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Most of the malignant melanomas are already in the middle and advanced stages when they are diagnosed, which is often accompanied by the metastasis and spread of other organs.Besides, the prognosis of patients is bleak. The characteristics of the local immune microenvironment in metastatic melanoma have important implications for both tumor progression and tumor treatment. In this study, data on patients with metastatic melanoma from the TCGA and GEO datasets were selected for immune, stromal, and estimate scores, and overlapping differentially expressed genes (DEGs) were screened. A nine-IRGs prognostic model (ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) was established by univariate COX regression, LASSO and multivariate COX regression. Receiver operating characteristic (ROC) curves were used to test the predictive accuracy of the model. Immune infiltration was analyzed by using CIBERSORT, Xcell and ssGSEA in high-risk and low-risk groups. The immune infiltration of the high-risk group was significantly lower than that of the low-risk group. Immune checkpoint analysis revealed that the expression of PDCD1, CTLA4, TIGIT, CD274, HAVR2 and LAG3 were significantly different in groups with different levels of risk scores. WGCNA analysis found that the yellow-green module contained seven genes (ALOX5AP, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) from the nine-IRG prognostic model, of which the yellow-green module had the highest correlation with risk scores. The results of GO and KEGG suggested that the genes in the yellow-green module were mainly enriched in immune-related biological processes. Finally, we analyzed the prognostic ability and expression characteristics of ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22 in metastatic melanoma. Overall, a prognostic model for metastatic melanoma based on the characteristics of the tumor immune microenvironment was established, which was helpful for further studies.It could function well in helping people to understand the characteristics of the immune microenvironment in metastatic melanoma and to find possible therapeutic targets.

Adoptive therapy using T cells modified with tumour antigen-specific T cell receptor (TCR) genes has become a popular area of research in tumour biotherapy research. However, the efficiency of this treatment is low. To increase the efficiency of this therapy, the antigen specific TCR expression in the T cells needs to be improved. Adenoviral vector-mediated gene expression is an attractive approach to bypass the issue of TCR gene modification. The efficiency of adenovirus vector serotype 5 (Ad5) infection is low due to the absence of coxsackievirus B-adenovirus receptor (CAR) expression in T cells. In the present study, a chimeric adenoviral vector (Ad5F35L) was generated; this construct contained both the natural long-shaft of Ad5 and the Ad35 knob. A transduction study showed that the Ad5F35L vector exhibited a higher transduction efficiency in human primary T lymphocytes than the Ad5 vector and the Ad5F35S vector, which contained the Ad35 natural short-shaft and the Ad35 knob. Similar transduction efficiencies were observed for both CD4(+) T lymphocytes and CD8(+) T lymphocytes and the transfection was independent of the expression of cell surface receptors. The activation of T lymphocytes resulted in an improvement of the Ad5F35L transduction efficiency in CD4(+) T cells and a decrease in Ad5F35L transduction efficiency in CD8(+) T cells. The results demonstrate that Ad5F35L is a promising viral vector and will facilitate the clinical application of tumour antigen-specific TCR gene therapy.

To investigate the value of Tei index and the sensitivity of left versus right ventricular Tei index in evaluating the fetal cardiac function in pregnancy-induced hypertension syndrome in the third trimester.Fetal echocardiograms were performed in 30 women with pregnancy-induced hypertension (PIH) syndrome and 55 with normal pregnancy of the third trimester. Tei index was obtained by calculating the ratio of the isovolumic time (isovolumic contraction and relaxation time) to the ejection time of the left and right ventricle. Comparisons of the Tei index were made between the PIH group and control group, and also between the left and right ventricles in each group.Significant difference was found in the left and right ventricular Tei index between PIH group and control group. No difference was noted between the left and right ventricular Tei index in the PIH group.Tei index is a useful indicator in evaluating fetal global cardiac function, for which purpose the left ventricular Tei index can be as sensitive as the right ventricular Tei index.

To explore the feasibility of using an intracavitary convex array probe for detecting the distal extracranial internal carotid artery (ICA) by transoral carotid ultrasonography (TOCU).Forty patients underwent examinations with bilateral ICA inspected with an intracavitary convex array probe by TOCU to observe the internal diameter, visible length, peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI).Eight of the 40 patients were excluded from the observation for the presence of carotid plaques. The examination was terminated in two patients due to sensitive throat and severe pharyngeal reflex. The rest of the patients completed the examination of the internal diameter, visible length, PSV, EDV and RI, which showed no statistically significant differences among them (P0.05).Using intracavitary convex array probe, the distal extracranial ICA disease can be diagnosed with higher accuracy.

To assess the value of an intracavitary convex array probe in detecting internal carotid artery (ICA) disease.Eighty-six carotid arteries in 43 cases were examined with intracavitary convex array probe, low-frequency convex array probe and high-frequency linear probe to collect the data including the ICA visible length, peak systolic velocity (PSV), internal diameter, blood vessel shape; common carotid artery (CCA) intimae-medial thickness (IMT), PSV, and internal diameter.Significant differences were noted in the visible length, PSV of ICA, and internal diameter detected by different frequency ultrasound probes. Intracavitary probe and high-frequency probe produced significantly different findings of the blood vessel shape.Intracavitary convex array probe has important clinical value in detecting of ICA disease.

To study the value of contrast-enhanced ultrasound with high-frequency linear-array transducer in the diagnosis of carotid stenosis.The carotid arteries of 31 patients was examined with color Doppler ultrasound (CDU), harmonic contrast ultrasound (HCU) and digital subtractive angiography (DSA), respectively. The result of DSA was used as the golden standard for evaluating the accuracy, sensitivity and specificity of CDU and HCU in the diagnosis of carotid stenosis.Satisfactory images of 62 carotid arteries were obtained from the patients using HCU with high-frequency linear-array transducer. After intravenous injection of contrast agent, densely dotted hyperechogenic signals were found in the vascular lumen, with stronger intensity than that of the vascular walls. The filling defect areas in the lumen indicated vascular stenosis. Thirty carotid stenoses were detected by DSA, and 25 by CDU. The accuracy, sensitivity and specificity of CDU was 83.3%, 82.0% and 84.9%, respectively. HCU identified 29 carotid stenoses with accuracy, sensitivity and specificity of 96.7%, 96.7% and 97.0%, respectively, significantly higher than those of CDU (P0.05).HCU with high frequency linear-array transducer has better the accuracy than CDU and may serve as a good alternative for diagnosis of carotid stenosis.

To investigate effect of tumor-specific T cell receptor gene transfection on memory T cell differentiation in vitro.TCRVbeta7.1 gene was transferred into peripheral blood mononuclear cells (PBMCs) obtained from healthy adults, and the expression of Vbeta7.1 was detected by flow cytometry before and after the transfection. Memory T cell differentiation was induced by stimulation with the hepatocarcinoma cell line BEL-7402 in vitro. The expression of surface molecules CD45RO, CD45RA and CCR7 was analyzed by flow cytometry to identify the phenotype and subsets of the memory T cells. Fluorescence-activated cell sorting was performed to detect the apoptosis of the tumor cells, and enzyme-linked immunoabsorbent assay was used to determine the production of interferon-gamma (IFN-gamma) for assessing the immune function of the memory T cells.Flow cytometry showed that TCRVbeta7.1 gene was efficiently expressed after transfection. After stimulation by the tumor cells in vitro, the expression of CD45RO in TCRVbeta7.1 gene-modified T cells increased gradually, and analysis of the coexpression of CD45RA and CCR7 revealed that the effector memory T cells constituted the majority of the differentiated memory T cells. The apoptotic rate of the tumor cells induced by the T cells increased significantly with also obviously increased INF-gamma secretion in the memory T cells.Tumor-specific TCRVbeta7.1 gene transfection can promote the differentiation of the memory T cells, the majority of which belongs to effector memory T cells that perform immune functions by inducing apoptosis and cytokine secretion.

To investigate the correlation between glycodelin and endometrial receptivity and the value of serum glycodelin detection in in vitro fertilization and embryo transfer (IVF-ET) cycles for evaluation of the outcome of pregnancy.Serum glycodelin level in women receiving IVF-ET on the day of oocyte retrieval and embryo transfer was measured by ELISA, and the condition of the endometrium was examined by transvaginal ultrasonography.There was no difference in serum glycodelin level on the day of oocyte retrieval or embryo transfer between the pregnant group and nonpregnant group, but the ratio and difference of serum glycodelin levels on the days of embryo transfer and retrieval were both higher in pregnant group than in the nonpregnant group (2.54-/+2.14 vs 0.96-/+0.51, and 0.91-/+1.22 vs -0.30-/+1.14, respectively). No correlation was found between serum glycodelin levels and endometrial thickness or echo patterns.Serum glycodelin levels on the days of retrieval and embryo transfer are not correlated to endometrial thickness or echo patterns, but their dynamic changes reflect endometrial receptivity to a certain extent, which might have prognostic value for pregnancy following IVF-ET.