OBJECTIVE:To observe the effects of Paclitaxel,Cisplatin combined with Recombinant human (Rh) endostatin on the efficacy and related indexes of patients with non-small cell lung cancer(NSCLC). METHODS:78 patients with Ⅲb or ⅣNSCLC were randomly divided into control group(39 cases)and observation group(39 cases). Control group received Paclitaxel injection 135-175 mg/m2,d1,intravenous infusion,once a day+Cisplatin injection 25 mg/m2,3 times a day,d1-3,intravenous infu-sion. Observation group additionally received Rh endostatin injection 15 mg/m2,adding into 500 ml 0.9% Sodium chloride injec-tion by slow intravenous infusion 3-4 h,d1-14,then stopped for 7 d. 21 d was regarded as 1 treatment course,it lasted 6 courses. Clinical efficacy,programmed death ligand-1(PD-L1)level,quality of life(QOL)score before and after treatment,and the inci-dence of adverse reactions in 2 groups were observed. RESULTS:All patients completed 2 courses of chemotherapy. There were 3 patients in observation group and 4 patients in control group quitted the study with uncompleted 6 weeks of chemotherapy due to in-tolerance or adverse reactions. The remission rate in observation group was significantly higher than control group,with statistical significance (P<0.05). Before treatment,there were no significant differences in PD-L1 level and QOL score in 2 groups (P>0.05). After treatment,PD-L1 level and QOL score in 2 groups were significantly lower than before,and observation group was lower than control group,with statistical significance (P<0.05). And there was no significant difference in the incidence of ad-verse reactions in 2 groups (P>0.05). CONCLUSIONS:Paclitaxel,Cisplatin combined with Rh endostatin can improve the short-term efficacy of patients with NSCLC,inhibit PD-L1 expression,improve QOL,and do not increase the incidence of adverse reactions.

Objective:To investigate the clinical effect of local and systemic zoledronic acid in the treatment of giant cell tumor of bone.Methods:The clinical data of 42 patients with giant cell tumor of bone who were treated in the Department of Joint and Sports Medicine Surgery of Shandong Provincial Third Hospital from January 2000 to January 2017 were retrospectively analyzed. According to whether zoledronic acid was used during and after operation, the patients were divided into zoledronic acid group ( n=21) and non zoledronic acid group ( n=21). The perioperative indexes, pain visual analogue scale (VAS), international Musculoskeletal Tumor Society (MSTS) score of lower extremity function, adverse reactions and the postoperative recurrence were compared between the two groups. Results:The operative time of zoledronic acid group and non zoledronic acid group were (158.4±20.5) min and (169.5±19.5) min, the intraoperative bleeding volume were (236.3±9.7) ml and (228.2±16.5) ml, the postoperative drainage volume were (163.3±7.4) ml and (161.4±9.3) ml, and the healing time of incision were (13.8±2.1) d and (14.0±2.0) d, respectively, with no significant difference ( t=-1.798, P=0.080; t=1.936, P=0.062; t=0.733, P=0.468; t=-0.290, P=0.774). The preoperative VAS scores of zoledronic acid group and non zoledronic acid group were 6.54±1.76 and 6.72±1.51 respectively, the MSTS scores were 13.56±2.35 and 12.79±1.98 respectively, and the differences were not statistically significant ( t=-0.356, P=0.724; t=1.148, P=0.258). The VAS scores of the two groups were 1.32±0.31 and 1.92±0.19 at 4 weeks after operation, 0.93±0.29 and 1.47±0.38 at 3 months after operation respectively, and the differences were statistically significant ( t=-7.562, P<0.001; t=-5.177, P<0.001). The VAS scores of the two groups were 0.31±0.12 and 0.35±0.23 at the last follow-up, with no significant difference ( t=0.707, P=0.485). The MSTS scores of zoledronic acid group and non zoledronic acid group were 24.89±3.86 and 21.82±2.95 at 4 weeks after operation, 26.78±2.57 and 24.62±2.62 at 3 months after operation respectively, and the differences were statistically significant ( t=2.896, P=0.006; t=2.697, P=0.010). The MSTS scores of the two groups were 27.31±2.21 and 26.69±2.93 at the last follow-up, with no significant difference ( t=0.774, P=0.443). The postoperative recurrence time of the two groups was (9.79±2.58) months and (7.31±1.73) months respectively, and the difference was statistically significant ( t=3.659, P=0.001). There was no significant difference in recurrence Campanacci grade and recurrence tumor location between the two groups ( U=7.000, P=0.860; χ2=1.062, P>0.999). The occurrence rates of fever in zoledronic acid group and non zoledronic acid group were 23.81% (5/21) and 4.76% (1/21), the occurrence rates of myalgia were 19.05% (4/21) and 4.76% (1/21), the incidences of influenza like symptoms were 14.29% (3/21) and 0 (0/21), the occurrence rates of gastrointestinal reaction were 9.52% (2/21) and 4.76 (1/21), and the differences were not statistically significant ( χ2=1.750, P=0.186; χ2=0.980, P=0.341; χ2=1.436, P=0.231; χ2<0.001, P>0.999). All the patients had no serious adverse reactions such as liver and kidney function damage and mandible necrosis. Conclusion:Local and systemic application of zoledronic acid in the treatment of giant cell tumor of bone can improve the early postoperative pain and limb function, delay the recurrence time, and can be used as an auxiliary treatment of giant cell tumor of bone.

BACKGROUND: Cell competition is an important feature in pancreatic cancer (PC) progression, but the underlying mechanism remains elusive. This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression. METHODS: PC cells and pancreatic stellate cells (PSCs) were treated with exosomes isolated from pancreatic ductal epithelial cells. Cell proliferation was assessed by CCK8 assays. Cell migration and invasion were assessed by Transwell assays. PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017. Tissue miR-485-3p and p21-activated kinase-1 (PAK1) expression was examined by real-time polymerase chain reaction (RT-PCR), and the relationship of the two was analyzed using Pearman's product-moment correlation. The clinical significance of miR-485-3p was analyzed using the Chi-square test, Wilcoxon rank-sum test, and Fisher exact probability, respectively. The binding of miR-485-3p to PAK1 5'-untranslated region (5'-UTR) was examined by luciferase assay. PC cells were xenografted into nude mice as a PC metastasis model. RESULTS: Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs. MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs, in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells. And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells, to inhibit PC cell migration and invasion. Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues (P < 0.05) and was negatively associated with lymphovascular invasion (P = 0.044). As a direct target of miR-485-3p, PAK1 was found to exert an inhibitory effect on PC cells, and there was a significantly negative correlation between the expression levels of miR-485-3p and PAK1 (r = -0.6525, P < 0.0001) in PC tissues. Moreover, miR-485-3p could suppress PC metastasis in vivo by targeting p21-activated kinase-1. CONCLUSIONS Exosomal miR-485-3p delivered by normal pancreatic ductal epithelial cells into PC cells inhibits PC metastasis by directly targeting PAK1. The restoration of miR-485-3p by exosomes or some other vehicle might be a novel approach for PC treatment.
Animals ; Mice ; MicroRNAs/metabolism* ; Mice, Nude ; p21-Activated Kinases/metabolism* ; Cell Line, Tumor ; Pancreatic Neoplasms/genetics* ; Epithelial Cells/metabolism* ; Pancreatic Ducts/pathology* ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.