miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1

Background: The aberrant expression of microRNA-140-5p (miR-140-5p) has been described in gastric cancer (GC). However, the role of miR-140-5p in GC remains unclear. In this study, the prognostic relevance of miR-140-5p in GC was investigated and YES1 was identified as a novel target of miR-140-5p in regulating tumor progression. Methods: miR-140-5p level was determined in 20 paired frozen specimens through quantitative real-time PCR, and analyzed in tissue microarrays through in situ hybridization. The target of miR-140-5p was verified through a dual luciferase reporter assay, and the effects of miR-140-5p on phenotypic changes in GC cells were investigated in vitro and in vivo. Results: Compared with that in adjacent normal tissues, miR-140-5p expression decreased in cancerous tissues. The downregulated miR-140-5p in 144 patients with GC was significantly correlated with the reduced overall survival of these patients. miR-140-5p could inhibit GC cell proliferation, migration and invasion by directly targeting 3'-untranlated region of YES1. miR-140-5p could also remarkably reduce the tumor size in GC xenograft mice. Conclusions: miR-140-5p serves as a potential prognostic factor in patients with GC, and miR-140-5p mediated YES1 inhibition is a novel mechanism behind the suppressive effects of miR-140-5p in GC

Dose-dependent effects of intravenous methoxamine infusion during hip-joint replacement surgery on postoperative cognitive dysfunction and blood TNF-α level in elderly patients: a randomized controlled trial

Abstract Background Postoperative cognitive dysfunction (POCD), common in elderly patients, is thought to be closely associated with intraoperative instability of hemodynamics and excessive excretion of tumor necrosis factor-α (TNF-α). Methoxamine is a blood-pressure increasing drug commonly used for maintaining intraoperative hemodynamics. Methoxamine potentially promotes TNF-α expression, leading to an increased risk of POCD. This study aimed to investigate the dose-dependent effect of methoxamine on the incidence of early POCD and blood TNF-α level. Methods This single-center prospective double-blind controlled clinical trial included a total of 300 adult patients (75–90 years old, American Society of Anesthesiologists class II–III) who underwent unilateral hip-joint replacement surgery under epidural anesthesia. Patients were randomly divided into three methoxamine groups (M1, M2, and M3), and one control group (n = 75 per group). During surgery, M1, M2, and M3 patients received intravenous infusion of methoxamine at 2, 3, or 4 μg·kg−1·min−1, respectively; the control group received saline of same volume at the same infusion rate. All patients received standard transfusion to maintain stable circulation. Hemodynamics, cardiovascular events, and serum TNF-α levels were monitored. Mini Mental State Examination was performed both before and after surgery to diagnose POCD. Results The primary outcome of this study was the incidence of POCD, which was higher in the M3 group (18.7%) than in the control group (5.3%), the M1 group (6.7%), or the M2 group (6.7%) (all P < 0.05). The secondary outcomes were the postoperative blood TNF-α level and intraoperative hemodynamic parameters. The postoperative TNF-α level was found to be higher than baseline in all groups and was highest in M3 patients (P < 0.05). The intraoperative hemodynamic parameters showed improved stability in the M1 and M2 groups compared with the control group. However, in the M3 group, abnormally increased intraoperative blood pressure, cardiac output, and systolic stroke volume were observed. Conclusions Intravenous infusion of methoxamine at 2–3 μg·kg−1·min−1 can maintain stable hemodynamics in elderly patients during epidural anesthesia for hip-joint replacement surgery, without increasing the incidence of POCD. Increasing the dose to 4 μg·kg−1·min−1 provided no further advantages but induced adverse effects on the intraoperative hemodynamics. Trial registration Chinese Clinical Trial Register (Unique identifier: ChiCTR-INR-15007607 , retrospectively registered 18 Dec 2015)

Exploring the influence of resiliency on physician trust in patients: An empirical study of Chinese incidents.

BackgroundThe tension in doctor-patient relationships is becoming progressively greater due to the high expectations of patients and the physicians' work pressure. Recent studies have addressed factors which affect the tension of doctor-patient relationships, and our study continues this trend by looking at the influence of resiliency and physician trust in the patient (PTP), that is, how much the doctor trusts the patient.MethodsBased on a survey of 329 physicians, a descriptive analysis of measured data was done using SPSS 19.0. Pearson correlation coefficient analysis was used to examine the correlation between PTP and resilience and the demographic variables. KMO and Bartlett methods were used to examine the correlation between PTPS and resilience. The method of factor analysis was used for multicollinearity tests, and multiple stepwise regression analysis was used to explore the demographic factors correlated with PTP and resilience.ResultOur results indicate that the level of PTP is influenced by the age, education, and income of the doctors. Physician age and income are significantly and positively correlated with PTP, but education is significantly and negatively related. Age, education, and income also affect the level of psychological resilience of physicians. Resilience is positively correlated with age and education but is negatively related to income. Resilience positively influences PTP.ConclusionThe direct factors of PTP include resilience, age, education, and income, while gender, title, and hospital department were found to be indirect influencing factors. To meet goals expressed in Chinese government policy related to these issues, we suggest improving the level of education of the doctors, providing reasonable annual salary increases for doctors, easing the tensions involved in medical treatment, reducing the physicians' work pressure, improving the physicians' work environment, and enhancing the physicians' professional sympathy. Through such measures, the level of PTP will be enhanced

Robotic total gastrectomy with π-shaped esophagojejunostomy using a linear stapler as a novel technique

Abstract Objective To evaluate the intraoperative and short-term postoperative outcomes of a novel robotic intracorporeal π-shaped esophagojejunostomy (EJS) after D2 total gastrectomy (TG) using the Da Vinci robotic surgical system for intracorporeal anastomosis after TG. Background Intracorporeal π-shaped EJS, using a linear stapler, was recently reported for laparoscopic total gastrectomy in patients with gastric cancer. However, robotic intracorporeal π-shaped EJS using a linear stapler has not been reported. This report aimed to describe the use of a novel technique for π-shaped EJS using the Da Vinci robotic system. Methods Robotic intracorporeal π-shaped esophagojejunostomy after total gastrectomy was performed in 11 consecutive patients diagnosed with early gastric cancer, and their perioperative outcomes were analyzed. Results All the operations were successful without conversion to open or laparoscopic surgery and postoperative complications. The total number of patients was 11 (7 males and 4 females). The mean age of the patients was 63.36 ± 10.56 years old. Seven patients were diagnosed with cardia cancer, 3 patients were diagnosed with gastric body cancer, and 1 patient was diagnosed with gastric antrum cancer. The patients’ mean proximal resection margin was 3.18 ± 1.17 cm, the distal resection margin was 6.18 ± 1.40 cm, the mean length of the incision was 4.55 ± 0.69 cm, the mean operative time was 287.27 ± 30.69 min, the mean day of first flatus was 3.27 ± 0.79 days, the mean day of the start of diet was 2.91 ± 0.94 days, the mean postoperative hospital stay was 11.45 ± 5.13 days, and the mean operative blood loss was 47.27 ± 31.33 ml. No complications were observed during anastomosis, and the median anastomosis time was 19.5 min. The mean number of lymph node dissections was 17.91 ± 4.59, the mean number of positive lymph nodes was 0.45 ± 0.69, all patients were diagnosed with stage I–II gastric cancer, and the mean maximum diameter of the tumor was 2.67 ± 1.30 cm. All the patients had a smooth hospital discharge. Conclusion A novel robotic gastrectomy with intracorporeal π-shaped EJS for esophagojejunal anastomosis described and shows acceptable resulted. This technique has the potential to offer better short-term surgical outcomes and overcomes the drawbacks of laparoscopy with a decreased risk of complications during and after surgery

Macrophage Inhibitory Cytokine-1 (MIC-1) as A Biomarker for Diagnosis and Prognosis of Stage I-II Non-small Cell Lung Cancer

Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1), member of transforming growth factor-β (TGF-β) superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC). Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001) and benign pulmonary disease patients (P<0.001). A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001), female (P=0.03) and T2 (P=0.022). A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL) was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%). Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035). Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC

Transmembrane protein 176B regulates amino acid metabolism through the PI3K-Akt-mTOR signaling pathway and promotes gastric cancer progression

Abstract Background The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC). Methods TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). The function of TMEM176B was determined by various in vitro assays including colony formation, 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and flow cytometry. Bioinformatics techniques were then used to elucidate the signaling pathways associated with TMEM176B activity. Tumor formation experiments were conducted on nude mice for in vivo validation of the preceding findings. TMEM176B expression was cross-referenced to clinicopathological parameters and survival outcomes. Results It was observed that TMEM176B was overexpressed in GC cells and tissues. Targeted TMEM176B abrogation inhibited colony formation, proliferation, migration, and invasion but promoted apoptosis in GC cell lines while TMEM176B overexpression had the opposite effects. Subsequent experimental validation disclosed an association between TMEM176B and the phosphatidylinositol 3-carboxykinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling axis. Moreover, TMEM176B affects GC cancer progression by regulating asparagine synthetase (ASNS). The in vivo assays confirmed that TMEM176B is oncogenic and the clinical data revealed a connection between TMEM176B expression and the clinicopathological determinants of GC. Conclusion The foregoing results suggest that TMEM176B significantly promotes the development of gastric cancer and is an independent prognostic factor of it

Additional file 2: Table S2. of miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1

Relationship between the clinicopathologic parameters and the overall survival of the patients with GC. (XLS 21 kb

Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment

Abstract The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors