Background 5-Florouracil (5-FU) is a commonly used chemotherapeutic drug for cholangiocarcinoma, whereas it has unsatisfactory effect, and patients often have chemo-resistance to it. The combination of chemotherapeutic agents and traditional Chinese medicine has already exhibited a promising application in oncotherapy. Huaier extract (Huaier) has been used in clinical practice widely, exhibiting good anti-tumor effect. This paper aims to investigate the possibility of combination 5-FU and Huaier as a treatment for cholangiocarcinoma. Methods A series of experiments were performed on the Huh28 cells in vitro, which involved cell proliferation, colony formation, apoptosis, cell cycle, migratory and invasive tests. Besides, western blots were also performed to examine the potential mechanism of 5-FU. Results The combination effect (antagonism, synergy or additive) was assessed using Chou-Talalay method. Using the CCK-8 and Colony formation assay, the anti-proliferation effect of 5-FU combined with Huaier was observed. Apoptosis inducing and cell cycle arrest effect of the combination of two drugs were assessed by flow cytometry. To determine the combined treatment on cell immigration and invasion ability, wound healing and Transwell assay were performed. The above experiment results suggest that the combined 5-FU and Huaier, compared with treatment using either drug alone, exhibited stronger effects in anti-proliferation, cycle arrest, apoptosis-induced and anti-metastasis. Further, western blot results reveal that the inhibition of STAT3 and its target genes (e.g. Ki67, Cyclin D1, Bcl-2 and MMP-2) might be set as the potential therapeutic targets. Besides, the inhibition of combination treatment in proteins expression associated with proliferation, apoptosis, cell cycle and metastasis was consistent with that of previous phenotypic experiments. Conclusions Huaier combined with 5-FU exhibited a synergistic anti-tumor effect in Huh28 cell. Furthermore, the mechanisms might be associated with the activation and translocation of STAT3, as well as its downstream genes. Electronic supplementary material The online version of this article (10.1186/s12906-019-2614-5) contains supplementary material, which is available to authorized users.
Purpose To develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with surgically resected intrahepatic cholangiocarcinoma (ICC). Patients and methods The nomograms were developed using a development cohort of 947 ICC patients after surgery selected from Surveillance, Epidemiology, and End Results database, and externally validated using a training cohort of 159 patients admitted at our institution. Nomograms for OS and CSS were established based on the independent prognostic factors identified by COX regression models and Fine and Grey’s models, respectively. The performance of the nomograms was validated internally and externally by using the concordance index (c-index), and calibration plot, and compared with that of AJCC 8th edition TNM staging system by using c-index and decision curve analysis. Results Age, T stage, M stage, lymph node ratio (LNR) level and tumor grade were independent prognostic predictors for OS in ICC patients, while T stage, M stage, LNR level and tumor grade were independent prognostic predictors for CSS. Nomogram predicting OS was with a c-index of 0.751 on internal validation and 0.725 up to external validation, while nomogram for CSS was with a c-index of 0.736 on internal validation and 0.718 up to external validation. Calibration plots exhibited that the nomograms-predicted and actual OS/CSS probabilities were fitted well on both internal and external validation. Additionally, the nomograms exhibited superiority over AJCC 8th edition TNM staging system with higher c-indices and net benefit gains, in predicting OS and CSS in ICC patients after surgery. Conclusion The constructed nomograms could predict OS and CSS with good performance, which could be served as an effective tool for prognostic evaluation and individual treatment strategies optimization in ICC patients after surgery in clinical practice.
Homeodomain-containing gene 10 (HOXC10) is associated with the progression of a variety of different types of human cancer; however, the role of HOXC10 in liver cancer is not completely understood. The present study aimed to investigate the mechanisms underlying the effects of HOXC10 on liver cancer tumorigenesis. Quantitative PCR and western blotting were used to detect the expression patterns of HOXC10 in cancer and adjacent healthy tissues. EdU, Cell Counting Kit-8 and colony formation assays were used to determine the functions of HOXC10 in liver cancer cell lines. ENCORI, TargetScan and miRTarBase were used to identify microRNAs that target HOXC10. The verification of the interaction between HOXC10 and microRNA-221 was determined by a luciferase assay. Compared with adjacent non-cancerous tissues, the expression of HOXC10 was markedly decreased in liver cancer tissues. A HOXC10 small interfering (si)RNA significantly attenuated HOXC10 expression at the mRNA and protein levels, and enhanced cell proliferation compared with the siRNA-negative control group. In addition, the luciferase reporter assay indicated that microRNA-221 directly bound to the 3'-untranslated region of HOXC10, and interfered with the inhibitory effect of HOXC10 on proliferation. In addition, HOXC10 knockdown elevated the expression levels of mitogen-activated protein kinase signaling pathway markers compared with the siRNA-negative control group. Therefore, the results of the present study may aid with the development of novel therapeutic regimens and diagnostic markers of liver cancer.
Recently, the increasing prevalence of diabetes mellitus has made it a major chronic illness which poses a substantial threat to human health. The prevalence of osteoporosis among patients with diabetes mellitus has grown considerably. Diabetic bone disease is a secondary osteoporosis induced by diabetes mellitus. Patients with diabetic bone disease exhibit variable degrees of bone loss, low bone mineral density, bone microarchitecture degradation, and increased bone fragility with continued diabetes mellitus, increasing their risk of fracture and impairing their ability to heal after fractures. At present, there is extensive research interest in diabetic bone disease and many significant outcomes have been reported. However, there are no comprehensive review is reported. This review elaborates on diabetic bone disease in the aspects of characteristics, pathogenesis, and treatment.
the 710th research institute of china shipbuilding industry corporation, Yichang, china ABSTRACT Unmanned aerial vehicle (UAV) positioning is one of the key techniques in the field of UAV navigation. Although the high positioning precision of UAV can be achieved through global positioning system (GPS), the frequency of updating signal in GPS is low and the energy consumption of GPS module is huge, which does not satisfy the real-time demand of UAV positioning. In this paper, a multi-sensor information fusion method based on GPS, inertial navigation system (INS), and the visible light sensors is proposed for UAV positioning. The Kalman filter combining with simulated annealing algorithm is used to estimate the position error between GPS or INS and the visible light sensors, and then the motion trajectory is corrected according to this position error information. Therefore, the positioning accuracy of UAV can be improved in case of only INS being available. Experimental results demonstrate that the proposed method can remarkably improve the positioning accuracy and greatly reduce the energy consumption.
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