Effects of Exogenous Nitric Oxide Treatment on Grape Berries Against Botrytis cinerea and Alternaria alternata Related Enzymes and Metabolites.

Postharvest losses of grape berries caused by the pathogenic fungi Botrytis cinerea and Alternaria alternata have been widely reported, and nitric oxide (NO) as a plant signaling molecule to control postharvest diseases has recently become an active research topic. This study aimed to investigate the regulatory effect of NO on the interaction between grape berries and fungi. During interactions between grape berries and pathogenic fungi, treatment with 10 mM sodium nitroprusside (SNP, an NO donor) delayed the decline of the physiological quality of the grape berries and had positive effects on the weight loss rate, firmness, and respiration intensity. SNP treatment increased the activities of superoxide dismutase (SOD) and polyphenol oxidase (PPO) and inhibited the activities of peroxidase (POD) and catalase (CAT) of grape berries during the resistance to fungal pathogen infection. In addition, the increase in browning degree and the accumulation of hydrogen peroxide were inhibited by SNP treatment. In the phenylpropane metabolic pathway, the activities of phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumaric acid coenzyme A ligase (4CL) were increased during the activation of grape berries during the resistance to pathogen infection by SNP, and the intermediate metabolites lignin, flavonoids, and total phenols were accumulated. In addition, SNP treatment had a regulatory effect on the gene expression levels of SOD, POD, PPO, PAL, and 4CL. These results suggested that SNP treatment was effective for the preservation and disease reduction of grape berries.

A 3'-tRNA-derived fragment enhances cell proliferation, migration and invasion in gastric cancer by targeting FBXO47.

Increasing evidence demonstrates that tRNA-derived fragments (tRFs) exert important effects and are dysregulated in various human cancer types. However, their roles in gastric cancer (GC) remain unknown. Here we identified the functional effects of tRF-3019a (derived from tRNA-Ala-AGC-1-1) in GC. We demonstrated that tRF-3019a was upregulated in GC tissues and cell lines. Phenotypic studies revealed that tRF-3019a overexpression enhances GC cell proliferation, migration and invasion. Conversely, tRF-3019a knockdown inhibits GC cell malignant activities. Mechanistic investigation implies that tRF-3019a directly regulates tumor suppressor gene FBXO47. Furthermore, tRF-3019a levels may discriminate GC tissues from nontumorous tissues. Taken together, our results reveal that tRF-3019a modulates GC cell proliferation, migration and invasion by targeting FBXO47, and it may serve as a potential diagnostic biomarker for GC.

HIP1R acts as a tumor suppressor in gastric cancer by promoting cancer cell apoptosis and inhibiting migration and invasion through modulating Akt.

BACKGROUND: Huntingtin-interacting protein 1-related (HIP1R) is a multi-domain gene that exerts many cellular functions including altering T cell-mediated cytotoxicity and controlling intracellular trafficking. However, its clinical significance and function in gastric cancer (GC) have not been described. METHODS: The expression levels of HIP1R were tested by the transcriptional and translational expression analysis and immunohistochemistry (IHC) in matched adjacent non-tumorous vs tumor tissue specimens. The biological function of HIP1R on apoptosis, migration, and proliferation was evaluated by flow cytometry, Transwell, Cell Counting Kit-8 (CCK-8) assays, colony formation assays, and EdU labeling assays, respectively. RESULTS: We found downregulated HIP1R in GC compared with adjacent non-tumorous tissue, and HIP1R expression associated with N classification. We further found that the expression of HIP1R could induce apoptosis and inhibit proliferation, migration, invasion of GC cells, possibly through modulating Akt. CONCLUSIONS: Our data indicate that HIP1R may act as a potential diagnostic biomarker and a tumor suppressor gene in GC, potentially representing a novel therapeutic target for future GC treatment.

ß-Glucuronidase- and OATP2B1-mediated drug interaction of scutellarin in Dengzhan Xixin Injection: A formulation aspect.

Scutellarin is the major and active constituent of Dengzhan Xixin Injection (DZXX), a traditional Chinese medicine prepared from the aqueous extract of Erigeron breviscapus and widely used for the treatment of various cerebrovascular diseases in clinic. In present study, the possible pharmacokinetic differences of scutellarin after intravenous administration of scutellarin alone or DZXX were explored. Additional, the potential roles of ß-glucuronidase (GLU) and OATP2B1 in drug-drug interaction (DDI) between scutellarin and constituents of DZXX were further evaluated in vitro. The plasma concentration, urinary and biliary excretion of scutellarin in rats after administration of DZXX, were significantly higher than those received scutellarin, while pharmacokinetic profile of Apigenin 7-O-glucuronide (AG) in rats was similar no matter AG or DZXX group. Furthermore, higher concentration in brain and plasma, however, lower level of scutellarin in intestine were observed after intravenous administration of DZXX. Finally, AG and caffeoylquinic acid esters were found to significantly inhibit GLU and OATP2B1 in vitro, which might explain, at least in part, the pharmacokinetic DDI between scutellarin and other chemical constituents in DZXX. The findings provided deep insight into the prescription-formulating principle in DZXX for treating the cerebrovascular diseases.

Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion.

Recent research suggests that the first-line oral antidiabetes drug metformin may prevent gastric cancer progression and improve prognosis. Many studies have also shown that long noncoding RNAs (lncRNAs) play important roles in many biological processes. Therefore, we aimed to explore whether lncRNAs participate in the mechanisms by which metformin affects gastric cancer cells. In the current study, we found that metformin significantly inhibited the cellular functions of gastric cancer cells through Cell Counting Kit-8 and invasion assays. We found that lncRNA H19 was greatly downregulated in gastric cancer cells treated with metformin using lncRNA microassays. Based on bioinformatics analyses of the Oncomine and The Cancer Genome Atlas databases, H19 is shown to be overexpressed in gastric cancer tissues, with increased expression of H19 relating to advanced pathological tumor stage and pathological tumor node metastasis stage, indicating that H19 may be associated with the invasive ability of gastric cancer. We knocked down H19 in AGS and SGC7901 cell lines and found that knocked-down H19 could decrease gastric cancer cell invasion and that metformin could not further decrease invasion after the knock down. Moreover, H19 depletion increased AMPK activation and decreased MMP9 expression, and metformin could not further activate AMPK or decrease MMP9 in H19 knocked-down gastric cancer cells. In summary, metformin has a profound antitumor effect on gastric cancer cells, and H19 is a key component in the process of metformin suppressing gastric cancer cell invasion.

Long non-coding RNA RUNX1-IT1 plays a tumour-suppressive role in colorectal cancer by inhibiting cell proliferation and migration.

Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the progression of various cancers. In this study, we aim to investigate the role of lncRNA RUNX1-IT1 in the development of colorectal cancer (CRC). The expression levels of lncRNA RUNX1-IT1 were measured using quantitative real-time Polymerase Chain Reaction(qRT-PCR). CCK8 proliferation assay, transwell assay, and flow cytometry were performed to evaluate the effect of lncRNA RUNX1-IT1 on CRC cell proliferation, migration, and apoptosis. The proliferation markers (PCNA, Ki67), apoptosis markers (cleaved-PARP, cleaved-caspase3), and MMP9 are detected by western blotting. Significant down regulation of lncRNA RUNX1-IT1 was measured in CRC tissues and three CRC cell lines (HCT116, HT29, and RKO) compared with paired nontumorous adjacent tissues (P < 0.01) or the normal colonic epithelial cell line FHC (P < 0.05), respectively. Moreover, the proliferative and migration potential of CRC cells were inhibited by overexpressing lncRNA RUNX1-IT1, which could be obviously improved by knocking down lncRNA RUNX1-IT1. The protein levels of PCNA, Ki67, and MMP9 were upregulated by overexpressing lncRNA RUNX1-IT1 and down regulated in si-RUNX1-IT1 cells. Besides, lncRNA RUNX1-IT1 could also promote the apoptosis of CRC cells. In conclusion, lncRNA RUNX1-IT1 is downregulated in CRC and plays a tumour-suppressive role due to the regulatory of cell proliferation, migration, and apoptosis. SIGNIFICANCE OF THE STUDY: We demonstrated that lncRNA RUNX1-IT1 was down regulated both in CRC tissues and cell lines. Besides, lncRNA RUNX1-IT1 could serve as a potential diagnostic biomarker and play a tumour-suppressive role owing to its good diagnostic efficacy and inhibition of CRC cell proliferation and migration.

The long noncoding RNA CTA-941F9.9 is frequently downregulated and may serve as a biomarker for carcinogenesis in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) participate in the carcinogenesis of many different cancers. This study aimed to detect expression of lncRNA CTA-941F9.9 in colorectal cancer tissues compared with matched nontumorous adjacent tissues (NATs). Moreover, we investigated whether this molecule is able to influence carcinogenesis in colorectal cancer (CRC). METHODS: Colorectal cancer tissues and NATs from two cohorts of patients were examined. Quantitative PCR was performed to quantify levels of CTA-941F9.9 expression in these samples. The association between CTA-941F9.9 expression and clinicopathological features, including receiver operating characteristic (ROC) curves, was also analyzed to evaluate the diagnostic value of CTA-941F9.9 in CRC. Potential effects of lncRNA CTA-941F9.9 on CRC cells were assessed via autophagy, transwell assay, CCK8 assays, and flow cytometry. RESULTS: Our experimental results showed lncRNA CTA-941F9.9 to be significantly downregulated in CRC tissues in both cohorts, with areas under the ROC curve (AUC) of 0.802 and 0.876. However, no significant correlations between CTA-941F9.9 expression levels and clinicopathological characteristics or patient outcomes were observed. We also found that CTA-941F9.9 promotes autophagy in CRC cell lines but no significant function of CTA-941F9.9 in regulating cancer cell proliferation or migration. CONCLUSIONS: LncRNA CTA-941F9.9 is frequently downregulated in CRC compared with NATs and might play an important role in CRC carcinogenesis.

CTD-2020K17.1, a Novel Long Non-Coding RNA, Promotes Migration, Invasion, and Proliferation of Serous Ovarian Cancer Cells In Vitro.

BACKGROUND Ovarian cancer is the most lethal malignant tumor of the female reproductive system, and the metastasis is one of the major factors that contribute to the poor outcome of patients with OC. Accumulating evidence indicates that lncRNAs are expressed and play important regulatory roles in ovarian cancer. MATERIAL AND METHODS Aberrant lncRNAs in primary ovarian cancer tissues (POCTs) and paired omental metastasis tissues (OMTs) of patients with HGSOC were studied via lncRNA microarray. Real-time PCR was performed to examine CTD-2020K17.1 expression in HGSOC tissues from 38 patients, a normal ovarian surface epithelium cell line, and 4 ovarian cancer cell lines. Additionally, Transwell assays, wound healing assays, CCK-8 proliferation assays, and flow cytometry were used to explore the biological function of CTD-2020K17.1 in ovarian cancer cells. Finally, Western blot analysis was used to verify the potential target gene of CTD-2020K17.1. RESULTS A novel lncRNA named CTD-2020K17.1 was identified via microarray analysis. Expression of CTD-2020K17.1 was significantly increased in OMTs and in 4 ovarian cancer cell lines compared with POCTs (P<0.05) or normal ovarian surface epithelial cell line (P<0.05). Moreover, CTD-2020K17.1 overexpression promoted migration, invasion, and proliferation of ovarian cancer cells, and CTD-2020K17.1 regulated the expression of CARD11. CONCLUSIONS CTD-2020K17.1 is significantly upregulated in OMTs and ovarian cancer cell lines. It can promote the migration, invasion, and proliferation of ovarian cancer cells, and CARD11 is regulated by CTD-2020K17.1.

The T Allele of rs8075977 in the 5'-Flanking Region of the PEDF Gene Is Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men.

Coronary artery disease (CAD) is a multifactorial disease with a genetic component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received increasing attention as a sensitive biomarker of atherosclerosis and CAD. To explore the potential association between PEDF single nucleotide polymorphisms (SNPs) and CAD, we performed this case-control study of consecutive elderly Chinese Han male patients (n = 416) and age-matched male controls (n = 528) without a history of CAD or electrocardiographic signs of CAD. The enrolled CAD patients (age ≥ 60 years) are not biologically related. A tag approach was used to examine 100% of common variations in the PEDF gene (r2 ≥ 0.8, minor allele frequency > 0.1). PEDF tag SNPs (tSNPs) were selected using the HapMap Data-CHB which describes the common patterns of human DNA sequence variation and Tagger program. SNPs were genotyped using ligase detection reaction (LDR). Seven tSNPs (rs8075977, rs11658342, rs1136287, rs12603825, rs12453107, rs6828 and rs11078634) were selected. Among them, only one SNP, rs8075977 (C/T) located in the 5'-flanking region, showed the significant effect on the susceptibility to CAD. The frequency of its T allele was significantly higher in the controls (52.7%) than that in the CAD group (46.2%) (adjusted OR = 0.88, 95% CI: 0.80-0.96; P = 0.005). In conclusion, the T allele of rs8075977 in the 5'-flanking region of the PEDF gene may be protective for CAD. Conversely, the C allele at this variation site is associated with CAD in elderly Chinese Han men.

Melatonin protects ADSCs from ROS and enhances their therapeutic potency in a rat model of myocardial infarction.

Myocardial infarction (MI) is a major cause of death and disability worldwide. In the last decade, mesenchymal stem cells (MSCs) based cell therapy has emerged as a promising therapeutic strategy. Although great advance have been made using MSCs to treat MI, the low viability of transplanted MSCs severely limits the efficiency of MSCs therapy. Here, we show evidence that ex vivo pre-treatment with melatonin, an endogenous hormone with newly found anti-oxidative activity, could improve survival and function of adipose tissue derived MSCs (ADSCs) in vitro as well as in vivo. ADSCs with 5 µM melatonin pre-treatment for 24 hrs showed increased expression of the antioxidant enzyme catalase and Cu/Zn superoxide dismutase (SOD-1), as well as pro-angiogenic and mitogenic factors like insulin-like growth factor 1, basic fibroblast growth factor, hepatocyte growth factor (HGF), epidermal growth factor. Furthermore, melatonin pre-treatment protected MSCs from reactive oxygen species (ROS) induced apoptosis both directly by promoting anti-apoptosis kinases like p-Akt as well as blocking caspase cascade, and indirectly by restoring the ROS impaired cell adhesion. Using a rat model of MI, we found that melatonin pre-treatment enhanced the viability of engrafted ADSCs, and promoted their therapeutic potency. Hopefully, our results may shed light on the design of more effective therapeutic strategies treating MI by MSCs in clinic.

The association study of plasma levels of pigment epithelium-derived factor with acute coronary syndrome in the chinese han population.

OBJECTS: To investigate the relationship between plasma levels of pigment epithelium-derived factor (PEDF) and acute coronary syndrome (ACS) in the Chinese Han population. METHODS: Plasma PEDF levels were measured in 200 consecutive ACS patients and 160 age- and sex-matched healthy control subjects. Logistic regression analysis was performed to determine whether PEDF was an independently protective factor against ACS. All ACS patients were followed up for 6 months and the short-term major adverse cardiovascular events (MACE) were obtained: cardiac death and recurrent angina. RESULTS: The ACS patients showed notably lower plasma PEDF levels relative to the control group (7.31 ± 2.21 vs. 8.44 ± 2.13 µg/ml, respectively, p = 0.001). Logistic regression analysis revealed that PEDF had a significant protective effect against ACS (OR = 0.76, 95% CI 0.623-0.935, p = 0.01). After 6 months of follow-up, we found that the mean PEDF concentration of the patients with short-term MACE was lower than the patients without (6.05 ± 2.18 vs. 7.52 ± 2.07 µg/ml, p = 0.031). The Kaplan-Meier survival curves suggested that patients with plasma PEDF levels <7.00 µg/ml showed a lower survival trend than those in the higher group, but the difference was not significant (p = 0.477). CONCLUSIONS: Our study indicates that plasma PEDF levels are significantly lower in ACS patients than in controls, and lower PEDF levels are further associated with adverse cardiac outcomes after ACS.

A dynamic decision-making approach for cabin unlawful interference emergency disposal using dynamic Bayesian network.

Disposal of unlawful interference incidents is essential for is crucial for the advancement of aviation security. Effective emergency disposal requires a comprehensive approach that includes the perspectives of airlines, airports, and passengers. In this context, each component of the disposal process can fail randomly. The objective of this research is to optimize emergency disposal decisions to enhance the efficiency of civil aviation operations, reduce accidents, and lower costs. Given the dynamic complexity of unlawful interference incidents, a dynamic fault tree consisting of 26 nodes was constructed to analyze the emergency disposal process. To explore the relationships and priorities of each event, the Dynamic Fault Tree is converted into a dynamic Bayesian network. Based on historical statistical data, simulation analysis is conducted in three aspects: posterior probability, sensitivity, and importance. Simulation results reveal that the top three critical nodes in cabin unlawful interference incidents are "structural damage to the cabin," "inadequate training by airlines," and "untimely airport police takeover of disruptive passengers." Further analysis shows that (1) most of the critical nodes are associated with airlines. (2) The decision-making rationale and pathways of the critical nodes can be clearly observed and prioritized. (3) Besides airlines, other entities such as airports can implement targeted emergency disposal measures. Through quantitative analysis and simulation, this study provides decision-making guidance for participating groups on dynamic emergency disposal, thereby enhancing civil aviation security.

Spatial-temporal heterogeneity in the influence of landscape patterns on trade-offs/synergies among ecosystem services: a case study of the Loess Plateau of northern Shaanxi.

Exploring the role of landscape patterns in the trade-offs/synergies among ecosystem services (ESs) is helpful for understanding ES generation and transmission processes and is of great significance for multiple ES management. However, few studies have addressed the potential spatial-temporal heterogeneity in the influence of landscape patterns on trade-offs/synergies among ESs. This study assessed the landscape patterns and five typical ESs (water retention (WR), food supply (FS), habitat quality (HQ), soil retention (SR), and landscape aesthetics (LA)) on the Loess Plateau of northern Shaanxi and used the revised trade-off/synergy degree indicator to measure trade-offs/synergies among ESs. The multiscale geographically weighted regression (MGWR) model was constructed to determine the spatial-temporal heterogeneity in the influence of landscape patterns on the trade-offs/synergies. The results showed that (1) from 2000 to 2010, the increase in cultivated land and the decrease in forestland and grassland increased landscape diversity and decreased landscape heterogeneity and fragmentation. During 2010-2020, the change range decreased, the spatial distribution was homogeneous, and the landscape diversity and fragmentation in the northwestern area increased significantly. (2) The supply of the five ESs continued to increase from 2000 to 2020. During 2000-2010, FS-SR, FS-LA and SR-LA were dominated by synergies. From 2010 to 2020, the proportion of trade-off units in all relationships increased, and HQ-FS, HQ-SR and HQ-LA were dominated by trade-offs. (3) Landscape patterns had complex impacts on trade-offs/synergies, and the same landscape variable could have the opposite impact on specific trade-offs/synergies in different periods and areas. The results of this study will inform managers in developing regional sustainable ecosystem management strategies and advocating for more research to address ecological issues from a spatial-temporal perspective.

Regulating bulb dormancy release and flowering in lily through chemical modulation of intercellular communication.

Lily is a bulbous plant with an endogenous dormancy trait. Fine-tuning bulb dormancy release is still a challenge in the development of bulb storage technology. In this study, we identified three regulators of symplastic transport, 2,3-Butanedione oxime (BDM), N-Ethyl maleimide (NEM), and 2-Deoxy-D-glucose (DDG), that also regulate bulb dormancy release. We demonstrated that BDM and DDG inhibited callose synthesis between cells and promoted symplastic transport and soluble sugars in the shoot apical meristem (SAM), eventually accelerating bulb dormancy release and flowering in lilies. Conversely, NEM had the opposite effect. These three regulators can be flexibly applied to either accelerate or delay lily bulb dormancy release.

miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition.

As a common complication of diabetes, diabetic pain neuropathy (DPN) is caused by neuron intrinsic and extrinsic factors. Neuron intrinsic factors include neuronal apoptosis and oxidative stress, while extrinsic factors are associated with glial activation. The present study was performed to reveal the functions of miR-130a-3p in apoptosis and oxidative stress of the high glucose (HG)-stimulated primary neurons as well as in the activation of microglial and astrocytes. Primary neurons, microglial, and astrocytes were isolated from newborn mice. Apoptosis was assessed by flow cytometry analysis and western blotting. Reactive oxygen species and glutathione levels were assessed to determine the oxidative stress. Markers of glial cells were detected by immunofluorescence staining. The results revealed that miR-130a-3p deficiency alleviated apoptosis and oxidative stress of HG-stimulated neurons as well as suppressed microglial and astrocyte activation. Moreover, sphingosine-1-phosphate receptor 1 (S1PR1) was found as a target downstream of miR-130a-3p. S1PR1 knockdown partially rescued the inhibitory effects of silenced miR-130a-3p on neuronal injury and glial activation. In conclusion, miR-130a-3p targets S1PR1 to activate the microglial and astrocytes and to promote apoptosis and oxidative stress of the HG-stimulated primary neurons. These findings may provide a novel insight into DPN treatment.

Elevated MMP10/13 mediated barrier disruption and NF-κB activation aggravate colitis and colon tumorigenesis in both individual or full miR-148/152 family knockout mice.

Dynamic miRNA alteration is known to occur in colitis-associated colon cancer (CAC), while the molecular mechanisms underpinning how miRNAs modulate the development from chronic inflammation to CAC is lacking. For the first time, we constructed knockout (KO) mice for individual miR-148/152 family members and entire miR-148/152 family. Based on these KO mice, we conduct the first comprehensive analysis of miR-148/152 family, demonstrating that deficiency of any member of miR-148/152 family aggravate colitis and CAC. Loss of individual miR-148/152 family members or full-family enhance MMP10 and MMP13 expression, causing disruption of intestinal barrier and cleaving pro-TNF-α into bioactive TNF-α fragments to activate NF-κB signaling, thereby aggravating colitis. Individual and full-family deletion also increase accumulation of IKKα and IKKß, resulting in further hyperactivation of NF-κB signaling, exacerbating colitis and CAC. Moreover, blocking NF-κB signaling exerts a restorative effect on colitis and CAC models only in KO mice. Taken together, these findings demonstrate deleting the full miR-148/152 family or individual members exhibit similar effects in colitis and CAC. Mechanically, miR-148/152 family members deficiency in mice elevates MMP10 and MMP13 to accelerate colitis and CAC via disrupting intestinal barrier function and activating NF-κB signaling, suggesting a potential therapeutic strategy for colitis and CAC.

Significance of CHA2DS2-VASC on the severity and hemorrhagic transformation in patients with non-valvular atrial fibrillation-induced acute ischemic stroke.

Atrial fibrillation causes a fivefold increase of stroke risk. CHA2DS2-VASC is widely used to evaluate the risk of cardiac embolism in patients with non-valvular atrial fibrillation (NVAF) and identify the patients eligible for anticoagulation therapy. This study aimed to identify the significance of CHA2DS2-VASC score on the severity and hemorrhagic transformation (HT) in patients with NVAF-induced acute ischemic stroke (NVAF-AIS). Total 113 patients diagnosed as NVAF-AIS were included in this study. Patients were categorized into severe stroke group (NIHSS > 10) and non-severe group (NIHSS ≤ 10), and the risk factors for severe stroke were investigated. Based on the results of repeated brain CT/MRI examination performed within 14 days from stroke onset or immediately in case of clinical worsening, patients were divided into HT group and non-HT group, and the predictors for HT were then analyzed. CHA2DS2-VASC score [median (interquartile range) 5 (3-5) vs. 3 (2-4); p = 0.002] in severe stroke group was significantly higher than that in non-severe group. The severe stroke group showed significantly increased prevalence of heart failure (20% vs. 48.5%, p = 0.002) and decreased hemoglobin (136.4 ± 18.0 vs.143.6 ± 15.6 g/L, p = 0.031) compared with non-severe group. Multivariate regression analysis revealed that CHA2DS2-VASc score was a powerful predictor for the severity of NVAF-AIS. Forty-seven of total recruited patients (43.2%) developed HT within 14 days after the onset of NVAF-AIS. CHA2DS2-VASc score as well as elevated glycated hemoglobin and intravenous rt-PA were the independent risk factors of HT. CHA2DS2-VASC score was closely associated with the severity of NVAF-AIS. Patients with higher CHA2DS2-VASC score were more likely to develop HT after NVAF-AIS.

Erratum: MicroRNA-1258: An invasion and metastasis regulator that targets heparanase in gastric cancer.

[This corrects the article DOI: 10.3892/ol.2017.5886.].

The efficacy and safety of adding bevacizumab in neoadjuvant therapy for locally advanced rectal cancer patients: A systematic review and meta-analysis.

BACKGROUND: Patients with locally advanced rectal cancer (LARC) are more likely to suffer local recurrence and distant metastases, contributing to worse prognoses. Considering the provided dramatic reduction of local recurrences, neoadjuvant CRT (nCRT) followed by curative resection with total mesorectal excision (TME) and adjuvant chemotherapy has been established as standard therapy for LARC patients. However, the efficacy of adding bevacizumab in neoadjuvant therapy, especially in induction therapy-containing nCRT for LARC patients remains uncertain. MATERIALS: PubMed, Embase, and Web of Science were searched to retrieve records on the application of bevacizumab in a neoadjuvant setting for LARC patients. The endpoints of interest were pCR and the rates of patients suffering Grade 3/4 bevacizumab-specific adverse events, namely bleeding, wound healing complications, and gastrointestinal perforation. RESULTS: 29 cohorts covering 1134 subjects were included in this systematic review. The pooled pCR rate for bevacizumab-relevant cohorts was 21% (95% confidence interval (95% CI), 17-25%; I2 = 61.8%), the pooled estimates of Grade 3/4 bleeding, Grade 3/4 wound healing complication, Grade 3/4 gastrointestinal perforation were 1% (95% CI, 0-3%; I2 = 0%), 2% (95% CI, 1-5%; I2 = 4.7%), and 2% (95% CI, 0-5%; I2 = 0%), respectively. CONCLUSION: The addition of bevacizumab in the nCRT, especially in the TNT, for LARC patients provides promising efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by future studies.