GLUL stabilizes N-Cadherin by antagonizing ß-Catenin to inhibit the progresses of gastric cancer.

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with ß-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of ß-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher ß-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing ß-Catenin to inhibit the progress of gastric cancer.

Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress.

Chemoresistance poses a significant impediment to effective treatments for non-small-cell lung cancer (NSCLC). P21-activated kinase 4 (PAK4) has been implicated in NSCLC progression by invasion and migration. However, the involvement of PAK4 in cisplatin resistance is not clear. Here, we presented a comprehensive investigation into the involvement of PAK4 in cisplatin resistance within NSCLC. Our study revealed enhanced PAK4 expression in both cisplatin-resistant NSCLC tumors and cell lines. Notably, PAK4 silencing led to a remarkable enhancement in the chemosensitivity of cisplatin-resistant NSCLC cells. Cisplatin evoked endoplasmic reticulum stress in NSCLC. Furthermore, inhibition of PAK4 demonstrated the potential to sensitize resistant tumor cells through modulating endoplasmic reticulum stress. Mechanistically, we unveiled that the suppression of the MEK1-GRP78 signaling pathway results in the sensitization of NSCLC cells to cisplatin after PAK4 knockdown. Our findings establish PAK4 as a promising therapeutic target for addressing chemoresistance in NSCLC, potentially opening new avenues for enhancing treatment efficacy and patient outcomes.

Oncogenic KRAS effector USP13 promotes metastasis in non-small cell lung cancer through deubiquitinating ß-catenin.

KRAS mutations are frequently detected in non-small cell lung cancers (NSCLCs). Although covalent KRASG12C inhibitors have been developed to treat KRASG12C-mutant cancers, effective treatments are still lacking for other KRAS-mutant NSCLCs. Thus, identifying a KRAS effector that confers poor prognosis would provide an alternative strategy for the treatment of KRAS-driven cancers. Here, we show that KRAS drives expression of deubiquitinase USP13 through Ras-responsive element-binding protein 1 (RREB1). Elevated USP13 promotes KRAS-mutant NSCLC metastasis, which is associated with poor prognosis in NSCLC patients. Mechanistically, USP13 interacts with and removes the K63-linked polyubiquitination of ß-catenin at lysine 508, which enhances the binding between ß-catenin and transcription factor TCF4. Importantly, we identify 2-methoxyestradiol as an effective inhibitor for USP13 from a natural compound library, and it could potently suppress the metastasis of KRAS-mutant NSCLC cells in vitro and in vivo. These findings identify USP13 as a therapeutic target for metastatic NSCLC with KRAS mutations.

Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study.

BACKGROUND & AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a microRNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication. METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n = 54) using microarray. Area under the receiver operator characteristic curve (AUROC) and least absolute shrinkage and selector operation regression analyses were used to prioritize miRNAs that discriminated patients with ESCC from controls. Using quantitative reverse transcription polymerase chain reaction, the candidates were measured in a discovery cohort (n = 72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n = 342) and validated in an internal cohort (n = 207) and an external cohort (n = 226). RESULTS: The microarray analysis identified 7 miRNAs for distinguishing patients with ESCC from control subjects. Because 1 was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified patients with all-stage ESCC in the training cohort (AUROC = 0.968) and was successfully validated in 2 independent cohorts. Importantly, this signature could distinguish patients with early-stage (stage Ⅰ/Ⅱ) ESCC from control subjects in the training cohort (AUROC = 0.969, sensitivity = 92.00%, specificity = 89.17%) and internal (sensitivity = 90.32%, specificity = 91.04%) and external (sensitivity = 91.07%, specificity = 88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival. CONCLUSIONS: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.

PTPRO suppresses lymph node metastasis of esophageal carcinoma by dephosphorylating MET.

Protein tyrosine phosphatase receptor-type O (PTPRO) is a membrane-bound tyrosine phosphatase. Notably, epigenetically silenced PTPRO due to promoter hypermethylation is frequently linked to malignancies. In this study, we used cellular and animal models, and patient samples to demonstrate that PTPRO can suppress the metastasis of esophageal squamous cell carcinoma (ESCC). Mechanistically, PTPRO can inhibit MET-mediated metastasis by dephosphorylating Y1234/1235 in the kinase activation loop of MET. Patients with PTPROlow/p-METhigh had significantly poor prognosis, suggesting that PTPROlow/p-METhigh can serve as an independent prognostic factor for patients with ESCC.

Development and validation of a prognostic nomogram for predicting cancer-specific survival in patients with metastatic clear cell renal carcinoma: A study based on SEER database.

Objectives: Clear cell renal cell carcinoma (ccRCC) is highly prevalent, prone to metastasis, and has a poor prognosis after metastasis. Therefore, this study aimed to develop a prognostic model to predict the individualized prognosis of patients with metastatic clear cell renal cell carcinoma (mccRCC). Patients and Methods: Data of 1790 patients with mccRCC, registered from 2010 to 2015, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The included patients were randomly divided into a training set (n = 1253) and a validation set (n = 537) based on the ratio of 7:3. The univariate and multivariate Cox regression analyses were used to identify the important independent prognostic factors. A nomogram was then constructed to predict cancer specific survival (CSS). The performance of the nomogram was internally validated by using the concordance index (C-index), calibration plots, receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). We compared the nomogram with the TNM staging system. Kaplan-Meier survival analysis was applied to validate the application of the risk stratification system. Results: Diagnostic age, T-stage, N-stage, bone metastases, brain metastases, liver metastases, lung metastases, chemotherapy, radiotherapy, surgery, and histological grade were identified as independent predictors of CSS. The C-index of training and validation sets are 0.707 and 0.650 respectively. In the training set, the AUC of CSS predicted by nomogram in patients with mccRCC at 1-, 3- and 5-years were 0.770, 0.758, and 0.757, respectively. And that in the validation set were 0.717, 0.700, and 0.700 respectively. Calibration plots also showed great prediction accuracy. Compared with the TNM staging system, NRI and IDI results showed that the predictive ability of the nomogram was greatly improved, and DCA showed that patients obtained clinical benefits. The risk stratification system can significantly distinguish the patients with different survival risks. Conclusion: In this study, we developed and validated a nomogram to predict the CSS rate in patients with mccRCC. It showed consistent reliability and clinical applicability. Nomogram may assist clinicians in evaluating the risk factors of patients and formulating an optimal individualized treatment strategy.

Novel lipometabolism biomarker for chemotherapy and immunotherapy response in breast cancer.

Emerging proof shows that abnormal lipometabolism affects invasion, metastasis, stemness and tumor microenvironment in carcinoma cells. However, molecular markers related to lipometabolism have not been further established in breast cancer. In addition, numerous studies have been conducted to screen for prognostic features of breast cancer only with RNA sequencing profiles. Currently, there is no comprehensive analysis of multiomics data to extract better biomarkers. Therefore, we have downloaded the transcriptome, single nucleotide mutation and copy number variation dataset for breast cancer from the TCGA database, and constructed a riskScore of twelve genes by LASSO regression analysis. Patients with breast cancer were categorized into high and low risk groups based on the median riskScore. The high-risk group had a worse prognosis than the low-risk group. Next, we have observed the mutated frequencies and the copy number variation frequencies of twelve lipid metabolism related genes LMRGs and analyzed the association of copy number variation and riskScore with OS. Meanwhile, the ESTIMATE and CIBERSORT algorithms assessed tumor immune fraction and degree of immune cell infiltration. In immunotherapy, it is found that high-risk patients have better efficacy in TCIA analysis and the TIDE algorithm. Furthermore, the effectiveness of six common chemotherapy drugs was estimated. At last, high-risk patients were estimated to be sensitive to six chemotherapeutic agents and six small molecule drug candidates. Together, LMRGs could be utilized as a de novo tumor biomarker to anticipate better the prognosis of breast cancer patients and the therapeutic efficacy of immunotherapy and chemotherapy.

The Correlation between the Use of the Proton Pump Inhibitor and the Clinical Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

Background: To determine if the use of the Proton Pump Inhibitors (PPI) impacts the clinical efficacy of Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC), a meta-analysis was conducted. Method: Eleven studies from PubMed, EMBASE, Cochrane Library, Web of Science, and other databases up to May 2022, were selected. The pertinent clinical outcomes were assessed by applying the Progression-free survival (PFS), Overall Survival (OS), Hazard Ratio (HR), and 95% Confidence Interval (CI). Result: This study included eleven articles containing 7,893 NSCLC patients. The result indicated that PPI use was dramatically related to poor OS (HR: 1.30 [1.10-1.54]), and poor PFS (HR: 1.25 [1.09-1.42]) in case of patients treated with ICIs. With regard to the subgroup analysis, PPI use was dramatically associated with poor OS (Europe: HR = 1.48 [1.26, 1.74], Worldwide: HR = 1.54 [1.24, 1.91]), and poor PFS (Europe: HR = 1.36 [1.18, 1.57], Worldwide: HR = 1.34 [1.16, 1.55]) in patients from Europe and multi-center studies across the world, poor OS in patients with age less than or equal to 65 (HR = 1.56 [1.14, 2.15]), poor PFS in patients aged more than 65 (HR = 1.36 [1.18, 1.57]), poor OS for patients receiving with PD-1 (HR = 1.37 [1.04, 1.79]), poor PFS for patients receiving with PD-L1 (HR = 1.33 [1.19, 1.49]), and poor OS (-30: HR = 1.89 [1.29, 2.78], ±30: HR = 1.44 [1.27, 1.64]) and poor PFS (-30: HR = 1.51 [1.11, 2.05], ±30: HR = 1.32 [1.20, 1.45]) for patients who received PPI at 30 days before and/or after starting the ICIs treatment. Conclusion: Our meta-analysis indicated that PPI combined with ICIs in the treatment of NSCLC patients could result in poor OS and PFS. PPI use should be extremely cautious in clinical practices to avoid the impact on the efficacy of the ICIs.

miR-203a-3p-DNMT3B feedback loop facilitates non-small cell lung cancer progression.

It has been reported that microRNA-203a-3p (miR-203a-3p) modulates cell proliferation, migration and invasion in a variety of cancer cell types. However, little is known about its role in lung cancer progression. The present study found that miR-203a-3p was downregulated in non-small cell lung cancer (NSCLC) cell lines and tissues. Overexpression of miR-203a-3p inhibits NSCLC cell proliferation, migration and invasion, and promotes cellular apoptosis in vitro. Restoration of miR-203a-3p expression in A549 and NCI-H520 cells enhances their chemosensitivity. Further experiments showed that DNA methyltransferase 3B (DNMT3B) was a direct target of miR-203a-3p. In addition, the present results revealed that promoter hypermethylation was the potential mechanism responsible for low miR-203a-3p expression in NSCLC. Notably, feedback regulation between miR-203a-3p and DNMT3B was observed in NSCLC. Moreover, Overexpression of miR-203a-3p reduces tumor growth in vivo. In summary, the present study has identified an miR-203a-3p-DNMT3B feedback loop that facilitates NSCLC progression.

Tyrosine Phosphatase PTPRO Deficiency in ERBB2-Positive Breast Cancer Contributes to Poor Prognosis and Lapatinib Resistance.

Despite the initial benefit from treating ERBB2-positive breast cancer with tyrosine kinase inhibitor lapatinib, resistance develops inevitably. Since the expression of protein tyrosine phosphatase receptor-type O (PTPRO), a member of the R3 subfamily of receptor protein tyrosine phosphatases (PTPs), is inversely correlated with the aggressiveness of multiple malignancies, we decided to explore the correlation between PTPRO and lapatinib resistance in ERBB2-positive breast cancer. Results of immunohistochemical (IHC) staining and the correlation analysis between the expression levels of PTPRO and the clinicopathological parameters indicate that PTPRO is downregulated in cancer tissues as compared with normal tissues and negatively associated with differentiation, tumor size, tumor depth, as well as the expression of ERBB2 and Ki67. Results from Kaplan-Meier analyses indicate that lower expression of PTPRO is correlated with shorter relapse-free survival for patients with ERBB2-positive breast cancer, and multivariable Cox regression analysis found that PTPRO can potentially serve as an independent prognostic indicator for ERBB2-positive breast cancer. Results from both human breast cancer cells with PTPRO knockdown or overexpression and mouse embryonic fibroblasts (MEFs) which derived from Ptpro +/+ and Ptpro -/- mice with then stably transfected plasmid FUGW-Erbb2 consistently demonstrated the essentiality of PTPRO in the lapatinib-mediated anticancer process. Our findings suggest that PTPRO is not only able to serve as an independent prognostic indicator, but upregulating PTPRO can also reverse the lapatinib resistance of ERBB2-positive breast cancer.

USP15 in Cancer and Other Diseases: From Diverse Functionsto Therapeutic Targets.

The process of protein ubiquitination and deubiquitination plays an important role in maintaining protein stability and regulating signal pathways, and protein homeostasis perturbations may induce a variety of diseases. The deubiquitination process removes ubiquitin molecules from the protein, which requires the participation of deubiquitinating enzymes (DUBs). Ubiquitin-specific protease 15 (USP15) is a DUB that participates in many biological cell processes and regulates tumorigenesis. A dislocation catalytic triplet was observed in the USP15 structure, a conformation not observed in other USPs, except USP7, which makes USP15 appear to be unique. USP15 has been reported to be involved in the regulation of various cancers and diseases, and the reported substrate functions of USP15 are conflicting, suggesting that USP15 may act as both an oncogene and a tumor suppressor in different contexts. The importance and complexity of USP15 in the pathological processes remains unclear. Therefore, we reviewed the diverse biological functions of USP15 in cancers and other diseases, suggesting the potential of USP15 as an attractive therapeutic target.

Long Intergenic Non-Protein Coding RNA 01089 Weakens Tumor Proliferation, Migration, and Invasion by Sponging miR-3187-3p in Non-Small Cell Lung Cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs), a class of endogenous non-coding RNAs, play an important role in the development and metastasis of non-small cell lung cancer (NSCLC). However, the function and mechanism of action of long intergenic non-protein coding RNA 1089 (LINC01089) in NSCLC remains unclear. This study aimed to identify the role of LINC01089 in cell proliferation, migration, and invasion of NSCLC. METHODS: Expression of LINC01089 and the relationship between LINC01089 and overall survival (OS) in NSCLC were determined using GEPIA 2.0. Similarly, microRNAs (miRNAs) that showed increased expression in NSCLC and correlated with OS were identified using the online OncomiR cancer database. Target miRNAs of LINC01089 were predicted using starBase. Cell models of LINC01089 and miR-3187-3p overexpression were constructed using transfection. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to analyze the expression of LINC01089 and miR-3187-3p. MTS assay was used to assess cell proliferation. Transwell was used for migration and invasion assays. RESULTS: LINC01089 expression was significantly reduced in NSCLC tissues and cells. Gain-of-function studies further demonstrated that LINC01089 overexpression inhibited proliferation, migration, and invasion of lung cancer cell lines, A549 and SK-MES-1. Based on starBase prediction and subsequent verification, we revealed that miR-3187-3p is a target miRNA of LINC01089. Additionally, miR-3187-3p expression was significantly increased in NSCLC tissues and cells. Overexpression of miR-3187-3p promoted proliferation, migration, and invasion of A549 and SK-MES-1 cells, thereby reversing the effect of LINC01089. CONCLUSION: LINC01089 attenuates tumor proliferation, migration, and invasion by sponging miR-3187-3p in NSCLC. LINC01089 acts as a tumor suppressor and represents a potential therapeutic target in NSCLC.

PTEN inhibits non-small cell lung cancer cell growth by promoting G0/G1 arrest and cell apoptosis.

Non-small cell lung cancer (NSCLC) is a major type of human lung cancer and the primary cause of cancer-associated cases of mortality worldwide. Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene in various human cancer types. The aim of the current study was to explore the role of PTEN and its associated regulatory mechanisms in NSCLC. Firstly, the expression of PTEN was detected using western blotting in a variety of NSCLC cell lines. The results revealed that compared with normal control cells, PTEN levels were significantly decreased in NSCLC cell lines (P<0.01). Short hairpin (sh)RNAs specific to PTEN were also used to knockdown endogenous PTEN in NSCLC cells. The results indicated that cell viability was significantly increased in PTEN-knockdown cells compared with those transfected with negative control shRNA (P<0.01). Conversely, overexpression of PTEN in A549 and SK-MES-1 cells significantly decreased the optical density of NSCLC cells (P<0.01). Flow cytometry was used to investigate the cell cycle; the results revealed that PTEN knockdown significantly increased the percentage of cells at G0/G1 phase (P<0.01) and decreased the number of cells at S phase (P<0.01). The molecular mechanism was further explored using western blotting and the results demonstrated that PTEN overexpression increased the levels of cleaved caspase-3 (P<0.01). These results suggest that PTEN may be a potential target gene for gene therapy in patients with NSCLCs.

A comparative study of the influence of two types of PHEMA stents on the differentiation of ASCs to myocardial cells.

In the present study, subcutaneous fat was obtained from adult women that had undergone conventional liposuction surgery. A comparative study was performed to investigate the effect of transparent and white poly­ß­hydroxyethyl methacrylate (PHEMA) stents, which have different surface and cross­sectional morphological characteristics, on the differentiation of adipose­derived stem cells (ASCs) into myocardial cells. The cell counting kit­8 assay revealed that cell growth increased at varying rates among the different treatment groups. The absorbance of the experimental transparent PHEMA treated group increased in a time­dependent manner with the duration of incubation. The highest levels of proliferation were observed in the transparent PHEMA group. In addition, the transparent PHEMA treated group exhibited the strongest cell adhesion ability, which was significantly different to that of the white PHEMA group (P<0.01 and P<0.05 for Matrigel and fibronectin assay, respectively). Comparisons between the two stent materials with the inducer control group revealed statistically significant differences in the rate of ASC differentiation (P<0.05). The level of differentiation was the greatest in the transparent PHEMA group, and was significantly different to the white PHEMA group (P<0.05) and the blank control group (P<0.01). The results suggest that the inducers 5-aza-2-deoxycytidin and laminin, and material microstructure stents effectively promote the proliferation, growth and adhesion of ASCs. However, the transparent material microstructure may be a more suitable candidate for ASC­associated injections. The present study provides further evidence that a PHEMA stent structure, comprised of a high number of matrixes and a low water content, induces a high level of ASC differentiation to myocardial cells.

Downregulation of miR-101 contributes to epithelial-mesenchymal transition in cisplatin resistance of NSCLC cells by targeting ROCK2.

Chemoresistance and epithelial-mesenchymal transition (EMT) in cancer are linked phenomena. EMT contributes to chemoresistance, however, little is known about whether chemotherapy can induce EMT in cancer cells. Here, we found that miR-101 expression was downregulated in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Restoration of miR-101 expression inhibited EMT and increased the sensitivity of cisplatin-resistant NSCLC cells to cisplatin in vitro by targeting ROCK2. Furthermore, ROCK2 protein level was inversely correlated with miR-101 level in NSCLC tissue samples. Kaplan-Meier analysis revealed that low miR-101 expression in NSCLC was correlated with poor survival time. In summary, our results provide novel mechanistic insights into the role of miR-101/ROCK2 signaling in the cisplatin resistance of NSCLC cells. Targeting of miR-101 is a potential therapeutic approach for NSCLC.

Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients.

The effect of antigen specific immunotherapy (SIT) on asthma is supposed to be improved. Published data indicate that administration of probiotics alleviates allergic diseases. B cells play important roles in the pathogenesis of allergic diseases. This study aims to modulate antigen specific B cell property by the administration of Clostridium butyrate (CB) in combination with SIT. The results showed that after a 3-month treatment, the total asthma clinical score and serum specific IgE were improved in the patients treated with SIT, which was further improved in those treated with both SIT and CB, but not in those treated with CB alone. Treatment with SIT and CB increased p300 and STAT3 activation, up regulated the IL-10 gene transcription and increased the frequency of peripheral antigen specific B cells. In conclusion, administration with SIT in combination with CB converts Der p 1 specific B cells to regulatory B cells in asthma patients allergic to Der p 1. The data suggest a potential therapeutic remedy in the treatment of allergic diseases.

Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury.

AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1ß, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway.

Intrathoracic extramedullary hematopoiesis presenting as tumor-simulating lesions of the mediastinum in α-thalassemia: A case report.

Extramedullary hematopoiesis (EMH) is a rare disease, where hematological disorder drives extramedullary hematopoietic tumor formation in multiple regions of the body. The present study reports a case of EMH presenting as multiple tumor-like lesions of mediastinum in a 61-year-old male with α-thalassemia, which was subjected to a video-assisted thoracoscopic surgery tissue biopsy to differentiate it from other mediastinal tumors. To date, only three cases of EMH in patients with α-thalassemia have been described in the literature. Patients with EMH typically exhibit no hematological disorder preoperatively and therefore EMH is frequently misdiagnosed. In the present study, along with a literature review of the clinicopathological features of EMH, the diagnosis and treatment of this rare case was discussed, in order to differentiate diagnosis, and particularly to distinguish EHM from extramedullary myeloid sarcoma.

Compensatory sweating after restricting or lowering the level of sympathectomy: a systematic review and meta-analysis.

OBJECTIVE: To compare compensatory sweating after lowering or restricting the level of sympathectomy. METHOD: A systematic review and meta-analysis were conducted of all randomized controlled trials published in English that compared compensatory sweating after lowering or restricting the level of sympathectomy. The Cochrane collaboration tool was used to assess the risk of bias, and the Mantel-Haenszel odds ratio method was used for the meta-analysis. RESULTS: A total of 11 randomized controlled trials were included, including a total of 1079 patients. Five of the randomized controlled trials studied restricting the level of sympathectomy, and the remaining six studied lowering the level of sympathectomy. CONCLUSIONS: The compiled randomized controlled trial results published so far in the literature do not support the claims that lowering or restricting the level of sympathetic ablation results in less compensatory sweating.

Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1.

MiR-145 has been implicated in the progression of non-small cell lung cancer (NSCLC); however, its exact mechanism is not well established. Here, we report that miR-145 expression is decreased in NSCLC cell lines and tumor tissues and that this low level of expression is associated with DNA methylation. MiR-145 methylation in NSCLC was correlated with a more aggressive tumor phenotype and was associated with poor survival time, as shown by Kaplan-Meier analysis. Additional multivariate Cox regression analysis indicated that miR-145 methylation was an independent prognostic factor for poor survival in patients with NSCLC. Furthermore, we found that restoration of miR-145 expression inhibited proliferation, migration and invasion of NSCLC by the direct targeting of mucin 1 by miR-145. Our results indicate that low miR-145 expression, due to methylation, promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1. Therefore, miR-145 may be a valuable therapeutic target for NSCLC.