miR-26a-5p restoration via EZH2 silencing blocks the IL-6/STAT3 axis to repress the growth of prostate cancer.

BACKGROUND: Interleukin-6 (IL-6) is involved in the activation of several oncogenic pathways in prostate cancer. However, its upstream trans-signaling pathway remains largely unknown. This work proposes a mechanistic explanation of IL-6's upstream effectors in prostate carcinogenesis. RESEARCH DESIGN & METHODS: Samples were harvested to validate the expression of EZH2, miR-26a-5p, and IL-6. Moreover, the protein and its phosphorylation of STAT3 (signal transducer and transcription activator 3) were assessed in prostate cancer cells. We explored the effects of these effectors on malignant phenotypes in vitro and tumor growth in vivo using functional assays. Bioinformatics analysis, dual-luciferase reporter gene assays, and chromatin immunoprecipitation (ChIP) assays were used to determine their binding relationships. RESULTS: Overexpression of EZH2 and IL-6, and under expression of miR-26a-5p was observed in prostate cancer. Silencing IL-6 repressed STAT3 to suppress the malignant phenotypes of prostate cancer cells. Mechanistically, EZH2 inhibited miR-26a-5p expression by promoting H3K27 histone methylation, and miR-26a-5p restricted the malignant phenotypes of prostate cancer by targeting IL-6. Ectopic EZH2 expression reduced xenograft growth by inhibiting miR-26a-5p and activating the IL-6/STAT3 axis. CONCLUSION: EZH2 May potentially be involved in regulating its expression by recruiting H3K27me3 to the miR-26a-5p promoter region, which could further impact the IL6/STAT3 pathway.

Recognizing pathology of renal tumor from macroscopic cross-section image by deep learning.

OBJECTIVES: This study aims to develop and evaluate the deep learning-based classification model for recognizing the pathology of renal tumor from macroscopic cross-section image. METHODS: A total of 467 pathology-confirmed patients who received radical nephrectomy or partial nephrectomy were retrospectively enrolled. The experiment of distinguishing malignant and benign renal tumor are conducted followed by performing the multi-subtypes classification models for recognizing four subtypes of benign tumor and four subtypes of malignant tumors, respectively. The classification models used the same backbone networks which are based on the convolutional neural network (CNN), including EfficientNet-B4, ResNet-18, and VGG-16. The performance of the classification models was evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Besides, we performed the quantitative comparison among these CNN models. RESULTS: For the model to differentiate the malignant tumor from the benign tumor, three CNN models all obtained relatively satisfactory performance and the highest AUC was achieved by the ResNet-18 model (AUC = 0.9226). There is not statistically significance between EfficientNet-B4 and ResNet-18 architectures and both of them are significantly statistically better than the VGG-16 model. The micro-averaged AUC, macro-averaged sensitivity, macro-averaged specificity, and micro-averaged accuracy for the VGG-16 model to distinguish the malignant tumor subtypes achieved 0.9398, 0.5774, 0.8660, and 0.7917, respectively. The performance of the EfficientNet-B4 is not better than that of VGG-16 in terms of micro-averaged AUC except for other metrics. For the models to recognize the benign tumor subtypes, the EfficientNet-B4 ranked the best performance, but had no significantly statistical difference with other two models with respect to micro-averaged AUC. CONCLUSIONS: The classification results were relatively satisfactory, which showed the potential for clinical application when analyzing the renal tumor macroscopic cross-section images. Automatically distinguishing the malignant tumor from benign tumor and identifying the subtypes pathology of renal tumor could make the patient-management process more efficient.

Complete transurethral resection of bladder tumor before radical cystectomy is not a risk factor for organ-confined bladder cancer: A case-control study.

Objectives: To investigate the role of complete transurethral resection of bladder tumor (TURBT) before radical cystectomy (RC) for organ-confined bladder cancer. Materials and methods: Data of patients who underwent RC in our center from January 2008 to December 2018 were retrospectively reviewed. Patients with >T2N0M0 disease and positive surgical margins and those who received neoadjuvant/adjuvant chemotherapy or radiotherapy were excluded. Complete TURBT was defined as no visible lesion under endoscopic examination after TURBT or in the bladder specimen after RC. Kaplan-Meier curves and log-rank tests assessed disease-free survival (DFS). Logistic and Cox regression analyses were performed to identify potential predictors. Results: A total of 236 patients were included in this review, including 207 males, with a median age of 61 years. The median tumor size was 3 cm, and a total of 94 patients had identified pathological T2 stage disease. Complete TURBT was correlated with tumor size (p = 0.041), histological variants (p = 0.026), and down-staging (p < 0.001). Tumor size, grade, and histological variants were independent predictors of complete TURBT. During a median follow-up of 42.7 months, 30 patients developed disease recurrence. Age and histological variants were independent predictors of DFS (p = 0.022 and 0.032, respectively), whereas complete TURBT was not an independent predictor of DFS (p = 0.156). Down-staging was not associated with survival outcome. Conclusions: Complete TURBT was correlated with an increased rate of down-staging before RC. It was not associated with better oncologic outcomes for patients with organ-confined bladder cancer.

Effects of intracoronary injection of nicorandil and tirofiban on myocardial perfusion and short-term prognosis in elderly patients with acute ST-segment elevation myocardial infarction after emergency PCI.

BACKGROUND: This study investigated the effects of the intracoronary injection of nicorandil and tirofiban on myocardial perfusion and short-term prognosis in elderly patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). METHODS: Seventy-eight STEMI patients with age >65 years who underwent emergency PCI were consecutively enrolled. These patients received conventional PCI and were randomly divided into a control group and a treatment group (n=39 per group). The control group received an intracoronary injection of tirofiban followed by a maintenance infusion for 36 hours after surgery. The treatment group received intracoronary injection of tirofiban and nicorandil, and then intravenous infusion of tirofiban and nicorandil 36 hours after surgery. The following parameters were measured: TIMI grade, corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), ST-segment resolution (STR) rate 2 hours post-operatively, resolution of ST-segment elevation (STR) at 2 hours postoperatively, peak level of serum CK-MB, left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) at 7-10 days postoperatively, and major adverse cardiac events (MACEs) in-hospital and within 30 days post-operatively. RESULTS: Compared with the control group, more patients in the treatment group had TIMI 3 and TMPG 3, and STR after PCI was significantly higher. The treatment group also had significantly lower cTFC, lower infarction relative artery (IRA), lower peak CK-MB, and no reflow ratio after PCI. The treatment group had significantly higher LVEDD and LVEF but lower incidence of MACEs than the control group. CONCLUSION: The intracoronary injection of nicorandil combined with tirofiban can effectively improve myocardial reperfusion in elderly STEMI patients after emergency PCI and improve short-term prognoses.

A rare case of meningoencephalitis by Listeria monocytogenes in systemic lupus erythematosus: case report and review.

Patients with systemic lupus erythematosus (SLE) have a high risk of infection. Central nervous system infection and neuropsychiatric SLE are both major causes of death. It is vital to distinguish between these two conditions to improve prognosis due to the treatment paradigms required for each condition. Here, we report one case of meningoencephalitis by Listeria monocytogenes (LM) in a patient with SLE who presented with fever and developed headache and altered in consciousness in the hospital. The cerebrospinal fluid culture was positive for LM, and magnetic resonance imaging (MRI) findings were suggestive of ependymitis and periventricular white matter lesions. Amoxicillin/sulbactam, trimethoprim-sulfamethoxazole, and rifampicin were administered for 8 weeks. The patient had a relative good recovery without serious neurological sequelae after a follow-up of nearly 2 years. MRI abnormalities also had obvious resolution.

Methylation of STK11 promoter is a risk factor for tumor stage and survival in clear cell renal cell carcinoma.

Inactivation of tumor suppressor gene serine-threonine kinase 11 (STK11) in clear cell renal cell carcinoma (ccRCC) has been demonstrated; however, the mechanism of this inactivation remains to be investigated. To investigate whether epigenetic alteration plays a role in the inactivation of STK11 in RCC, the present study aimed to investigate the methylation status of the STK11 promoter and its association with tumor stage and survival in ccRCC patients. Paraffin-embedded specimens were obtained from 42 ccRCC patients. The specimens were analyzed for the methylation status of the STK11 promoter CpG island using methylation-specific polymerase chain reaction. Survival, tumor-node-metastasis (TNM)/American Joint Committee on Cancer (AJCC) stages, and hematological parameters were compared between patients with unmethylated (U), partially methylated (P) and methylated (M) STK11 promoter. Among the 42 patients, there were 12 (28.6%), 18 (42.9%) and 12 (28.6%) patients in the M, P and U groups, respectively. The methylation status of the STK11 promoter was associated with T, N and AJCC stages in RCC. Survival analysis showed that the M group had a significantly shorter survival time compared with the P and U groups. These findings suggested that methylation of the STK11 promoter in RCC is a not rare event, and it may have an important role in the pathogenesis of RCC and be a risk factor for the prognosis of RCC.

Evaluating osteoporotic fracture risk with the Fracture Risk Assessment Tool in Chinese patients with rheumatoid arthritis.

This study aims to evaluate the discriminative and predictive capacity of the Fracture Risk Assessment Tool (FRAX) to determine the 10-year risk of osteoporotic fracture in Chinese rheumatoid arthritis (RA) patients.This study included 168 RA patients and 168 healthy individuals as controls. The Chinese mainland FRAX model was applied to calculate the 10-year risk of osteoporotic fractures, defined as fracture of the spine, forearm, hip, or shoulder.The incidence of osteoporosis was significantly increased in RA patients compared to controls (P < .05). Bone mineral density (BMD), lumbar vertebra T-score, and femoral neck T-score were significantly lower in RA patients compared to controls (P < .05). BMD, disease duration, DAS28, and glucocorticoid use were important risk factors for osteoporotic fractures in Chinese RA patients. Ten-year osteoporotic fracture risk in Chinese RA patients was higher when BMD was incorporated in FRAX.There was a higher incidence of osteoporosis and reduced BMD in RA patients compared to controls. The FRAX model should integrate femoral neck BMD with other risk factors to evaluate osteoporotic fracture risk in RA patients, making it a valuable screening tool.

The effect of TMEFF2 methylation on the tumor stage and survival outcome of clear cell renal cell carcinoma.

AIM: This study aimed to investigate the methylation status of EGF-like and two follistatin-like domains 2 (TMEFF2) promoter and its correlation with tumor stage and survival outcome in renal cell carcinoma (RCC). MATERIALS AND METHODS: Paraffin-embedded specimens from 42 RCC patients were analyzed for TMEFF2 methylation by methylation-specific polymerase chain reaction. The distribution of TNM/AJCC stages and survival time were compared among patients with unmethylated and methylated TMEFF2. RESULTS: There were 25 (59.5%) and 17 (40.5%) cases with methylated (M group) and unmethylated (M group) TMEFF2, respectively. There were more early-stage cancer patients in U group than in M group. Kaplan-Meier survival analysis showed that U group had a better but not significant survival outcome than M group (P = 0.123). CONCLUSION: These findings showed that TMEFF2 methylation is not rare in RCC, and methylation may play an important role in the tumorigenesis of ccRCC.

Effects of febuxostat on insulin resistance and expression of high-sensitivity C-reactive protein in patients with primary gout.

We aimed to investigate the effects of febuxostat on IR and the expression of high-sensitivity C-reactive protein (hs-CRP) in patients with primary gout. Forty-two cases of primary gout patients without uric acid-lowering therapy were included in this study. After a physical examination, 20 age- and sex-matched patients were included as normal controls. The levels of fasting insulin (INS), fasting blood glucose (FBG), and hs-CRP were determined. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Gout patients had higher levels of UA, INS, HOMA-IR, and hs-CRP than normal controls (P < 0.05). After 4-, 12-, and 24-week febuxostat treatments, UA and hs-CRP concentrations were significantly lower than baseline (P < 0.05). INS and HOM-IR decreased slightly after a 4-week treatment with febuxostat but declined significantly after 12 and 24 weeks of treatment. Importantly, hs-CRP values positively correlated with those of HOMA-IR (r = 0.353, P = 0.018) and INS (r = 0.426, P = 0.034). Our findings confirm that IR exists in gout patients and implicate that febuxostat can effectively control the level of serum UA and increase insulin sensitivity in primary gout patients.

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.

[Risk factors of postoperative intravesical recurrence of transitional cell carcinoma of the ureter].

OBJECTIVE: To define the clinicopathological risk factors of intravesical recurrence of primary transitional cell carcinoma of the ureter after surgical intervention. METHODS: Patients with primary carcinoma of the ureter treated between January 2000 and December 2010 were retrospectively analyzed. The intravesical recurrence-free survival rate was calculated using Kaplan-Meier method. Multivariate analysis was conducted with Cox's regression. RESULTS: A total of 104 patients were enrolled, who were followed up for a median of 46 months (13-89 months). Thirty-nine of the patients showed postoperative intravesical recurrence. Urine exfoliative cytology (P=0.000), number of tumors (P=0.006), tumor grade (P=0.039) and co-existence of bladder tumor (P=0.014) were found to independently influence the postoperative intravesical recurrence. Patients with more risk factors had poorer intravesical recurrence-free survival. CONCLUSION: Urine exfoliative cytology, number of tumors, tumor grade and co-existence of bladder tumor are independent risk factors for postoperative intravesical recurrence of primary transitional cell carcinoma of the ureter. Close follow-up and rigorous treatment are essential for patients with high risk factors.

Knockdown of p21-activated kinase 6 inhibits prostate cancer growth and enhances chemosensitivity to docetaxel.

OBJECTIVES: To investigate whether silencing of p21-activated kinase 6 (PAK6) would inhibit prostate cancer growth and to assess the effect of PAK6 silencing when used in combination with docetaxel. PAK6 is a serine/threonine kinase belonging to the PAK family and has been implicated in cell motility, apoptosis, and transformation. METHODS: Expression of PAK6 in PC-3, DU145, and LAPC4 prostate cancer cell lines was knocked down by small, interfering RNA (siRNA). Cellular proliferation, cell cycle distribution, the ability to undergo apoptosis, and the invasive capacity through matrigel were evaluated. Furthermore, in vivo growth of prostate cancer in nude mice treated with PAK6-siRNA alone or in combination with docetaxel was examined. RESULTS: PAK6 was overexpressed in prostate cancer tissues. PAK6-siRNA efficiently and specifically downregulated the expression of PAK6 and inhibited cell growth of prostate cancer. It also suppressed invasive ability in matrigel and caused cell cycle arrest at the G(2)/M phase. Xenograft tumor growth in nude mice was inhibited significantly by PAK6-siRNA. The average weight of the harvested tumor was 46 +/- 8.5 mg in the PAK6-siRNA group, lower than the 451 +/- 22.3 mg in the control group (P < .05). Combined use of PAK6-siRNA and docetaxel produced a greater effect than docetaxel alone in both in vitro and in vivo models. CONCLUSIONS: Knockdown of PAK6 expression produced an inhibitory effect on prostate cancer growth and enhanced chemosensitivity of docetaxel. PAK6 could be a valuable molecular target for the treatment of prostate cancer.