Xinxiang Central Hospital

BACKGROUND: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. METHODS: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)-EGFP infusion. RESULTS: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. CONCLUSION: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

Abstract N6-methyladenosine (m 6 A) serves as the most common and conserved internal transcriptional modification. However, the roles of m 6 A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the m 6 A profiles in CC cells. Functionally, METTL3 promoted the proliferation and Warburg effect (aerobic glycolysis) of CC cells. Mechanistically, METTL3 targeted the 3’-Untranslated Region (3’-UTR) of hexokinase 2 (HK2) mRNA. Moreover, METTL3 recruited YTHDF1, a m 6 A reader, to enhance HK2 stability. These findings demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated m 6 A modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment.

The aim of this study is to explore the roles of circular RNA (circRNA) Cdr1as on cisplatin resistance in ovarian cancer and explore the underlying mechanisms. We investigated the expression of circRNAs in five paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The quantitative real-time PCR analysis was to investigate the expression pattern of Cdr1as in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then, the effects of Cdr1as on cisplatin resistance, cell proliferation, and apoptosis were assessed in ovarian cancer cells. In this study, Cdr1as was observed to be downregulated in cisplatin-resistant patient tissues and cell lines. Overexpression of Cdr1as inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed Cdr1as promoted the miR-1270 expression, and miR-1270 could bind to the predicted binding site of Cdr1as. Furthermore, we found that miR-1270 displayed its role via modulating the Suppressor of Cancer Cell Invasion (SCAI) expression. Importantly, we demonstrated that Cdr1as was downregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that Cdr1as sensitizes ovarian cancer to cisplatin by regulating the miR-1270/SCAI signaling pathway.

To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.

Background Initial observational studies and a systematic review published recently have suggested that nonsteroidal anti-inflammatory drug (NSAID) use has the trend to be associated with reduced risk of Alzheimer's disease (AD), while results remain conflicting. Thus we performed an updated meta-analysis to reevaluate the evidence on this association. Methods Data sources from PUBMED, Embase and Cochrane Library from inception through April 2017 were searched by two independent reviewers. Eligible cohort studies were selected according to predefined keywords. We did a meta-analysis of available study data using a random-effects model to calculate overall relative risks (RRs) for associations between NSAID exposure and AD risk. Results From 121 potentially relevant studies, 16 cohort studies including 236022 participants, published between 1995 and 2016, were included in this systematic review. Meta-analysis demonstrated that current or former NSAID use was significantly associated with reduced risk of AD (RR, 0.81, 95% CI0.70 to 0.94) compared with those who did not use NSAIDs. This association existed in studies including all NSAID types, but not in aspirin (RR, 0.89, 95% CI 0.70 to 1.13), acetaminophen (RR, 0.87, 95% CI 0.40 to 1.91) or non-aspirin NSAID (RR, 0.84, 95% CI 0.58 to 1.23). Conclusions Current evidence suggests that NSAID exposure might be significantly associated with reduced risk of AD. However, further large-scale prospective studies are needed to reevaluate this association, especially the associations in individual NSAID type.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorder. It is characterized by the formation of amyloid plaques and neurofibrillary tangles in the brain, the degeneration of cholinergic neurons and neuronal cell death. The present study aimed to investigate the effect of luteolin, a flavonoid compound, on memory impairment in a streptozotocin (STZ)‑induced Alzheimer's rat model. Morris water maze and probe tests were performed to examine the effect of luteolin treatment on cognition and memory. The effect of luteolin on CA1 pyramidal layer thickness was also examined. The results demonstrated that luteolin significantly ameliorated the spatial learning and memory impairment induced by STZ treatment. STZ significantly reduced the thickness of CA1 pyramidal layer and treatment of luteolin completely abolished the inhibitory effect of STZ. Our results suggest that luteolin has a potentially protective effect on learning defects and hippocampal structures in AD.

Gastric cancer (GC) is one of the most prevalent gastrointestinal malignancies. Long noncoding RNA (lncRNA) DANCR is a newly identified oncogenic lncRNA. However, the functional role and underlying molecular mechanisms of DANCR involved in GC progress remain unclear. In the present study, we investigated the biological function and underlying mechanisms of DANCR in GC cell migration and invasion. The results showed that knockdown of DANCR inhibited migration and invasion of GC cells, whereas overexpression of DANCR showed the opposite effect. Further investigation demonstrated that lncRNA-LET was a bona fide target gene of DANCR. In addition, high DANCR and low lncRNA-LET were significantly correlated with lymph node metastasis and late clinical stage. DANCR associated with EZH2 and HDAC3 to epigenetically silence lncRNA-LET and then regulated GC migration and invasion. Taken together, these findings indicate an important role for DANCR–lncRNA-LET axis in GC cell migration and invasion, and reveal a novel epigenetic mechanism for lncRNA-LET silencing.

<h3>Objective</h3> Because metabolic syndrome is a significant risk factor for cardio-cerebrovascular diseases and the relationship between metabolic syndrome (including its components) and the prognosis of stroke is controversial, this study was conducted to evaluate whether metabolic syndrome is associated with a high recurrence and mortality of stroke. <h3>Methods</h3> This study was registered in the PROSPERO database (CRD42020177118). We searched for relevant observational cohort studies published from inception to April 23, 2020, using PubMed, Embase, and the Cochrane Library. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. The primary and secondary outcomes were stroke recurrence and all-cause mortality, respectively. Leave-one-out sensitivity analyses and nonparametric trim-and-fill method were used to identify the stability of the results. <h3>Results</h3> Thirteen cohort studies comprising 59,919 participants &gt;60 years of age were included for analysis. Overall, metabolic syndrome was significantly associated with stroke recurrence (relative risk [RR] 1.46, 95% CI 1.07–1.97, <i>p</i> = 0.02). Among the metabolic syndrome components, low levels of high-density lipoprotein cholesterol (HDL-C) (RR 1.32, 95% CI 1.11–1.57, <i>p</i> = 0.002) and ≥2 metabolic syndrome components (RR 1.68, 95% CI 1.44–1.94, <i>p</i> &lt; 0.001) significantly predicted stroke recurrence, whereas elevated triglycerides, elevated waist circumference, hyperglycemia, and hypertension failed to account for risk factors for stroke recurrence. Moreover, metabolic syndrome, not its components, was significantly associated with all-cause mortality (RR 1.27, 95% CI 1.18–1.36, <i>p</i> &lt; 0.001). The stability of these results was further confirmed by the leave-one-out sensitivity analyses and nonparametric trim-and-fill method. <h3>Conclusions</h3> The present study indicates that metabolic syndrome and some of its components (low HDL-C and number of metabolic syndrome components) seem to be risk factors for stroke recurrence. Although metabolic syndrome is also associated with all-cause mortality, the role of its components in predicting all-cause mortality deserves further study.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

The aberrant expression of microRNAs (miRNAs) is associated with colorectal carcinogenesis, but the underlying mechanisms are not clear. This study showed that the miRNA-27a (miR-27a) was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages-miR-27a was lower at stages III/IV than that at stage II. Bioinformatic and systemic biological analysis predicted several targets of miR-27a, among them SGPP1 and Smad2 were significantly affected. SGPP1 and Smad2 at mRNA and protein levels were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines. Increased miR-27a significantly repressed SGPP1 and Smad2 at transcriptional and translational levels. Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3. In vivo, miR-27a inhibited colon cancer cell growth in tumor-bearing mice. Taken together, this study has revealed miR-27a as a tumor suppressor and has identified SGPP1 and Smad2 as novel targets of miR-27a, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in colorectal cancer. Therefore, miR-27a could be a useful biomarker for monitoring colorectal cancer development and progression, and also could have a therapeutic potential by targeting SGPP1, Smad2 and STAT3 for colorectal cancer therapy.

BACKGROUND: Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. METHODS: In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014-8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695-5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. CONCLUSIONS: This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01874691.

Articular cartilage (AC), a bone-to-bone protective device made of up to 80% water and populated by only one cell type (i.e. chondrocyte), has limited capacity for regeneration and self-repair after being damaged because of its low cell density, alymphatic and avascular nature. Resulting repair of cartilage defects, such as osteoarthritis (OA), is highly challenging in clinical treatment. Fortunately, the development of tissue engineering provides a promising method for growing cells in cartilage regeneration and repair by using hydrogels or the porous scaffolds. In this paper, we review the therapeutic strategies for AC defects, including current treatment methods, engineering/regenerative strategies, recent advances in biomaterials, and present emphasize on the perspectives of gene regulation and therapy of noncoding RNAs (ncRNAs), such as circular RNA (circRNA) and microRNA (miRNA).

AIMS: MicroRNAs (miRNAs) are dysregulated in a wide range of malignant diseases, confirming their crucial role in tumor metastasis. MiRNA-30a-5p, a member of the miR-30 family, has been implicated in many types of cancers, including colorectal cancer, a leading cause of death worldwide. METHODS: qRT-PCR, Western blot, Transwell assay,luciferase reporter assay were performed in the present study. RESULTS: In this study, miR-30a-5p was found to be significantly downregulated in human colorectal cancer tissue specimens and cell lines compared with non-cancerous tissues and cells. The overexpression of miR-30a-5p inhibited the migratory and invasive abilities of colorectal cancer cells and suppressed the epithelial-mesenchymal transition, a crucial process in metastasis. Bioinformatic algorithms and luciferase reporter assays revealed that integrin β3 (ITGB3) is a direct target of miR-30a-5p. Importantly, overexpression of ITGB3 in colorectal cancer cells rescued these cells from miR-30a-5p-mediated suppression of metastasis and restored the epithelial-mesenchymal transition. CONCLUSION: Taken together, our study provides the first evidence that miR-30a-5p suppresses colon cancer metastasis through the inhibition of ITGB3. Thus, targeting miR-30a-5p might serve as a promising therapeutic strategy for the treatment of colorectal cancer.

Background: Most previous studies have found that human intestinal microbiota affect the symptoms of autism spectrum disorder (ASD), especially gastrointestinal (GI) symptoms, but there is limited data of non-western ethnicity. Probiotics can reconstitute the host intestinal microbiota and strengthen gastrointestinal function, whereas it lacks clinical data proving the effect of probiotics treatment for ASD. Methods: This study explored the significant differences between ASD and neurotypical (NT), and the improvement of applied behavior analysis (ABA) training in combination with probiotics versus ABA training only. Results: We found significant differences between the ASD group and the NT group in the evenness of the intestinal microbiota and the relative abundance of the bacterial phyla and genus. At the phylum level, relative abundance of Bacteroidetes in the ASD group was significantly lower than in the NT group. At the genus level, the relative abundance of Bacteroides, Bifidobacterium, Ruminococcus, Roseburia, and Blautia in the ASD group was significantly lower than that in the NT group. After 4-week ABA training program in combination with probiotics treatment, the ATEC and GI scores decreased more than the control group with ABA training only. Conclusion: Our findings suggest that intestinal microbiota is different between the NT children and the ASD children with or without GI. In combination with ABA training, probiotics treatment can bring more benefit to ASD children. Clinical trials with a more rigorous design and larger sample size are indispensable for further validation.

The combined chemotherapy and photodynamic therapy have significant advantages for cancer treatments, which have higher therapeutic effects compared with other medicines. Herein, we focused on the synthesis of carbon quantum dot (CQD) based nanocarrier system. CQD and 5-aminolevulinic acid (5-ALA) were conjugated with mono-(5-BOC-protected-glutamine-6-deoxy) β-cyclodextrin (CQD-Glu-β-CD) moiety, and finally, the anticancer chemotherapy doxorubicin (DOX) drug was loaded in the 5-ALA-CQD-Glu-β-CD system. The stepwise physicochemical changes for the preparation of the DOX loaded 5-ALA-CQD-Glu-β-CD system were investigated by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM), and Raman fluorescence spectroscopy. The encapsulation efficiency of DOX in 5-ALA-CQD-Glu-β-CD was observed at ∼83.0%, and the loading capacity of DOX is ∼20.37%. The in vitro releasing of DOX and 5-ALA was observed through the UV–vis spectroscopy by the λmax value of 487 nm and 253 nm, respectively. By the investigation against the breast MCF-7 cancer cells, the high cytotoxicity and morphological changes of cancer cells were observed by the treating of DOX/5-ALA-CQD-Glu-β-CD. The generation of reactive oxygen species (ROS) upon 635 nm (25 mW cm−2) for 15 min laser irradiation-induced improved the therapeutic effects. In vitro cellular uptake studies recommend the synthesized DOX/5-ALA-CQD-Glu-β-CD nanocarrier could significantly enhance the cell apoptosis and assist in the MCF-7 cell damages. The result suggests a multifunctional therapeutic system for chemo/photodynamic synergistic effects on cancer therapy.

INTRODUCTION: Osteoarthritis is an inflammatory disorder associated with oxidative stress and apoptosis leading to cartilage destruction and impairment of cartilage formation. In the present study, we studied the protective effect of lutein against monosodium iodoacetate (MIA)-induced osteoarthritis in primary chondrocyte cells. MATERIAL AND METHODS: Oxidative stress was determined through testing antioxidant status, reactive oxygen species levels and lipid peroxide content. Also, Nrf2 expression and its downstream target genes HO-1 and NQO-1 were determined. Inflammation was analyzed through NF-κB, COX-2 and pro-inflammatory cytokines (IL-6, TNF-α, IL-1β). In addition, the effects of MIA and lutein on mitochondrial membrane potential and caspase-3 levels were analyzed. RESULTS: The results showed that lutein treatment significantly increased the cell viability of chondrocytes and offered significant cytoprotection by enhancing the antioxidant defense mechanisms and reducing oxidative stress (reactive oxygen species and lipid peroxidation). Lutein treatment showed anti-inflammatory effects by downregulating inflammatory proteins (NF-κB, COX-2) and pro-inflammatory cytokines (IL-6, TNF-α, IL-1β). Lutein reduced MIA-induced apoptosis through maintaining mitochondrial membrane potential and downregulating caspase-3 activity. CONCLUSIONS: The present study shows significant cytoprotection offered by lutein against MIA-induced oxidative stress, inflammation and apoptosis by the modulatory effect of NF-κB and Nrf2 activation.

INTRODUCTION: Long non-coding RNA MEG3 (lncRNA MEG3) has been showed to involve in a variety of cancers. However, the association between lncRNA MEG3 expression level and the prognosis of osteosarcoma is still unclear. METHODS: The expression levels of lncRNA MEG3 in osteosarcoma tissues and adjacent non-tumor tissues were detected using quantitative real-time PCR (qRT-PCR). Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. RESULTS: Our findings showed that expression of lncRNA MEG3 was clearly lower in osteosarcoma tissues compared with adjacent non-tumor tissues. The expression of lncRNA MEG3 was associated with clinical stage and distant metastasis (P<0.05). Kaplan-Meier analysis showed that patients with low lncRNA MEG3 expression had a shorter overall survival (log-rank test, P<0.05). Furthermore, multivariate analysis revealed that decreased expression of lncRNA MEG3, advanced clinical stage and distant metastasis were all independent predictors to overall survival of osteosarcoma patients. CONCLUSIONS: Downregulation of lncRNA MEG3 was associated with poor overall survival of osteosarcoma. LncRNA MEG3 could be a useful biomarker for progression and prognosis of osteosarcoma.

Breast cancer with metastasis especially brain metastasis represents a significant cause of morbidity and mortality in patients. In this study, we aimed to investigate the hub genes and potential molecular mechanism in brain metastasis breast cancer. Expression profiles of the genes were extracted from the Gene Expression Omnibus (GEO) database. GO and KEGG pathway enrichment analyses were conducted at Database for Annotation, Visualization, and Integrated Discovery. Protein-protein interaction (PPI) network was established by STRING database constructed by Cytoscape software. Hub genes were identified by the molecular complex detection (MCODE) plugin and the CytoHubba plugin. The transcription factor (TF) that regulates the expression of hub genes was analyzed using the NetworkAnalyst algorithm. Kaplan-Meier curve was used to analyze the effects of hub genes on overall survival. Two GEO databases (GSE100534 and GSE52604) were downloaded from GEO databases. A total of 102 overlapped genes were identified, and the top five KEGG pathways enriched were pathways in cancer, HTLV-I infection, focal adhesion, ECM-receptor interaction, and protein digestion and absorption. By combing the results of MCODE and CytoHubba, a total of 10 hub genes were selected. Kaplan-Meier curve showed that ANLN, BUB1, TTK, and SKA3 were closely associated with the overall survival of breast cancer patients. TF analysis results showed that E2F4, KDM5B, and MYC were crucial regulators for these four hub genes. The current study based on the GEO database provided novel understanding regarding the mechanism of breast cancer metastasis to brain and may provide novel therapeutic targets.

<h3>Objective</h3> Accumulating evidence suggests that cancer survivors may have a relatively higher risk of stroke. The aim of this meta-analysis was to determine whether cancer survivors have a relatively higher risk of stroke than cancer-free populations on the basis of published data from population-based cohort studies. <h3>Methods</h3> PubMed, Embase, and Cochrane Library were searched from inception to February 8, 2020, for population-based cohort studies. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. We conducted subgroup analyses and meta-regression to explore sources of heterogeneity and the stability of the results. <h3>Results</h3> Twenty population-based cohort studies involving 10,479,530 participants were identified. Overall, the relative risk (RR) for stroke in cancer survivors was 1.66 (95% CI 1.35–2.04; <i>p</i> &lt; 0.001) compared with that in cancer-free controls; survivors of head and neck, hematologic, lung, pancreas, and stomach cancer (all <i>p</i> &lt; 0.05) showed consistently significant results, whereas no significant increased risk was observed for patients with other cancer types. The effects were more prominent in cancer survivors with female sex (RR 1.38, 95% CI 1.18–1.61; <i>p</i> &lt; 0.001), younger age at cancer diagnosis (&lt;45 years) (RR 2.57, 95% CI 1.27–5.19; <i>p</i> = 0.009), and shorter cancer survival duration (≥1–2 years) (RR 1.69, 95% CI 1.18–2.42; <i>p</i> = 0.004). Moreover, cancer survivors had a significantly increased risk of ischemic stroke (RR 1.53, 95% CI 1.28–1.84; <i>p</i> &lt; 0.001) compared with hemorrhagic stroke. <h3>Conclusions</h3> Cancer plays a critical role in the etiologic of stroke. Due to the existence of substantial heterogeneity among the included studies, the results should be interpreted with caution. However, early prevention and effective intervention of stroke in cancer survivors require attention from health policy makers.

Single-nucleotide polymorphisms in microRNAs (miRNAs) may dramatically affect gene expression and subsequently alter individual susceptibility to cancer, and thus has become a research hotspot for many cancer types, including breast cancer. We recruited 321 breast cancer patients and 290 controls in our study. Four established miRNA single-nucleotide polymorphisms (mir-499 rs3746444 A>G; miR-27a rs895819 A>G; miR-196a2 rs11614913 T>C; miR-146a rs2910164 G/C) were detected using Taqman assays. Mature miRNA expression, allele distribution, and the association with clinical features were further analyzed. Our results showed that the miR146a rs2910164 G/C polymorphism was associated with an elevated risk of breast cancer (odds ratio = 1.85, 95% confidence interval = 1.03-3.32; P < 0.05). Compared with the ancestral T allele in miR-196a2 rs11614913, the variant C allele was consistently associated with an increased risk of breast cancer (odds ratio = 2.20, 95% confidence interval = 1.19-4.09, P < 0.01) and clinical pathological type (P < 0.01). miR-27a rs895819 A>G and miR-499 rs3746444 A>G were not associated with breast cancer risk. Analysis of mature miRNA expression confirmed that the variant C allele in miR146a rs2910164 and miR-196a2 rs11614913 dramatically inhibited production of their mature products. Our results suggested that miR-146a rs2910164 G>C and miR-196a2 rs11614913 T>C may be biomarkers for predicting breast cancer risk in the Chinese population.