Objective To establishment the model of angiotensin Ⅱ (AngⅡ) inducinged cardiomyocyte hypertrophy in H9c2 myocardial cells, and observinge the the changes of ubiquitin binding protein leveljunction protein ubiquitination level. Methods Myocardial cell isolated and subcultured H9c2 were cultured in vitro andmyocardial cell, they were divided into three groups in different AngⅡ concentration (10-8, 10-7, 10-6 mol/L), with in different hours (0, 6, 12, 24, 48, 72 h), and there is also a control group; measured the total protein contentlevel were measured useby BCA method , measured the number of cardiomyocytes in the same area were measured, and the relative surface area of myocardial cells were calculated. The expression of ubiquitin binding protein cardiomyocyte hypertrophy was time- and concentration-dependently induced by AngⅡ, wheremanifested, as total cellular protein content,relative cell surface area and the expression of ubiquitin binding proteinubiquitinated desmin significantly increasing compared with the control group (P < 0.05), which were most significant in 10-7 mol/L AngⅡtreated group for 48 h. Conclusions Cardiomyocyte hypertrophy model induced by 10-7 mol/L AngⅡ for 48 h , was successfully established , where H9c2 cardiomyocyte hypertrophy was induced by 10-7 mol/L AngⅡ in 48 h, and ubiquitin binding proteinubiquitinated desmin significantly increased in cardiomyocyte hypertrophy.

In the treatment of non-small cell lung cancer (NSCLC), immunotherapies represented by immune checkpoint inhibitors are developing rapidly. It is the premise of precise treatment to clarify the influencing factors of NSCLC immunotherapy. In the course of immunotherapy for advanced NSCLC, elderly patients can obtain specific effect from immunotherapy; male patients benefit more from monotherapy; when steroid hormones are used for related symptoms caused by tumors, they are poor prognostic factors for patients. The occurrence of immune-related adverse events is a favorable prognostic factor while driving gene mutations and the use of antibiotics will reduce the efficacy of immunotherapy.

Objective:To evaluate the effects of proton pump inhibitors (PPIs) on the clinical outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors (ICIs).Methods:A total of 204 patients with advanced solid tumors who received ICIs in the Affiliated Hospital of Yangzhou University from November 2016 to December 2020 were retrospectively analyzed. The patients were divided into PPIs group ( n=73) and Non-PPIs group ( n=131) according to whether they received PPIs within 1 month before or after the initiation of ICIs treatment. The correlations between the uses of PPIs and the clinical characteristics of patients were explored, and the clinical efficacy of the two groups was evaluated. Kaplan-Meier survival curve was applied to analyze the effects of PPIs uses on overall survival (OS) and progression-free survival (PFS) of patients. The Cox proportional hazards model was used to clarify whether PPIs was an independent indicator of patients′ prognosis. Results:During ICIs treatment of advanced solid tumors, the use of PPIs was not correlated with the patients′ gender, age, tumor type, the score of the United States Eastern Collaborative Group, types of immunotherapy drugs and treatment strategy (all P>0.05). The objective response rate of the Non-PPIs group was better than that of the PPIs group (45.0% vs. 24.7%, χ2=8.286, P=0.004). The disease control rate of the Non-PPIs group was better than that of the PPIs group (75.6% vs. 52.0%, χ2=11.755, P=0.001). In patients with advanced solid tumors, the median OS (3.4 months vs. 6.1 months) and median PFS (2.8 months vs. 4.0 months) in the PPIs group were shorter than those in the Non-PPIs group ( χ2=9.563, P=0.002; χ2=5.761, P=0.016). Univariate analysis showed that among patients with advanced solid tumors treated with ICIs, PPIs uses was significantly correlated with OS ( HR=1.85, 95% CI: 1.24-2.76, P=0.003); PPIs uses( HR=1.65, 95% CI: 1.09-2.51, P=0.019) and age ( HR=1.56, 95% CI: 1.05-2.32, P=0.029) were significantly correlated with PFS. Multivariate analysis showed that PPIs uses was an independent prognostic factor affecting OS ( HR=1.90, 95% CI: 1.27-2.85, P=0.002) and PFS ( HR=1.73, 95% CI: 1.12-2.65, P=0.013). Meanwhile, subgroup analysis discovered that in the course of ICIs treatment of lung cancer patients, the median OS (3.2 months vs. 6.2 months) and median PFS (2.2 months vs. 3.8 months) in the PPIs group ( n=64) were shorter than those in the Non-PPIs group ( n=34) ( χ2=16.187, P<0.001; χ2=5.106, P=0.020). Univariate analysis showed that PPIs uses was associated with OS ( HR=2.97, 95% CI: 1.70-5.22, P<0.001) and PFS ( HR=1.97, 95% CI: 1.09-3.55, P=0.025) in lung cancer patients treated with ICIs. Multivariate analysis showed that PPIs uses was an independent prognostic factor for OS ( HR=3.38, 95% CI: 1.87-6.11, P<0.001) and PFS ( HR=2.31, 95% CI: 1.22-4.38, P=0.010) in lung cancer patients treated with ICIs. Conclusion:The use of PPIs reduces the effect of ICIs in the treatment of advanced solid tumor, especially in lung cancer. PPIs should be used cautiously in patients with advanced solid tumors treated with ICIs.

Objective:To investigate the effect of bupivacaine on Apelin/APJ pathway and subsequent gene expression in Sprague-Dawley (SD) rat cardiomyocytes.Methods:H9c2 cardiomyocytes were cultured in vitro and treated with 0-1 mmol/L bupivacaine for 6 h. The concentration of Apelin was detected by enzyme-linked immunosorbent assay (ELISA), and the expression of APJ was detected by Western blot; Fifteen adult male SD rats were randomly divided into sham group (sham group), bupivacaine 30 mg/kg group (Bupi group), bupivacaine 30 mg/kg+ [Pyr 1] apelin-13 0.15 mg/kg (Bupi-A) group. After corresponding treatment, myocardial tissue was taken to detect the expression of Apelin and APJ, and high-throughput sequencing was performed. Results:Western blot and ELISA results showed that bupivacaine down regulated the expression of Apelin and APJ in H9c2 cardiomyocytes (all P<0.05). The expression levels of Apelin and APJ in the myocardial tissue of SD rats in Bupi group were lower than those in sham group (all P<0.05). The expression of Apelin in myocardial tissue of Bupi-A group was higher than that of Bupi group ( P=0.006), but the expression of APJ had no significant difference ( P>0.05). High throughput sequencing revealed that compared with sham group, the top five differentially expressed genes that were significantly upregulated in Bupi group but significantly downregulated in Bupi-A group were ubiquinone NADH dehydrogenase Fe-S protein 3, enolase 1, aquaporin 1, ATP synthase F0 complex C subunit 1 lipid binding protein, and peroxidase 2 (all P<0.001); The top five genes that were significantly down regulated in Bupi group but significantly up-regulated in Bupi-A group were mesothelin, Rho GTPase activating protein 29, sten20 like kinase, carbonic anhydrase, and paraplatelet lysin (all P<0.001). These genes were associated with increased cardiomyocyte apoptosis, energy metabolism disorders and exercise attenuation. Conclusions:bupivacaine can reduce the expression of Apelin, leading to the changes of gene expression related to increased apoptosis, energy metabolism disorder and exercise attenuation in rat cardiomyocytes.