Objective To investigate the value of qualitative and quantitative characteristics of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI in preoperative prediction of vessels encapsulating tumor clusters(VETC)pattern in hepatocellular carcinoma(HCC).Methods A total of 234 patients diagnosed with HCC by pathology were analyzed retrospectively.A total of 101 VETC-positive HCC patients and 133 VETC-negative HCC patients were included.All patients were divided into training group and validation group according to 7︰3.The training group data were used to construct a prediction model for VETC-positive HCC.Receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated to verify the diagnostic efficiency of the model.Calibration curve was drawn to verify the calibration of the model.Results Multivariate logistic regression analysis predicted the independent risk factors for VETC-positive HCC:portal phase peripheral washout[odds ratio(OR)6.493],necrosis or severe ischemia(OR 4.756),targetoid transitional phase or hepatobiliary phase(OR 0.307),and lesion to liver signal intensity ratio(LLR)on arterial phase(OR 0.074).The AUC of the training group in predicting VETC-positive HCC was 0.790[95%confidence interval(CI)0.720-0.859].The AUC of the validation group in predicting VETC-positive HCC was 0.779(95%CI 0.668-0.889).The calibration curve diagram showed that the calibration curve(the slope was 0.91)almost coincides with the ideal curve,indicating that the prediction model had better calibration.Conclusion The qualitative and quantitative characteristics of Gd-EOB-DTPA enhanced MRI can be used to predict VETC-positive HCC preoperatively,the independent risk factors of VETC include portal phase peripheral washout,necrosis or severe ischemia,targetoid transitional phase or hepatobiliary phase,and LLR on arterial phase.

Objective To investigate the value of the liver imaging reporting and data system v2018(LI-RADS v2018)and other imaging features in predicting preoperative risk and postoperative prognosis of isolated macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Patients with isolated hepatocellular carcinoma(HCC)confirmed by pathology after preoperative MRI examination were selected,and all patients were randomly assigned to a training group(n=146)and a validation group(n=62)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were used to screen independent prognostic factors of MTM-HCC and construct a nomogram.Patients were stratified into high-risk and low-risk subgroups based on the nomogram scores.Kaplan-Meier survival curves and Log-rank tests were used to compare the recurrence-free survival(RFS)among different subgroups of patients.Results Multivariate logistic regression analysis revealed that intratumoral vessels[odds ratio(OR)=3.480,95％confidence interval(CI)1.110-10.912,P=0.032],arterial phase hypovascular component ≥20％(OR=4.615,95％CI 1.728-12.321,P=0.002),and corona enhancement(OR=4.814,95％CI 1.816-12.766,P=0.002)were independent predictors of MTM-HCC.The nomogram constructed based on these indicators demonstrated area under the curve(AUC)of the receiver operating characteristic(ROC)curve was 0.834 and 0.764 for predicting MTM-HCC in the training and validation groups,respectively.The RFS predicted by the nomogram was significantly different between the high-risk and low-risk subgroups and both the pathologically confirmed MTM-HCC positive and negative groups(P＜0.05).Conclusion Intratumoral vessels,arterial phase hypovascular component ≥20％,and corona enhancement are independent predictors of MTM-HCC.The constructed nomogram based on these predictors demonstrates good diagnostic efficacy for MTM-HCC and has significant prognostic value for patients'RFS.

Objective To observe the value of the scoring model of MRI features for predicting proliferative hepatocellular carcinoma(HCC).Methods Data of 241 patients with pathologically confirmed HCC,including 90 cases of proliferative HCC and 151 cases of non-proliferative HCC were analyzed retrospectively.Univariate and multivariate logistic regression were used to compare the clinical and MRI findings evaluated according to liver imaging reporting and data system version 2018 between groups.The independent predictive factors of proliferative HCC were screened,and scores were assigned according to the weight,then a scoring model was constructed.Receiver operating characteristic(ROC)curve was drawn,and the area under the curves(AUC)were calculated to assess the predictive efficacy of this model.The patients were divided into high and low proliferation risk subgroups based on the optimal score thresholds.The recurrence free survival(RFS)rates and early RFS rates were compared between groups and subgroups.Results MRI showed tumor corona enhancement,arterial phase annular hyper-enhancement,intratumoral vessels,much focus parenchymal low enhancement and irregular tumor margins were all independent predictive factors for proliferative HCC(OR=3.287,2.362,4.542,2.997,2.379,all P＜0.05),which were then were scored with 7,5,9,7 and 5,respectively,with a total score of 0-33.AUC of the obtained scoring model for predicting proliferative HCC was 0.818.Taken 9 points as the optimal score thresholds,97 cases were assigned into high proliferation subgroup and 144 into low proliferation risk subgroups).Significant differences of RFS rates and early RFS rates were found between groups and subgroups(all P＜0.05).Conclusion MRI features scoring model could effectively predict proliferative HCC.

Objective:To develop a nomogram to predict vessels that encapsulate tumor cluster and/or microvascular invasion-positive hepatocellular carcinoma (VM-HCC) based on multiregional radiomics score derived from multisequence MRI.Methods:Clinical data of 209 patients with HCC undergoing radical liver resection at Affiliated Nantong Hospital 3 of Nantong University from January 2016 to December 2021 were retrospectively analyzed, including 149 males and 60 females, aged (58.5±9.2) years. Patients were divided into a training set ( n=146) and a testing set ( n=63). The patients in training set were further classified into two groups based on pathological results: the VM-HCC group ( n=76) and the non-VM-HCC group ( n=70). Radiomics features were extracted from the arterial phase and hepatobiliary phase images within the tumor, peritumor, and combined regions of interest. The arterial phase and hepatobiliary phase features from the same regions were integrated to obtain dual-sequence features. After feature selection, linear support vector machines (SVM) and linear regression machine learning classifiers were employed to construct radiomics models for different sequences and regions. The optimal radiomics model was selected based on the area under the receiver operating characteristic (ROC) curve from the testing set. Logistic regression analysis was performed to identify independent predictors of VM-HCC, and a visual nomogram was constructed using the results of the multivariate logistic regression analysis and the radiomics score of the optimal radiomics model. ROC curves were plotted, and area under curve (AUC) were calculated to evaluate the models’ discriminatory ability. Calibration curves and decision curve analysis (DCA) were utilized to assess the model’s calibration and clinical utility. Results:Among the radiomics models, the dual-sequence-combined region model based on the SVM classifier exhibited the best AUC in the testing set (AUC=0.764, 95% CI: 0.646-0.882). Multivariate logistic regression analysis indicated that HCC patients with protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels >40 mAU/ml ( OR=4.266, 95% CI: 1.921-9.473, P<0.001) had a higher risk of VM-HCC. The nomogram combining PIVKA-II>40 mAU/ml and radiomics score achieved AUC of 0.806 (95% CI: 0.733-0.867) in the training set and 0.817 (95% CI: 0.699-0.903) in the testing set for predicting VM-HCC. The calibration curves of the nomogram showed good fit in both the training and testing sets. DCA indicated that the model possesses good clinical utility. Conclusion:The nomogram based on multiregional radiomics score derived from multisequence MRI demonstrates a good predictive performance for VM-HCC, which could facilitate the risk stratification of recurrence in HCC patients.

Objective:To develop a nomogram to predict vessels that encapsulate tumor cluster and/or microvascular invasion-positive hepatocellular carcinoma (VM-HCC) based on multiregional radiomics score derived from multisequence MRI.Methods:Clinical data of 209 patients with HCC undergoing radical liver resection at Affiliated Nantong Hospital 3 of Nantong University from January 2016 to December 2021 were retrospectively analyzed, including 149 males and 60 females, aged (58.5±9.2) years. Patients were divided into a training set ( n=146) and a testing set ( n=63). The patients in training set were further classified into two groups based on pathological results: the VM-HCC group ( n=76) and the non-VM-HCC group ( n=70). Radiomics features were extracted from the arterial phase and hepatobiliary phase images within the tumor, peritumor, and combined regions of interest. The arterial phase and hepatobiliary phase features from the same regions were integrated to obtain dual-sequence features. After feature selection, linear support vector machines (SVM) and linear regression machine learning classifiers were employed to construct radiomics models for different sequences and regions. The optimal radiomics model was selected based on the area under the receiver operating characteristic (ROC) curve from the testing set. Logistic regression analysis was performed to identify independent predictors of VM-HCC, and a visual nomogram was constructed using the results of the multivariate logistic regression analysis and the radiomics score of the optimal radiomics model. ROC curves were plotted, and area under curve (AUC) were calculated to evaluate the models’ discriminatory ability. Calibration curves and decision curve analysis (DCA) were utilized to assess the model’s calibration and clinical utility. Results:Among the radiomics models, the dual-sequence-combined region model based on the SVM classifier exhibited the best AUC in the testing set (AUC=0.764, 95% CI: 0.646-0.882). Multivariate logistic regression analysis indicated that HCC patients with protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels >40 mAU/ml ( OR=4.266, 95% CI: 1.921-9.473, P<0.001) had a higher risk of VM-HCC. The nomogram combining PIVKA-II>40 mAU/ml and radiomics score achieved AUC of 0.806 (95% CI: 0.733-0.867) in the training set and 0.817 (95% CI: 0.699-0.903) in the testing set for predicting VM-HCC. The calibration curves of the nomogram showed good fit in both the training and testing sets. DCA indicated that the model possesses good clinical utility. Conclusion:The nomogram based on multiregional radiomics score derived from multisequence MRI demonstrates a good predictive performance for VM-HCC, which could facilitate the risk stratification of recurrence in HCC patients.

Objective:To study the risk factors of surgical therapy in neonates with necrotizing enterocolitis (NEC).Methods:From January 2016 to July 2020, neonates with a confirmed diagnosis of NEC (Bell's Stage Ⅱ and above) admitted to our hospital were retrospectively enrolled. They were assigned into surgical group and conservative group according to whether surgeries were performed. The conditions during perinatal period, clinical characteristics and laboratory examinations at the onset of NEC were compared between the two groups. Multivariate Logistic regression analysis was used to determine the risk factors of surgical therapy.Results:A total of 177 neonates with NEC were identified, including 62 cases (35.0%) in the surgical group and 115 cases (65.0%) in the conservative group. Multivariate Logistic regression analysis showed that male gender ( OR=3.178,95% CI 1.457~6.929, P=0.004), comorbidity with shock ( OR=3.434, 95% CI 1.112~10.607, P=0.032), mechanical ventilation>7 d before NEC onset ( OR=3.663, 95% CI 1.098~12.223, P=0.035) and lymphocytes <2.0×10 9/L ( OR=4.121, 95% CI 1.801~9.430, P=0.001) at the onset of NEC were independent risk factors for surgical therapy. Conclusions:Male gender, comorbidity with shock, mechanical ventilation >7 d before NEC and lymphocytopenia at the onset are independent risk factors for surgical therapy in neonates with NEC (Stage Ⅱ and above).

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Objective: To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the I_f inhibitor ivabradine trial (SHIFT). Method: A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes). Results: A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, P<0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), HR=0.56, 95%CI 0.33-0.97, P=0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), P=0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes). Conclusions: Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study. Clinical Trial Registry International standard randomized controlled trials registry, ISRCTN 70429960.

OBJECTIVETo investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/- mice and explore the effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro.

METHODSThe uremic apoE-/- mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/- mice, sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1, ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents using oil red O staining.

RESULTSThe relative area of the atherosclerotic plaques in the aortic root increased significantly in uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 µmol/L) obviously increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression of other cholesterol transporting receptors.

CONCLUSIONCRI can accelerate the progression of atherosclerosis through the mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36, which contributes to the formation of foam cells.

Animals ; Apolipoproteins E ; Cell Line ; Foam Cells ; chemistry ; Humans ; Indican ; pharmacology ; Lipids ; chemistry ; Macrophages ; chemistry ; Mice ; Mice, Inbred C57BL ; Plaque, Atherosclerotic ; pathology ; Renal Insufficiency, Chronic ; blood

Objective To investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/-mice and explore the effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro. Methods The uremic apoE-/-mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/-mice, sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1, ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents using oil red O staining. Results The relative area of the atherosclerotic plaques in the aortic root increased significantly in uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 μmol/L) obviously increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression of other cholesterol transporting receptors. Conclusion CRI can accelerate the progression of atherosclerosis through the mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36, which contributes to the formation of foam cells.