BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Objective:To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats.Methods:UcMSC was amplified and cultured in vitro. Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results:Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P<0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P<0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P<0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P<0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P<0.000 1). Conclusion:Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.

Objective To explore the value of contrast-enhanced ultrasound(CEUS)for predicting differentiation degree of hepatocellular carcinoma(HCC).Methods Totally 86 HCC patients confirmed by postoperative pathology were retrospectively enrolled and divided into poorly differentiated,moderately differentiated and highly differentiated groups according to postoperative Edmondson-Steiner grading.Preoperative CEUS parameters were compared among groups,and binary logistic regression was used to analyze CEUS-related independent predictors of HCC with different differentiation.The receiver operating characteristic curves of parameters being significant different among groups were drawn,the areas under the curve(AUC)were calculated,and the efficacy for predicting HCC with different differentiation degree was evaluated.Results There were 29 cases in poorly differentiated group,37 in moderately differentiated group and 20 cases in highly differentiated group.The arrival time of contrast agent in poorly differentiated group was earlier than that in moderately and high differentiated groups(both P＜0.05),while in moderately differentiated group was not significantly different with that in highly differentiated group(P＞0.05).The washout grade were significantly different between each 2 groups(all P＜0.05).The arrival time of contrast agent and washout grade were independent predictors of highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC,and washout grade also was independent predictor of highly or moderately differentiated HCC(all P＜0.05).The AUC of the arrival time of contrast agent for predicting highly or moderately differentiated,highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC was 0.615,0.787,0.690 and 0.724,respectively,while of washout grade was 0.801,0.927,0.795 and 0.841,respectively.Conclusion CEUS could be used to effectively predict differentiation degree of HCC.

Objective To investigate the clinical effect of transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) (TACE-MWA) versus repeat resection (RR) in the treatment of recurrent hepatocellular carcinoma (RHCC). Methods A total of 178 patients with RHCC who were admitted to The Second People's Hospital of Neijiang from June 2015 to September 2020 were enrolled, and according to the treatment modality, they were divided into RR group with 64 patients and TACE-MWA group with 114 patients. Baseline demographic data, liver function, and tumor conditions before treatment were recorded, and the patients were followed up to October 2021 to compare postoperative overall survival (OS) time and recurrence-free survival (RFS) time between the two groups. Subgroup analysis based on recurrence pattern (recurrence time and tumor size) was performed, and the influencing factors for prognosis were analyzed. The independent samples t -test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data; the Kaplan-Meier method was used for postoperative survival rate, the Log-rank test was used for survival difference analysis, and a multivariate Cox regression analysis was used to investigate independent risk factors for survival. Results The multivariate analysis showed that tumor diameter, alpha-fetoprotein (AFP) level, alanine aminotransferase, albumin, and time to recurrence were independent prognostic factors for OS (all P < 0.05), and AFP level and time to recurrence were independent prognostic factors for RFS (both P < 0.05). For RHCC with late recurrence (> 2 years), there were significant differences between the two groups in median OS (54.0 months vs 36.0 months, χ 2 =6.171, P =0.013) and median RFS (28.0 months vs 21.0 months, χ 2 = 5.211, P =0.022). For RHCC with a tumor diameter of ≤5 cm, there was a significant difference in median OS between the two groups (33.0 months vs 27.0 months, χ 2 =6.447, P =0.011). Conclusion RR has a similar clinical effect to TACE-MWA in RHCC with early recurrence or a tumor diameter of > 5 cm, but RR should be the first choice for RHCC with late recurrence or a tumor diameter of ≤5 cm.

In order to meet the needs of contemporary society for medicine and cultivate high-quality compound medical talents, Chongqing Medical University has carried out the "organ system-centered" urogenital system integration curriculum reform. In the practice of integrated curriculum teaching, students have deepened their systematic understanding of medical knowledge, enhanced their enthusiasm and initiative in classroom learning, cultivated students' logical thinking ability, and improved students' innovative scientific research ability, by reorganizing the curriculum system, rewriting textbooks, improving the teaching environment, forming a teaching team, and reforming teaching methods, which laids the foundation for the further improvement of the medical curriculum.

In order to meet the social demand for ultrasound talents, a layered training system of ultrasound medical talents suitable for China's national conditions has been explored. The department of ultrasound of West China Hospital of Sichuan University has formulated and implemented a "three-layers" ultrasound education and training system in combination with its own reality. The first layer mainly refers mastering the basic ultrasound examination ability mainly through relevant ultrasound theoretical knowledge and basic operation skills training. The second layer is based on the first level to further master the ability of ultrasound diagnosis and differential diagnosis of common and frequently occurring diseases in various systems, and to be capable of engaging in basic ultrasound teaching and scientific research. The third layer means mastering the ability of ultrasound diagnosis, evaluation and interventional diagnosis and treatment of difficult and specialized diseases, grasping the latest development direction of the sub-specialty, and having the ability to engage in ultrasound teaching and clinical research. The results show that the "three-layers" ultrasound education and training system conforms to China's national conditions and is worthy of reference and promotion.

Objective To observe manifestations of neuroendocrine tumors of pancreas (NETP) in conventional ultrasound and contrast enhanced ultrasonography (CEUS).Methods Imaging features of histopathologically proved NETP in 90 patients were retrospectively analyzed.Results Conventional ultrasound was performed in all 90 patients,while CEUS was performed in 15 patients.Among all 90 cases,single lesion was found in 85 cases,while multiple lesions were found in 5 cases.The tumors located in pancreatic head (n =41),pancreatic body (n =13) or tail (n =36),respectively.The lesions in 81 cases were hypoechoic,8 were complex echoic and 1 was anechoic,with diameters ranged from 0.80 cm to 12.50 cm.Well-defined boundary of lesions were found in 67 cases,and ill-defined boundary of lesions were found in the other 23 cases.Regular shape lesions were found in 64 cases,while irregular shape lesions were found in 26 cases.Color Doppler ultrasound showed abundant tumor blood flow signals in 35 cases.Main pancreatic duct dilatation was found in 14 cases.Among 15 cases underwent CEUS,hyper-enhancement of tumors during the artery phase and slight hyper-enhancement or iso-enhancement during the delayed phase were observed in 9 cases,while slightly hyperenhancement of tumors during artery phase and hypo-enhancement during delayed phase were observed in 4 cases.Slightly hypo-enhancement peripheral to the masses during artery phase and wash-out during delayed phase with plate-shaped regions without enhancement in the center of tumors were observed in 2 cases.Conclusion NETP mainly manifested as well-defined hypoechoic lesions with regular shape in pancreas in conventional ultrasound,hyper-enhancement during artery phase and no obvious wash-out during delayed phase in CEUS.

Assessment of liver function reserve has important clinical significance,which can be used to decide the safe range of liver resection,to identify the potential liver injury early,to evaluate the treatment effect and to predict the prognosis of middle/end-stage liver diseases.There are a number of methods to assess liver function reserve.The indocyanine green (ICG) elimination test is the most commonly used and widely acknowledged approach for this assessment.With the development of functional imaging,evaluation of liver function reserve can be non-or minimalinvasive,more convenient and accurate.The application of imaging in assessment of liver function reserve and the relationship with ICG elimination test were reviewed in this article.

Objective To analyze the changes of portal venous velocity (PVV) ratio (PVVR) in different degrees of portal vein stenosis (PVS) following 70％ partial hepatectomy (PH) in rats.Methods According to different surgical methods,102 SD rats were randomly subjected into sham operation rats group (n=6),non PVS group,mild,moderate and severe PVS group (each group n=24).Models of 70％ PH without PV ligation were established in non-PVS group,while in PVS groups were produced with partially ligating PV in different degrees following 70％ PH.PVV was measured 1,3,7 and 14 days after operation,and PVVR was calculated in PVS groups.Combined with mitotic index (MI) 3 days after operation and liver regeneration degree (LRD) 7 days after operation,the changes of PVVR in different groups were analyzed.Results MI of non-PVS and moderate PVS groups were significantly higher than that of mild PVS group (both P＜0.05),while of severe PVS group was significantly lower than that of moderate PVS group (P＜0.05).LRD of severe PVS group was significantly lower than that of non PVS and moderate PVS groups (both P＜0.05).In non-PVS group,PVV decelerated to the lowest 3 days after operation,and recovered 7 and 14 days.In PVS groups,PVVR decelerated to the lowest 7 days after operation,and recovered until 14 days.PVVR of severe PVS group was significantly higher than that of mild and moderate PVS groups 1 and 3 days after operation (all P＜0.05),while there was no statistical differences among PVS groups 7 and 14 days after operation (all P＞0.05).Conclusion Ultrasound can well demonstrate blood flow changes of PVS following 70％ PH in rats.Changes of PVVR may relate to pathological changes in hepatocytes,the nuclear division and the volume of regenerated liver in rats.

OBJECTIVE:To prepare nifedipine (NF) hollow controlled-release microspheres and evaluate the quality. METH-ODS:Solvent diffusion volatilization method was used to prepare microspheres,using comprehensive scores of cumulative release in 2,12,24 h(Q2 h,Q12 h,Q24 h)as indexes,orthogonal test was designed to screen the carrier material ethyl cellulose(EC),poly-vinyl pyrrolidone(PVP)and main drug NF amounts;appearance,particle size distribution,drug loading,floating and cumulative release of the microspheres prepared by optimal formulation were evaluated and compared of in vitro release behavior with imported preparation of Nifedipine controlled-release tablets (Adalat?). RESULTS:The optimal formulation was as follow as NF 3.00 g, PVP 1.60 g,EC 15.65 g. Prepared NF hollow controlled-release microspheres were spherical in shape with particle size distribution of 24-40 mesh and drug loading of 8.66%;24 h floating rate in release medium was 97.93%,Q2 h,Q12 h,Q24 h were 20.49%, 52.90%,91.00%(RSD<10%,n=3). Compared with the imported preparation,similarity factor f2 values of cumulative release were higher than 50,showing in vitro drug-release was consistent with the zero-order kinetic equation (r=0.9993);n of Rit-ger-Peppas equation (r=0.9807) was 0.478. CONCLUSIONS:Prepare NF hollow controlled-release microspheres show similar drug-release behavior with the imported preparation,the drug is released by the combination of diffusion and erosion.