Pancreatic cancer （PC） has a high degree of malignancy and a 5-year survival rate of <10%， with the core molecular mechanisms of Kirsten rat sarcoma viral oncogene homolog （KRAS） mutations （90%）， inactivation of tumor protein p53/cyclin-dependent kinase inhibitor 2A/SMAD family member 4， and epigenetic dysregulation （including DNA methylation and non-coding RNA alterations）， which promotes the progression of PC. In recent years， breakthroughs have been made in targeted therapy， including the clinical application of KRASG12C inhibitors （sotorasib， adagrasib） and KRASG12D inhibitors， and the strategies targeting epidermal growth factor receptor， DNA repair （PARP inhibitors）， and immune microenvironment （combined therapies targeting PD-1 and PD-L1） have significantly improved the treatment outcome of PC. Nevertheless， drug resistance and tumor heterogeneity remain huge challenges. Precision medicine and combined therapies should be adopted in the future to improve the prognosis of patients.

Objective To assess the toxicity of anthracyclinc to left ventricle function in patients withbreast cancer,and to compare the clinical values between two-dimensional speckle tracking echocardiography (2D-STE) and 3D-STE.Methods 50 patients with breast cancer who had received surgical treatment and epirubicinbased chemotherapy were recruited to study groups.All the patients had undergone up to 6 cycles of chemotherapy.Different stages wcre identified according to accumulated doses of epirubicin reaching 0 mg/m2,120 mg/m2,240 mg/m2 and 360 mg/m2.2D-STE and 3D-STE parameters were measured before chemotherapy and after different stage of chemotherapy.The receiver operating characteristics curves (ROC) of parameters (2D-GLS,3D-GLS,3D-GCS,3DGAS) were graphed to evaluate the specificity and sensitivity of detecting dysfunction of the left ventricles.25 healthy volunteers were recruited to a control group.Results As compared with the control group and the baselines,2D-GLS and 3D-GCS was significantly declined (P ＜ 0.05),3D-GAS and 3D-GLS were significantly lowered after interim period and later period (P ＜ 0.05),while 3D-GRS was not changed significantly during the whole chemotherapy period.The ROC curves revealed the sensitivity of 2D-GLS,3D-GCS,3D-GLS and 3D-GAS for assessing dysfunction of the left ventricles was 60.7％,65.3％,62.7％,and 80.7％,while the specificity was 50.0％,54.0％,64.0％,and 82.0％,respectively.Conclusions As compared with 2D-STE,3D-STE can detect the dysfunction of left ventricles earlier and more accurately.Furthermore,the specificity and sensitivity of 3D-GAS are the highest among all parameters in detecting the early dysfunction of left ventricles.

BACKGROUND:Polychlorinated biphenyls inhibit the differentiation of P19 cels into cardiomyocytes. In the meanwhile, microRNAs play an important role in regulating cel differentiation.
OBJECTIVE:To explore the effect of microRNA-32(miR-32) on the polychlorinated biphenyls-inhibited differentiation of P19 cels into cardiomyocytes.
METHODS:P19 cels were co-cultured with 2.5 μmol/L polychlorinated biphenyls and 1% dimethyl sulfoxide. Afterwards, α-actinin, desmin, cTnI and GATA4 were identified by western blot assay.Wddwxrof polychlorinated biphenyls on the expression of miR-32 was evaluated by real-time PCR. Mouse eukaryotic vector expressing miR-32 was constructed by gene recombination technology,andtransfected into P19 celsfolowed byco-culturedwith2.5 μmol/Lpolychlorinated biphenylsand1% dimethyl sulfoxide. Then, expressions of differentiation-related proteins were detected by western blot assay.
RESULTS AND CONCLUSION:Polychlorinated biphenylsinhibited the differentiation of P19 cels into cardio myocytes anddecreased the miR-32 expression. Cel lines overexpressing miR-32 was successfuly established in mice.Furthermore, we found thatoverexpression of miR-32 weakens the inhibition of polychlorinated biphenyls to the differentiation of P19 cels into cardiomyocytes.