Compared to single gemcitabine treatment, the combination of gemcitabine and erlotinib has shown effective response in patients with locally advanced or metastatic pancreatic cancer. However, the combination therapy has not proven effective in patients with pancreatic cancer after R0 or R1 resection. In the present study, a nude mice model of orthotopic xenotransplantation after tumor resection was established using pancreatic cancer cell lines, BxPC-3 and PANC-1. Mice were divided in four groups (each with n=12) and were treated as follows: the control group received a placebo via intraperitoneal injection (i.p.), while the other three groups were treated with gemcitabine (50 mg/kg i.p., twice a week), erlotinib (50 mg/kg oral gavage, once every three days), and combined treatment of gemcitabine and erlotinib, respectively. The treatment lasted for 21 days, after which all mice were sacrificed and tumors were examined ex vivo. We determined that the combination of gemcitabine and erlotinib inhibited recurrent tumor growth and induced apoptosis in vivo by downregulating phosphorylation levels of JAKs and STATs, which in turn downregulated the downstream proteins HIF-1α and cyclin D1, and upregulated caspase-9 and caspase-3 expression. To sum up, the combination of gemcitabine with erlotinib was effective in treating patients with pancreatic cancer after R0 or R1 resection.

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BackgroundBone is a dynamically hierarchical material that can be divided into length scales of several orders of magnitude. Exercise can cause bone deformation, which in turn affects bone mass and structure. This study aimed to study the effects of treadmill running with different intensities on the long bone integrity and muscle biomechanical properties of adult male rats.MethodsForty-eight 5-month-old male SD rats were randomly divided into 4 groups: i.e., sedentary group (SED), exercise with speed of 12 m/min group (EX12), 16 m/min group (EX16), and 20 m/min group (EX20). The exercise was carried out for 30 min every day, 5 days a week for 4 weeks. The femurs were examined using three-point bending test, microcomputer tomography scanning and nanoindentation test; the soleus muscle was dissected for tensile test; ALP and TRACP concentrations were measured by serum analysis.ResultsThe failure load was significantly increased by the EX12 group, whereas the elastic modulus was not significantly changed. The microstructure and mineral densities of the trabecular and cortical bone were significantly improved by the EX12 group. The mechanical properties of the soleus muscle were significantly increased by treadmill exercise. Bone formation showed significant increase by the EX12 group. Statistically higher nanomechanical properties of cortical bone were detected in the EX12 group.ConclusionThe speed of 12 m/min resulted in significant changes in the microstructure and biomechanical properties of bone; besides, it significantly increased the ultimate load of the soleus muscle. The different intensities of treadmill running in this study provide an experimental basis for the selection of exercise intensity for adult male rats.

Coronavirus disease 19 (COVID-19) is still a major public health concern in many nations today. COVID-19 transmission is now controlled mostly through early discovery, isolation, and therapy. Because of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the contributing factor to COVID-19, establishing timely, sensitive, accurate, simple, and budget detection technologies for the SARS-CoV-2 is urgent for epidemic prevention. Recently, several electrochemical DNA biosensors have been developed for the rapid monitoring and detection of SARS-CoV-2. This mini-review examines the latest improvements in the detection of SARS-COV-2 utilizing electrochemical DNA biosensors. Meanwhile, this mini-review summarizes the problems faced by the existing assays and puts an outlook on future trends in the development of new assays for SARS-CoV-2, to provide researchers with a borrowing role in the generation of different assays.

Background: The prognosis of patients with hepatocellular carcinoma (HCC) is negatively affected by the lack of effective prognostic indicators. The change of tumor immune microenvironment promotes the development of HCC. This study explored new markers and predicted the prognosis of HCC patients by systematically analyzing immune characteristic genes.Methods: Immune-related genes were obtained, and the differentially expressed immune genes (DEIGs) between tumor and para-cancer samples were identified and analyzed using gene expression profiles from TCGA, HCCDB, and GEO databases. An immune prognosis model was also constructed to evaluate the predictive performance in different cohorts. The high and low groups were divided based on the risk score of the model, and different algorithms were used to evaluate the tumor immune infiltration cell (TIIC). The expression and prognosis of core genes in pan-cancer cohorts were analyzed, and gene enrichment analysis was performed using clusterProfiler. Finally, the expression of the hub genes of the model was validated by clinical samples.Results: Based on the analysis of 730 immune-related genes, we identified 64 common DEIGs. These genes were enriched in the tumor immunologic related signaling pathways. The first 15 genes were selected using RankAggreg analysis, and all the genes showed a consistent expression trend across multi-cohorts. Based on lasso cox regression analysis, a 5-gene signature risk model (ATG10, IL18RAP, PRKCD, SLC11A1, and SPP1) was constructed. The signature has strong robustness and can stabilize different cohorts (TCGA-LIHC, HCCDB18, and GSE14520). Compared with other existing models, our model has better performance. CIBERSORT was used to assess the landscape maps of 22 types of immune cells in TCGA, GSE14520, and HCCDB18 cohorts, and found a consistent trend in the distribution of TIIC. In the high-risk score group, scores of Macrophages M1, Mast cell resting, and T cells CD8 were significantly lower than those of the low-risk score group. Different immune expression characteristics, lead to the different prognosis. Western blot demonstrated that ATG10, PRKCD, and SPP1 were highly expressed in cancer tissues, while IL18RAP and SLC11A1 expression in cancer tissues was lower. In addition, IL18RAP has a highly positive correlation with B cell, macrophage, Neutrophil, Dendritic cell, CD8 cell, and CD4 cell. The SPP1, PRKCD, and SLC11A1 genes have the strongest correlation with macrophages. The expression of ATG10, IL18RAP, PRKCD, SLC11A1, and SPP1 genes varies among different immune subtypes and between different T stages.Conclusion: The 5-immu-gene signature constructed in this study could be utilized as a new prognostic marker for patients with HCC.