Heart Rate Response Predicts 6-Minutes Walking Distance in Pulmonary Arterial Hypertension.

Because the 6-minute walking test (6MWT) is a self-paced submaximal test, the 6-minute walking distance (6MWD) is substantially influenced by individual effort level and physical condition, which is difficult to quantify. We aimed to explore the optimal indicator reflecting the perceived effort level during 6MWT. We prospectively enrolled 76 patients with pulmonary arterial hypertension and 152 healthy participants; they performed 2 6MWTs at 2 different speeds: (1) at leisurely speed, as performed in daily life without extra effort (leisure 6MWT) and (2) an increased walking speed, walking as the guideline indicated (standard 6MWT). The factors associated with 6MWD during standard 6MWT were investigated using a multiple linear regression analysis. The heart rate (HR) and Borg score increased and oxygen saturation (SpO2) decreased after walking in 2 6MWTs in both groups (all p <0.001). The ratio of difference in HR before and after each test (ΔHR) to HR before walking (HRat rest) and the difference in SpO2 (ΔSpO2) and Borg (ΔBorg) before and after each test were all significantly higher in both groups after standard 6MWT than after leisure 6MWT (all p <0.001). Multiple linear regression analysis revealed that ΔHR/HRat rest was an independent predictor of 6MWD during standard 6MWT in both groups (both p <0.001, adjusted R2 = 0.737 and 0.49, respectively). 6MWD and ΔHR/HRat rest were significantly lower in patients than in healthy participants (both p <0.001) and in patients with cardiac functional class III than in patients with class I/II (both p <0.001). In conclusion, ΔHR/HRat rest is a good reflector of combined physical and effort factors. HR response should be incorporated into 6MWD to better assess a participant's exercise capacity.

COL11A1 as a potential prognostic target for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a malignant tumor occurring in the oral cavity. However, the molecular mechanism of OSCC is not clear. Bioinformatics was used to screen and identify role of collagen type X1 alpha 1 (COL11A1) on OSCC. 200 patients with OSCC were recruited. Clinical and follow-up data were recorded and COL11A1 expression levels were tested. Pearson chi-square test and Spearman correlation coefficient were used to analyze relationship between prognosis and related parameters in patients with OSCC. Univariate and multivariate Logistic regression, univariate and multivariate Cox proportional risk regression were used for further analysis, survival curve was drawn. Through bioinformatics analysis, OSCC patients with higher expression of COL11A1 have poor overall survival compare with OSCC patients with lower expression of COL11A1 (hazard ratios [HR] = 1.32, P = .047). Pearson chi-square test showed that age (P = .011), tumor grade (P = .023), COL11A1 (P < .001) was significantly correlated with prognosis of OSCC. Univariate Logistic regression analysis showed age (odds ratio [OR] = 2.102, 95% confidence intervals [95%CI]: 1.180-3.746, P = .012), tumor grade (OR = 1.919, 95%CI: 1.093-3.372, P = .023) and COL11A1 (OR = 12.775, 95%CI: 6.509-25.071, P < .001). Multivariate Logistic regression analysis showed that COL11A1 (OR = 12.066, 95%CI: 6.042-24.096, P < .001) was significantly associated with prognosis of patients with OSCC. Univariate Cox regression analysis showed that age (HR = 1.592, 95%CI: 1.150-2.205, P = .005), tumor grade (HR = 1.460, 95%CI: 1.067-1.999, P = .018) and COL11A1 (HR = 1.848, 95%CI: 1.340-2.548, P < .001) were significantly correlated with survival time of OSCC patients. Multivariate Cox regression analysis showed that tumor grade (HR = 1.466, 95%CI: 1.064-2.020, P = .019) and COL11A1 (HR = 1.645, 95%CI: 1.164-2.325, P = .005) were significantly correlated with survival time of OSCC patients. COL11A1 is significantly correlated with occurrence of OSCC. When COL11A1 is highly expressed, prognosis of patients with OSCC is worse and the survival time is shorter.

Corneodesmosin as a potential target of oral squamous cell carcinoma.

OBJECTIVE: The relationship between oral squamous cell carcinoma (OSCC) and Corneodesmosin (CDSN) remains unclear. This study aims to explore the correlation between CDSN and the prognosis and survival time of patients with OSCC. METHODS: Bioinformatics were used to identify the hub role of CDSN in the OSCC. A total of 200 patients with OSCC were recruited. Clinical and follow-up data were recorded, and the expression level of CDSN was detected. Pearson chi-square test and Spearman correlation coefficient were used to analyze the relationship between prognosis and related parameters in patients with OSCC. Univariate and multivariate Logistic regression and Cox proportional risk regression were applied for further analysis, and receiver operating characteristic curve and survival curve of subjects were plotted. RESULTS: CDSN was identified as the most significant hub gene of the OSCC by the cytoHubba. By the comparative toxicogenomics database (CTD) analysis, there was strong relationship between the CDSN and mouth neoplasms, head and neck neoplasms, squamous cell carcinoma of head and neck. The OSCC patients with low expression level of CDSN have poor overall survival compared with the high expression level of CDSN (HR = 0.75, 95% confidence interval [95%CI]: 0.57-0.98, P = .036). Spearman correlation coefficient analysis showed that CDSN expression level was significantly correlated with prognosis (ρ = -0.528, P < .001). Multivariate Logistic regression analysis showed that poor prognosis (odds ratio [OR] = 0.096, 95%CI: 0.049-0.189, P < .001) was significantly associated with low expression of CDSN. Cox regression analysis showed that the survival time of OSCC patients was shorter when CDSN expression was low (HR = 0.588, 95%CI: 0.420-0.823, P = .002). Strong predictive value of CDSN for the OSCC survival time was obtained by the biological process (BP)-neural network and support vector machine (SVM). CONCLUSION: CDSN was significantly correlated with OSCC, and the shorter the survival time of patients with OSCC was, the worse the prognosis was.

Effect of pembrolizumab on T lymphocyte subsets in patients with advanced oral cancer and its therapeutic effect.

BACKGROUND: The aim of this study is to investigate changes of peripheral blood lymphocyte subsets before and after treatment with pembrolizumab for advanced oral cancer and its clinical sig-nificance. METHODS: 32 patients with advanced oral cancer who received pembrolizumab treatment were selected as observation group, 30 healthy people during the same period were selected as control group. Before treatment and in cycles 1, 2, 3 and 4 after treatment, fluid cytometry was used to detect changes in levels of lymphocyte subsets in peripheral blood of patients. RESULTS: CD3+, CD4+, CD4+/CD8 + indexes of patients with advanced oral cancer before treatment were significantly lower than those in control group (P < .05), CD8 + level was significantly increased (P < .05); After 1 cycle of pembrolizumab treatment, there was no significant difference in changes of lymphocyte subsets compared with before immunotherapy; After 2 and 3 cycles of treatment, CD3+, CD4+, CD4+/CD8 + values were higher than before the treatment (P > .05), CD8 + index was slightly lower than before treatment (P < .05); After fourth cycle of treatment, CD3+, CD4+, CD4+/CD8 + values were significantly improved compared to before treatment (P < .05), CD8 + index was significantly lower than before treatment (P < .05); In treatment process of patients with stable disease (SD)/partial response (PR), the CD3+, CD4+, CD4+/CD8 + values of fourth cycles were higher than before treatment (P < .05), CD8 + index was lower than before treatment (P < .05); During treatment of progressive disease (PD) patients, changes of lymphocyte subsets in fourth cycles were not significantly different from those before treatment (P > .05). This article shows through analysis that expression of programmed cell death ligand 1 (PD-L1) and pathological types have no obvious influence on effect of immunotherapy. Multi-factor analysis shows that it is more meaningful to observe the changes of CD3+, CD4 + and CD8 + at the same time to predict effect of immunotherapy. CONCLUSION: Pembrolizumab can regulate changes of T lymphocyte subsets in patients with advanced oral cancer, improve immune status of patients, there is no obvious adverse reaction. Monitoring changes of lymphocyte subsets during treatment can predict effect of immunotherapy.

SPP1 and FN1 are significant gene biomarkers of tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumor types in the oral and maxillofacial region. The etiology and pathogenesis behind TSCC is complicated. In the present study, three gene expression profiles, namely GSE31056, GSE13601 and GSE78060, were downloaded from the Gene Expression Omnibus (GEO). The GEO2R online tool was utilized to identify differentially expressed genes (DEGs) between TSCC and normal tissue samples. Furthermore, a protein-protein interaction (PPI) network was constructed and hub genes were validated and analyzed. A total of 83 common DEGs were obtained in three datasets, including 48 upregulated and 35 downregulated genes. Pathway enrichment analysis indicated that DEGs were primarily enriched in cell adhesion, extracellular matrix (ECM) organization, and proteolysis. A total of 63 nodes and 218 edges were included in the PPI network. The top 11 candidate hub genes were acquired, namely plasminogen activator urokinase (PLAU), signal transducer and activator of transcription 1, C-X-C motif chemokine ligand 12, matrix metallopeptidase (MMP) 13, secreted phosphoprotein 1 (SPP1), periostin, MMP1, MMP3, fibronectin 1 (FN1), serpin family E member 1 and snail family transcriptional repressor 2. Overall, 83 DEGs and 11 hub genes were screened from TSCC and normal individuals using bioinformatics and microarray technology. These genes may be used as diagnostic and therapeutic biomarkers for TSCC. In addition, SPP1 and FNl were identified as potential biomarkers for the progression of TSCC.

[Effect of miR-204-5p on the proliferation, migration, and invasion on tongue squamous cell carcinoma SCC25 cells by targeting bromodomain-containing protein 4].

OBJECTIVE: This study aimed to explore the target relationship between miR-204-5p and bromodomain-containing protein (BRD) 4, as well as their effects on cell proliferation, migration, and invasion in tongue squamous cell carcinoma SCC25. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-204-5p and BRD4 expression levels in tongue squamous cell carcinoma and different cell lines. TargetScan and dual luciferase reporter assay were used to confirm the target relationship between miR-204-5p and BRD4. The effects of miR-204-5p on SCC25 cell proliferation were examined by cell counting kit (CCK) 8 assay, whereas those on SCC25 cell migration and invasion were determined by Transwell assay. RT-qPCR and Western blot were used to detect the effects of miR-204-5p mimics and inhibitors on BRD4 expression. Transwell and CCK8 assays were used to detect the effects of miR-204-5p on proliferation, migration, and invasion through BRD4 regulation. RESULTS: miR-204-5p was significantly downregulated in the tissues and cells of squamous cell carcinoma, and BRD4 showed the opposite result. The increase in miR-204-5p expression can inhibit the proliferation, migration, and invasion of SCC25 cells. TargetScan and luciferase test confirmed that miR-204-5p and BRD4 had a negative regulatory relationship with BRD4, respectively. Moreover, miR-204-5p mimics can inhibit BRD4 expression, and miR-204-5p inhibitors can promote BRD4 expression upregulation. When miR-204-5p and BRD4 were overexpressed in SCC25 cells, BRD4 can make up for the inhibitory effect of miR-204-5p on SCC25 cells. CONCLUSIONS: miR-204-5p could inhibit proliferation, migration and invasion in tongue squamous cell carcinoma SCC25 cells by targeting BRD4 gene.

[Effect of EDTA and hyaluronic acid on the activity of periodontal ligament fibroblasts and the expression of cytokines].

PURPOSE: To investigate the effect of ethylenediaminetetraacetic acid (EDTA) and hyaluronic acid (HA) on the activity of periodontal ligament fibroblasts (PDLFs) and the expression of cytokines. METHODS: Twelve wisdom teeth extracted due to orthodontics treatment were selected and prepared into 5 mm×4 mm root pieces, then divided into EDTA group, HA group, EDTA+HA group and untreated group according to different treatment methods. They were placed in the well plate and PDLFs inoculated on the root piece. After 24 and 48 h of inoculation, the cell proliferation of each group was detected by MTT assay. The adhesion of PDLFs was observed under microscope. The inflammatory cytokines (IL-6, IL-8 and IL-1ß and TNF-α) levels produced by PDLFs were determined by ELLISA and Western Blot. SPSS 22.0 software package was used for statistical analysis. RESULTS: After 24 h and 48 h inoculation, all the treatments promoted cell proliferation and adhesion of PDLFs compared with the untreated group, and the combined treatment promoted cell proliferation and adhesion significantly better than single treatment (P<0.05). The cell proliferation and adhesion effect of EDTA group and HA group increased with the inoculation time, without significant difference between the groups (P>0.05). The results of ELLISA and Western blot showed that compared with the untreated group, the treatment groups inhibited the expression of inflammatory factors IL-6, IL-1ß and TNF-α, and promoted the expression of IL-8, and the effect of EDTA+HA group was much more significant(P<0.05). CONCLUSIONS: EDTA+HA can significantly promote the growth of periodontal ligament fibroblasts and inhibit the expression of inflammatory cytokines, which may be related to its ability to enhance the adhesion of fibroblasts and then improve their viability.

[Expression and clinical significance of Spindly and Bub3 in oral squamous cell carcinoma].

PURPOSE: To investigate the expression and significance of Spindly and Bub3 in oral squamous cell carcinoma(OSCC). METHODS: Sixty-five patients with OSCC admitted to the Fourth Hospital of Hebei Medical University from March 2017 to March 2019 were enrolled. RT-PCR was used to detect the expression of Spindly and Bub3 mRNA in oral squamous cell carcinoma and adjacent normal tissues from the patients. OSCC cell line was cultured. After siRNA transfection interference with the expression of Spindly and Bub3 genes, cell viability was detected by MTT assay, and the cell migration ability was detected by scratch test. Statistical analysis was performed with SPSS 22.0 software package RESULTS: The expression levels of Spindly and Bub3 mRNA in OSCC were significantly higher in adjacent tissues(P<0.05). The expression of Spindly and Bub3 mRNA was related to TNM staging, clinical staging and lymph node metastasis (P<0.05). The 5-year survival rate of patients with high expression of Spindly, Bub3, Spindly/Bub3 were significantly higher than the counterparts with low expression, and the 5-year survival rate of patients with high expression of Spindly/Bub3 was significantly lower than that of patients with high expression of Spindly and Bub3(P<0.05). The expression level of Spindly in siRNA-Spindly group was significantly lower than that in Spindly negative control group and blank control group, and the expression level of Bub3 in siRNA-Bub3 group was also significantly lower than that in Bub3 negative control group and blank control group. The expression level of Spindly in siRNA-Spindly group was significantly lower than that in Spindly negative control group and blank control group, and the expression level of Bub3 in siRNA-Bub3 group was also lower than that in Bub3 negative control group and blank control group. The migration ability of cells in siRNA-Spindly group at 24 and 48 hours was significantly lower than that in Spindly negative control group and blank control group; the migration ability at 24 and 48 hours was significantly lower than that of Bub3 negative control group and blank control group(P<0.05). CONCLUSIONS: Spindly and Bub3 are highly expressed in OSCC. Specific inhibition of Spindly and Bub3 gene expression can reduce the proliferation and migration of cancer cells, which might be used as one of the targets for the treatment of OSCC.

Performance of ethanol electro-oxidation on Ni-Cu alloy nanowires through composition modulation.

To reduce the cost of the catalyst for direct ethanol fuel cells and improve its catalytic activity, highly ordered Ni-Cu alloy nanowire arrays have been fabricated successfully by differential pulse current electro-deposition into the pores of a porous anodic alumina membrane (AAMs). The energy dispersion spectrum, scanning and transmission electron microscopy were utilized to characterize the composition and morphology of the Ni-Cu alloy nanowire arrays. The results reveal that the nanowires in the array are uniform, well isolated and parallel to each other. The catalytic activity of the nanowire electrode arrays for ethanol oxidation was tested and the binary alloy nanowire array possesses good catalytic activity for the electro-oxidation of ethanol. The performance of ethanol electro-oxidation was controlled by varying the Cu content in the Ni-Cu alloy and the Ni-Cu alloy nanowire electrode shows much better stability than the pure Ni one.