Objective To establish a uremic apoE-/- mouse model to observe serum biochemical parameters and features of aortic root atherosclerosis (AS) in the model. Methods A uremic model was induced surgically in apoE-/- mice: electrocautery of the right kidney at 8 weeks of age and nephrectomy (NX) of the left one 2 weeks later. Control mice were sham-operated. Two weeks after NX, renal functions were detected in the uremic and control mice to evaluate the efficiency of the model. After 10 weeks of NX, blood samples were taken to determine serum biochemical parameters, and aortic root was collected for frozen sections to investigate the lesion features of AS. Results Two weeks after NX, renal functions declined significantly in the uremic mice compared with the control ones, and remained stable 8 weeks later either in males or in females. Ten weeks after NX, serum levels of TCH, TG and LDL-C were dramatically higher in the uremic mice than in the controls, whereas no differences in serum HDL-C or glucose concentration were found between the two groups. Aortic root plaque relative area increased significantly in the uremic mice compared with the controls either in males or in females; more-over, the lesion area was larger in female mice than in male ones. Conclusion We established a uremic apoE-/- mouse model successfully, and this model is characterized by accelerated atherogenesis which is associated with an increase in serum lipid profile. This experimental model can be a useful tool to study the pathogenesis and therapeutic strategies of uremic AS.

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 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).

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.

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