Case report: A cystic capillary hemangioma located at the conus medullaris mimicking hemangioblastoma.

Capillary hemangiomas, usually found in skin and mucosal tissues, are rarely encountered within the spinal cord, presenting a significant diagnostic challenge. We report a rare case of intradural extramedullary capillary hemangioma at the conus medullaris in a 66-year-old female patient. Our initial diagnosis leaned towards a cystic hemangioblastoma based on MRI findings due to the presence of cystic formation with an enhanced mural nodule. However, surgical exploration and subsequent pathological examination revealed the lesion as a capillary hemangioma. To the authors' knowledge, this case may represent the first documented instance of a spinal capillary hemangioma that mimics a cystic hemangioblastoma.

Efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma.

To explore the clinical efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma. We conducted a retrospective study to analyze the clinical data of patients with chronic subdural hematoma. Patients receiving atorvastatin treatment after surgery were divided into the study group while others were divided into the control group. As the primary outcome, we compared the hematoma recurrence rate. The secondary outcomes were the remaining volume of hematoma and the activities of daily living (Barthel index) score at 3 months after discharge. A total of 53 patients were included in the study: 30 patients in the study group (n = 30) and 23 patients in the control group (n = 23). The baseline clinical data were similar in the 2 groups (P > .05). Four patients had recurrence of hematoma in the study group, while 5 patients had recurrence of hematoma in the control group [4/30 (13.3%) versus 5/23 (21.7%), P = .661] at 3 months after discharge. The mean remaining volume of hematoma was 12.10 ±â€…8.80 mL in the study group and 17.30 ±â€…9.50 mL in the control group at 3 months after discharge, respectively. The remaining volume of hematoma in the study group was less than that in the control group (P = .045).The activities of daily living score in the study group were higher than those in the control group (97.83 ±â€…4.48 vs 94.78 ±â€…5.73, P = .034) at 3 months after discharge. Atorvastatin administration after surgery barely reduce the recurrence rate of chronic subdural hematoma, however, reduced the remaining volume of hematoma and improved neurological function.

Claudin 4 enhances the malignancy of glioma cells via NNAT/Wnt signaling.

Gliomas are the most common malignancies of the central nervous system and are associated with high mortality rates. However, the pathogenesis of gliomas is unclear. In this study, we show that elevated claudin-4 (CLDN4) levels in glioma tissues are associated with poor clinical outcomes. We found that upregulating the expression of CLND4 enhanced the proliferative and migratory capacities of glioma cells. Mechanistically, CLND4 upregulated Neuronatin (NNAT) by activating Wnt3A signaling, and aided in the progression of the glioma. Most importantly, our in vivo data demonstrated that CLND4 overexpression caused rapid tumor growth in mice injected with LN229 cells and reduced the survival of these mice. Our findings reveal that CLND4 modulates malignancy in glioma cells; targeting CLDN4 may open up new avenues for glioma treatment.

The relationship between emotional neglect and non-suicidal self-injury among middle school students in China: the mediating role of social anxiety symptoms and insomnia.

BACKGROUND: Non-suicidal self-injury (NSSI) is a vital public concern around the world, and it often starts in adolescence. Emotional neglect (EN) has been considered a distal risk factor for NSSI, but the effects of social anxiety symptoms (SA) and insomnia on this relationship have remained unclear. This study aimed to investigate the potential pathways from EN to NSSI, examining the role of SA and insomnia in this association. METHODS: One thousand three hundred thirty seven Chinese middle school students (Mage = 13.040, SD = 0.981, 50.2% males) in China were enrolled in this cross-sectional study. Participants completed the Emotional Neglect sub-scale of Childhood Trauma Questionnaire (CTQ-SF), the Social Anxiety Scale for Adolescent (SAS-A), Athens Insomnia Scale (AIS) and non-suicidal self-injury assessment. Structural equation modelling (SEM) was used to test the possible mediation model among these variables. RESULTS: 231(17.3%) students reported NSSI history during last year and 322 (24.1%) participants reported experiences of EN. Students who experienced EN have higher rates of NSSI compared to students without EN history (29.2% vs 13.5%). EN, SA, insomnia and NSSI were positively related to each other. Furthermore, both SA and insomnia played a mediating role in the relationship between EN and NSSI, the series mediating effect of SA and insomnia on this association was also significant after controlling for demographics. Indirect effects accounted for 58.26% of the total effects (EN → NSSI). CONCLUSIONS: Our study revealed that EN was associated with NSSI, SA and insomnia play indirect roles in the association between EN and NSSI. The findings of our research may have implications for clinicians, families, and schools in their efforts to lower the risk of NSSI in adolescents.

Carotenoid fates in plant foods: Chemical changes from farm to table and nutrition.

Carotenoids in plant foods are sources of pro-vitamin A and nutrients with several health benefits, including antioxidant and anticancer activities. However, humans cannot synthesize carotenoids de novo and must obtain them from the diet, typically via plant foods. We review the chemical changes of carotenoids in plant foods from farm to table and nutrition, including nutrient release and degradation during processing and metabolism in vivo. We also describe the influencing factors and proposals corresponding to enhancing the release, retention and utilization of carotenoids, thus benefiting human health. Processing methods influence the release and degradation of carotenoids, and nonthermal processing may optimize processing effects. The carotenoid profile, food matrix, and body status influence the digestion, absorption, and biotransformation of carotenoids in vivo; food design (diet and carotenoid delivery systems) can increase the bioavailability levels of carotenoids in the human body. In this review, the dynamic fate of carotenoids in plant foods is summarized systematically and deeply, focusing on changes in their chemical structure; identifying critical control points and influencing factors to facilitate carotenoid regulation; and suggesting multi-dimensional strategies based on the current state of food processing industries to achieve health benefits for consumers.

Validation of the Committed Action Questionnaire-8 and Its Mediating Role Between Experiential Avoidance and Life Satisfaction Among Chinese University Students.

Background: Committed action is one of the core processes of psychological flexibility derived from acceptance and commitment therapy. It has not been widely investigated in mainland China as appropriate measures are lacking. The current study aimed to validate a Chinese (Mandarin) version of the Committed Action Questionnaire (CAQ-8) in a non-clinical college sample and to explore whether committed action would have a mediating effect in the association between experiential avoidance (EA) and life satisfaction. Methods: We translated the CAQ-8 into Chinese (Mandarin). A total of 913 Chinese undergraduates completed a set of questionnaires measuring committed action, EA, mindful awareness, anxiety, depression, stress, and life satisfaction. For test-retest reliability, 167 respondents completed the CAQ-8 again 4 weeks later. Results: The entire scale of CAQ-8 (Mandarin) and two subscales showed adequate internal consistency and acceptable test-retest reliability. Confirmatory factor analyses confirmed the two-factor structure and the convergent and criterion validity were acceptable. Committed action was correlated with less EA, more mindful awareness, less depressive symptoms, less anxiety, less stress, and more life satisfaction. In bootstrap mediation analyses, committed action partially mediated the association between EA and life satisfaction. Conclusion: The results suggest that the CAQ-8 (Mandarin) is a brief, psychometrically sound instrument to investigate committed action in Chinese populations, and the relationship between EA and life satisfaction was partially explained by committed action. This study provides new information about the usefulness of CAQ-8 and supports the assumption that committed action may be considered a promising factors for improving life satisfaction who have involved in EA among an educated non-clinical population.

Effects of Molecular Distillation on the Chemical Components, Cleaning, and Antibacterial Abilities of Four Different Citrus Oils.

Essential oils (EOs) from citrus fruits are excellent aromatic resources that are used in food, cosmetics, perfume, and cleaning products. EOs extracted from four citrus varieties, sweet orange, grapefruit, mandarin, and lemon, were separated into two fractions by molecular distillation. The composition, physicochemical properties, cleaning ability, and antimicrobial activity of each EO were then systematically evaluated. The relationships between each of the aforementioned characteristics are also discussed. In keeping with the principle of "like dissolves like," most citrus EOs show better cleaning ability than acetone and all tend to dissolve the fat-soluble pigment. The key components of citrus EOs are 1-Decanol, α-terpineol, geraniol, and linalool for the inhibition of Staphylococcus aureus, Escherichia coli, Candida albicans, and Vibrio parahaemolyticus, respectively. The findings of this study will be of significant importance for the effective utilization of citrus peel resources and in the development of future applications for citrus EOs. Chemical Compounds Studied in This Article: (+)-α-Pinene (PubChem CID: 6654); ß-Phellandrene (PubChem CID: 11142); 3-Carene (PubChem CID: 26049); ß-Myrcene (PubChem CID: 31253); D-Limonene (PubChem CID: 440917); γ-Terpinene (PubChem CID: 7461); Octanal (PubChem CID: 454); Decanal (PubChem CID: 8175); Linalool (PubChem CID: 6549); 1-Octanol (PubChem CID: 957); ß-Citral (PubChem CID: 643779); α-Terpineol (PubChem CID: 17100); Hedycaryol (PubChem CID: 5365392); α-Citral (PubChem CID: 638011); 1-Decanol (PubChem CID: 8174); Geraniol (PubChem CID: 637566).

Histone demethylase JMJD1C promotes the polarization of M1 macrophages to prevent glioma by upregulating miR-302a.

Glioma is regarded as an aggressive lethal primary brain tumor. Jumonji domain containing 1C (JMJD1C) is a H3K9 demethylase which participates in the progression of various tumors, but its specific function and underlying mechanism in glioma development remain undefined, which is the purpose of our work. We initially assessed JMJD1C expression in glioma tissues and cells using the assays of RT-qPCR and immunohistochemistry. Meanwhile, the H3K9 level at the microRNA (miR)-302a promoter region was measured by chromatin immunoprecipitation assay, while luciferase-based reporter assay was performed for validation of the binding affinity between miR-302a and methyltransferase-like 3 (METTL3). The effect of METTL3 on suppressor of cytokine signaling 2 (SOCS2) was subsequently analyzed by MeRIP-RT-qPCR. Finally, a xenograft tumor model was established in nude mice, followed by measurement of tumor-associated macrophages using flow cytometry. JMJD1C was poorly expressed in glioma tissues. Furthermore, JMJD1C increased miR-302a expression through promoting H3K9me1 demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. JMJD1C promoted M1 macrophage polarization and suppressed the growth of glioma xenografts through the miR-302a/METTL3/SOCS2 axis both in vivo and in vitro. In conclusion, JMJD1C could enhance M1 macrophage polarization to inhibit the onset of glioma, bringing a new insight into the contribution of JMJD1C to the pathobiology of glioma, with possible implications for targeted therapeutic method.

Urothelial carcinoma of the renal pelvis with renal vein and inferior vena cava tumor thrombus: case series and literature review.

BACKGROUND: Urothelial carcinoma (UC) of the renal pelvis with renal vein and inferior vena cava (IVC) tumor thrombus (TT) was extremely rare. We aimed to explore the clinical and pathological characteristics, diagnosis and treatment of renal pelvis UC with renal vein and IVC TT. METHODS: From March 2016 to January 2019, eight patients of renal pelvis UC with renal vein and IVC TT were diagnosed and underwent operation in our hospital. Clinical features, operative details, pathological outcomes, and prognosis data were reviewed and collected. RESULTS: There were five males and three females (52-84 years old). Their main symptoms were flank pain and hematuria. According to the Mayo classification, the TT was 4 level-0 (1 left and 3 right), 2 level-I (right), and 2 level-II (right). Half the patients underwent retroperitoneal laparoscopic radical nephroureterectomy with thrombectomy, and the other underwent open procedures. The mean operative time was 298.9 minutes. Pathological outcomes revealed high-grade UC, with positive lymph nodes in 6 cases. Four patients received adjuvant chemotherapy, one target therapy and one adjuvant chemotherapy combined with immunotherapy after surgery. The mean follow-up time was 11.1 months. Three patients are alive, and two of them developed recurrence and lung metastasis. CONCLUSIONS: Preoperative differentiation between renal pelvis UC and renal cell carcinoma with venous TT was very important for the management. Radical nephroureterectomy with thrombectomy might be a reasonable method for renal pelvis UC with venous TT. The prognosis of such cases was poor even if adjuvant therapy was scheduled.

Outcomes of renal cell carcinoma with associated venous tumor thrombus: experience from a large cohort and short time span in a single center.

BACKGROUND: The surgical management and outcomes of renal cell carcinoma (RCC) with venous tumor thrombus (VTT) have been reported in limited sample size, and there remain discrepancies over the factors that influence oncologic outcomes after radical nephrectomy with thrombectomy (RNTE). The aim of the study was to analyze the outcomes of the patients with RCC with VTT in our institution and identify the independent prognostic factors. METHODS: Patients with RCC with VTT were enrolled for the study from February 2015 to December 2018. All patients underwent RNTE. Clinical data were compared using Mann-Whitney U test and the chi-square test for continuous and categorical variables respectively. Survival analysis was estimated using the Kaplan-Meier method. Univariable and multivariable survival analyses were performed using Cox regression model. RESULTS: 121 patients (91 men & 30 women) were identified with a median age of 60 years. VTT level was 0 in 25 patients, I in 20, II in 50, III in 12 and IV in 14. The median follow-up time was 24 months. During the follow-up period, 51 (42%) patients died and 69 (57%) patients experienced recurrence or metastasis. The 3-year and 5-year over-all survival (OS) were 58 and 39%. Among the several factors examined, positive lymph node (P = 0.016), metastasis at surgery (P = 0.034), tumor necrosis (P = 0.023) and sarcomatoid differentiation (P < 0.001) were demonstrated as independent significant risk factors on multivariable analysis. CONCLUSION: The OS was poor for patients with RCC with VTT. Rather than VTT level, positive lymph node, metastasis at surgery, tumor necrosis and sarcomatoid differentiation were independent prognostic predictors.

Ferroptosis-Related Gene-Based Prognostic Model and Immune Infiltration in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Ferroptosis plays a vital role in ccRCC development and progression. We did an update of ferroptosis-related multigene expression signature for individualized prognosis prediction in patients with ccRCC. Differentially expressed ferroptosis-related genes in ccRCC and normal samples were screened using The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses and machine learning methods were employed to identify optimal prognosis-related genes. CARS1, CD44, FANCD2, HMGCR, NCOA4, SLC7A11, and ACACA were selected to establish a prognostic risk score model. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these genes were mainly enriched in immune-related pathways; single-sample Gene Set Enrichment Analysis revealed several immune cells potentially related to ferroptosis. Kaplan-Meier survival analysis demonstrated that patients with high-risk scores had significantly poor overall survival (log-rank P = 7.815 × 10-11). The ferroptosis signature was identified as an independent prognostic factor. Finally, a prognostic nomogram, including the ferroptosis signature, age, histological grade, and stage status, was constructed. Analysis of The Cancer Genome Atlas-based calibration plots, C-index, and decision curve indicated the excellent predictive performance of the nomogram. The ferroptosis-related seven-gene risk score model is useful as a prognostic biomarker and suggests therapeutic targets for ccRCC. The prognostic nomogram may assist in individualized survival prediction and improve treatment strategies.

Pure retroperitoneal laparoscopic radical nephrectomy and thrombectomy with delayed occlusion of the proximal inferior vena cava (DOPI) technique for renal tumor with level II-III venous tumor thrombus.

PURPOSE: To explore the safety and effectiveness of delayed occlusion of the proximal inferior vena cava (DOPI) technique in retroperitoneal laparoscopic radical nephrectomy (LRN) and thrombectomy for renal tumor with level II-III venous tumor thrombus (VTT). MATERIALS AND METHODS: From August 2016 to October 2018, a total of 145 patients with renal tumor and VTT were admitted to our centre. Seventy-five patients underwent laparoscopic surgery, and 70 patients underwent open surgery. Among these patients, 17 patients underwent retroperitoneal LRN and thrombectomy with the DOPI technique. Clinical data were collected retrospectively, and a descriptive statistical analysis was conducted. RESULTS: All the patients successfully underwent retroperitoneal laparoscopic surgery. The mean operation time was 345.9 ± 182.9 min, the mean estimated blood loss was 466.7 ± 245.5 ml. Postoperative complications occurred in three patients, including two patients of Clavien grading system level IVa and one patient of level II. There were no complications related to carbon dioxide pneumoperitoneum, such as gas embolism, acidosis, and subcutaneous emphysema. During 21 months of median follow-up time, no local recurrence was found, and distant metastasis occurred in four patients. Cancer-specific death occurred in two patients. CONCLUSIONS: The DOPI technique is safe and feasible in the treatment of renal tumor and level II-III VTT. With the DOPI technique, the procedures of dissociating and exposing proximal inferior vena cava are simplified.

Identification of a Two-m6A RNA Methylation Regulator Risk Signature as an Independent Prognostic Biomarker in Papillary Renal Cell Carcinoma by Bioinformatic Analysis.

N6-Methyladenosine (m6A), the most common form of mRNA modification, is dynamically regulated by the m6A RNA methylation regulators, which play an important role in regulating the gene expression and phenotype in both health and disease. However, the role of m6A in papillary renal cell carcinoma (pRCC) is unknown. The purpose of this work is to investigate the prognostic value of m6A RNA methylation regulators in pRCC; thus, we can build a risk score model based on m6A RNA methylation regulators as a risk signature for predicting the prognosis of pRCC. Here, we investigated the expression and corresponding clinical data by bioinformatic analysis based on 289 pRCC tissues and 32 normal kidney tissues obtained from TCGA database. As a result, we identified the landscape of m6A RNA methylation regulators in pRCC. We grouped all pRCC patients into two clusters by consensus clustering to m6A RNA methylation regulators, but we found that the clusters were not correlated to the prognosis and clinicopathological features of pRCC. Therefore, we additionally built a two-m6A RNA methylation regulator risk score model as a risk signature by the univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. The risk signature was constructed as follows: 0.031HNRNPC + 0.199KIAA1429. It revealed that the risk score was associated with the clinicopathological features such as pT status and pN status of pRCC. More importantly, the risk score was an independent prognostic marker for pRCC patients. Thus, m6A RNA methylation regulators contributed to the malignant progression of pRCC influencing its prognosis.

In-vivo biotransformation of citrus functional components and their effects on health.

Citrus, one of the most popular fruits worldwide, contains various functional components, including flavonoids, dietary fibers (DFs), essential oils (EOs), synephrines, limonoids, and carotenoids. The functional components of citrus attract special attention due to their health-promoting effects. Food components undergo complex biotransformation by host itself and the gut microbiota after oral intake, which alters their bioaccessibility, bioavailability, and bioactivity in the host body. To better understand the health effects of citrus fruits, it is important to understand the in-vivo biotransformation of citrus functional components. We reviewed the biotransformation of citrus functional components (flavonoids, DFs, EOs, synephrines, limonoids, and carotenoids) in the body from their intake to excretion. In addition, we described the importance of biotransformation in terms of health effects. This review would facilitate mechanistic understanding of the health-promoting effect of citrus and its functional components, and also provide guidance for the development of health-promoting foods based on citrus and its functional components.

Psychometric Properties of the Chinese Version of the Intolerance of Uncertainty Inventory in Chinese College Students.

BACKGROUND: Intolerance of uncertainty (IU) is considered to be associated with emotional disorders, such as generalized anxiety disorder (GAD), depression, obsessive compulsive disorder (OCD), and social anxiety. Therefore, a comprehensive instrument to measure IU is needed. The purposes of the present study were as follows: 1) developing a Chinese version of the Intolerance of Uncertainty Inventory (CIUI) and 2) measuring the reliability and validity of CIUI. METHODS: We translated the Intolerance of Uncertainty Inventory (IUI) into Chinese. A sample consisting of Chinese college students from three universities was used to evaluate the internal consistency, test-retest reliability, and validity of the CIUI. Participants answered the CIUI, IUS-12, GAD-7, BDI-II, and PSWQ. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were run to explore the factor structure of CIUI. RESULTS: The results demonstrated an acceptable internal consistency for CIUI (Part A of CIUI [CIUIA]: α = 0.920; Part B of CIUI [CIUIB]: α = 0.947) and test-retest reliability (CIUIA: ICC = 0.788; CIUIB: ICC = 0.859). The results of EFA and CFA all supported a two-factor structure for CIUIA (Intolerance of the unexpected and difficulty waiting in an uncertain situation and Intolerance of uncertainty and of uncertain situations) and a four-factor structure for CIUIB (Overestimation, Control, Uncertainty makes one feel stressful, and Reassurance), and acceptable validity was obtained. CONCLUSION: The CIUI is an appropriate instrument for measuring IU in Chinese populations. Future studies should confirm the psychometric properties using a comprehensive sample.

Long non-coding RNA LINC01234 regulates proliferation, migration and invasion via HIF-2α pathways in clear cell renal cell carcinoma cells.

Long non-coding RNAs (lncRNAs) have been proved to have an important role in different malignancies including clear cell renal cell carcinoma (ccRCC). However, their role in disease progression is still not clear. The objective of the study was to identify lncRNA-based prognostic biomarkers and further to investigate the role of one lncRNA LINC01234 in progression of ccRCC cells. We found that six adverse prognostic lncRNA biomarkers including LINC01234 were identified in ccRCC patients by bioinformatic analysis using The Cancer Genome Atlas database. LINC01234 knockdown impaired cell proliferation, migration and invasion in vitro as compared to negative control. Furthermore, the epithelial-mesenchymal transition was inhibited after LINC01234 knockdown. Additionally, LINC01234 knockdown impaired hypoxia-inducible factor-2a (HIF-2α) pathways, including a suppression of the expression of HIF-2α, vascular endothelial growth factor A, epidermal growth factor receptor, c-Myc, Cyclin D1 and MET. Together, these datas showed that LINC01234 was likely to regulate the progression of ccRCC by HIF-2α pathways, and LINC01234 was both a promising prognostic biomarker and a potential therapeutic target for ccRCC.

The influence of venous tumor thrombus combined with bland thrombus on the surgical treatment and prognosis of renal cell carcinoma patients.

OBJECTIVE: To describe the clinical characteristics of renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and bland thrombus (BT), and to evaluate the influence of BT on surgical treatment and cancer-specific survival (CSS) of RCC with VTT. METHODS: We retrospectively reviewed clinical data of 123 patients with RCC and VTT, who underwent surgical treatment in our center between February 2015 and May 2018. Patients were divided into the BT group (21 patients) and non-BT group (102 patients). Chi-square and Mann-Whitney U test were used for categorical and continuous variables respectively. Univariable log-rank tests and multivariable Cox regressions were conducted to evaluate the prognostic significance of each variable. Kaplan-Meier plots were performed to evaluate the influence of BT. RESULTS: In the delayed phase of enhanced magnetic resonance imaging (MRI), BT and VTT had difference. Patients were divided according to the relative position of BT: proximal end BT (one patients), contralateral renal vein BT (two patients), distal end BT (12 patients), and multiple BT (six patients). The average length of BT was 8.4 ± 5.8 cm (range: 0.6-20.0 cm). Patients with BT had longer operative time (P = .001), more surgical blood loss (P = .004), higher proportion of open surgery (P = .006), more postoperative complications (P = .011). BT (hazard ratio [HR] = 3.323, P = .007) were independent risk factors for poor prognosis. CONCLUSIONS: In the delayed phase of enhanced MRI, BT showed no obvious enhancement, while VTT usually showed enhancement. This was an important basis for preoperative imaging diagnosis of BT. The presence of BT increases the difficulty of surgery, and is correlated with adverse survival outcomes in patients with RCC and VTT.

Clinical significance of circulating tumor cells detection in renal cell carcinoma with thrombus: A STROBE-compliant study.

The aim of the study was to evaluate the potential role of circulating tumor cell (CTC) detection in the surgical assessment of renal cell carcinoma (RCC) patients with thrombi.Nine patients diagnosed with renal mass and thrombi were enrolled from June 2018 to January 2019. Blood samples were collected for CTC detection using SE-iFISH assay. CD45, DAPI, programmed death ligand 1, and fluorescence in situ hybridization with the centromere of chromosome 8 (CEP8) were immune-stained for analysis. Patient demographics, clinical features, pathological characteristics, and CTC detection results were extracted for analysis.Seven of 9 patients (77.8%) had 12 detectable CTCs, 5 of which were with CEP8-positive signal ≥5 and the others were CEP8-positive signal = 3. All 3 patients (100%) with IVC invasion had detectable CTCs, whereas CTCs were detected in 4 of 6 patients (66.7%) without IVC invasion. CEP8 analysis revealed that CTCs in IVC invasion patients were all of CEP8-positive signal ≥5 status, whereas only half of the CTCs in patients without IVC invasion were of CEP8-positive signal ≥5 pattern.In conclusion, both CTC subtype and total CTC number may serve as a marker for predicting inferior vena cava invasion in RCC patients.

High expression of SMYD3 indicates poor survival outcome and promotes tumour progression through an IGF-1R/AKT/E2F-1 positive feedback loop in bladder cancer.

The AKT/mTOR pathway is critical for bladder cancer (BC) pathogenesis and is hyper-activated during BC progression. In the present study, we identified a novel positive feedback loop involving oncogenic factors histone methyltransferase SMYD3, insulin-like growth factor-1 receptor (IGF-1R), AKT, and E2F-1. SMYD3 expression was significantly up-regulated in BC tumors and positively associated with histological grade, lymph node metastasis, and shorter patient survival. Depletion of SMYD3 inhibited BC cell proliferation, colony formation, migration, invasion, and xenograft tumor growth. Mechanistically, SMYD3 inhibition led to the diminished AKT/mTOR signaling activity, thereby triggering deleterious effects on BC cells. Furthermore, SMYD3 directly activates the expression of IGF-1R, a critical activator of AKT in BC, by inducing hyper-methylation of histone H3-K4 and subsequent chromatin remodeling in the IGF-1R promoter region. On the other hand, E2F-1, a downstream factor of the AKT pathway, binds to the E2F-1 binding motifs at the SMYD3 promoter and consequently induces SMYD3 transcription and expression. Thus, SMYD3/IGF-1R/AKT/E2F-1 forms a positive feedback loop leading to the hyper-activated AKT signaling. Our findings provide not only profound insights into SMYD3-mediated oncogenic activity but also present a unique avenue for treating BC by directly disrupting this signaling circuit.