Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

The mental health status of 237 patients with coronary heart disease who participated in cardiac rehabilitation (CR) after coronary artery bypass grafting and 148 non-participating patients(control group) in three hospitals was evaluated,and the related factors for mental health of patients with CR were analyzed.The results showed that the anxiety,depression,and quality of life scores of patients after 2 months of participation in CR were significantly lower than those before CR (P＜0.05),and the incidence of anxiety and depressive symptoms was significantly lower than that in control group (18.5％ vs.31.1％ and 14.8 vs.25.0％,respectively,P＜0.05).The risk of anxiety and depressive symptoms was higher in CR participants with lower monthly income [OR=0.335(0.150-0.751),P=0.008],unemployment [OR=0.427(0.244-0.749),P=0.003] and knowing their own disease [OR=3.243(1.427-7.371),P=0.005].This study shows that CR can effectively improve the state of depression and anxiety and improve the quality of life.The implementation of CR shoμld fully consider a variety of influencing factors and develop a targeted rehabilitation program.

Objective     To analyze the clinical efficacy and safety of endostar or carboplatin combined with endostar intracavitary perfusion in the treatment of malignant serous cavity effusion. Methods     We retrospectively reviewed the clinical data of 78 cancer patients with malignant serous cavity effusion who received paracentesis and intracavitary endostar, or carboplatin combined with endostar in Shengjing Hospital of China Medical University between November 2011 and November 2016. There were 42 males and 36 females at a median age of 62 years ranging from 17 to 78 years. According to treatment methods, 78 patients were divided into two groups, in which 33 patients received intracavitary endostar combined with carboplatin (a combination group, 15 males and 18 females at a median age of 56 years ranging from 17 to 66 years), and 45 patients received intracavitary endostar (an endostar group, 27 males and 18 females at a median age of 63 years ranging from 38 to 78 years). The efficacy and safety of two methods were analyzed and compared. Results     The response rate in the combination group was 75.8%, which was higher than that in the endostar group (60.0%, P=0.035). In quality of life improvement, there was no statistical difference between the two groups (P=0.113). The incidence of fatigue, myelosuppression and gastrointestinal reactions in the endostar group was significantly lower than that of the combination group (P=0.006, 0.000 and 0.017, respectively). Analysis of long-term efficacy revealed that the median time to progress (TTP) in the combination group and endostar group was 171 days and 143 days, respectively (P=0.030). Conclusion     Intracavitary infusion of endostar alone, or carboplatin combined with  endostar is effective and tolerable for controlling malignant serous cavity effusion. But for the patients with poor physical state who can not tolerant platinum perfusion, intracavitary infusion of endostar alone can be adopted to control malignant serous cavity effusion.

Objective: To investigate the expression and prognostic value of alpha smooth muscle actin(α-SMA) and Ki-67 in retroperitoneal leiomyosarcoma. Methods: Fifty retroperitoneal leiomyosarcoma patients who underwent operation in Chinese People′s Liberation Army General Hospital from May 2002 to December 2015 were retrospectively analyzed. There were 14 males and 36 females form 21 to 79 and an average age of 48. Kaplan-Meier estimations and Cox regression analyses were performed. Results: Of the 50 cases, 45 patients underwent complete resection, and others are not. The overall 1, 3, 5-year survival rates were 86.0%, 46.0% and 28.0%, respectively. Tumor size, extent of resection, pathological stage, and expression levels of Ki-67 and alpha smooth muscle actin (α-SMA) were closely related to the survival of retroperitoneal leiomyosarcoma patients (all P<0.05), respectively. Multivariate analysis showed that pathological grade and degree of surgical resection were independent risk factors in the prognosis of patients (P<0.05). Conclusion The high expression of α-SMA and Ki-67 are indicators of poor prognosis in retroperitoneal leiomyosarcoma, which can be used as a potential survival predictor in patients with retroperitoneal leiomyosarcoma.

In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; genetics ; pathology ; Mutation ; Prognosis

Objective: To observe the effect of herba artemisiae capillaris extracts (HACE) on the expression profile of microRNA (miRNAs) in the kidney tissue of the diabetic rats, and to explore the protective effect of HACE on the kidney tissue of diabetic rats from the miRNA angle. Methods: A total of 60 male Wistar rats were divided into control group (n=12), model group (n=24) and HACE group (n=24). The urinary albumin excretion rate and urinary protein excretion rate of the rats in various groups were detected. HE staining was used to detect the morphology of the kidney tissue of the rats in various groups after treated for 8 and 16 weeks; miRNAs chips were used to screen the expressions of miRNAs in the kidney tissue of the rats. The positive miRNAs were screened out from those with differentially expression amounts higher than 1. 74 times as well as high abundance, and RT-qPCR was used to verify the relative expression amounts of miRNAs. Results: Compared with model group, the glomeruli matrix accumulation of the rats in HACE group (after treated for 8 and 16 weeks) was significantly improved and the urinary albumin excretion rates were decreased (P<0. 05). The miRNAs chips results showed that there were 35 differentially expressed miRNAs in control and model groups and there were 17 differentially expressed miRNAs in model and HACE groups. The RT-qPCR results showed that after treated for 8 weeks, compared with control group, the relative expression amounts of miR-1306-3p (P<0. 05), miR-672-5p (P<0. 05) and miR-3550 (P<0. 01) in the kidney tissue of the rats in model group were decreased; compared with model group, the relative expression amount of miR-672-5p in the kidney tissue of the rats in HACE group was increased (P<0. 05). After treated for 16 weeks, compared with control group, the relative expression amount of miR-21-5p in the kidney tissue of the rats in model group was increased (P

Objective:This study was performed using preclinical transplanted animal experiments to analyce the effects and mechanisms of third-generation EGFR-TKIs combined with anti-angiogenic therapy, thereby providing theoretical basis for further clinical trials. Methods:Researchers constructed the transplant BALB/C nude mice models with H1975 lung adenocarcinoma cell line (EGFR T790M) and divided the mice into four groups and treated them with osimertinib (2.5 or 5 mg/kg/day, gavage) alone or plus bevacizumab (5 mg/kg/twice weekly, i.p.) when the tumors reached approximately 0.4-0.6 cm3 in volume. The tumor growth curve of tumor volume was drawn according to the time in every group. After 2 weeks of treatment, the mice were killed and the tumors were processed for immunohistochemical staining and Western blot analysis. Immunostaining was performed to detect:HIF-1α, VEGF, and microvessel density (MVD) by using SP method on paraffin sections. Western blot analysis was used to analyze the protein expression levels of EGFR, AKT, and ERK signal transduction pathways. Results:After 2 weeks of treatment in high-and low-dose osimertinib alone, tumor volume in the high-dose group was significantly less than in low-dose osimertinib-alone group (P<0.05). VEGF, HIF-1αexpression, and MVD were significantly low in the high-dose osimertinib-alone group (P<0.05). Increasing doses of osimertinib induced dose-dependent weakening of the p-EGFR, p-AKT, and p-ERK expression levels (P<0.05). In the low-dose osimertinib-plus-bevacizumab group and low-dose osimertinib-alone group, no significant difference in tumor volume and the above factors was observed. In the low-dose osimertinib-plus-bevacizumab group and high-dose osimertinib-alone group, tumor volumes did not exhibit significant difference (P=0.178). Moreover, VEGF, HIF-1αexpression, and MVD exhibited no significant difference. No significant difference in the p-EGFR, p-AKT, and p-ERK expression levels was found between high-dose osimertinib-alone group and low-dose osimertinib-plus-bevacizumab group (P>0.05). In the high-dose osimertinib-plus-bevacizumab group, tumor growth was not significantly greater than that in the high-dose osimertinib-alone group (P=0.642). No significant difference was observed in the above factors.In the high-and low-dose osimertinib-plus-bevacizumab groups, tumor volume and the above factors did not exhibit significant differences (P>0.05). Conclusion:Osimertinib has obvious antitumor effects in EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab has a synergetic inhibitory effect with osimertinib against EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab enhanced the antitumor effects of osimertinib by reducing VEGF expression and the microvascular density of the tumor, thereby improving the tumor microenvironment. Bevacizumab can enhance the effect of osimertinib by suppressing EGFR, ERK, and AKT phosphorylation, thereby synergistically inhibiting EGFR activation and downstream signaling.

Objective:To investigate the effect of the extract of Schisandra chinensis on the matrix metalloproteinases(MMPs) system in kidney tissue of the diabetic rats,and to explore its protective effect on the kidney tissue from the matrix degradation perspective.Methods:STZ was used to establish rat models of diabetes mellitus.A total of 45 diabetic rats were randomly divided into model group,extract of Schisandra chinensis group and Benazepril group,and there were 15 rats in each group.Another 15 rats were selected and used as normal control group.12 weeks after administration,the routine blood and urine biochemical indexes,the histological changes,blood glucose (BG),blood urea nitrogen(BUN),serum creatinine(Scr),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterin(LDL-C),total cholesterol(T-CHO),and triglyceride(TG) levels,excretion rates of albuminuria and proteinuria of the rats in various groups were detected;the expression amounts of fibronectin (FN),type Ⅳ collagen (Col Ⅳ),and matrix metalloproteinase inhibitor metalloproteinase-2 (TIMP-2) in kidney tissue of the rats were detected by immunohistochemical method;the activity of matrix metalloproteinase-2 (MMP-2) was detected by zymography.Results:Compared with model group,the glomeruli matrix accumulation of the rats in extract of Schisandra chinensis group was significantly improved,the excretion rate of albuminuria,LDL-C level and serum MDA level were decreased(P<0.05),the activities of CAT(P<0.01)and SOD(P<0.05)in kidney tissue were increased,and the level of MDA in kidney tissue was decreased(P<0.05).The immunohistochemistry results showed that compared with model group,the expression amounts of FN,Col Ⅳ,and TIMP-2 in kidney tissue of the rats in extract of Schisandra chinensis group were significantly decreased.The zymography results showed that compared with model group,the activity of MMP-2 in kidney tissue of the rats in extract of Schisandra chinensis group was significantly increased(P<0.05).Conclusion:Extract of Schisandra chinensis has protective effect on the kidney tissue of the diabetic rats induced by STZ,and the mechanism may be related to the inhibition of oxidative stress and the improvement of MMP-2 activity as well as the inhibition of TIMP-2 expression which could improve the matrix degradation.

Objective To identify the expression of CD68-tumor-associated macrophages (TAMs) and proliferative marker Ki-67 in retroperitoneal malignant fibrous histiocytoma (MFH) and their clinical significance. Methods Clinical data about 35 patients with retroperitoneal MFH managed with surgery from February 2002 to December 2015 were retrospectively analyzed and all patients were followed up. There were 24 male and 11 female patients, and they were 18-71 years old, with mean age (53.0 ± 10.8) years old. Patients were divided into CD68 positive group (21 patients) and CD68 negative group (14 patients), while they were also divided into Ki-67 low expression (< 20%) group and Ki-67 high expression ( ≥ 20%) group, according to the immunohistochemical staining results. The overall survival time and all clinical data between two groups were compared. Kaplan-Meier estimations, Cox regression analysis, Fisher exact probabilities and Spearman correlations were performed. Results Of the 35 patients, 18 patients received radical resection, and 17 patients received palliative operation. The overall 1-, 3-, 5-year survival rates were 65.7%, 22.9%and 8.6%and the median survival was 17 (1-86) months. Factors associated with postoperative survival were FNCLCC grade (x2=7.002, P=0.008), modusoperandi of the tumor resection(x2=7.134, P=0.008), and CD68(x2=4.634, P=0.031) and Ki-67 overexpression (≥20%) (x2=8.898, P=0.003 ) . The difference between gender, age, tumor size, blood loss, removal of the joint organs and adjuvant therapy got no statistical significances (P > 0.05). Multivariate analysis showed that survival was associated with modusoperandi of the tumor resection and Ki-67 overexpression (P=0.003, 0.002, respectively). Conclusions Retroperitoneal malignant fibrous histiocytoma is a rare malignancy that display poor prognosis and high mortality. Complete resection remains the mainstream for retroperitoneal malignant fibrous histiocytoma. The patients' life span in CD68 positive or Ki-67 high expression is shorter. CD68 and Ki-67 plays a critical role in retroperitoneal malignant fibrous histiocytoma carcinogenesis and their high expression may be used as a potential survival predictor in patients with retroperitoneal MFH.