Identification of Potential Therapeutic Target Genes in Osteoarthritis.

Objective: Osteoarthritis (OA), also known as joint failure, is characterized by joint pain and, in severe cases, can lead to loss of joint function in patients. Immune-related genes and immune cell infiltration play a crucial role in OA development. We used bioinformatics approaches to detect potential diagnostic markers and available drugs for OA while initially exploring the immune mechanisms of OA. Methods: The training set GSE55235 and validation set GSE51588 and GSE55457 were obtained from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis (GSEA) was performed on the GSE55235 dataset using the cluster profiler package. At the same time, DEGs were analyzed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, protein-protein interaction (PPI) analysis was performed on the common DEGs of the three datasets using the STRING database. Proteins with direct linkage were identified as hub genes, and the relation of hub genes was subsequently analyzed using the GOSemSim package. Hub genes' expression profiles and diagnostic capabilities (ROC curves) were analyzed and validated using three datasets. In addition, we performed RT-qPCR to validate the levels of hub genes. The immune microenvironment was analyzed using the CIBERSORT package, and the relationship between hub genes and immune cells was evaluated. In addition, we used a linkage map (CMAP) database to identify available drug candidates. Finally, the GSEA of hub genes was used to decipher the potential pathways corresponding to hub genes. Results: Three hub genes (CX3CR1, MYC, and TLR7) were identified. CX3CR1 and TLR7 were highly expressed in patients with OA, whereas the expression of MYC was low. The results of RT-qPCR validation were consistent with those obtained using datasets. Among these genes, CX3CR1 and TLR7 can be used as diagnostic markers. It was found that CX3CR1, MYC, and TLR7 affect the immune microenvironment of OA via different immune cells. In addition, we identified a potential drug for the treatment of OA. Altogether, CX3CR1, MYC, and TLR7 affect the immune response of OA through multiple pathways. Conclusion: CX3CR1, MYC, and TLR7 are associated with various immune cells and are the potential diagnostic markers and therapeutic targets for OA.

A novel method of bedside hyperthermic intraperitoneal chemotherapy as adjuvant therapy for stage-III gastric cancer.

OBJECTIVE: To investigate the efficacy and safety of a novel method of hyperthermic intraperitoneal chemotherapy (HIPEC) as adjuvant therapy for stage-III gastric cancer. METHODS: Patients with stage-III gastric cancer who underwent D2 radical gastrectomy were randomly assigned to the HIPEC or control group four weeks after surgery. The HIPEC group was treated with cisplatin (60 mg/m2) administered with a HIPEC device on days 1 and 3 (30 mg/m2 each time), along with oral S-1, 40-60 mg, twice daily, for 14 days. The control group was treated with cisplatin (60 mg/m2) administered intravenously plus oral S-1 (40-60 mg, 2/d for 14 days). The primary outcome of the study was disease-free survival (DFS). RESULTS: Total 114 patients were included in the study, with 57 patients in each group. The median DFS was 29.0 months in the HIPEC group, which was significantly longer than that in the control group (15.0 months, p = 0.006). The two-year DFS rate in the HIPEC group was higher than that in the control group (50.4% vs. 25.5%). Median OS was 42.0 month in the HIPEC group and 31.0 month in the control (p = 0.042). Peritoneal metastasis occurred in six patients in the HIPEC group (10.5%) and 12 patients in the control (21.1%, p = 0.198). No significant difference in the incidence of adverse event except for thrombocytopenia. CONCLUSION: HIPEC with cisplatin plus oral S-1 is a safe and effective adjuvant therapy for patients with advanced gastric cancer following D2 radical gastrectomy. Trial registration: This study was registered at ClinicalTrials.gov with the identifier (NCT number): NCT02396498.

Retrospective analysis on the safety of 5,759 times of bedside hyperthermic intra-peritoneal or intra-pleural chemotherapy (HIPEC).

The current study was designed to analyze safety of the bedside hyperthermic intra-pleural or intra-peritoneal chemotherapy (HIPEC) from September 2007 to July 2015. Total of 5,759 times of bedside HIPEC in 985 cases of malignant pleural or peritoneal carcinomatosis were analyzed. Of them, 1,510 times was given to 315 cases of malignant pleural effusion, while 4,249 times was performed in 402 patients with malignant ascites and 268 patients without ascites (total 670 patients for peritoneal carcinomatosis). In average, patients with pleural effusion was given 5 times bedside HIPEC and stayed in the hospital for 6.7 days; while patients with peritoneal carcinomatosis was given 6 times of HIPEC and stayed in the hospital for 6.5 days. Overall HIPEC-associated mortality was zero. Overall HIPEC-associated incidence of side effect in the intra-pleural HIPEC was 2.0%. Specifically, 0.6% was pneumothorax, 0.3% was cytotoxic agent-induced pleural inflammation, 0.5% was pain at puncture location, and 0.3% was failure of HIPEC procedure. Overall HIPEC-associated incidence of side effect in the intra-peritoneal HIPEC was 2.4%, i.e., failure of HIPEC procedure in 1.3%, pain at puncture location was 0.5%, cytotoxic agent-induced peritoneal inflammation was 0.1%, intestinal obstruction was 0.1% and intestinal perforation was 0.07%. These findings indicated that bedside HIPEC applied in the current study is safe to be performed by a Physician or Oncologist under local anesthesia at a patient's bedside. The procedure is easy to perform and well-tolerated by the patients with late stage cancer or post-surgery recurrent cancer.