The mTORC1 pathway participate in hyper-function of B cells in immune thrombocytopenia.

B cell hyper-function plays an important role in the pathogenesis of immune thrombocytopenia (ITP), but the molecular mechanisms underlying such changes remain unclear. We sought to identify regulators of B cell dysfunction in ITP patients through transcriptome sequencing and the use of inhibitors. B cells were isolated from PBMC of 25 ITP patients for B cell function test and transcriptome sequencing. For the potential regulatory factors identified by transcriptome sequencing, the corresponding protein inhibitors were used to explore the regulatory effect of the regulatory factors on B cell dysfunction in vitro. In this study, increased antibody production, enhanced terminal differentiation and highly expressed costimulatory molecules CD80 and CD86 were found in B cells of patients with ITP. In addition, RNA sequencing revealed highly activated mTOR pathway in these pathogenic B cells, indicating that the mTOR pathway may be involved in B cell hyper-function. Furthermore, mTOR inhibitors rapamycin or Torin1 effectively blocked the activation of mTORC1 in B cells, resulting in reduce antibody secretion, impaired differentiation of B cells into plasmablasts and downregulation of costimulatory molecules. Interestingly, as an unspecific inhibitor of mTORC2 besides mTORC1, Torin1 did not show a stronger capacity to modulate B cell function than rapamycin, suggesting that the regulation of B cells by Torin1 may depend on blockade of mTORC1 rather than mTORC2 pathway. These results indicated that the activation of mTORC1 pathway is involved in B cell dysfunction in patients with ITP, and inhibition of mTORC1 pathway might be a potential therapeutic approach for ITP.

Cognitive emotion regulation for improved mental health: A chain mediation study of Chinese high school students.

High school is a critical time for individual development, during which significant physical and mental changes related to puberty occur. Therefore, high school students' mental health requires more attention from schools, families, and society. Our study explored high school students' present status and family functioning characteristics, psychological capital, cognitive-emotion regulation, and life satisfaction by surveying 917 students in China. Data were analysed using independent sample t-tests, one-way analysis of variance, regression analysis, structural equation modelling, and path analysis. Our results showed that family function was positively correlated with life satisfaction, psychological capital, and positive emotion regulation strategies. Negative emotion regulation strategies were inversely correlated with these variables. The variable of cognitive emotion regulation has two dimensions, positive and negative. Cognitive-emotional regulation and psychological capital had sequential mediating effects between family function and life satisfaction. The results of this study offer new explanations for the mechanisms of family functioning on life satisfaction, how family functioning affects life satisfaction via cognitive-emotional regulation and psychological capital, and have some implications for family parenting. It also provides critical theoretical and practical guidance for schools to emphasise the use of positive cognitive-emotional regulation and the development of students' psychological capital levels in teaching and learning, thereby improving individual life satisfaction further. These findings highlight the importance of considering emotion regulation strategies and psychological capital when determining students' life satisfaction, and ensuring a healthy family environment.

MicroRNA-590-3p inhibits T helper 17 cells and ameliorates inflammation in lupus mice.

T helper 17 (Th17) cells have a pathogenic effect in many autoimmune diseases. Inhibition of Th17 cells can alleviate the inflammatory damage in autoimmune diseases. Our previous study found that microRNA-590-3p (miR-590-3p) was involved in the differentiation of Th17 cells in systemic lupus erythematosus (SLE). Here, we demonstrated that an increase in Th17 cells was correlated with low expression of miR-590-3p in patients with SLE and in lupus mice. Upregulation of miR-590-3p reduced the differentiation and promoted apoptosis of Th17 cells. Subsequent experiments demonstrated that miR-590-3p promoted apoptosis in Th17 cells by inhibiting autophagy. Autophagy-related 7 (Atg7) was the direct target of miR-590-3p that blocked the autophagy pathway. Finally, treatment of MRL/lpr mice with miR-590-3p agomir ameliorated lupus nephritis and skin lesions. Our work revealed that miR-590-3p inhibited Th17 cells by suppressing autophagy and that increased miR-590-3p expression was able to ameliorate the clinical symptoms of lupus. Therefore, miR-590-3p may be a promising therapeutic target for SLE and other Th17 cell-dependent autoimmune diseases.

Comprehensive analysis of CTLA-4 in the tumor immune microenvironment of 33 cancer types.

Immunotherapy has recently become a powerful weapon against cancer. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) was the first immune checkpoint used for immunotherapy. However, CTLA-4-related mechanisms in various cancers have not been comprehensively investigated. This aim of this study was an in-depth investigation of CTLA-4 in the tumor microenvironment and its relationship with other immunomodulators, immune-related pathways and survival outcomes of 33 cancer types. Overall 9,743 tumor samples and 710 normal samples of 33 cancer types from The Cancer Genome Atlas (TCGA) database were included. CTLA-4 expression level was compared between tumor and normal tissues in 22 cancer types. The microenvironment cell populations (MCP)-counter method was used to analyze the correlation between CTLA-4 and immune cell infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to investigate its relationship with immune pathways. Survival analysis was conducted using the Kaplan-Meier method with log-rank test. CTLA-4 expression was found to be increased in some types of cancer and decreased in other cancer types (P < 0.05). When comparing between different tumor tissues, CTLA-4 was lowest in uveal melanoma (UVM). MCP analysis demonstrated that CTLA-4 had a strong correlation with T cells in almost all cancer types and that CTLA-4 showed a positive correlation with most immune cells in UVM. Immune pathway analysis found that CTLA-4 is involved in a variety of immune pathways. Survival analysis revealed that CTLA-4 can predict patients' survival outcomes. This comprehensive analysis of CTLA-4 will promote anti-CTLA-4 therapy and personalized combined immunotherapy.

Identification of Prognostic Signatures for Predicting the Overall Survival of Uveal Melanoma Patients.

Uveal melanoma (UM) is an aggressive cancer which has a high percentage of metastasis and with a poor prognosis. Identifying the potential prognostic markers of uveal melanoma may provide information for early detection of metastasis and treatment. In this work, we analyzed 80 uveal melanoma samples from The Cancer Genome Atlas (TCGA). We developed an 18-gene signature which can significantly predict the prognosis of UM patients. Firstly, we performed a univariate Cox regression analysis to identify significantly prognostic genes in uveal melanoma (P<0.01). Then the glmnet Cox analysis was used to generate a powerful prognostic gene model. Further, we established a risk score formula for every patient based on the 18-gene prognostic model with multivariate Cox regression. We stratified patients into high- and low-risk subtypes with median risk score and found that patients in high-risk group had worse prognosis than patients in low-risk group. Multivariate Cox regression analysis demonstrated that 18-gene model risk score was independent of clinical prognostic factors. We identified four genes whose mutations were closely to UM patients' prognosis or risk score. We also explored the relationship between copy number variation and risk score and found that high risk group showed more chromosome aberrations than low risk group. Gene Set Enrichment Analysis (GSEA) analysis showed that the different biological pathways and functions between low and high risk group. In summary, our findings constructed an 18-gene signature for estimating overall survival (OS) of UM. Patients were categorized into two subtypes based on the risk score and we found that high risk group showed more chromosome aberrations than low risk group.

The efficacy of early immunosuppression in a morphea patient complicated with pulmonary interstitial fibrosis.

Currently seldom cases have been reported that generalized morphea could accompany with organ dysfunction. However, our study reveals not only morphea could complicate with intranet organ involvements but it may also be the early phase of systemic sclerosis. Furthermore, our therapy challenged the traditional morphea treatment to prove that cyclophosphamide and glucocorticoid are efficient to treat morphea with organ dysfunction.

Efficacy and safety of radiofrequency ablation for lung cancers: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of radiofrequency ablation(RFA) for patients with lung cancers using meta-analysis. METHODS AND MATERIALS: A literature search (PubMed, Embase, Web of science and China National Knowledge Infrastructure) was undertaken until August 2017 to identify sufficient studies evaluating the efficacy and safety of RFA. Pooled proportions of estimates were calculated by performing the random effect model, including technical success rate, recurrence rate, local tumor progression rate and complications. RESULTS: A total of 25 eligible studies were collected, giving a sample size of 1989 patients with 3025 lung tumors. In the present series, the pooled technical success rate was 96%(95%CIs: 93%-100%). Further, we observed pooled recurrence rate of 35%(95%CIs: 12%-59%) following RFA. Additionally, the pooled rate of local tumor progression was 26%(95%CIs: 20%-32%). One hundred and ninety major complications of RFA were reported in 20 studies, giving a pooled proportion of 6% (95%CIs: 3%-8%) for major RFA complications. Pooled rate of minor complications was 27% (95%CIs:14%-41%). CONCLUSION: In this meta-analysis, RFA was found to be a safe and efficient treatment for the patients with lung cancers. The efficacy and safety of RFA for lung cancer deserve future investigation in further well-designed randomized controlled trials.

Analysis of PD-1 related immune transcriptional profile in different cancer types.

BACKGROUND: Programmed cell death 1 (PD-1) functions as an immune checkpoint in the process of anti-tumor immune response. The PD-1 blockade is now becoming a fundamental part in cancer immunotherapy. So it's essential to elicit the PD-1 related immune process in different types of cancer. METHODS: The Cancer Genome Atlas was used to collect the RNA-seq data of 33 cancer types. The microenvironment cell populations-counter was used to analyze the immune cell infiltrates. KEGG and GO analysis were performed to investigate PD-1 associated biological process. Kaplan-Meier survival curves and Cox's proportional hazards model were performed for prognostic value analysis. RESULTS: We demonstrated that PD-1 expression varied in different cancer types. The uveal melanoma had a low PD-1 expression and poor infiltrated with immune cells. But it showed the strong correlation of PD-1 with the most types of immune cells. The PD-1 demonstrated a robust relationship with other immunomodulators and showed its involvement in critical functions correlated with anti-tumor immune pathways. Survival analysis indicated the PD-1 expression suggested different prognosis in different cancer types. CONCLUSIONS: Our investigations promote a better understanding of the PD-1 blockade and provide PD-1 related personized combined immunotherapy for different types of cancer patients.

Prognostic role of microRNA-210 in various carcinomas: a meta-analysis.

BACKGROUND: MicroRNA (miRNA) expressive alterations are associated with cancer and have potential diagnostic and prognostic values in various malignancies. Here, we summarize the global predictive role of miR-210 expression for survival in patients with a variety of carcinomas. METHODS: Eligible studies were identified through multiple search strategies. Data were assembled from studies investigating the relationship between miR-210 expression and survival in cancer patients. Hazard ratio (HR) was used as the common measure of association across studies: relative risk (RR) was considered equivalent to HR. Combined hazard ratios (HRs) of miR-210 for outcome were analyzed. RESULTS: A total of 10 studies dealing with various carcinomas were included for this global meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-210 expression in cancerous tissue was 2.41 (95% CI: 1.31-4.44), which could significantly predict poorer survival in general carcinomas. For distant-free, relapse-free or progressive-free survival, elevated miR-210 was also a significant predictor, with a pooled HR of 2.84 (95% CI: 2.10-3.83). Importantly, subgroup analysis suggested that higher expression of miR-210 correlated with worse OS in breast cancer: HR 4.34, 95% CI: 1.63-11.55. CONCLUSIONS: Our findings reveal that miR-210 detection has a prognostic value in patients with cancer, especially in breast cancer.