2) Follow-up and survival:72 patients were followed up for 2-66 months after treatment,with a median time of 34 months.The 1-year tumor recurrence rates after treatment in group A,B and C were respectively 19.4％,13.6％ and 10.5％,with no statistically significant difference (x2=0.714,P＞0.05).The median tumor recurrence times in group A,B and C were respectively 24.0 months,30.0 months and 33.0 months,with no statistically significant difference (x2 =3.283,P＞0.05).The median overall survival times in group A,B and C were respectively 46.0 months,56.0 months and 57.0 months,with a statistically significant difference (x2=7.079,P＜0.05).There were statistically significant differences between group A and group B and C (x2 =4.566,4.243,P＜0.05),and no statistically significant difference between group B and group C (x2 =0.078,P＞0.05).(3) Analysis of prognostic factors after RFA:results of univariate analysis showed that initial tumor,tumor number,Barcelona clinic liver cancer (BCLC)staging and sequential IM after RFA were related factors affecting prognosis of early HCC patients [hazard ratio (HR)=2.636,2.530,0.145,0.582,95％ confidence interval (CI):1.218-5.703,1.110-5.767,0.041-0.517,0.321-0.867,P＜0.05].Results of multivariate analysis showed that tumor number ＞ 1,staging B of BCLC and without sequential IM after RFA were independent risk factors affecting prognosis of early HCC patients (HR=2.376,2.683,0.567,95％CI:1.080-5.229,1.530-21.112,0.335-0.962,P＜0.05).Conclusions The non-specific sequential IM of thymalfasin + IL-2 can prolong survival time of early HCC patients after RFA.Tumor number ＞ 1,staging B of BCLC and without sequential IM after RFA are independent risk factors affecting prognosis of early HCC patients.

The article is study about range of motion on lower extremities on Guides to the Evaluation of Permanent Impairment. We reviewed the latest range of motion concept about lower extremities evaluation of GEPI. We also introduced measurement and procedure of range of motion evaluation. To provide advice for construction of disability evaluation system in China.