Identification of immune subtypes of melanoma based on single-cell and bulk RNA sequencing data.

The tumor microenvironment plays a crucial role in melanoma. In this study, the abundance of immune cells in melanoma samples was assessed and analyzed using single sample gene set enrichment analysis (ssGSEA), and the predictive value of immune cells was assessed using univariate COX regression analysis. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis was applied to construct an immune cell risk score (ICRS) model with a high predictive value for identifying the immune profile of melanoma patients. The pathway enrichment between the different ICRS groups was also elucidated. Next, five hub genes for diagnosing the prognosis of melanoma were screened by two machine learning algorithms, LASSO and random forest. The distribution of hub genes in immune cells was analyzed on account of Single-cell RNA sequencing (scRNA-seq), and the interaction between genes and immune cells was elucidated by cellular communication. Ultimately, the ICRS model on account of two types of immune cells (Activated CD8 T cell and Immature B cell) was constructed and validated, which can determine melanoma prognosis. In addition, five hub genes were identified as potential therapeutic targets affecting the prognosis of melanoma patients.

The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ERα and enhances ERα target gene expression in breast cancer cells.

Estrogen/ERα signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ERα to potentiate ERα target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ERα, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ERα transcriptional activity and concomitantly enhances ERα acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ERα responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ERα and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer.

The Efficacy and Safety of Tamsulosin Combined with Extracorporeal Shockwave Lithotripsy for Urolithiasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND PURPOSE: Many studies have been conducted to investigate adjunctive tamsulosin therapy after extracorporeal shockwave lithotripsy (SWL) for urolithiasis. The results from those studies, however, are still inconsistent. Therefore, we performed a meta-analysis to provide an update on the clinical efficacy and safety of tamsulosin combined with SWL for urolithiasis. METHODS: A systematic search was performed in PubMed, Cochrane Library, and Embase to identify all relevant randomized controlled trials until January 2015. Two reviewers independently assessed trial quality and extracted data. Meta-analysis was conducted with Review Manager (RevMan), version 5.1. RESULTS: Twenty-one studies (2093 subjects in total) were identified in the current meta-analysis. Compared with a control group, the experimental group (tamsulosin combined with SWL) showed an increased overall benefit for stone expulsion, with pooled risk ratio (RR) of 1.20 (95% confidence interval [CI], 1.15-1.26). With respect to the different geographic regions, European and American had a high possibility of improvement in stone expulsion (RR: 1.33, 95% CI, 1.19-1.49). According to the stone locations (renal, upper and lower ureteral) and sizes (4-10 mm and 11-24 mm), tamsulosin is more useful for lower ureteral stone (RR: 1.28; 95% CI, 1.14-1.43) and larger sized stones (RR: 1.49; 95% CI, 1.28-1.75). The effect estimates did not vary markedly when stratified by follow-up durations but varied by dose of tamsulosin. Furthermore, a shorter expulsion time, reduced occurrence of steinstrasse, fewer incidences of colic, and lower analgesic requirements were observed within the experimental group. In addition, tamsulosin is well tolerated, and its adverse events rarely led to dropouts of patients. CONCLUSIONS: Overall, evidence suggests that tamsulosin combined with SWL is safe and effective in enhancing stone expulsion for patients with urolithiasis. Furthermore, high-quality, randomized and placebo-controlled trials evaluating the efficacy and safety of tamsulosin should be performed.

[Association of estrogen receptor gene polymorphisms and primary trigeminal neuralgia].

OBJECTIVE: To investigate the association of estrogen receptor (ER) gene polymorphism and primary trigeminal neuralgia. METHODS: By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), ER gene polymorphism was analyzed in 20 trigeminal neuralgia (TR) patients and 20 control individuals, and the distribution of ER genotype was compared in TR group and control group. RESULTS: There was no significant difference in frequencies of allele and genotype in XbaI or PvuII polymorphism or XbaI with PvuII polymorphisms together between TR group and control group (P > 0.05). The genotypic distribution of Xx or PpXx in TR group was higher than control group, and it was contary to xx, ppxx or Ppxx in TR group and control group. CONCLUSION: XbaI or PvuII polymorphism may be related to TR. Women with PpXx genotype may be a dangerous factor to primary trigeminal neuralgia.