Integrins are a family of cell adhesion receptors that mediate cell-cell and cell-extracellular matrix adhesion, and interact with cytokines through a bidirectional signal transduction,thus regulating the biological behavior of pancreatic cancer cells,such as proliferation,apoptosis,invasion,and migration etc. Molecular and animal studies indicated that integrins targeted methods might benefit the early diagnosis and drug therapy of pancreatic cancer,which offered a new approach for the study of diagnosis and treatment of pancreatic cancer.

Objective To explore the effects of vinblastine on abcb4 tumor resistance gene expression in early development zebrafish and lay an important foundation for multi-drug resistant antineoplastic screening in zebrafish model.Methods Zebrafish embryos of 0.5~1.5 hours post-fertilization were exposured to different concentrations of vinblastine, and then calculated the IC50 of vinblastine.Zebrafish embryos of 0.5~1.5 hours post-fertilization were treated with different concentrations of vinblastine and embryo culture medium respectively, and then observed zebrafish embryo development in 24~120 hours post-fertilization and recorded the number of death, hatch and malformation.Evaluating the impact of vinblastine on abcb4 gene expression in zebrafish with quantitative real-time PCR and whole-mount in situ hybridization by collecting zebrafish embryos exposed to different concentrationsof vinblastine.Results Vinblastine IC50 in zebrafish embryos was 3.08 μmol/L.The mRNA level of abcb4 gene in vinblastine treated embryos was significantly increased compared to blank control group.Moreover, abcb4 gene positive hybridization signals were found in the small intestine of zebrafish embryos after 120 hours post-fertilization and also found in the brain and heart of zebrafish embryos by the method of whole-mount in situ hybridization.Conclusions Vinblastine can significantly increase the expression level of abcb4 tumor resistancegene in early development zebrafish embryos, which indicates that zebrafish can be used as a tumor resistant drug screening model.

Objective To investigate the effect of Shenmai injection on purine content in rat cerebral cortex in order to provide a theoretical basis concerning its brain protective mechanism. Methods Sixteen Sprague-Dawley (SD) rats were randomly divided into two groups:normal saline control group and Shenmai injection group, with 8 rats in each group. Shenmai injection 15 mL/kg was injected intraperitoneally into the rats in Shenmai injection group, while in the normal saline group, an equal volume of normal saline was intraperitoneally injected. After the injection for 24 hours, the rats were sacrificed, and the cerebral cortex was removed on ice, homogenized and its supernatant was extracted;then high performance liquid chromatography (HPLC) was used to detect adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine and inosine contents in the supernatant of cerebral cortex. Results Compared with normal saline control group, ATP, ADP, AMP, adenosine and creatinine content in the cerebral cortex of Shenmai injection group were significantly higher, the differences being statistically significant [ATP (ng/L): 31.62±5.12 vs. 20.25±4.53, ADP (ng/L): 37.04±6.72 vs. 25.12±7.35, AMP (ng/L): 87.82±20.37 vs. 33.23±10.34, adenosine (ng/L): 2.82±0.15 vs. 1.12±0.61, creatinine (ng/L): 11.72±1.05 vs. 6.05±2.55, P < 0.05 or P<0.01]. Conclusion Shenmai injection can elevate ATP, ADP, AMP, adenosine and creatinine contents in the cerebral cortex of rats, possibly that is the theoretical basis for brain protective mechanism of Shenmai injection.

Objective To determine the expression of TM4SF1 mRNA in 5 human pancreatic cancer cell lines,and investigate its effect on the proliferation,migration and invasion of pancreatic cancer cells.Methods The expression of TM4SF1 mRNA in MPanc96,MiaPaCa-2,PANC1,AsPC-1,HPAC cells was determined by qRT-PCR,and the results were compared with that of human pancreatic ductal epithelial (HPDE) cells.RNA interference method was used to transiently transfect siRNA targeting at TM4SF1 and negative control siRNA into MPanc96,MiaPaCa-2 cells.The proliferation of cells were measured by MTS method,and migration and invasion of cells were determined by Transwell.Results The expression levels of TM4SF1 mRNA in pancreatic cancer cell lines MPanc96,MiaPaCa-2,PANC1,AsPC-1 and HPAC were 1.205 ± 0.073,1.096 ± 0.260,1.382 ± 0.075,1.374 ± 0.363 and 0.744 ± 0.096,which were significantly highly than that in HPDE (0.020 ± 0.003,P ＜ 0.01).Compared with cells transfected with negative control siRNA,the proliferation of MPanc96 and MiaPaCa-2 cells transfected with siRNA targeting at TM4SF1 was not significantly changed,but the migration abilitiy was decreased by (62.5 ± 7.6) ％ and (72.8 ± 4.0) ％,and invasion abilitiy was decreased by (69.5 ± 5.7) ％ and (78.6 ± 6.3) ％.Conclusions TM4SF1 is highly expressed in pancreatic cancer cells and appears to promote the migration and invasion abilities of the cancer cells.

Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with transjugular intrahepatic portosystemic shunt (TIPS) in the patients with primary liver cancer complicating cirrhosis portal hypertension.Methods Twenty-two cases of TACE combined with TIPS due to decompensation of liver cancer complicating cirrhosis portal hypertension in this hospital from January 2011 to January 2015 were collected as the combined group and 28 cases of liver cancer complicating cirrhosis portal hypertension treated only by TACE without conducting TIPS were screened out as the control group.The curative effect and prognosis of the two groups were observed.Results The success rate of TIPS was 100％,the preoperative portal pressure was (38.4±7.6) cm H2O and the postoperative portal pressure was (28.4±7.7)cm H2O,the difference was statistically significant (P＜ 0.05);the preoperative portal vein diameter was (16.2 ±2.5)mm and postoperative portal vein diameter was (13.3±1.8)mm,the difference was statistically significant (P＜0.05).The postoperative 1-year stent patency rate was 95％ and 2-year stent patency rate was 90％.The postoperative 1-year and 2-year re-bleeding rates in the control group were 60.7 ％ and 78.5 ％ respectively,which in the combined group were 9.1％ and 13.6 ％ respectively,the differences were statistically significant (P＜0.05).The 1-year accumulated survival rate in the combined group was 81％,2-year accumulated survival rate was 68％,and the median survival time was 53 months,while the 1-year accumulated survival rate in the control group was 78 ％,2-year accumulated survival rate was 15 ％,and the median survival time was 17 months,the differences were statistically significant (P＜0.05).Conclusion Conducting TACE combined with TIPS in the patients with primary liver cancer complicating cirrhosis portal hypertension can safely and effectively control the tumor development,reduce and even eliminate the portal hypertension syndrome,and increase the life quality and survival rate.

Objective To investigate the correlation of body mass index (BMI) on pathological complete response (pCR) and prognosis of breast cancer patients receiving neoadjuvant chemotherapy.Methods A retrospective analysis was performed on 98 cases of breast cancer patients in the Tumor Hospital Affiliated to Zhengzhou University from December 2013 to November 2015.Patients were divided into normal or underweight (N/U,BMI ＜25.0 kg/m2) group,overweight (OW,BMI 25.0-29.9 kg/m2)group and obese (OB,BMI ≥30.0 kg/m2) group according to BMI.A total number of 50 (51.0％) patients were N/U,32 (32.6％) patients were OW,and 16 (16.3％) patients were OB.The pathological complete remission after neoadjuvant chemotherapy was observed,and the prognostic evaluation index was disease-free survival rates.Univariate analysis of BMI and pCR correlations was performed by Chi-square test or Fisher exact test,and logistic regression for multivariate analysis.Kaplan-Meier analysis and log-rank test were used to analyze survival status,and Cox proportional hazard model analysis for multivariate analysis.Results In this study,A statistically significant difference was found in the molecular subtypes of the three groups(P ＜ 0.05).Twenty-nine(29.6％) patients achieved pCR,pCR rates in N/U group,OW group and OB group were 36.0％ (18/50),25.0％ (8/32),and 18.8％ (3/16),respectively,but the difference was not statistically significant (P ＞ 0.05).Multivariate logistic regression analysis showed that obesity and molecular subtype were independent factors of pCR in all patients (P ＜ 0.05).The 3-year disease free survival rates of the N/U,OW,and OB groups were 84.0％,93.5％ and 80.4％,respectively (P ＞ 0.05).Multivariate survival analysis showed that the BMI was not an independent prognostic factor for the 3-year disease free survival rate (P ＞ 0.05).Conclusion Excessive BMI (obesity) is an independent predictor of pCR in breast cancer patients receiving neoadjuvant chemotherapy,but does not affect the prognosis of these patients.

Objective:To assess the left ventricular (LV) myocardial mechanical dysfunction in patients with cirrhosis using ultrasonic layer-specific strain imaging and to explore its value in clinical application.Methods:A total of 80 consecutive cirrhosis patients without cardiovascular diseases were prospectively enrolled from October 2020 to March 2021 in Sichuan Provincial People′s Hospital, 39 of whom were assigned to the compensated group and 41 were assigned to the decompensated group according to the occurrence of portal hypertension. Forty-three healthy volunteers during the same period were randomly recruited as the control group. Transthoracic echocardiography was performed to assess the LV configuration and functional parameters. LV global longitudinal strain in endocardial, middle and epicardial myocardium (GLSendo, GLSmid, GLSepi), and longitudinal strain (LS) in basal, middle and apical segments, and peak strain dispersion (PSD) were obtained using ultrasonic layer-specific strain imaging. ΔLS was calculated by the formula of GLSendo-GLSepi. Then, the differences of related parameters among three groups were compared.Results:①Conventional echocardiography: compared with the control group, the interventricular septum end-diastolic thickness (IVSTd), left ventricular posterior wall end-diastolic thickness (LVPWd), left ventricular mass (LVM) and LVM index (LVMI) were increased in compensated and decompensated groups (all P<0.05), while no significant differences in conventional echocardiographic parameters were identified between the two cirrhosis groups (all P>0.05). ②Global layer-specific strain: compared with the control group, GLSendo, GLSmid, GLSepi and ΔLS were decreased and PSD was increased in compensated and decompensated groups (all P<0.05); Moreover, the decompensated group showed a more impaired GLSendo, GLSmid and GLSepi than compensated group (all P<0.05), whereas there were no significant differences of ΔLS and PSD between the two groups(all P>0.05). ③Segmental layer-specific strain: compared with the control group, LS values of three layers in compensated and decompensated groups were reduced at basal, middle and apical levels (all P<0.05); Compared with the compensated group, LS values of three layers in decompensated group tended to be reduced at above there levels, but only apical segments had significant differences (all P<0.05). Conclusions:There are different degrees of LV mechanical dysfunction in patients with variable severity of cirrhosis. Ultrasonic layer-specific strain imaging has the potential to quantitatively assess the state of cardiac involvement in patients with cirrhosis and to provide visual evidence for the early and accurate diagnosis of myocardial injuries.

Purpose: We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them. Methods: The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses. Results: Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64–0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%. Conclusion A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

Objective To investigate the current status of overcrowding in emergency departments of Tertiary level A hospitals in order to discover and analyze key factors limiting the performance efficiency of staff to raise a suggestion of improvements.Methods The data regarding the distribution of the total number of available beds and total number of patients registered were collected from 19 tertiary level A hospitals to construct a regression model correlating variables including number of patients waiting,time of appointment and number of patients delivered by ambulances.The national grading system of crowdedness for emergency departments was used to estimate the NEDOCS_ BJ value for Beijing Friendship Hospital.Results Statistical analyses of key factors hampering the work efficiency and correlation between ESI triage and clinical decisions revealed overcrowding in the emergency department in a pattern across hospitals and time periods.The extent of overcrowding can be alleviated by way of increase in performance efficiency.Conclusions The proposed improvements regarding the hierarchical medical system,the development of treatment plans,and working procedure were recommended.

Objective To investigate the effects of Danusertib on the changes in Aurora kinase B (Aurora B)/ribosomal protein p70S6 kinase (p70S6K)/ribosomal protein 15 (RPL15) signaling pathway and autophagy in human leukemia cells and its mechanism.Methods Myeloid leukemia cell lines THP-1 and K562 were selected as the research subjects.The experiment was divided into 2 phases.Phase 1:each cell line was treated with the concentration of Danusertib in 0.1 p mol/L,1.0 p mol/L and 5.0 μ mol/L.In control group,2 mL/L dimethyl sulfoxide (DMSO)was given.All the treated cells were cultured for 24 hours.The viability of each cell line was examined by methyhhiazoletrazolium assay and the autophagy was assessed by flow cytometry.In addition,the protein levels of p70S6K,AuroraB,phosphatidylinositol 3-kinase (PI3K),AKT(phosphorylated protein kinase B),mammalian target of rapamycin (mTOR),microtubule-associated protein (LC3),Beclin1 and RPL15 were determined by using Western blot.Part 2:Aurora B and RPL15 were down-regulated in THP-1 and K562 cells,respectively.DMSO was used to dissolve Danusertib(5.0 μ mol/L).The grouping was designed as following:DMSO group (blank control group),Danusertib treated group,empty plasmid group,small interfering RNA(siRNA) group,empty plasmid + Danusertib-treated group and siRNA + Danusertib treated group.The protein levels of Aurora B,p70S6K,RPL15,Beclinl and LC3 were detected by using Western blot.Results (1) Danusertib decreased the viability of THP-1 and K562 cells and the half maximal inhibitory concentration values were 26.9 pmol/L and 30.2 μmol/L for THP-1 and K562 cells,respectively.(2)The protein levels of p-Aurora B/Aurora B,p-p70S6K/p70S6K,RPL15,p-mTOR/mTOR and p-AKT/AKT decreased compared with control cells after being treated with 0.1 μmol/L,1.0 μ mol/L and 5.0 pmol/L of Danusertib in THP-1 and K562 cells,and the differences were statistically significant (all P ＜ 0.05).(3) In THP-1 cells,compared with the empty plasmid group,the protein levels of p70S6K and RPL15 decreased by 22.1％,61.3％ (F =18.1,P =0.001) and 55.4％,56.1％ (F =19.4,P =0.001) in siRNA group and siRNA + Danusertib-treated group after knockdown of Aurora B.In contrast,the protein levels of LC3 increased by 13.6％ and 17.1％ (F =15.4,P =0.001)compared with the empty plasmid group.In addition,the protein levels of Beclin1 and LC3 increased by 39.5％,92.3％ (F=25.2,P=0.001) and 40.2％,58.3％ (F=23.9,P=0.001) in siRNA group and siRNA + Danusertib treated group,compared with the empty plasmid group after down-regulation of RPL15.In K562 cells,compared with the empty plasmid group,the protein levels of p70S6K and RPL15 decreased by 24.2％,62.7％ (F =20.4,P=0.001) and 57.2％,60.1％ (F =23.9,P =0.001) in siRNA group and siRNA + Danusertib treated group after downregulation of Aurora B.But the protein levels of LC3 increased by 17.9％ and 56.7％ (F =20.9,P =0.001)compared with the empty plasmid group.Moreover,the protein levels of Beclin1 and LC3 were increased by 20.6％,98.4％ (F=22.4,P =0.001) and 41.5％,70.1％ (F=26.2,P =0.001) in siRNA group and siRNA + Danusertib treated group,compared with the empty plasmid group after downregulation of RPL15.Conclusion Danusertib can induce autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway and can negatively regulate Aurora B/p70S6K/RPL15 axis in THP-1 and K562 cells.In addition,RPL15 may be a key target of Aurora B/p70S6K/RPL15signaling pathway in the inhibition of tumor proliferation.