Carboxyamidotriazole (CAI), originally developed as a non-cytotoxic anti-cancer drug, was shown to have anti-inflammatory activity according to recent studies in a number of animal models of inflammation. However, its mechanism of action has not been characterized. Therefore, the present study was performed to identify the anti-inflammatory action of CAI in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and to identify the signal transduction pathways involved. The in vitro results revealed that CAI had no direct effect on the activity of cyclooxygenase (COX), suggesting a different anti-inflammatory mechanism compared with that of COX-inhibiting non-steroidal anti-inflammatory drugs. Further investigation in RAW264.7 macrophages revealed that CAI decreased the production of nitric oxide via decreasing the LPS-stimulated expression of inducible nitric oxide synthase, and downregulated both mRNA and protein expression levels of the cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. CAI atory diseases with excessive macrophage activation.Previous studies have identified ~50 genes that contribute to non-syndromic autosomal dominant sensorineural deafness (DFNA). However, in numerous families with hearing loss, the specific gene mutation remains to be identified. In the present study, the clinical characteristics and gene mutations were analyzed in a Chinese pedigree with hereditary hearing loss. The clinical characteristics of the family members were assessed and a detailed audiology function examination was performed. Whole-exome sequencing (WES) was performed to identify the gene mutation responsible for the hearing loss. Sanger sequencing was used to verify the candidate mutation detected in the family. The family consisted of 31 members, seven of whom were diagnosed with sensorineural deafness of varying degrees. No mutation was identified by the general deafness gene chip. However, a novel heterozygous mutation in exon 3 (c.152C>T; Pro51Leu) of the gene crystallin µ (CRYM) was identified by WES. This result was further verified by Sanger sequencing. Co-segregation of genotypes and phenotypes suggested that this novel mutation was instrumental for the hearing loss/DFNA. In conclusion, the present study identified a novel pathogenic mutation, NM_001888.5(CRYM) c.152C>T(Pro51Leu), associated with DFNA. This mutation has not been reported previously and further functional studies are warranted.Sequential invasive-noninvasive ventilation (NIV) improves the outcomes of patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no clear consensus on the optimal timing of the switch to sequential invasive-NIV in these patients. In the present study, a potential role for the modified Glasgow Coma Scale (GCS) score to guide sequential weaning was investigated. Patients with AECOPD and respiratory failure were prospectively recruited from three study centers (Wenling Hospital Affiliated to Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University and Changsha Central Hospital) between January 1st 2016 and December 31st 2018. Patients were randomly assigned to group A and B, with the switching point for sequential weaning strategy in the two groups being a modified GCS score ≥13 and 10 points, respectively. Each group included 240 patients. Baseline demographic characteristics were comparable in the two groups. The duration of invasive mechanical ventilation (IMV) in group A was significantly shorter than that in group B. However, there were no significant between-group differences with respect to the incidence of re-intubation, ventilator-associated pneumonia, in-hospital mortality or the length of hospital stay. Use of a modified GCS score ≥13 as the switching point for sequential invasive-NIV may help decrease the duration of IMV in patients with AECOPD and respiratory failure.Chemoresistance of colorectal cancer (CRC) leads to tumor recurrence and metastasis and new strategies are urgently needed to improve the outcomes of conventional chemotherapy. Sirtuin (SIRT) inhibitors prevent tumor cell growth by increasing the levels of acetylated histones and non-histones, as well as disrupting survival-related pathways. The aim of the present study was to determine the effect of SIRT inhibitors on CRC chemotherapy. The CompuSyn software program was used to evaluate the synergistic or antagonistic effects of various drugs, and the status of the protein deacetylation regulatory genes in microarray datasets were analyzed using bioinformatics. In HCT116 cells expressing wild-type (wt) TP53, SIRT inhibitors were found to act antagonistically with multiple chemotherapeutic agents (cisplatin, 5-fluorouracil, oxaliplatin, gefitinib, LY294002 and metformin), and decreased the anti-tumor effects of these agents. By contrast, SIRT inhibitors sensitized TP53-mutant (mut) SW620 cells to various chemotherapeutic drugs. Bioinformatics analysis indicated that SIRT1 and protein deacetylation related genes were highly expressed in TP53wt CRC cells when compared to TP53mut cells. Therefore, it was hypothesized that the likely mechanism underlying the antagonistic effect of SIRT inhibitors on TP53wt CRC cells was a reduction in the level of stable p53 protein. Selleck PARP inhibitor The present results indicated that divergent TP53 status may translate to a different chemosensitivity profile, and suggested that a combination therapy of SIRT inhibitors and first-line chemotherapeutic drugs may be beneficial for the treatment of patients with TP53mut CRC.Metastasis of endometrial cancer (EC) is known to be the major cause of relapse and death of patients. However, the mechanisms of this process are not well understood. Focal adhesion kinase (FAK) is known for its essential role in integrin signaling and is highly expressed in many human tumors. FAK also plays important roles in a variety of cellular processes. Collagen triple helix repeat containing 1 (CTHRC1) is a secreted protein that has been detected in many human solid cancers. In the present study, CTHRC1 was found to be highly expressed in EC tissues when compared with normal tissues. In addition, overexpression of CTHRC1 promoted the migration of EC cells in vitro. Recombinant CTHRC1 protein also promoted the migration of EC cells in vitro. The results of the present study suggested that CTHRC1 mediated EC cell migration via the FAK signaling pathway. Taken together, these data indicated that CTHRC1 and the FAK signaling pathway may be potential therapeutic targets for EC metastasis treatment.