VBP1 promotes tumor proliferation as a part of the hypoxia-related signature in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in East Asia. Hypoxia, a hallmark of solid tumors, significantly alters redox homeostasis inside tumor microenvironment. This alteration drives tumor proliferation, invasion, and metastasis, leading to poor prognostic outcomes. However, the role of hypoxia-related genes in ESCC remains poorly understood. We employed RNA sequencing to identify differentially expressed genes in ESCC. Clinical data, transcriptome profiles, and a hypoxia-related gene set were extracted from open-source databases. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression, which was then validated through Cox regression analysis. Within this prognostic model, we pinpointed and investigated a key hypoxia-related gene affecting prognosis. The gene's expression was validated using real-time PCR and immunohistochemistry in both esophageal carcinoma and normal tissues. Tumor proliferation was examined through in vitro and in vivo assays, including the Cell Counting Kit-8, EdU, colony formation, and subcutaneous tumor models. A robust four-gene prognostic model (VBP1, BGN, CDKN1A, and PPFIA1) was successfully constructed and validated. Among these, VBP1 emerged as a key gene, exhibiting high expression levels that correlated with poor prognosis in ESCC. Functional experiments confirmed that VBP1 significantly accelerated tumor proliferation both in vitro and in vivo. VBP1 is identified as a pivotal gene within the hypoxia-related prognostic signature, and it significantly promotes tumor proliferation in ESCC.

B-Type Natriuretic Peptide Can Distinguish Ischemic Stroke Subtypes Better than Other Cardiac Biomarkers.

BACKGROUND The primary benefit to patients of being able to distinguish among subtypes of ischemic stroke (IS) is creation of a better treatment decision-making process. Current classification methods are complex and time-consuming, requiring hours to days. Blood-based cardiac biomarker measurements have the potential to improve mechanism classification of ischemic stroke. MATERIAL AND METHODS In this study, 223 patients with IS were selected as the case group and 75 healthy people who underwent physical examination at the same time were selected as the control group. The chemiluminescent immunoassay (CLIA) method established in this study was used to quantitatively detect plasma B-type natriuretic peptide (BNP) levels in subjects. All subjects were assessed for serum creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I (cTnI), and myoglobin (MYO) after admission. We investigated the effectiveness of BNP and other cardiac biomarkers in the diagnosis of different subtypes of IS. RESULTS The levels of the 4 cardiac biomarkers were increased in IS patients. BNP could better diagnose different types of IS compared to other cardiac biomarkers, and BNP combined with other cardiac biomarkers was better than a single indicator in diagnosing IS. CONCLUSIONS Compared with other cardiac biomarkers, BNP is a better marker for the diagnosis of different subtypes of ischemic stroke. Routine screening for BNP in IS patients is recommended to improve the treatment decision-making process and minimize the time to thrombosis, thereby providing a more precise treatment for patients with different subtypes of stroke.

CircSCAP interacts with SF3A3 to inhibit the malignance of non-small cell lung cancer by activating p53 signaling.

BACKGROUND: Circular RNA (circRNA) has been recently identified as a critical regulator during carcinogenesis. However, the biological function and potential underlying mechanisms of circRNAs in lung cancer remain to be further elucidated. METHODS: Here, we first evaluated the differentially expressed circRNAs between tumor and the matched adjacent nontumor tissues (3 pairs) of lung cancer patients via circRNA microarray. The expression of top five dysregulated circRNAs were tested in lung cancer cell lines and the circSCAP with concordant alteration in microarray data and cell lines was selected for further investigation. Then we validated the expression level of circSCAP in tumor and corresponding adjacent tissues (161 pairs) from a lung cancer cohort by RT-PCR analysis followed by correlation and prognosis analysis between circSCAP and clinical characteristics. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnosis (about 80% in the cohort used in this study). Therefore, we focused the role of circSCAP in NSCLC in the present study. In vitro and in vivo assays were performed to study the biological function of circSCAP in NSCLC. Biotin-labeled RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to identify the proteins directly interacting with circSCAP. The molecular mechanism of circSCAP-driven tumor suppression was demonstrated by immunoblotting, immunoprecipitation and luciferase reporter assays. In vitro and in vivo rescue experiments were conducted to verify the role of the circSCAP/SF3A3/p53 signaling axis in NSCLC. RESULTS: We screened the expression profiles of human circRNAs in lung cancer tissues and found that hsa_circ_0065214 (termed as circSCAP) was significantly decreased. Kaplan-Meier analysis showed that patients with low level of circSCAP had a significantly poor prognosis. Gain- and loss-of-function experiments suggested that circSCAP played an important role in NSCLC cell proliferation, cell migration and apoptosis. Mechanistically, circSCAP directly binds to the SF3A3 protein, facilitating the reduction of SF3A3 by promoting its ubiquitin-proteasome-mediated degradation, which enhances the expression of MDM4-S to finally activate its downstream p53 signaling. CONCLUSION: These findings illustrate a novel circSCAP/SF3A3/p53 signaling axis involved in suppressing the malignance of NSCLC and provide a promising target for NSCLC prognosis prediction and treatment.

Comprehensive analysis of the autophagy-dependent ferroptosis-related gene FANCD2 in lung adenocarcinoma.

BACKGROUND: The development of lung adenocarcinoma (LUAD) involves the interactions between cell proliferation and death. Autophagy-dependent ferroptosis, a distinctive cell death process, was implicated in a multitude of diseases, whereas no research revealing the relationship between autophagy-dependent ferroptosis and LUAD pathogenesis was reported. Thus, the primary objective was to explore the role and potential function of the autophagy-dependent ferroptosis-related genes in LUAD. METHODS: Clinical information and transcriptome profiling of patients with LUAD were retrieved and downloaded from open-source databases. Autophagy-dependent ferroptosis-related genes were screened by published articles. The critical gene was identified as the intersection between the differentially expressed genes and prognosis-related genes. Patients were divided into high- and low-risk groups using the expression level of the critical gene. The validity of the key gene prognosis model was verified by survival analysis. The correlation between the clinical characteristics of LUAD and the expression level of the key gene was analyzed to explore the clinical significance and prognosis value. And the roles of the key gene in response to chemotherapy, immune microenvironment, and tumor mutation burden were predicted. The validation of key gene expression levels was further performed by quantitative real-time PCR and immunohistochemistry staining. RESULTS: FANCD2, an essential autophagy-dependent ferroptosis-related gene by searching database, was confirmed as an independent prognostic factor for LUAD occurrence. The high expression level of FANCD2 was associated with an advantaged TNM stage, a less chemotherapy sensitivity, a low ImmuneScore, which indicated a deactivation status in an immune microenvironment, a high tumor mutation burden, and poor survival for LUAD patients. Pathway enrichment analysis showed that FANCD2 responded to oxidative stress and neutrophil-mediated immunity. Quantitative real-time PCR and immunohistochemistry staining showed that the expression level of FANCD2 is higher in LUAD patients than in normal tissue samples, which was in accordance with the database report. CONCLUSION: FANCD2, an essential gene related to autophagy-dependent ferroptosis, could work as a biomarker, predicting the survival, chemotherapy sensitivity, tumor immunity, and mutation burden of LUAD. Researching autophagy-dependent ferroptosis and targeting the FANCD2 may offer a new perspective for treating and improving prognosis in LUAD.

Cellular mechanism of action of forsythiaside for the treatment of diabetic kidney disease.

Background: Diabetic kidney disease (DKD) becomes the leading cause of death for end-stage renal disease, whereas the potential mechanism is unclear and effective therapy is still rare. Our study was designed to investigate the cellular mechanism of Forsythiaside against DKD. Materials and Methods: The targets of Forsythiaside and the DKD-related targets were obtained from databases. The overlapping targets in these two sets were regarded as potential targets for alleviation of DKD by Forsythiaside. The targets of diabetic podocytopathy and tubulopathy were also detected to clarify the mechanism of Forsythiaside ameliorating DKD from the cellular level. Results: Our results explored that PRKCA and RHOA were regarded as key therapeutic targets of Forsythiaside with excellent binding affinity for treating DKD podocytopathy. Enrichment analysis suggested the underlying mechanism was mainly focused on the oxidative stress and mTOR signaling pathway. The alleviated effects of Forsythiaside on the reactive oxidative species accumulation and PRKCA and RHOA proteins upregulation in podocytes were also confirmed. Conclusion: The present study elucidates that Forsythiaside exerts potential treatment against DKD which may act directly RHOA and PRKCA target by suppressing the oxidative stress pathway in podocytes. And Forsythiaside could be regarded as one of the candidate drugs dealing with DKD in future experimental or clinical researches.

Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases.

BACKGROUND: The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. METHODS: Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. RESULTS: A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3-4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. CONCLUSIONS: Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

Protective Effects of Vitamin E on Chemotherapy-Induced Peripheral Neuropathy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a common symptom, but prophylactic measures cannot still be carried out effectively. In addition, the efficacy of vitamin E in preventing peripheral neurotoxicity caused by chemotherapy is inconclusive. Therefore, we collected the relevant randomized controlled trials (RCTs) and performed a meta-analysis to examine whether the vitamin E has a positive effect in CIPN. METHODS: We searched PubMed, EMBASE, Cochrane, and other databases in December 2019 for eligible trials. Two reviewers conducted the analysis independently when studies were homogeneous enough. RESULTS: Eight RCTs, involving 488 patients, were identified. Upon pooling these RCTs, patients who received vitamin E supplementation of 600 mg/day had a lower incidence of CIPN (risk ratio [RR] 0.31; 95% confidence interval [CI] 0.14-0.65; p = 0.002) than the placebo group. Vitamin E played a key role in decreasing the incidence of peripheral neuropathy in the cisplatin chemotherapy group (RR 0.28; 95% CI 0.14-0.54; p = 0.0001). Moreover, vitamin E supplementation significantly decreased patients' sural amplitude after 3 rounds of chemotherapy (RR -2.66; 95% CI -5.09 to -0.24; p = 0.03) in contrast with that of placebo supplementation, while no significant difference was observed when patients were treated with vitamin E after 6 rounds of chemotherapy. In addition, the vitamin E-supplemented group had better improvement in the neurotoxicity score and lower incidence of reflexes and distal paraesthesias than the control group. CONCLUSION: Available data in this meta-analysis showed that vitamin E supplementation can confer modest improvement in the prevention of CIPN.

Survival outcomes and prognostic factors of primary small cell carcinoma of the esophagus.

BACKGROUND: Primary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive malignancy. It has a poor survival rate, and there is no consensus as to a standard therapeutic modality. In this study, we aimed to investigate the prognostic factors and evaluate the outcomes of patients with PSCCE who had been treated with different therapeutic methods. METHODS: We retrospectively evaluated 113 consecutive patients with PSCCE who received treatment at our center from 2003 to 2016. The primary endpoint was overall survival (OS). The Cox regression model was used to analyze the prognostic factors. The survival analysis was calculated using the Kaplan-Meier and log-rank methods. RESULTS: The 12- and 36-month OS rates of all 113 enrolled patients were 45% and 12%, respectively. A significantly prolonged OS rate was associated with lymph node stages N0-N1 (P=0.022), the Veterans' Administration Lung Study Group (VALSG) system limited-disease (LD) staging (P=0.040), and multimodality treatments (P=0.047). Patients with regional lymph node metastasis benefited more from surgery combined with chemotherapy than surgery or chemotherapy alone (P=0.046). Concerning chemotherapy, cisplatin plus etoposide was the regimen most commonly used to treat PSCCE patients (67.5%). CONCLUSIONS: An early lymph node stage, the VALSG LD staging, and multimodality treatments were identified as independent prognostic factors of PSCCE. Surgery combined with adjuvant chemotherapy was especially necessary for LD stage PSCCE patients with lymph node stages N1-3.

Minimal invasive versus open esophagectomy for patients with esophageal squamous cell carcinoma after neoadjuvant treatments.

BACKGROUND: Although previous studies have discussed whether the minimally invasive esophagectomy (MIE) is superior to open surgery, the data concerning esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant treatment followed by radical resection is limited. The purpose of our study was to compare the short- and long-term clinical outcomes of the two surgical approaches in treating ESCC patients. METHODS: Between January 2010 and December 2016, ESCC patients who had received neoadjuvant therapy and underwent Mckeown esophagectomy at our institute were eligible. The baseline characteristics, pathological data, short-and long-term outcomes of these patients were collected and compared based on the surgical approach. RESULTS: A total of 195 patients was included in the current study. Compared to patients underwent open surgery, patients underwent MIE had shorter operative time and less intraoperative bleeding (390 min vs 330 min, P = 0.001; 204 ml vs 167 ml, P = 0.021). In addition, the risk of anastomotic leakage was decreased in MIE group (20.0% vs 3.3%, P < 0.001), while the occurrence of other complications did not have statistical significance between two groups. Overall survival (OS) and disease-free survival (DFS) was no difference in patients received neoadjuvant chemotherapy between the two approaches. For the patients underwent neoadjuvant chemoradiotherapy, OS was significantly better in the MIE group (log rank = 6.197; P = 0.013). CONCLUSION: Minimally invasive Mckeown esophagectomy is safe and feasible for ESCC patients who underwent neoadjuvant therapy. MIE approach presented better perioperative results than open esophagectomy. The effect of surgical approaches on survival was depending on the scheme of neoadjuvant treatment.

Identification of an immune-related six-long noncoding RNA signature as a novel prognosis biomarker for adenocarcinoma of lung.

BACKGROUND: Lung adenocarcinoma (LUAD) is a heterogeneous disease with high mortality. Close attention has been paid to immunotherapy in LUAD treatment. However, immunotherapy has produced different therapeutic effects because of immune heterogeneity. Long noncoding RNAs (lncRNAs) are survival prognostic indicators with functions in the immune process. The present study was designed to examine the predictive power of immune-related lncRNAs in LUAD prognosis and investigated potential molecular mechanisms. METHODS: Transcriptome profiling and LUAD sample clinical information were retrieved from online database. The immune-related lncRNAs signature was identified by Cox regression. Survival analysis was used to verify the validity of the prognosis model. Then, possible biological functions were predicted and the abundance of infiltrating immune cells in LUAD samples were further analyzed. RESULTS: An immune-associated lncRNAs signature was established by combining six lncRNAs. Patients with LUAD were stratified into high- and low-risk groups using the six lncRNAs signature. Patients in different risk levels had significantly different prognoses (P<0.001), and the immune-associated lncRNAs signature was identified as an independent prognostic factor for LUAD. The functions of the lncRNA signature were confirmed as ubiquitin mediated proteolysis and signal sequence binding. The lncRNA signature negatively correlates with B-cell immune infiltration. CONCLUSION: A reliable immune-related lncRNAs prognosis model for LUAD was identified. lncRNAs played a vital role in the tumor immune process and were associated with the LUAD prognosis. Research of lncRNAs in B-cell immune infiltration could provide new insight into the immunotherapy of LUAD.

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.

A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Identification of key genes for esophageal squamous cell carcinoma via integrated bioinformatics analysis and experimental confirmation.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) as the main subtype of esophageal cancer (EC) is a leading cause of cancer-related death worldwide. Despite advances in early diagnosis and clinical management, the long-term survival of ESCC patients remains disappointing, due to a lack of full understanding of the molecular mechanisms. METHODS: In order to identify the differentially expressed genes (DEGs) in ESCC, the microarray datasets GSE20347 and GSE26886 from Gene Expression Omnibus (GEO) database were analyzed. The enrichment analyses of gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Set Enrichment Analysis (GSEA) were performed for the DEGs. The protein-protein interaction (PPI) network of these DEGs was constructed using the Cytoscape software based on the STRING database to select as hub genes for weighted co-expression network analysis (WGCNA) with ESCC samples from TCGA database. RESULTS: A total of 746 DEGs were commonly shared in the two datasets including 286 upregulated genes and 460 downregulated genes in ESCC. The DEGs were enriched in biological processes such as extracellular matrix organization, proliferation and keratinocyte differentiation, and were enriched in biological pathways such as ECM-receptor interaction and cell cycle. GSEA analysis also indicated the enrichment of upregulated DEGs in cell cycle. The 40 DEGs were selected as hub genes. The MEblack module was found to be enriched in the cell cycle, Spliceosome, DNA replication and Oocyte meiosis. Among the hub genes correlated with MEblack module, GSEA analysis indicated that DEGs of TCGA samples with DLGAP5 upregulation was enriched in cell cycle. Moreover, the highly endogenous expression of DLGAP5 was confirmed in ESCC cells. DLGAP5 knockdown significantly inhibited the proliferation of ESCC cells. CONCLUSIONS: DEGs and hub genes such as DLGAP5 from independent datasets in the current study will provide clues to elucidate the molecular mechanisms involved in development and progression of ESCC.

Prognostic significance of neutrophil-to-lymphocyte ratio in middle thoracic esophageal squamous cell carcinoma patients undergoing radical esophagectomy.

BACKGROUND: It is widely accepted that the pretreatment neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of prognosis in multiple malignancies, including esophageal squamous cell carcinoma (ESCC). However, its predictive value in middle thoracic esophageal carcinoma is still unclear. Therefore, the purpose of this study was to investigate the preoperative serum levels of NLR in middle thoracic esophageal carcinoma patients to clarify their clinical significance as predictors of prognosis. METHODS: This study investigated 556 patients with middle thoracic ESCC treated by esophagectomy from January 2010 to December 2012. The prognostic impact of serum NLR level was analyzed. A receiver operating characteristic (ROC) curve was used to identify the NLR for predicting survival. Correlation between the NLR and clinicopathological characteristics was analyzed by χ2 test. Prognostic influence was calculated by using the Kaplan-Meier method and the difference was compared by log-rank test. Cox regression analysis was performed to evaluate the significant prognostic factors. RESULTS: The cutoff value for the NLR was 2.43 ng/mL, the area under the curve was 0.553 (95% CI: 0.504-0.601; P=0.035), and the sensitivity and specificity were 53.3% and 58.7% respectively. It is demonstrated that preoperative NLR (P=0.003), T stage (P<0.001), N stage (P<0.001), surgical approach (P=0.004), and gender (P=0.008) were independent prognostic factors in middle thoracic ESCC by univariate analysis. Multivariate analysis showed that preoperative NLR (P=0.036), T stage (P=0.004), N stage (P<0.001), surgical approach (P=0.002), and age (P=0.019) were independent prognostic factors for survival. CONCLUSIONS: Pretreatment NLR >2.43 ng/mL could serve as an indicator of poor prognosis in middle thoracic ESCC patients after surgical treatment.

Redox regulation by SOD2 modulates colorectal cancer tumorigenesis through AMPK-mediated energy metabolism.

Colorectal cancer (CRC) is a common malignancy. Many reports have implicated aberrant mitochondrial activity in the progression of CRC, with particular emphasis on the dysregulation of redox signaling and oxidative stress. In this study, we focused on manganese superoxide dismutase (MnSOD/SOD2), a key antioxidant enzyme, which maintains intracellular redox homeostasis. Current literature presents conflicting mechanisms for how SOD2 influences tumorigenesis and tumor progression. Here, we explored the role of SOD2 in CRC specifically. We found high levels of SOD2 expression in CRC tissues. We carried out a series of experiments to determine whether knockdown of SOD2 expression in CRC cell lines would reverse features of tumorigenesis. We found that reduced SOD2 expression decreased cell proliferation, migration, and invasion activity in CRC cells. Results from an additional series of experiments on mitochondrial function implicated a dual role for SOD2 in promoting CRC progression. First, proper level of SOD2 helped CRC cells maintain mitochondrial function by disposal of superoxide (O2.- ). Second, over-expression of SOD2 induced H2 O2 -mediated tumorigenesis by upregulating AMPK and glycolysis. Our results indicate that SOD2 may promote the occurrence and development of CRC by regulating the energy metabolism mediated by AMPK signaling pathways.

Surgery and subsequent risk of non-small cell lung cancer recurrence: a meta-analysis of observational studies.

BACKGROUND: Surgery is the main treatment for stage I, II, and IIIA non-small cell lung cancer (NSCLC). However, the relationship between surgery and NSCLC recurrence is unclear. Thus, we performed a meta-analysis to determine whether surgery is associated with an increased risk of NSCLC recurrence. METHODS: We used the electronic databases in PubMed, Web of Science, EMBASE, Cochrane Library and MEDLINE to carry out a systematic literature search before December 1st, 2017. All studies on the association between surgery and subsequent risk of NSCLC recurrence were included and then analyzed using RevMan 5.3. RESULTS: Eleven studies were included in the meta-analysis involving 3,190 patients. The relationship between surgery and NSCLC recurrence was evaluated by pooled odds ratio (OR) and 95% confidence interval (CI). The results suggested that surgery does not increase the risk of NSCLC recurrence (OR =0.42, 95% CI, 0.25-0.72, P=0.001). CONCLUSIONS: Our results showed that surgery decreased the risk of NSCLC recurrence in stage I-IV.

THUMPD3-AS1 Is Correlated With Non-Small Cell Lung Cancer And Regulates Self-Renewal Through miR-543 And ONECUT2.

BACKGROUND: Of all malignancies, lung cancer is the leading cause of death, and non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. In this study, the long non-coding RNA (lncRNA) THUMPD3-AS1 was observed to be highly expressed in NSCLC and correlated with TNM stages and relapse, suggesting that THUMPD3-AS1 is involved in the regulation of NSCLC. METHODS: The aim of this study was to investigate the regulatory function and mechanism of THUMPD3-AS1 in NSCLC cells by cellular function and molecular biology experiments. RESULTS: Overexpression and knockdown analysis revealed that THUMPD3-AS1 promoted tumor progression by increasing cell proliferation and self-renewal of NSCLC cells. Moreover, THUMPD3-AS1 may act as an endogenous sponge of microRNA-543 (miR-543) which can regulate the target gene ONECUT2 in NSCLC cells. CONCLUSION: Our study indicated that THUMPD3-AS1 regulated NSCLC cell self-renewal by regulating the expression of miR-543 and ONECUT2, and THUMPD3-AS1 can potentially act as a biomarker or therapeutic target in NSCLC.

Atrial Hemangioma: A Case Report and Review of the Literature.

A primary cardiac tumor is a rare clinical entity which was reported an incidence of 0.03% in previous autopsy series. 75% cardiac tumors are cardiac myxoma and cardiac hemangiomas constitute only 1-2% of primary cardiac tumors. With the development of modern medical imaging technology and the enhancement of people's health awareness, more and more asymptomatic cardiac hemangiomas were found and confirmed eventually. Here, we described a case of a 71-year-old man, who was hospitalized with intermittent palpitation for 1 year and a large mass of the heart was removed successfully via sternotomy which was confirmed as atrial hemangioma by postoperative histopathology. Furthermore, a comprehensive review of atrial hemangioma was conducted to date and a few recommendations for the diagnosis and treatment of this uncommon disorder were provided for clinicians.

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis.

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.

Role of mtDNA haplogroups in the prevalence of knee osteoarthritis in a southern Chinese population.

Mitochondrial DNA (mtDNA) has been implicated in various human degenerative diseases. However, the role of mtDNA in Osteoarthritis (OA) is less known. To investigate whether mtDNA haplogroups contribute to the prevalence of knee OA, we have carried out a comprehensive case-control study on 187 knee OA patients and 420 geographically matched controls in southern China. OA patients were classified on the Kellgren/Lawrence scale from two to four for the disease severity study and the data were analyzed by adjusting for age and sex. We found that patients with haplogroup G (OR = 3.834; 95% CI 1.139, 12.908; p = 0.03) and T16362C (OR = 1.715; 95% CI 1.174, 2.506; p = 0.005) exhibited an increased risk of OA occurrence. Furthermore, patients carrying haplogroup G had a higher severity progression of knee OA (OR = 10.870; 95% CI 1.307, 90.909; p = 0.007). On the other hand, people with haplogroup B/B4 (OR = 0.503; 95% CI 0.283, 0.893; p = 0.019)/(OR = 0.483; 95% CI 0.245, 0.954; p = 0.036) were less susceptible for OA occurrence. Interestingly, we found OA patients also exhibited a general increase in mtDNA content. Our study indicates that the mtDNA haplogroup plays a role in modulating OA development.