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Background Breast cancer is ranked as the most common cancer worldwide. The use of CDK4/6 inhibitors has improved the prognosis and has become a new strategy for hormone receptor -positive, human epidermal growth factor receptor-2-negative breast cancer; however, such drugs have been found to increase the risk of thrombosis in randomized controlled trials (RCTs), and this risk may be higher in the real-world setting. This study aimed to compare the thromboembolic risk of CDK4/6 inhibitors plus endocrine therapy (ET) and ET alone in RCTs and determine the incidence of thromboembolic events associated with the use of CDK4/6 inhibitors in RCTs and in the real world. Methods PubMed and EMBASE databases were searched up to December 31, 2022, for RCTs and cohort studies of CDK4/6 inhibitors in patients with breast cancer. The quality of the literature was assessed using the Cochrane Handbook and Newcastle–Ottawa Scale, and meta-analysis was performed using Review Manager 5.4 and R version 4.2.2. Results A total of 13 RCTs and 9 real-world studies were identified and included in this analysis. RCTs only reported venous thromboembolic events (VTEs); VTEs occurred in 192 patients (2.1%) in the CDK4/6 inhibitor group and 55 patients (0.7%) in the control group. Compared with ET alone, receiving CDK4/6 inhibitors plus ET increased the risk of VTEs in patients with breast cancer, with an odds ratio of 2.67 (95% confidence interval [CI]: 1.98, 3.59, p

Background: Butyrate is a major subgingival microbial metabolite that is closely related to periodontal disease. It affects the proliferation and differentiation of mesenchymal stem cells. However, the mechanisms by which butyrate affects the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remain unclear. Here, we investigated the effect of sodium butyrate (NaB) on the osteogenic differentiation of human PDLSCs. Methods: PDLSCs were isolated from human periodontal ligaments and treated with various concentrations of NaB in vitro. The cell counting kit-8 assay and flow cytometric analysis were used to assess cell viability. The osteogenic differentiation capabilities of PDLSCs were evaluated using the alkaline phosphatase activity assay, alizarin red staining, RT-PCR, western blotting and in vivo transplantation. Results: NaB decreased PDLSC proliferation and induced apoptosis in a dose- and time-depend manner. Additionally, 1 mM NaB reduced alkaline phosphatase activity, mineralization ability, and the expression of osteogenic differentiation-related genes and proteins. Treatment with a free fatty acids receptor 2 (FFAR2) antagonist and agonist indicated that NaB inhibited the osteogenic differentiation capacity of PDLSCs by affecting the expression of Smad1. Conclusion: Our findings suggest that NaB inhibits the osteogenic differentiation of PDLSCs by activating FFAR2 and decreasing the expression of Smad1.

Background: Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas.Method: The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization. Results: Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level. Conclusion: Based on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.

Background: Rotator cuff tear is one of the most common diseases in orthopedics, which seriously affects the quality of patients’ lives. And the arthroscopic repair of rotator cuff has recently become more and more popular. Systematic rehabilitation makes great significance for improving the prognosis of postoperative patients. Yet, the traditional outpatient rehabilitation is hard to popularize in developing countries like China due to the limitation of traffic and geography. Given this, we plan to develop a telerehabilitation system to facilitate doctors' remote guidance on patients' rehabilitation.Methods/design: Our study is a single-center, prospective randomized controlled trial. 124 patients who underwent arthroscopic rotator cuff repair will be recruited for the study. They will be randomly divided into 2 groups (62 cases in each group) based on the stratification factors of the operator, operation and preoperative diagnosis. The patients in the control group will get clinic and booklet based rehabilitation treatment after operation. However, patients in the experimental group will receive mobile phone and motion-capture device based programs for telerehabilitation after surgery. The primary outcome will be measured by the American Shoulder and Elbow Surgeons (ASES). Secondary outcomes include the Range of motion (ROM), Visual Analogue Scales (VAS), EuroQol-5 Dimension health questionnaire (EQ-5D), University of California at Los Angeles（UCLA）and the retear rate.Discussion: We hypothesize that patients who utilized mobile phone and motion-capture device based telerehabilitation will benefit more in the range of motion and shoulder function than those who received outpatient and manual based rehabilitation. If the hypothesize was confirmed, we could facilitate telerehabilitation for doctors and overcome the geographical and traffic limitations of traditional clinical based rehabilitation.Trial registration: ChiCTR.org.cn, ChiCTR2000030150, Registered on 24 February 2020

BackgroundSarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas.MethodThe “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization.ResultsMacrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway.CD48, P2RY10andRASAL3were identified and validated at the protein level.ConclusionBased on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.