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Objective To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients with cancer- associated venous thromboembolism (VTE). Study design Observational study. Place and duration of study Department of Oncology, the Second Affiliated Hospital of Soochow University, between January 2017 and September 2019. Methodology Patients with active cancer, diagnosed with VTE and who received sequential treatment with dalteparin and rivaroxaban, were retrospectively reviewed. Logistic regression analysis was used to identify risk factors associated with VTE recurrence. Results Ninety-nine patients with active cancer were enrolled in the study. The median delteparin treatment time was nine days (5-20 days), and 2.8 months (1-6 months) for rivaroxaban. Sixty (60.6%) patients had eliminated VTE, and 39 (39.4%) had persistent VTE, but with relieved symptoms. No major bleeding was observed. Eleven (11.1%) patients had minor bleeding, including melena (5.1%), hematuria (3.0%), vaginal bleeding (1.0%), gingival bleeding (1.0%), and subcutaneous hemorrhage (1.0%). During the 6 months follow-up period, one (1.0%) developed pulmonary embolism, and seven (7.1%) experienced recurrent VTE. Univariate logistic regression analysis showed that bleeding occurrence and anticoagulant treatment duration were the two significant factors affecting VTE recurrence (p Conclusion Maintenance of rivaroxaban after initial dalteparin treatment could effectively reduce the risk of VTE recurrence and was well tolerated by patients with cancer-associated VTE. However, in the clinical practice, the treatment duration is often insufficient, so it is essential to follow-up these patients to ensure sufficient treatment time. Key Words: Venous thromboembolism, Low-molecular-weight heparins, Directly oral anticoagulants, Cancer.

bBackground:/bChitinase-3-like protein 1 (CHI3L1) is overexpressed in various types of tumors, especially in glioma, and contributes to tumor progression. However, the definite role of CHI3L1 and involved pathway in glioma progression are not completely understood.bMethods:/bCHI3L1 expression in human gliomas and its association with patient survival was determined using enzyme-linked immunosorbent assay, western blot, immunohistochemistry, and public databases. Single-cell RNA-seq was used to characterize the landscape of tumor and myeloid cells. Human proteome microarray assay was applied to identify the binding partners of CHI3L1. Protein-protein interactions were analyzed by co-immunoprecipitation and cellular co-localization. The roles of CHI3L1 in glioma proliferation and invasion were investigated in tumor cell lines by gain- and loss- of function, as well asiin vivo/ianimal experiments.bResults:/bCHI3L1 was up-regulated in all disease stages of glioma, which was closely related with tumor survival, growth, and invasion. CHI3L1 was primarily expressed in glioma cells, followed by neutrophils. Moreover, glioma cells with high expression of CHI3L1 were significantly enriched in NF-κB pathway. Pseudo-time trajectory analysis revealed a gradual transition from CHI3L1suplow/supto CHI3L1suphigh/supglioma cells, along with the NF-κB pathway gradually reversed from inhibition to activation. Intriguingly, CHI3L1 binds to actinin alpha 4 (ACTN4) and NFKB1, and enhances the NF-κB signaling pathway by promoting the NF-κB subunit nuclear translocation in glioma cells. Further, CHI3L1 were released into the tumor microenvironment (TME) and interacted with CD44 expressed on tumor-associated macrophages to activate AKT pathway, thereby contributing to M2 macrophage polarization. In addition, CHI3L1 positively correlated to the expression of immune checkpoints, such as CD274 (PD-L1) and HAVCR2 (LAG3), which then remodeled the TME to an immunosuppressive phenotype.bConclusion:/bOur research revealed that CHI3L1 facilitated NF-κB pathway activation within glioma cells and reprogramed the TME, thereby serving as a promising therapeutic target for glioma.

In this paper, the energy dissipation in a bolted lap joint is studied using a continuum microslip model. Five contact pressure distributions compliant with the power law are considered, and all of them have equal pretension forces. The effects of different pressure distributions on the interface stick-slip transitions and hysteretic characteristics are presented. The calculation formulation of the energy dissipation is introduced. The energy dissipation results are plotted on linear and log-log coordinates to investigate the effect of the pressure distribution on the energy distribution. It is shown that the energy dissipations of the lap joints are related to the minimum pressure in the overlapped area, the size of the contact area and the value of the power exponent. The work provides a theoretical basis for further effective use of the joint energy dissipation.

The liver is the most common site of metastasis for colorectal cancer (CRC). Metastasis suppressor 1 (MTSS1), a potential tumor suppressor gene associated with tumor metastasis, has been reported to play an important role in cancer development. The present study aimed to investigate the effects and underlying mechanisms of MTSS1 on the biological behavior of CRC cells both in vitro and in vivo. A CRC mouse model with a high liver metastatic potential was established by injecting mice with SW1116 cells, and the association between MTSS1 expression levels and the metastatic potential of forming liver metastasis lesions was subsequently analyzed. MTSS1 gain‑ and loss‑of‑function experiments were performed by transfecting the CRC cell lines, SW1116 and DLD‑1, with Plvx‑IRES‑ZsGreen1‑MTSS1 plasmid and short hairpin RNA, respectively. Cell proliferation, migration, invasion and cell cycle distribution were analyzed by MTT, Transwell and flow cytometric assays, respectively. To further determine the underlying mechanisms of MTSS1 in CRC, the expression levels of cell surface chemokine C‑X‑C receptor 4 (CXCR4) and its downstream signaling factors, Rac and cell division cycle 42 (CDC42), were analyzed with or without C‑X‑C motif chemokine ligand 12 (CXCL12) stimulation. The results revealed that as the CRC metastatic potential increased, the expression levels of MTSS1 decreased. The overexpression of MTSS1 exerted an inhibitory effect on cell proliferation, migration and invasion, while the knockdown of MTSS1 exerted the opposite effects in vitro. Flow cytometric analysis and western blot analysis demonstrated that MTSS1 negatively regulated the expression levels of cell surface CXCR4 and its downstream signaling pathway activation. On the whole, the results of the present study indicate that MTSS1 may play an important negative role in CRC metastasis and the underlying mechanisms may involve the downregulation of the CXCR4/CXCL12 signaling axis.

OBJECTIVE This study is aimed to assess the efficacy and toxicity of weekly liposome-paclitaxel and S-1 combination therapy as first-line treatment for advanced gastric cancer. METHODS The chemotherapy regime was 80 mg/m(2) liposome-paclitaxel given on days 1, 8, 15 and 22, combined with S-1 60 mg (body surface area > 1.5) or 50 mg (1.25 < body surface area < 1.5) twice a day on days 1-28, 6 weeks as one cycle. The patients continued to be treated until they received four cycles or until they developed either progressive disease or untolerated toxicity. The response rate, progression-free survival, overall survival and toxicity were evaluated. RESULTS A total of 56 patients were enrolled, and the median age was 60 years (range = 38-70 years; 39 males and 17 females). The response rate and disease control rate were 25% (14/56) and 87.5% (49/56), respectively. The median progression-free survival was 6.1 months (95% confidence interval: 5.0-7.2), and the median overall survival was 10.6 months (95% confidence interval: 7.2-14.0). The most frequent hematological toxicities were neutropenia and anemia, which occurred in 22 (48.9%) and 11 (19.6%) patients, respectively. CONCLUSIONS The weekly administration of a combined regimen of liposome-paclitaxel plus S-1 is effective and has a favorable toxicity profile for advanced gastric cancer.