Ultrasound-guided percutaneous microwave ablation of gallbladder polyps: A case report.

RATIONALE: Gallbladder polyps are a general term for localized lesions in which the gallbladder wall protrudes into the gallbladder cavity, and benign lesions are common. Although current guidelines recommend cholecystectomy for gallbladder polyps ≥ 10 mm in size, the probability of finding cancer in postoperative pathological specimens is low. We should avoid unnecessary cholecystectomy and treat polyps with gallbladder preservation. Microwave ablation is safe and effective for the treatment of solid lesions, and can inactivates polyps while preserving gallbladder. Hence, we report a case of ultrasound-guided percutaneous microwave ablation of gallbladder polyps. PATIENT CONCERNS: A 72-year-old female patient had previously diagnosed a gallbladder polyp, but it was not taken seriously. Recently, the patient had occasional right upper abdominal discomfort and a desire to preserve gallbladder. DIAGNOSES: Ultrasound showed a medium hyperechoic papillary protrusion in the gallbladder without echo behind, and the changed position did not move. Contrast-enhanced ultrasound (CEUS) showed no malignant signs. The diagnosis was a gallbladder polyp. INTERVENTIONS: The bile is drained and the drainage tube is fixed under real-time ultrasound guidance, then the gallbladder cavity is flushed and filled. Saline was injected between the serous and mucosal layers of the gallbladder to form an "edema band" to protect the gallbladder wall. Then, ultrasound-guided biopsy of gallbladder polyps was performed and sent for histological examination. Finally, the microwave needle was inserted into the target area under real-time ultrasonic guidance, and ablation was performed for 3 minutes (20 W). Postoperative CEUS: No significant enhancement was observed in the lesion. OUTCOMES: Within 6 months of follow-up, the patient's gallbladder systolic function was normal, and there was no discomfort and no recurrence. The lesion reduction rate reached 100% at 1 week after surgery. LESSONS: Ultrasound guided percutaneous microwave ablation of gallbladder polyps not only preserves the gallbladder but also inactivates the polyps without affecting the systolic function of the gallbladder, which provides a new idea for the treatment of gallbladder polyps.

Novel synergistic treatment for depression: involvement of GSK3ß-regulated AMPA receptors in the prefrontal cortex of mice.

Previous evidence has suggested a vital role of glycogen synthase kinase 3ß-mediated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors trafficking in depression. Considering the antidepressant effect of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors activation in the prefrontal cortex, we hypothesized that glycogen synthase kinase 3ß-induced alterations in α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors function in the prefrontal cortex participate in depression. Herein, we confirmed that the levels of phosphorylated glycogen synthase kinase 3ß and GluA1, the latter being a subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, were decreased in the prefrontal cortex of the chronic social defeat stress model mice presenting with depressive-like behaviors. We then found that a glycogen synthase kinase 3ß (p.S9A) point mutation downregulated GluA1 and induced depressive-like behaviors in mice, whereas an agonist of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, PF-4778574 (2 mg/kg) did not reversed the molecular changes. On the other hand, the antidepressant effect of PF-4778574 was dose dependent, and the single administration of PF-4778574 at a lower dose (0.5 mg/kg) or of the glycogen synthase kinase 3ß inhibitor SB216763 (5 and 10 mg/kg) did not evoke an antidepressant effect. In contrast, co-treatment with PF-4778574 (0.5 mg/kg) and SB216763 (10 mg/kg) led to antidepressant effects similar to those of PF-4778574 (2 mg/kg). Our results suggest that glycogen synthase kinase 3ß-induced α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors dysfunction in the prefrontal cortex is one of the key mechanisms of depression, and the combination of a lower dose of PF-4778574 with SB216763 shows potential as a novel synergistic treatment for depression.

Initial ablation radio predicting volume reduction from microwave ablation of benign thyroid nodules.

OBJECTIVE: Our research sought to investigate the relationship between initial ablation ratio (IAR) and internal composition of benign thyroid nodules treated by microwave ablation (MWA). MATERIALS AND METHODS: Patients who underwent MWA at the Affiliated Hospital of Jiangsu University from January 2018 to December 2022 were enrolled in our research. All the patients were followed up for at least one year. We analyzed the relationship between IAR at 1 month of solid nodules (solid >90%), predominantly solid nodules (90% >solid > 75%), mixed solid alongside cystic nodules (75% >solid > 50%) as well as volume reduction rate (VRR) at 1, 3, 6 and 12 months follow-up. OBJECTIVE: The mean IAR of the solid nodules (solid >90%) was 94.32±7.87%,#x0025;, that of the predominantly solid nodules (90% >solid > 75%) and mixed solid alongside cystic nodules (75% >solid > 50%) were 86.51±6.66% and 75.19±4.97%,#x0025;, respectively. Almost all the thyroid nodules were significantly decreased in size after MWA. After 12 months of MWA treatment, the average volume of the aforementioned thyroid nodules decreased from 8.69±8.79 to 1.84±3.11 ml, 10.94±9.07 to 2.58±3.34 ml, 9.92±6.27 to 0.25±0.42 ml, respectively. The mean symptom and cosmetic scores of the nodules showed significant (p < 0.000) improvement. The rates of the complications or side effects of MWA against the above-mentioned nodule types were 8.3% (3/36), 3.2% (1/31) and 0% (0/36), respectively. CONCLUSIONS: The application of the IAR to quantify the success rate of thyroid nodule microwaves in the short term demonstrated that IAR was related to the internal components of the nodule. Although the IAR was not high when the thyroid component was mixed solid and cystic nodules (75% >solid > 50%), the final therapeutic effect was still satisfactory.

Numerical Simulation on the Hydrogen Storage Performance of Magnesium Hydrogen Storage Reactors.

Magnesium hydride (MH) is one of the most promising hydrogen storage materials. Under the hydrogen storage process, it will emit a large amount of heat, which limits the efficiency of the hydrogen storage reaction. In this paper, the hydrogen storage performance of the magnesium hydrogen storage reactor (MHSR) and the effect of structural parameters were studied by numerical simulation. The effect of different operating conditions on the hydrogen storage performance of the MHSR is analyzed. The volume energy storage rate (VESR) was taken as the comprehensive evaluation index (CEI). The results show that fins and heat exchange tubes can improve the heat transfer performance of the MHSR. Increasing fin thickness can reduce hydrogen storage time, but increasing fin spacing is the opposite. With the increase of fin thickness and fin spacing, VESR increases first and then decreases. With the increase of inlet temperature, the hydrogen storage time decreases first and then increases. When the inlet velocity is more than 5 m/s, the hydrogen storage time basically stays at 900 s. By optimizing the operating conditions, the hydrogen storage time can be shortened by 57.8%.

Genetic associations between bipolar disorder and brain structural phenotypes.

Patients with bipolar disorder (BD) and their first-degree relatives exhibit alterations in brain volume and cortical structure, whereas the underlying genetic mechanisms remain unclear. In this study, based on the published genome-wide association studies (GWAS), the extent of polygenic overlap between BD and 15 brain structural phenotypes was investigated using linkage disequilibrium score regression and MiXeR tool, and the shared genomic loci were discovered by conjunctional false discovery rate (conjFDR) and expression quantitative trait loci (eQTL) analyses. MiXeR estimated the overall measure of polygenic overlap between BD and brain structural phenotypes as 4-53% on a 0-100% scale (as quantified by the Dice coefficient). Subsequent conjFDR analyses identified 54 independent loci (71 risk single-nucleotide polymorphisms) jointly associated with BD and brain structural phenotypes with a conjFDR < 0.05, among which 33 were novel that had not been reported in the previous BD GWAS. Follow-up eQTL analyses in respective brain regions both confirmed well-known risk genes (e.g. CACNA1C, NEK4, GNL3, MAPK3) and discovered novel risk genes (e.g. LIMK2 and CAMK2N2). This study indicates a substantial shared genetic basis between BD and brain structural phenotypes, and provides novel insights into the developmental origin of BD and related biological mechanisms.

Bidirectional genetic overlap between bipolar disorder and intelligence.

BACKGROUND: Bipolar disorder (BD) is a highly heritable psychiatric illness exhibiting substantial correlation with intelligence. METHODS: To investigate the shared genetic signatures between BD and intelligence, we utilized the summary statistics from genome-wide association studies (GWAS) to conduct the bivariate causal mixture model (MiXeR) and conjunctional false discovery rate (conjFDR) analyses. Subsequent expression quantitative trait loci (eQTL) mapping in human brain and enrichment analyses were also performed. RESULTS: Analysis with MiXeR suggested that approximately 10.3K variants could influence intelligence, among which 7.6K variants were correlated with the risk of BD (Dice: 0.80), and 47% of these variants predicted BD risk and intelligence in consistent allelic directions. The conjFDR analysis identified 37 distinct genomic loci that were jointly associated with BD and intelligence with a conjFDR < 0.01, and 16 loci (43%) had the same directions of allelic effects in both phenotypes. Brain eQTL analyses found that genes affected by the "concordant loci" were distinct from those modulated by the "discordant loci". Enrichment analyses suggested that genes related to the "concordant loci" were significantly enriched in pathways/phenotypes related with synapses and sleep quality, whereas genes associated with the "discordant loci" were enriched in pathways related to cell adhesion, calcium ion binding, and abnormal emotional phenotypes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between BD and intelligence and identified multiple genomic loci and risk genes. This study provides hints for the mesoscopic phenotypes of BD and relevant biological mechanisms, promoting the knowledge of the genetic and phenotypic heterogeneity of BD. The essential value of leveraging intelligence in BD investigations is also highlighted.

Integrating BRAFV600E mutation, ultrasonic and clinicopathologic characteristics for predicting the risk of cervical central lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: The advantages of prophylactic central lymph node dissection (CLND) for clinically node-negative patients remained a great deal of controversies. Our research was aimed to analyze the relationship between cervical central lymph node metastasis (CLNM) and BRAFV600E mutation, ultrasonic and clinicopathologic characterizes in papillary thyroid carcinoma (PTC). METHODS AND MATERIALS: In current study, a total of 112 consecutive PTC patients who experienced thyroidectomy plus cervical central neck dissection were included in our research. All PTC were pre-operatively analyzed by ultrasonic features, including tumor size, multifocality or not, tumor location, internal components, echogenicity, microcalcification, margins, orientation, taller than wide shape, and internal vascularity. The presence of clinicopathologic factors, including age, sex, T stage, Hashimoto's thyroiditis, and BRAFV600E mutation was then investigated. Univariate and multivariate analysis were conducted to check into the relationship between predictive factors and cervical CLNM in PTC patients, and then a predictive model was also established. RESULTS: Pathologically, 58.0% (65/112) of the PTC patients harbored cervical CLNM. Univariate and multivariate analysis were conducted to identify age < 55 years, tumor size > 10 mm, microcalcification, non-concomitant Hashimoto's thyroiditis and BRAFV600E mutation were predictive factors for cervical CLNM in PTC. The risk score for cervical CLNM in PTC patients was calculated: risk score = 1.284 × (if age < 55 years) + 1.241 × (if tumor size > 10 mm) + 1.143 × (if microcalcification) - 2.097 × (if concomitant Hashimoto's thyroiditis) + 1.628 × (if BRAFV600E mutation). CONCLUSION: Age < 55 years old, PTC > 10 mm, microcalcification, non-concomitant Hashimoto's thyroiditis and BRAFV600E mutation are predictive factors for cervical CLNM. BRAFV600E mutation by pre-operative US-FNA technology synergized with clinicopathologic and ultrasonic features is expected to guide the appropriate surgical management for PTC patients.

The role of upper and lower genital tract microbiota alterations in term chorionamnionitis: A prospective study.

Objective: This study aimed to compare the dynamics of lower and upper genital tract microbiota in normal term pregnancy, histological chorioamnionitis (HCA), and clinical chorioamnionitis (CCA) patients to provide a reference for the diagnosis and treatment of chorioamnionitis (CAM) patients. Methods: We prospectively collected vaginal and cervical secretions, as well as placenta tissues, fetal membranes, and amniotic fluid from normal-term pregnant women, HCA and CCA patients. Then, we performed genomic DNA extraction and PCR amplification for all samples. The eligible samples were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Additionally, all placenta tissues were histopathologically examined, and neonatal pharyngeal swabs and placenta tissues from the HCA and CCA groups were subjected to microbial culture. Results: A total of 85 term pregnant women were enrolled in this study, including 34 in the normal group (N), 37 in the HCA group, and 14 in the CCA group. A total of 171 qualified samples were analyzed by 16S rRNA sequencing. The results suggested that the cervical microbiota was highly similar to the vaginal microbiota in normal term parturients, with Lactobacillus as the dominant bacterium. Moreover, there was no difference in the alpha and beta diversity of vaginal microbiota between the N, HCA, and CCA groups at the genus level. Besides, no significant differences were detected in cervical microbiome among the three groups. Regarding intrauterine microorganisms, the N and HCA groups had similar microbial composition but were different from the CCA group. No microbe was detected in the placental tissue of normal term parturients, while some microorganisms were found in the intrauterine amniotic fluid and fetal membrane samples. Regardless of cultivation or 16S rRNA sequencing, an extremely low microbial positive rate was detected in HCA and CCA intrauterine samples. Compared to the normal group, Lactobacillus was significantly reduced in the CCA group intrauterine, and Ureaplasma and Enterococcus increased with no statistically significant. Conclusion: The N, HCA and CCA groups had similar composition of vaginal and cervical microflora. Some normal-term pregnant women can harbor non-pathogenic microbiota in the uterine cavity. Sterile inflammation is more frequent than microbial-associated inflammation in term HCA and CCA parturients.

Identification of biomarkers associated with cervical lymph node metastasis in papillary thyroid carcinoma: Evidence from an integrated bioinformatic analysis.

Integrated analysis of accumulated data is an effective way to obtain reliable potential diagnostic molecular of cervical lymph node metastases (LNM) in papillary thyroid carcinoma (PTC). The benefits of prophylactic lymph node dissection (PLND) for these clinically node-negative (cN0) patients remained considerable controversies. Hence, elucidation of the mechanisms of LNM and exploration of potential biomarkers and prognostic indicators are essential for accurate diagnosis of LNM in PTC patients. Up to date, advanced microarray and bioinformatics analysis have advanced an understanding of the molecular mechanisms of disease occurrence and development, which are necessary to explore genetic changes and identify potential diagnostic biomarkers. In present study, we performed a comprehensive analysis of the differential expression, biological functions, and interactions of LNM-related genes. Two publicly available microarray datasets GSE60542 and GSE129562 were available from Gene Expression Omnibus (GEO) database. Differentially expressed genes between clinically node-positive (cN1) and cN0 PTC samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Our results identified 48 differentially expressed genes (DEGs) genetically associated with LNM in PTC patients. Gene ontology (GO) analyses revealed the changes in the modules were mostly enriched in the regulation of MHC class II receptor activity, the immune receptor activity, and the peptide antigen binding. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs displayed the intestinal immune network for IgA production, staphylococcus aureus infection, and cell adhesion molecules (CAMs). To screen core genes related to LNM of PTC from the protein-protein interaction network, top 10 hub genes were identified with highest scores. Our results help us understand the exact mechanisms underlying the metastasis of cervical LNM in PTC tissues and pave an avenue for the progress of precise medicine for individual patients.

Exploration of DNA Methylation-Driven Genes in Papillary Thyroid Carcinoma Based on the Cancer Genome Atlas.

Although the incidence of thyroid carcinoma is reported to be the highest among malignancies of endocrine system, its diagnosis is still unsatisfactory. This study sought to explore the key DNA methylation-driven genes in the development of papillary thyroid carcinoma (PTC) via a bioinformatic analysis based on the Cancer Genome Atlas (TCGA) database and was validated using the Gene Expression Omnibus (GEO) database. The level 3 DNA methylation, mRNA expression, and clinical data of 499 patients with PTC were obtained from the TCGA database. The R package LIMMA, edgeR, and MethylMix were applied to explore the DNA methylation-driven genes in PTC. The ConsensusPathDB software, DAVID, and STRING databases were used for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses, as well as protein/protein interaction network construction individually. To verify the result, the explored genes were validated using GSE97466 data set retrieved from the GEO database. Fifty-seven (57) methylation-driven genes were detected via MethylMix based on a beta mixture model that compared the DNA methylation state of tumor tissues with that of the normal tissues. Eventually, three genes (TNFRSF1A, CLDN1, and CASP1) were identified to be the most potential biomarkers for the diagnosis or treatment of PTC. These results suggest the crucial roles of TNFRSF1A, CLDN1, and CASP1 in the tumorigenesis of PTC and provide a vital bioinformatic basis for further experimental validations and clinical applications.

The associated factors for spontaneous intranodular hemorrhage of partially cystic thyroid nodules: A retrospective study of 101 thyroid nodules.

ABSTRACT: Spontaneous intranodular hemorrhaging in benign partially cystic thyroid nodules was reported to cause neck swelling, difficulty swallowing, and other oppressive symptoms attributed to their growing progressively at high rates. In our study, the risk factors for hemorrhaging in these nodules were investigated.We retrospectively analyzed benign partial cystic thyroid nodules from September 2017 to December 2019, and divided them into 2 groups according to the occurrence of intranodular hemorrhage. Age, gender, follow-up time nodules initial maximum diameter, blood supply, spongiform content, nodules solid components, and internal solid portion were compared between the 2 groups at the first ultrasound examination. Chi-Squared and multivariate analysis were performed to evaluate the association of hemorrhage with clinical and ultrasonographic characteristics. ROC analysis was performed to evaluate the utility of factors in predicting hemorrhage.There were 59 occurrences of intranodular hemorrhage, which were associated with abundant blood supply, spongiform contents, and unsmooth margin of the internal solid portion. After multivariate analysis, abundant blood supply, and spongiform content were independent predictors for hemorrhage. In ROC analysis integrating these predictors, the sensitivity was 62.7% and specificity was 95.2% with the AUC 0.881.Partially cystic thyroid nodules with abundant blood supply, non-smooth margin of the internal solid portion and a spongiform internal content were apt to spontaneous intranodular hemorrhaging, which can be recognized as soon as possible by ultrasound.

A multivariable model of BRAFV600E and ultrasonographic features for predicting the risk of central lymph node metastasis in cN0 papillary thyroid microcarcinoma.

Background: Prophylactic central lymph node dissection (CLND) in papillary thyroid microcarcinoma (PTMC) patients without clinical evidence of central lymph node metastasis (CLNM) remains controversial. The purpose of our study is to identify preoperative predictive factors for finding CLNM in Chinese PTMC patients, which may allow tailored CLND. Methods: We retrospectively reviewed 182 consecutive Chinese PMTC patients with negative central lymph nodes who underwent total thyroidectomy plus central neck dissection from October 2015 to December 2017. Chi-squared and multivariate analysis were performed to evaluate the association of CLNM with ultrasonographic and clinicopathologic characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the utility of markers in predicting CLNM. Results: The CLNM was found in 39.0% (71 of 182) of cN0 PTMC patients. In multivariate analysis, tumor size>7 mm (OR: 3.636, 95% CI: 1.671-7.914), marked hypoechogenicity (OR: 2.686, 95% CI: 1.080-6.678), multifocality (OR: 4.184, 95% CI: 1.707-10.258) and BRAFV600E mutation (OR: 5.339, 95% CI: 2.529-11.272) were independent predictors of CLNM. In ROC analysis integrating these predictors, the sensitivity was 63.4% and specificity was 80.2%, and the area under the ROC (AUC) was 0.755. Conclusion: In conclusion, we found tumor size>7 mm, marked hypoechogenicity, multifocality, and BRAFV600E mutation were risk factors for CLNM. In term of these preoperative risk factors for CLNM, prophylactic CLND should be cautiously performed in cN0 PTMC patients.

Association of BRAFV600E mutation with ultrasonographic features and clinicopathologic characteristics of papillary thyroid microcarcinoma: A retrospective study of 116 cases.

OBJECTIVE: To analyze the association of BRAFV600E mutation with ultrasonographic (US) features and clinicopathologic characteristics in Chinese patients with papillary thyroid microcarcinoma (PTMC). METHODS AND MATERIALS: We retrospectively reviewed 116 consecutive Chinese patients with PTMC diagnosed by postoperative pathology. The incidence of the BRAFV600E mutation was calculated. The US features and clinicopathologic characteristics were compared between BRAF-positive and BRAF-negative patients. RESULTS: The BRAFV600E mutation was detected in 60.3% of patients (70 of 116). Multifocality (OR: 3.681, P = 0.031), non-parallel orientation (OR: 3.181, P = 0.041) and lymph node metastasis (OR: 4.615, P = 0.009) were significantly associated with BRAFV600E mutation. Other US and clinicopathologic characteristics were not significantly related to the presence of BRAF mutation. CONCLUSION: Multifocality, non-parallel orientation and cervical lymph node metastasis are risk factors for BRAFV600E mutation in PTMC. These factors potentially guide treatment planning or prognosis evaluation.

Netrin-1 promotes cell neural invasion in gastric cancer via its receptor neogenin.

Neural invasion (NI) is one of the important routes for local spread of gastric cancer (GC) correlated with poor prognosis. However, the exact cellular characteristics and molecular mechanisms of NI in GC are still unclear. Netrin-1(NTN1) as an axon guidance molecule was firstly found during neural system development. Importantly, NTN1 has an essential role in the progression of malignant tumor and specifically mediates the induction of invasion. In this study, we found NTN1 expression was significantly increased in 97 tumor tissues from GC patients and positively correlated with NI (p<0.05). In addition, we detected NTN1 knockdown significantly suppressed GC cells migration and invasion. Moreover, our results showed that reciprocity was observed between GC cells and neurites colonies in dorsal root ganglia (DRG)-GC cells co-culture vitro model. GC cells with NTN1 silencing could suppress their abilities to navigate along surrounding neuritis and this effect was depended on its receptor neogenin. In vivo, NTN1 inhibition also decreased GC cells sciatic nerve invasion. Taken together, our findings argue that NTN1 and its receptor neogenin might act synergistically in promoting GC cells neural invasion. Inhibiting the activity of NTN1 could be a potential strategy targeting NI in GC therapy.

Anti-Diabetic and Anti-Nephritic Activities of Grifola frondosa Mycelium Polysaccharides in Diet-Streptozotocin-Induced Diabetic Rats Via Modulation on Oxidative Stress.

Grifola frondosa is an edible fungus with a variety of potential pharmacological activities. This study investigates the hypoglycemic, anti-diabetic nephritic, and antioxidant properties of G. frondosa polysaccharides in diet-streptozotocin-induced diabetic rats. After a 4-week treatment with 100 mg/kg of metformin and 200 mg/kg of one of four different G. frondosa polysaccharide mixtures (especially GFPS3 and GFPS4), diabetic rats had enhanced body weight and suppressed plasma glucose, indicating the hypoglycemic activities of the G. frondosa polysaccharides. G. frondosa polysaccharides regulated the level of serum creatinine, blood urea nitrogen, N-acetyl-ß-D-glucosaminidase, and albuminuria; inhibited the serum levels of interleukin (IL)-2, IL-6, and TNF-α; and enhanced the serum levels of matrix metalloproteinase 9 and interferon-α, confirming their anti-diabetic nephritic activities. G. frondosa polysaccharides ameliorated the pathological alterations in the kidneys of diabetic rats. Moreover, G. frondosa polysaccharides modulated the serum levels of oxidant factors such as superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, and reactive oxygen species, revealing their antioxidant properties. Furthermore, the administration of G. frondosa polysaccharides inhibited nuclear factor kappa B activities in the serum and kidneys. All of the data revealed that the activation of nuclear factor kappa B plays a central role in G. frondosa polysaccharide-mediated anti-diabetic and anti-nephritic activities.

[Corrigendum] Netrin­1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation.

During the preparation of the figures in the above article, the authors inadvertently selected images for the shCTL experiments portrayed in Fig. 5I and J (for the MGC803 and SGC7901 cell lines, respectively) that were generated from the same original data source. A corrected version of Fig. 5 is shown opposite, showing the correct data for the shCTL experiment performed in SGC7901 cells (Fig. 5J). This error did not affect the major conclusions reported in the paper. All the authors have agreed to this Corrigendum. The authors regret this error, and apologize for any confusion that it may have caused. [the original article was published in Oncol Rep 40: 2325­2333, 2018; DOI: 10.3892/or.2018.6614].

Netrin­1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation.

Netrin­1 (NTN1) has been demonstrated to promote tumorigenesis in multiple types of cancer; however, its role in the growth of gastric cancer (GC) cells has not been described in detail. In the present study, the data suggested that NTN1 knockdown significantly decreased the proliferation of GC cells, whereas NTN1 overexpression had an opposing effect. Furthermore, the use of focal adhesion kinase (FAK) inhibitor decreased the proliferation of GC cells. It was also revealed that NTN1 markedly induced the phosphorylation of FAK, extracellular signal­regulated kinase (ERK) and c­Jun N­terminal kinase (JNK), but did not induce the phosphorylation of P38. In addition, the expression of ERK and JNK was markedly inhibited by treatment with FAK inhibitor. Xenograft analysis using GC cells revealed that NTN1 overexpression promoted tumor growth. Furthermore, the expression of NTN1 in samples collected from nude mice was downregulated in the NTN1 knockdown group and upregulated in the NTN1 overexpression group compared with the control short hairpin RNA group. These results suggest that NTN1­induced GC cell proliferation is mediated by activating ERK/MAPK signaling cascades via the distinct activation of FAK.

Netrin-1 promotes metastasis of gastric cancer by regulating YAP activity.

Yes-associated protein (YAP) is a major downstream molecular of the Hippo pathway, which plays important role in cancer development. Netrin-1 conveys oncogenic activity in many types of malignant tumors. However, the downstream signaling of netrin-1 mediating its oncogenic effects in gastric cancer (GC) is not well defined. Here, we aim to investigate the role of netrin-1 in metastasis potential of GC by regulating YAP. In this study, we showed that netrin-1 inhibition significantly decreased migration and invasion abilities of GC cells, while netrin-1 overexpression effectively reversed this effect. We also demonstrated that netrin-1 upregulated YAP expression via its transmembrane receptor neogenin. Furthermore, our in vitro and in vivo results showed that the effect of netrin-1 on GC cells migration and invasion abilities was regulated by YAP. Collectively, our results defined netrin-1 as a positive regulator of malignant tumor metastasis in GC by activating the YAP signaling, with potential implications for new approaches to GC therapy.