Objective To study the protective effects and mechanism of sacubitril(Sac)/valsartan(Val)on cardiomyocytes of rabbits with heart failure induced by doxorubicin(DOX).Methods Thirty New Zealand rabbits were selected to establish DOX-induced heart failure rabbit model.Twenty-five rabbits with successful modeling were randomly assigned to model group(DOX group,n=9),DOX+Val group(n=8),and DOX+Sac/Val group(n=8);and another 8 New Zealand rabbits were selected as blank group.The DOX+Val group was gavaged with 4.65 mg/kg Val suspension each time,the DOX+Sac/Val group was gavaged with 9.3 mg/kg Sac/Val suspension each time,and the blank group and DOX group were gavaged with equal volume of distilled water each time.Each group was gavaged twice a day for 8 weeks.After 8 weeks of administration,echocardiography was used to measure left ventricular end-diastolic diameter(LVDD),left ventricular end-systolic diameter(LVSD),left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS).The heart mass index(HMI)and left ventricular mass index(LVMI)were calculated.The pathological morphology and myocardial fibrosis of myocardial tissue were observed by hematoxylin-eosin(H-E)and Masson staining.The ultrastructure of cardiomyocytes was observed by transmission electron microscope.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining was used to observe cardiomyocytes apoptosis and apoptosis rate was calculated.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),high-sensitivity cardiac troponin I(Hs-cTNI),angiotensin Ⅱ(Ang Ⅱ),aldosterone(ALD),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),cyclic guanosine monophosphate(cGMP),and protein kinase G(PKG)in serum.Quantitative polymerase chain reaction(qPCR)was used to detect the expression of natriuretic peptide receptor A(NPR-A),cGMP-specific phosphodiesterase 5A(PDE5A[cGMP]),PKG,B-cell lymphoma 2(Bcl-2),Bcl-2 associated X protein(Bax),and cysteine aspartate protease 3(caspase 3)mRNA in myocardial tissue.Western blotting was used to detect the expression of phosphorylated cAMP response element-binding protein(p-CREB),phosphorylated Bcl-2 related death promoting factor(p-Bad),Bcl-2,Bax,and caspase 3 proteins in myocardial tissue.Results Compared with the blank group,the LVDD and LVSD in the DOX group were increased(both P<0.01),the LVEF and LVFS were decreased(both P<0.01)and the HMI and LVMI were increased(both P<0.01);the apoptosis and apoptosis rate of cardiomyocytes were increased(P<0.01);the levels of NT-proBNP,Hs-cTNI,Ang Ⅱ,ALD,ANP,BNP,cGMP and PKG and the expression of NPR-A,PDE5A(cGMP),PKG,p-CREB,Bax and caspase 3 were all increased(all P<0.01),while the expression of Bcl-2 was decreased(P<0.01),and the expression of p-Bad had no significant difference(P>0.05).Compared with the DOX group,the LVDD and LVSD of the DOX+Sac/Val group and DOX+Val group were decreased(all P<0.01),the LVEF and LVFS were increased(all P<0.01)and the HMI and the LVMI were decreased(all P<0.01);the apoptosis and apoptosis rate of cardiomyocytes were decreased(all P<0.01);the levels of NT-proBNP,Hs-cTNI,Ang Ⅱ,ALD,ANP,BNP,cGMP and PKG and the expression of NPR-A,PDE5A(cGMP),PKG,Bax and caspase 3 were all decreased(all P<0.01),while the expression of Bcl-2 was increased(P<0.01);and the expression of p-CREB and p-Bad was increased in the DOX+Sac/Val group(both P<0.01),but there was no significant difference in the DOX+Val group(both P>0.05).Compared with the DOX+Val group,the DOX+Sac/Val group showed a decrease in all indicators except for LVEF,LVFS,NPR-A,ANP,BNP,cGMP,PDE5A(cGMP),PKG,p-CREB,p-Bad,and Bcl-2,which were all elevated(all P<0.05).Myocardial pathology and transmission electron microscopy showed that Sac/Val effectively protected cardiomyocytes,reduced cardiomyocytes apoptosis and myocardial fibrosis,and these effects were significantly better than those of Val.Conclusion Sac/Val can effectively reduce cardiomyocytes apoptosis,improve cardiac function and reduce myocardial fibrosis in rabbits with heart failure,and these effects are superior to Val.Its mechanism may be related to activating the NPR-A/cGMP/PKG signaling pathway and inhibiting renin-angiotensin-aldosterone system.

Purpose To investigate the value of T2WI MR-based radiomics nomogram for predicting deep stromal invasion of cervical cancer preoperatively.Materials and Methods Retrospective analysis of 164 consecutive patients with early-stage cervical cancer with postoperative pathological findings and preoperative MR images admitted to two medical centers in the Affiliated Hospital of Southwest Medical University(first center)and the Huaihe Hospital of Henan University(second center)from May 2018 to August 2022.The data in the first center(n=1 14)and the second center(n=50)were divided into the training and validation cohorts,respectively.To segment T2WI images in the 3D Slicer software and to extract image features in the python software.The radiomic features were selected in the training cohort.Based on the selected features,support vector machine prediction model was constructed.Univariate Logistic regression was used to select clinicopathological risk factors,then,multi-variate Logistic regression combined with radiomics score was used to construct radiomics nomogram,diagnostic performance of the radiomics model,clinical prediction model and radiomics nomogram model were assessed by receiver operating characteristic analysis.The predictive efficacy of the different models were compared.Results The 12 radiomics features were selected out.The FIGO staging and radiomics score were included in the multifactor Logistic regression to build the radiomics nomogram for predicting deep stromal invasion.The results showed that the predictive performance for the radiomics nomogram model was better than the clinical prediction model(in validation cohort:area under the curve was 0.845 vs.0.717;Z=2.728,P=0.006).Conclusion Radiomics nomogram based on T2WI is of high value for predicting deep stromal invasion of cervical cancer preoperatively.

Objective:To investigate the current situation of intravenous infusions of outpatients in our hospital to obtain the infor-mation and data of infusion characteristics in order to provide the basis for the safe and reasonable application of infusions. Methods:Totally 346 cases of outpatients with infusions were selected from the infusion room during May and June in 2017. The rationality of in-fusions was analyzed according to the guidelines of clinical application of antibiotics(2015 edition) and the diagnosis and treatment of related diseases. Results:In the 346 cases of infusion patients,men accounted for 36.13% and women accounted for 63.87%. The order of department ranked top was department of reproductive medicine, dermatology, respiratory medicine and urology respectively accounting for 18.79%,16.47%,13.29% and 10.12%. The order of intravenous infusions ranked top was phloroglucinol,levoflox-acin,moxifloxacin and human serum albumin respectively accounting for 11.46%,8.05%,6.83% and 5.85%. Antimicrobial drugs accounted for 42.77% and the unreasonable prescription accounted for 29.76%. The main unreasonable reasons were without indica-tions,appropriate usage and unsuitable solvent respectively accounting for 51.46%,40.78% and 5.83%. The lack of infusion neces-sity accounted for 10.98%. Conclusion: The irrational proportion in the hospital outpatient intravenous infusion room is high (29.76%),and antibiotics use accounts for higher proportion(42.77%). Most patients still have the necessity of infusion,so outpa-tient infusion can not be canceled,however,management should be strengthened.

Objective: To analyze the serum concentration results of sodium valproate (VPA) and carbamazepine (CBZ) and explore the relationship between the serum concentration and age, clinical efficacy and adverse reactions to provide reference for the rational clinical use.Methods: Retrospective analysis was used to collect the clinical data of the patients from March 2015 to March 2016, including gender, age, clinical diagnosis, medication, usage and dosage, the last medication time, sampling time, blood concentration and the other related data, and the data were compared and analyzed.Results: Totally 2608 samples were collected, including 2 205 ones for VPA and 403 ones for CBZ.Totally 1 123 cases (50.93%) of VPA and 292 cases (72.46%) of CBZ were within the range of therapeutic windows.In the 2 205 cases of VPA, 1 814 cases (82.27%) were with single drug treatment, and the serum concentration lower than the lower limit of therapeutic window accounted for 790 cases (43.55%) with the effective rate of 43.55% for epilepsy.The serum concentration within the range of therapeutic window accounted for 921 cases (50.77%) with the effective rate of 88.27% for epilepsy, and that higher than the higher limit of therapeutic window accounted for 103 cases (5.68%) with the effective rate of 81.55%.As for CBZ, the number was 58 cases (22.39%) with the effective rate of 48.28%, 195 cases (72.29%) with the effective rate of 79.49% and 6 cases (2.32%) with the effective rate of 83.34%, respectively.Totally 391 cases (87.21%) of VPA combined with the other antiepileptic drugs, such as levetiracetam and lamotrigine.The effect of age on the serum concentration of VPA and CBZ was significant (P<0.05).Conclusion: There are great individual differences in serum concentration of VPA and CBZ among patients.The therapeutic effect and adverse reactions of VPA and CBZ are closely related to the serum concentration.Monitoring the serum concentrations may provide evidence for the rational administration and plays an important role in the treatment of epilepsy.