A Nomogram Including Sarcopenia for Predicting Progression-Free Survival in Patients with Localized Papillary Renal Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Because of to the removal of subclassification of papillary renal cell carcinoma (pRCC), the survival prognostification of localized pRCC after surgical treatment became inadequate. Sarcopenia was widely evaluated and proved to be a predictive factor for prognosis in RCC patients. Therefore, we comprehensively investigated the survival prediction of the body composition parameters for localized pRCC. METHODS: Patients pathologically diagnosed with pRCC between February 2012 and February 2022 in our center were enrolled. The body composition parameters, including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and perirenal adipose tissue (PRAT), were measured by the images of preoperative computed tomography (CT). The primary outcome was set as progression-free survival (PFS), and the cutoff values of body composition parameters were calculated by using the Youden from receiver operating characteristic curve (ROC) curves. Univariate and multivariate Cox proportional regression analyses were performed to explore independent risk factors for survival prediction. Then, significant factors were used to construct a prognostic nomogram. The performance of the nomogram was evaluated by Harrell's C-index, calibration curves and time-dependent ROC curves. RESULTS: A total of 105 patients were enrolled for analysis. With a median follow-up time of 30.48 months, 25 (23.81%) patients experienced cancer progression. The percentage of sarcopenia was 74.29%. Univariate Cox analysis identified that gender, PRAT, SAT, skeletal muscle (SM), sarcopenia, surgical technique, and tumor diameter were associated with progression. Further multivariate analysis showed that sarcopenia (hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.03-0.66), SAT (HR 6.36, 95% CI 2.39-16.93), PRAT (HR 4.66, 95% CI 1.77-12.27), tumor diameter (HR 0.35, 95% CI 0.14-0.86), and surgical technique (HR 2.85, 95% CI 1.06-7.64) were independent risk factors for cancer progression. Then, a prognostic nomogram based on independent risk factors was constructed and the C-index for progression prediction was 0.831 (95% CI 0.761-0.901), representing a reasonable discrimination, the calibration curves, and the time-dependent ROC curves verified the good performance of the nomogram. CONCLUSIONS: A prognostic nomogram, including sarcopenia, SAT, PRAT, tumor diameter, and surgical technique, was constructed to calculate the probability of progression for localized pRCC patients and needs further external validation for clinical use in the future.

Multimodal neuroimaging with optically pumped magnetometers: A simultaneous MEG-EEG-fNIRS acquisition system.

Multimodal neuroimaging plays an important role in neuroscience research. Integrated noninvasive neuroimaging modalities, such as magnetoencephalography (MEG), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), allow neural activity and related physiological processes in the brain to be precisely and comprehensively depicted, providing an effective and advanced platform to study brain function. Noncryogenic optically pumped magnetometer (OPM) MEG has high signal power due to its on-scalp sensor layout and enables more flexible configurations than traditional commercial superconducting MEG. Here, we integrate OPM-MEG with EEG and fNIRS to develop a multimodal neuroimaging system that can simultaneously measure brain electrophysiology and hemodynamics. We conducted a series of experiments to demonstrate the feasibility and robustness of our MEG-EEG-fNIRS acquisition system. The complementary neural and physiological signals simultaneously collected by our multimodal imaging system provide opportunities for a wide range of potential applications in neurovascular coupling, wearable neuroimaging, hyperscanning and brain-computer interfaces.

Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox-LDL.

BACKGROUND: It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presence of lipid abnormalities. Few studies have investigated in full-scale if the intervention time for lipids abnormality or NLRP3 activation have a significant effect on autophagy, NLRP3 or the apoptotic status in macrophages. METHODS: Human THP-1 monocyte-derived macrophages were established by challenging THP-1 monocytes with 80 µg/ml oxidized low-density lipoprotein (ox-LDL) for specific durations. Foam cell formation was observed by Oil Red O (ORO) staining. Western blots were employed to determine protein expression. Transmission electron microscope (TEM) and immunofluorescence microscopy were applied to observe the autophagic status of cells. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). RESULTS: The cells were treated with ox-LDL for 12 h and 36 h, which were considered to represent early and advanced stages of atherogenesis for this study. The results showed that inhibition of ox-LDL phagocytosis by cytochalasin D in the early stage improved autophagic status, reduced NLRP3 activation and the apoptotic response significantly. In contrast, cytochalasin D had little effect on blocking the detrimental effect of ox-LDL at the advanced stage. Moreover, the changes in autophagy, apoptosis and NLRP3 expression after treatment with small interfering (si) RNA targeting NLRP3 in the early and advanced stages of atherogenesis were consistent with the above data. CONCLUSIONS: Interventions against lipid disorders or inflammatory reactions in the early or advanced stages of atherogenesis may have different results depending on when they are applied during the process of atherosclerotic pathogenesis. These results may help improve therapeutic strategies for atherosclerosis prevention. Furthermore, a healthy lifestyle should still be recommended as the most important and inexpensive measure to prevent atherogenesis.

Fast Sleep Stage Classification Using Cascaded Support Vector Machines with Single-Channel EEG Signals.

Long-term sleep stage monitoring is very important for the diagnosis and treatment of insomnia. With the development of wearable electroencephalogram (EEG) devices, we developed a fast and accurate sleep stage classification method in this study with single-channel EEG signals for practical applications. The original sleep recordings were collected from the Sleep-EDF database. The wavelet threshold denoising (WTD) method and wavelet packet transformation (WPT) method were applied as signal preprocessing to extract six kinds of characteristic waves. With a comprehensive feature system including time, frequency, and nonlinear dynamics, we obtained the sleep stage classification results with different Support Vector Machine (SVM) models. We proposed a novel classification method based on cascaded SVM models with various features extracted from denoised EEG signals. To enhance the accuracy and generalization performance of this method, nonlinear dynamics features were taken into consideration. With nonlinear dynamics features included, the average classification accuracy was up to 88.11% using this method. In addition, with cascaded SVM models, the classification accuracy of the non-rapid eye movement sleep stage 1 (N1) was enhanced from 41.5% to 55.65% compared with the single SVM model, and the overall classification time for each epoch was less than 1.7 s. Moreover, we demonstrated that it was possible to apply this method for long-term sleep stage monitor applications.

Breast lesions excised via vacuum-assisted system: could we get any clues for B3 lesions before excision biopsy?

BACKGROUND: The purpose of this study was to determine the validity of the ultrasound features as well as patient characteristics assigned to B3 (uncertain malignant potential) breast lesions before vacuum-assisted excision biopsy (VAEB). METHODS: This study population consisted of 2245 women with breast-nodular abnormalities, which were conducted ultrasound-guided VAEB (US-VAEB). Patient's clinical and anamnestic data and lesion-related ultrasonic feature variables of B3 captured before US-VAEB were compared with those of benign or malignant cases, using histopathological results as a benchmark. RESULTS: The proportions of benign, B3 and malignant breast lesions diagnosed post-US-VAEB were 88.5, 8.2 and 3.4% respectively. B3 high frequent occurred in BI-RADS-US grade 3 (7.7%), grade 4a (11.0%) and grade 4b (9.1%). The overall malignancy underestimation rate of B3 was 4.4% (8/183). Malignant lesions were found mostly in the range of BI-RADS grade 4b (27.3%), grade 4c (33.3%) and grade 5 (100%). Multivariate binary logistic regression analyses (B3 vs benign) showed that non-menopausal patients (95% CI 1.628-8.616, P = 0.002), single (95% CI 1.370-2.650, P = 0.000) or vascularity (95% CI 1.745-4.150, P = 0.000) nodules in ultrasonic features were significant risk factors for B3 occurrences. In addition, patients elder than 50 years (95% CI 3.178-19.816, P = 0.000), unclear margin (95% CI 3.571-14.119, P = 0.000) or suspicious calcification (95% CI 4.010-30.733, P = 0.000) lesions were significantly associated with higher risks of malignant potentials for B3 cases (malignant vs B3). CONCLUSION: The results of this study indicate that ultrasound findings and patients' characteristics might provide valuable information for distinguishing B3 lesions from benign breast abnormalities before VAEB, and help to reduce malignancy underestimation of B3.

A clinicopathological analysis of adrenal tumors in patients with history of extra-adrenal cancers.

BACKGROUND: Adrenal tumors in patients with previous/synchronous extra-adrenal malignancy are diverse and are a dilemma in clinical practice. This study investigated the differentiation of adrenal malignant and benign tumors in these patients. METHODS: Data from patients with a pathological diagnosis of adrenal tumors were retrospectively retrieved from April 1991 to November 2015. Patients without extra-adrenal malignancy were excluded. Clinical and imaging characteristics, including sex, age, tumor size, tumor location, isolated lesion, time interval between the diagnosis of the two tumors and retrieved imaging diagnosis, were collected and analyzed. The selected patients were divided into 2 groups: those with primary or secondary malignancies (PSM) and those with primary benign tumors (PB). Chi-squared tests were used to evaluate differences between the two groups. Logistic regression was performed to explore potential risk factors related to the differentiation of PSM and PB, and a receiver operating characteristic (ROC) curve was used to evaluate their diagnostic values. RESULTS: Ninety-one patients were selected; 54 were male, and the median age was 56 years old. Between the groups of PSM and PB, sex (p = 0.004), age (p = 0.029), tumor size (p < 0.001), isolated lesion (p < 0.001) and imaging diagnosis (p < 0.001) were significantly different, while tumor size (p = 0.001), sex (p = 0.047) and imaging diagnosis (p = 0.002) were independent predictors of PSM. With ROC curve analysis, risk factors ≥2 was the optimal cutoff to differentiate these adrenal tumors, and their sensitivity and specificity were 73 and 77%, respectively. With a median follow-up of 32 months, only 4 of 32 patients with PB died from cancer, and 24 of 47 patients with PSM died from cancer, although aggressive treatment was performed. CONCLUSIONS: Tumor size, sex and imaging diagnosis were independent predictors of adrenal primary or secondary malignancies. These predictors might be helpful for differentiation of adrenal tumors in patients with previous/synchronous extra-adrenal cancers.

Relapse in children with clinical stage I testicular yolk sac tumors after initial orchiectomy.

PURPOSE: To evaluate risk factors of relapse in pediatric patients with clinical stage I (CS1) testicular yolk sac tumors. METHODS: With retrospective analysis, the medical records of children with pure testicular yolk sac tumors who were referred to Sun Yat-sen University Cancer Center and The First Affiliated Hospital from January 1995 to December 2015 were selected and recorded. Histopathology and staging were retrieved and multivariate analysis was performed with SPSS 20.0 software. RESULTS: 90 children with CS1 testicular yolk sac tumors were selected, and 21 of them underwent chemotherapy following initial orchiectomy. The median age of them was 17 months. With a median follow-up of 61 months (range 11-183 months), 84 patients were alive and 3 patients died, whereas the status was unknown in 3 patients. 30 patients experienced relapse within a median time of 4 months, including only 1 patient who underwent primary chemotherapy, and 28 of these patients underwent salvage chemotherapy. According to adjusted analysis, lymphovascular invasion (LVI) (P < 0.001), necrosis (P = 0.003) and primary chemotherapy (P = 0.008) were independent predictors of event-free survival. The 4-year event-free survival of high- and low-risk patients was 46.5% and 85.1%, respectively (P < 0.001). CONCLUSIONS: LVI and necrosis were independent risk factors for relapse in pediatric patients with CS1 testicular yolk sac tumors, and primary chemotherapy was effective. Thus, individualized management might be feasible for these patients according to risk classification.

RBFOX3 Regulates the Chemosensitivity of Cancer Cells to 5-Fluorouracil via the PI3K/AKT, EMT and Cytochrome-C/Caspase Pathways.

BACKGROUND/AIMS: RBFOX3, an RNA-binding fox protein, plays an important role in the differentiation of neuronal development, but its role in the chemosensitivity of hepatocellular carcinoma (HCC) to 5-FU is unknown. METHODS: In this study, we examined the biological functions of RBFOX3 and its effect on the chemosensitivity of HCC cells to 5-FU in vitro and in a mouse xenograft model. RESULTS: RBFOX3 was found to have elevated expression in HCC cell lines and tissue samples, and its knockdown inhibited HCC cell proliferation. Moreover, knockdown of RBFOX3 improved the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and enhanced the apoptosis induced by 5-FU. However, overexpression of RBFOX3 reduced the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and decreased the apoptosis induced by 5-FU. We further elucidated that RBFOX3 knockdown synergized with 5-FU to inhibit the growth and invasion of HCC cells through PI3K/AKT and epithelial-mesenchymal transition (EMT) signaling, and promote apoptosis by activating the cytochrome-c/caspase signaling pathway. Finally, we validated that RBFOX3 regulated 5-FU-mediated cytotoxicity in HCC in mouse xenograft models. CONCLUSIONS: The findings from this study indicate that RBFOX3 regulates the chemosensitivity of HCC to 5-FU in vitro and in vivo. Therefore, targeting RBFOX3 may improve the inhibition of HCC growth and progression by 5-FU, and provide a novel potential therapeutic strategy for HCC.

Activator Protein-2ß Promotes Tumor Growth and Predicts Poor Prognosis in Breast Cancer.

BACKGROUND/AIMS: Activator protein-2 (AP-2) transcription factors have been proved to be essential in maintaining cellular homeostasis and regulating the transformation from normal growth to neoplasia. However, the role of AP-2ß, a key member of AP-2 family, in breast cancer is rarely reported. METHODS: The effect of AP-2 on cell growth, migration and invasion in breast cancer cells were measured by MTT, colony formation, wound-healing and transwell assays, respectively. The expression levels of AP-2ß and other specific markers in breast cancer cell lines and tissue microarrays from the patients were detected using RT-PCR, Western blot and immunohistochemical staining. The regulation of AP-2ß on tumor growth in vivo was analyzed in a mouse xenograft model. RESULTS: We demonstrated the tumor-promoting function of AP-2ß in breast cancer. AP-2ß was found to be highly expressed in breast cancer cell lines and tumor tissues of breast cancer patients. The shRNA-mediated silencing of AP-2ß led to the dramatic inhibition of cell proliferation, colony formation ability, migration and invasiveness in breast cancer cells accompanied by the down-regulated expression of some key proteins involved in cancer progression, including p75, MMP-2, MMP-9, C-Jun, p-ERK and STAT3. Overexpression of AP-2ß markedly up-regulated the levels of these proteins. Consistent with the in vitro study, the silencing or overexpression of AP-2ß blocked or promoted tumor growth in the mice with xenografts of breast cancers. Notably, the high AP-2ß expression levels was correlated with poor prognosis and advanced malignancy in patients with breast cancer. CONCLUSIONS: Our study demonstrates that AP-2ß promotes tumor growth and predicts poor prognosis, and may represent a potential therapeutic target for breast cancer.

ß-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells.

BACKGROUND/AIMS: ß-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down ß-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between ß-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of ß-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. RESULTS: ß-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with ß-catenin and contributed to ß-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/ß-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and ß-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. CONCLUSIONS: Our study has provided new evidence for the role of ß-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of ß-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.

Management of adrenal incidentaloma: the role of adrenalectomy may be underestimated.

BACKGROUND: To demonstrate clinical characteristics of adrenal incidentaloma in South China and explore its comprehensive management. METHODS: The clinical data of patients with adrenal neoplasm from Jan 1998 to Dec 2012 were retrospectively analysed. Patients with suspicion of adrenal abnormalities or those in whom adrenal abnormalities were detected in the staging procedures of other cancers were excluded. Most patients with adrenal incidentaloma chose to have adrenalectomy, and some chose surveillance. The relationships between clinical features were analysed with a chi-square test and rank sum test. RESULTS: In total, 634 patients with adrenal incidentaloma were studied. Their age ranged from 17 to 85 years old with a median age of 50 years. Of 478 cases with pathological results, adenoma was the most common tumour (233/478), with 84 cases of pheochromocytoma and 36 cases of adrenocortical carcinoma were 84 and 36. When the tumour size was ≤4 cm, >95 % were benign; when the tumour size was >6 cm, 33 % were malignant. For patients with a tumour size ≤4 cm, 249/376 cases had an adrenalectomy performed. Due to anxiety over a potential malignant transformation and enlargement, most patients (>80 %) under surveillance preferred to undergo adrenalectomy. CONCLUSIONS: Pheochromocytoma and adrenocortical carcinoma were not rare tumours of adrenal incidentaloma, and 4 cm is a good size cutoff to use in the diagnosis of an adrenal incidentaloma. Other than surveillance, laparoscopic adrenalectomy may become the method of choice for management of small adrenal incidentaloma.

Percutaneous ultrasound-guided radiofrequency ablation treatment and genetic testing for renal cell carcinoma with Von Hippel-Lindau disease.

Percutaneous ultrasound-guided radiofrequency ablation is increasingly being studied in the treatment of renal tumors. Because percutaneous ultrasound-guided radiofrequency ablation is a minimally invasive and nephron-sparing procedure, it is ideally suited for patients with a single kidney, multiple tumors, or contraindications to conventional surgery. We report on a patient with Von Hippel-Lindau (VHL) disease who had multicentric tumors in the single kidney that was successfully treated with percutaneous ultrasound-guided radiofrequncy ablation. The one-year follow-up showed that there was no local recurrence or metastasis. And genetic testing showed the patient had a T to G heterozygotic missense mutation at nucleotide 515 of VHL gene exon 1.

Prognostic value of JAK3 promoter methylation and mRNA expression in clear cell renal cell carcinoma.

INTRODUCTION: Janus kinase 3 (JAK3) is a well-established oncogene in clear cell renal cell carcinoma (ccRCC). The methylation status of oncogene promoters has emerged as biomarkers for cancer diagnosis and prognosis. OBJECTIVE: This study aims to investigate the biological and clinical significance of JAK3 promoter methylation in ccRCC. METHODS: We analyzed the relationship of JAK3 promoter methylation with its mRNA expression, overall survival, and immune cell infiltration in a cohort obtained from The Cancer Genome Atlas (TCGA), which was further validated by another independent cohort. We further validated correlations of JAK3 promoter methylation with JAK3 expression, overall survival, and immune cell infiltration in an independent ccRCC cohort (Sun Yat-sen University Cancer Center (SYSUCC) cohort) by methods of immunohistochemistry (IHC) and pyrosequencing. RESULTS: We found JAK3 promoter was significantly hypomethylated in tumor tissues compared to normal adjacent tissues in ccRCC, and JAK3 promoter hypomethylation was strongly correlated with high JAK3 mRNA expression in all three ccRCC cohorts we examined. JAK3 promoter hypomethylation predicted advanced clinicopathological characteristics and shorter overall survival (TCGA cohort and SYSUCC cohort). Furthermore, we found that JAK3 promoter methylation was significantly associated with immune cell infiltration and expression of immune checkpoint molecules (TCGA cohort and CPTAC cohort). Finally, our SYSUCC cohort validated that JAK3 promoter methylation was correlated with CD4+ and CD8+ T cell infiltration in ccRCC tumor tissues. CONCLUSION: Our data demonstrated that the crucial role of JAK3 promoter methylation in its expression regulation and tumor microenvironment. JAK3 promoter methylation and expression are associated with clinicopathological characteristics, overall survival, and immune cell infiltration in ccRCC. We propose a rationale for further validation of JAK3 promoter methylation as a molecular biomarker for predicting responses to immune checkpoint inhibitors in ccRCC.

Glycosylated serum protein may improve our ability to predict endothelial and erectile dysfunction in nonorganic patients.

INTRODUCTION: Early prediction of erectile dysfunction (ED) is critical in the treatment of impotence. Underlying pathogenesis may be the reason for ED without organic causes in young men. AIM: We evaluated the early predictive value of glycosylated serum protein (GSP) in young patients whose ED was diagnosed as "nonorganic" in origin according to general criteria. METHODS: A total of 150 young men with ED and 27 healthy men without ED were evaluated, including International Index of Erectile Function-5 (IIEF-5), causes of ED, influential or risk factors for ED, vascular parameters, and serum biochemical markers. Fifty-two ED patients aged 20-40 years without known etiology and 22 age-matched normal subjects were enrolled. The further assessment of two groups focused on vascular endothelial function and glycometabolic state. MAIN OUTCOME MEASURES: Relationships among the IIEF-5 scores, flow-mediated dilation (FMD), and GSP were analyzed in cases vs. controls, using Pearson's correlation and multiple linear regression analysis. RESULTS: No significant differences in baseline characteristics, cardiovascular risks, and conventional biomarkers were found between testing and control groups, except fasting blood glucose level (4.69 ± 0.50 vs. 4.29 ± 0.48, P = 0.003). FMD values were significantly reduced in cases compared with controls and correlated positively with IIEF-5 scores (r = 0.629, P < 0.001). GSP levels were significantly increased in the ED cases compared with controls and correlated negatively with IIEF-5 scores (r = -0.504, P < 0.001) and FMD values (r = -0.469, P < 0.001). These parameters independently predicted ED presence. The positive predictive value of FMD > 11.55% for excluding ED and of GSP > 210.50 mg/L for diagnosing ED were 86.4% (area under the curve [AUC]: 0.942, specificity: 88.4%) and 84.5% (AUC: 0.864, specificity: 72.7%), respectively. CONCLUSIONS: Underlying glycometabolic disorder and subclinical endothelial dysfunction may be served as early markers for organic ED in young ED patients without well-known related risk factors. GSP level may improve our ability to predict endothelial dysfunction and erectile dysfunction.

The prognostic value of lymph node ratio in comparison to positive lymph node count in penile squamous cell carcinoma.

PURPOSE: Penile cancer is a rare male neoplasm with a wide variation in its global incidence. In this study, the prognostic value of lymph node ratio (LNR) was compared to that of positive lymph node count (PLNC) in penile squamous cell carcinoma. METHODS: A total of 249 patients with penile squamous cell carcinoma were enrolled from The Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-tile program was used to calculate the optimal cut-off values of LNR and PLNC that discriminate survival. We used the χ2 or the Fisher exact probability test to assess the association between clinical-pathological characteristics and LNR or PLNC. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for survival. Spearman correlation analysis was used to determine the correlation between LNR and PLNC. RESULTS: We found that patients with high LNR tended to have advanced N stage, the 7th AJCC stage, and higher pathological grade, while patients with high PLNC had advanced N stage and the 7th AJCC stage. Univariate Cox regression analysis revealed that the N stage, M stage, the 7th AJCC stage, lymph-vascular invasion, LNR, and PLNC were significantly associated with prognosis. Multivariate Cox regression analysis demonstrated that LNR rather than PLNC was an independent prognostic factor for cancer-specific survival. Subgroup analysis of node-positive patients showed that LNR was associated with CSS, while PLNC was not. CONCLUSION: LNR was a better predictor for long-term prognosis than PLNC in patients with penile squamous cell carcinoma.

Lymph Node Ratio Rather Than Positive Lymph Node Counts Has Better Prognostic Value in Patients With Testicular Germ Cell Tumors.

BACKGROUND: Testicular cancer represents the most common malignancy in young adult men. In the current study, we sought to analyze and compare the prognostic value of lymph node ratio (LNR) as well as positive lymph node counts (LNC) to understand its clinical significance in testicular germ cell tumors. METHODS: We employed eligibility criteria to recruit a total of 931 patients, with testicular cancer, from 2010 to 2015 from The Surveillance, Epidemiology, and End Results (SEER) database. We then used the X-Tile program to calculate LNR and LNC cutoff values and discriminate survival. We then calculated the overall and cancer specific survival rates and analyzed the association between LNR/LNC and clinical pathological characteristics using the χ2 test. Finally, we assessed the relationships between clinical pathological factors and patient survival using univariate Cox proportional hazard analysis. RESULTS: Univariate analysis revealed a significant association between prognosis with age (HR, 5.169; 95% CI, 1.758-15.200; P = 0.003), AJCC stage (III vs I: HR, 9.298; 95% CI, 2.691-32.131; P < 0.001), M stage (HR, 7.897; 95% CI, 3.417-18.251; P < 0.001) and LNR (HR, 3.009; 95% CI, 1.275-7.098; P = 0.012). On the other hand, LNC (HR, 1.743; 95% CI, 0.687-4.420; P = 0.242) was not significantly associated with prognosis. Analysis of the association between LNR/LNC and clinical pathological characteristics showed that high LNR patients tended to have significantly larger tumor sizes (χ2 = 7.877, P = 0.005), as well as advanced T (χ2 = 13.195, P = 0.004), N ( χ2 = 86.775, P < 0.001), M (χ2 = 19.948, P < 0.001) and 7th AJCC (χ2 = 103.074, P < 0.001) stages. In addition, high LNC patients were significantly associated with T (χ2 = 8.799, P = 0.032), N (χ2 = 74.390, P < 0.001) and 7th AJCC (χ2 = 111.759, P < 0.001) stages. CONCLUSION: LNR was a better predictor for long-term prognosis and was closely associated with clinical pathological characteristics than LNC in patients with testicular germ cell tumors.

A Nomogram for Predicting Intraoperative Hemodynamic Instability in Patients With Pheochromocytoma.

Purpose: Surgical removal of pheochromocytoma (PCC), including open, laparoscopic, and robot-assisted adrenalectomy, is the cornerstone of therapy, which is associated with high risk of intraoperative and postoperative life-threatening complications due to intraoperative hemodynamic instability (IHD). This study aims to develop and validate a nomogram based on clinical characteristics as well as computed tomography (CT) features for the prediction of IHD in pheochromocytoma surgery. Methods: The data from 112 patients with pheochromocytoma were collected at a single center between January 1, 2010, and December 31, 2019. Clinical and radiological features were selected with the least absolute shrinkage and selection operator regression analysis to predict IHD then constitute a nomogram. The performance of the nomogram was assessed in terms of discrimination, calibration, and clinical utility. Results: Age, tumor shape, Mayo Adhesive Probability score, laterality, necrosis, body mass index, and surgical technique were identified as risk predictors of the presence of IHD. The nomogram was then developed using these seven variables. The model showed good discrimination with a C-index of 0.773 (95% CI, 0.683-0.862) and an area under the receiver operating characteristic curve (AUC) of 0.739 (95% CI, 0.642-0.837). The calibration plot suggested good agreement between predicted and actual probabilities. Besides, calibration was tested with the Hosmer-Lemeshow test (P = 0.961). The decision curve showed the clinical effectiveness of the nomogram. Conclusions: Our nomogram based on clinical and CT parameters could facilitate the treatment strategy according to assessment of the risk of IHD in patients with pheochromocytoma.

Chronic administration of sildenafil modified the impaired VEGF system and improved the erectile function in rats with diabetic erectile dysfunction.

INTRODUCTION: Men frequently develop diabetic erectile dysfunction (DMED), as a result of endothelial dysfunction. DMED patients often have reduced efficacy with phosphodiesterase type 5 inhibitors therapy. AIM: To determine whether chronic sildenafil administration can modify the impaired vascular endothelial growth factor (VEGF) system and improve the erectile function in rats with diabetic erectile dysfunction. METHODS: A group of Sprague Dawley rats (n = 30) with DMED were induced by intraperitoneal injection of streptozotocin (40 mg/kg) and screened by subcutaneous injection of Apomorphine (100 mg/kg). They were then exposed to either vehicle or sildenafil (prescribed in our hospital, 5 mg/kg and 10 mg/kg, respectively) for 10 weeks. An additional nondiabetic and age-matched control group (n = 10) was also allocated and given the routine diet for the same period. Assessments were performed to both groups at 36 hours after the last dose of sildenafil. Penile intracavernous pressure (ICP), mean arterial pressure (MAP), penile tissue morphology, immunohistologic analysis, and Western blot analysis of VEGF, VEGFR1, and eNOS were determined. MAIN OUTCOME MEASURE: Functional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined. RESULTS: A significant increase of ICP, ICP/MAP ratio, and area under the curve were observed in the both groups treated by sildenafil (5 mg/kg and 10 mg/kg, respectively), compared with the DMED rats without receiving Sildenafil. Immunohistochemical staining of their penile tissue showed a decrease in VEGF, VEGFR1, and eNOS staining in the controlled group compared with an improvement in the chronic sildenafil administration group. Western blot analysis demonstrated exactly the same results. CONCLUSION: We demonstrated that daily sildenafil administration can restore the impaired VEGF system in the penis of DMED rats and progressively improve both erectile function and endothelial function, suggesting a potential general mechanism of improved signaling through the VEGF/eNOS signaling cascade.

[Daily medication of low-dose tadalafil improves endothelial function and erectile hardness of ED patients].

OBJECTIVE: To evaluate the effects of daily medication of low-dose tadalafil on the improvement of endothelial function and erectile hardness in erectile dysfunction (ED) patients. METHODS: A total of 60 ED patients and 24 controls were treated with oral tadalafil at 5 mg/d for 6 - 8 weeks, and evaluated by international index of erectile function-5 (IIEF-5), erectile hardness grading scale (EHGS) and brachial artery flow-mediated dilation (FMD) test before and after the treatment. All the data obtained were analyzed by independent-sample and paired-sample t tests, respectively. RESULTS: The treatment and follow-up were accomplished in 51 of the ED cases. Compared with the controls, the ED patients showed significantly lower scores on IIEF-5 (23.6 +/- 1.0 vs 10.3 +/- 4.5, P < 0.01), EHGS (3.7 +/- 0.5 vs 2.0 +/- 0.6, P < 0.01) and FMD (14.1 +/- 2.1 vs 8.1 +/- 1, P < 0.01). Daily medication of tadalafil achieved an effectiveness rate of 96.1% (49/51) in the treatment of the ED patients, and significantly improved their scores on IIEF-5 (16.9 +/- 3.9 vs 10.6 +/- 4.5, P < 0.01), EHGS (2.6 +/- 0.7 vs 2.0 +/- 0.6, P < 0.01) and FMD (9.2 +/- 1.7 vs 8.1 +/- 0.9, P < 0.01), as compared with pretreatment. CONCLUSION: Long-term daily medication of low-dose tadalafil can significantly improve endothelial function and erectile hardness of ED patients.

PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer.

Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 (PUF60) as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics analysis of TCGA bladder cancer expression data. The expression of PUF60 was significantly higher in tumor tissues, while high PUF60 expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A (AURKA) as a new downstream target of PUF60 in bladder cancer cells. PUF60 knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereas AURKA overexpression reversed this inhibition effect. Overexpression of PUF60 significantly promoted cell viability and colony formation in bladder cancer cells, while treatment with AURKA specific inhibitor reversed this promotive effect. Mechanistically, PUF60 specifically bound to the AURKA promoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation between PUF60 and AURKA expression in bladder cancer tissues, and PUF60 and AURKA expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that the PUF60/AURKA axis plays a key role in regulating tumorigenesis and progression of bladder cancer, and may be a potential prognostic biomarker and therapeutic target for bladder cancer patients.