PI-RADS v2.1 evaluation of prostate "nodule in nodule" variants: clinical, imaging, and pathological features.

OBJECTIVES: To analyze the correlation among the imaging features of prostate "nodule in nodule," clinical prostate indices, and pathology results. METHODS: We retrospectively analyzed the prostate images from 47 male patients who underwent MRI scans and pathological biopsy from January 2022 to July 2023. Two radiologists (R1/R2) evaluated the morphology and signal intensity of the "nodule in nodule" in a double-blind manner and calculated the PI-RADS v2.1 score, which was compared with clinical prostate indices and pathological results. RESULTS: 34.04% (16/47) of patients were pathologically diagnosed with clinically significant prostate cancer (csPCa). Total prostate-specific antigen (tPSA), free/t PSA, PSA density (PSAD), and prostate gland volume (PGV) were significantly different between csPCa patients and benign prostatic hyperplasia (BPH) patients with prostate "nodule in nodule". R1/R2 detected 17/17 prostate "nodule in nodule" pathologically confirmed as csPCa on MRI; 10.60% (16/151) (R1) and 11.11% (17/153) (R2) had diffusion-weighted imaging (DWI) PI-RADS v2.1 score of 4, and 0.66% (1/151) (R1) had a score of 3. The percentages of encapsulated, circumscribed, and atypical nodules and obscured margins were 0.00% (0/151), 0.00% (0/151), 5.96% (9/151), and 5.30% (8/151), respectively, for R1, and 0.00% (0/153), 0.00% (0/153), 5.88% (9/153), and 4.58% (7/153) for R2. CONCLUSION: When the inner nodules of "nodule in nodule" lesions in PI-RADS v2.1 category 1 in the TZ show incomplete capsulation or obscured margins, they are considered atypical nodules and might be upgraded to PI-RADS v2.1 category 3 if they exhibit marked diffusion restriction. However, further validation is needed. CRITICAL RELEVANCE STATEMENT: This study first analyzed the relationship between clinical and pathological findings and the size, margin, and multimodal MRI manifestations of the prostate "nodule in nodule." These findings could improve the diagnostic accuracy of PI-RADS v2.1 for prostate lesions. KEY POINTS: • The margin of the prostate inner nodules affects the PI-RADS v2.1 score. • The morphology of prostate "nodule in nodule" is related to their pathology. • The PI-RADS v2.1 principle requires consideration of prostate "nodule in nodule" variants.

Inhibitory effects and reactions of gallic acid, catechin, and procyanidin B2 with nitrosation under stomach simulating conditions.

Nitrite widely exists in meat products, and has the functions of bacteriostasis, antisepsis, and color development. However, in an acidic environment, nitrite will react with amines, and further generate nitrosamines with carcinogenic and teratogenic effects. Polyphenols have good antioxidant and nitrite-scavenging effects. This study aimed to evaluate the inhibitory effects of gallic acid, catechin, and procyanidin B2 on the nitrosation reaction under stomach simulating conditions and discuss the potential inhibitory mechanism. The nitrite scavenging rate and nitrosamine synthesis blocking rate of gallic acid, catechin, and procyanidin B2 under different reaction times and contents was determined by UV-vis spectrophotometry. The possible products of the reaction of the three polyphenols with nitrite were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) to reveal the mechanism of inhibiting nitrification. The results showed that the scavenging rate of the three polyphenols on nitrite and the blocking rate of nitrosamine synthesis increased with the increase of the content and reaction time. The ability of the three polyphenols to inhibit nitrosation was catechin > procyanidin B2 > gallic acid. HPLC-MS analysis showed that under simulated gastric juice conditions, the three phenolics were oxidized by nitrous acid to form their semiquinone radicals as the intermediates and nitrosated derivatives, while nitrite might be converted to ˙NO. These results suggested that gallic acid, catechin, and procyanidin B2 could inhibit nitrosation reactions in an acidic environment and may be used as food additives to reduce nitrite residues and nitrosamines in food.

Study of the effect of calcium signal participating in the antioxidant mechanism of yeast under high-sugar environment.

BACKGROUND: Saccharomyces cerevisiae is susceptible to high-sugar stress in the production of bioethanol, wine and bread. Calcium signal is widely involved in various physiological and metabolic activities of cells. The present study aimed to explore the effects of Ca2+ signal on the antioxidant mechanism of yeast during high-sugar fermentation. RESULTS: Compared to yeast without available Ca2+, yeast in the high glucose with Ca2+ group had higher dry weight, higher ethanol output at 12 and 24 h and higher glycerol output at 24 and 36 h. During the whole growth process, the trehalose synthesis capacity of yeast in the high glucose with Ca2+ group was lower and intracellular reactive oxygen species content was higher compared to yeast without available Ca2+. Intracellular malondialdehyde content of yeast under high glucose with Ca2+ was significantly lower than yeast under high glucose without available Ca2+ except for 6 h. The superoxide dismutase and catalase activities of yeast and glutathione content were higher in the high glucose with Ca2+ group compared to yeast in high glucose without available Ca2+. The expression levels of SOD1, GSH1, GPX2 genes were higher for high glucose without available Ca2+ at 6 h, while yeast in the high glucose with Ca2+ group had a higher expression of antioxidant-related genes except SOD1 and CTT1 at 12 h. The expression levels of antioxidant-related genes of yeast for high glucose with Ca2+ were higher at 24 h, and those of genes except SOD1 of yeast in the high glucose with Ca2+ group were higher at 36 h. CONCLUSION: High-glucose stress limited the growth of yeast, while a moderate extracellular Ca2+ signal could improve the antioxidant capacity of yeast in a high-glucose environment by regulating protectant metabolism and enhancing the antioxidant enzyme activity and expression of antioxidant genes in a high-sugar environment. © 2024 Society of Chemical Industry.

The signature of cuproptosis-related immune genes predicts the tumor microenvironment and prognosis of prostate adenocarcinoma.

Background: Cuproptosis plays a crucial role in cancer, and different subtypes of cuproptosis have different immune profiles in prostate adenocarcinoma (PRAD). This study aimed to investigate immune genes associated with cuproptosis and develop a risk model to predict prognostic characteristics and chemotherapy/immunotherapy responses of patients with PRAD. Methods: The CIBERSORT algorithm was used to evaluate the immune and stromal scores of patients with PRAD in The Cancer Genome Atlas (TCGA) cohort. Validation of differentially expressed genes DLAT and DLD in benign and malignant tissues by immunohistochemistry, and the immune-related genes of DLAT and DLD were further screened. Univariable Cox regression were performed to select key genes. Least absolute shrinkage and selection operator (LASSO)-Cox regression analyse was used to develop a risk model based on the selected genes. The model was validated in the TCGA, Memorial Sloan-Kettering Cancer Center (MSKCC) and Gene Expression Omnibus (GEO) datasets, as well as in this study unit cohort. The genes were examined via functional enrichment analysis, and the tumor immune features, tumor mutation features and copy number variations (CNVs) of patients with different risk scores were analysed. The response of patients to multiple chemotherapeutic/targeted drugs was assessed using the pRRophetic algorithm, and immunotherapy was inferred by the Tumor Immune Dysfunction and Exclusion (TIDE) and immunophenoscore (IPS). Results: Cuproptosis-related immune risk scores (CRIRSs) were developed based on PRLR, DES and LECT2. High CRIRSs indicated poor overall survival (OS), disease-free survival (DFS) in the TCGA-PRAD, MSKCC and GEO datasets and higher T stage and Gleason scores in TCGA-PRAD. Similarly, in the sample collected by the study unit, patients with high CRIRS had higher T-stage and Gleason scores. Additionally, higher CRIRSs were negatively correlated with the abundance of activated B cells, activated CD8+ T cells and other stromal or immune cells. The expression of some immune checkpoints was negatively correlated with CRIRSs. Tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH) and copy number variation (CNV) scores were all higher in the high-CRIRS group. Multiple chemotherapeutic/targeted drugs and immunotherapy had better responsiveness in the low-CRIRS group. Conclusion: Overall, lower CRIRS indicated better response to treatment strategies and better prognostic outcomes.

Regulation of fructose levels on carbon flow and metabolites in yeast during food fermentation.

In this study, the effects of fructose levels on yeast growth, metabolic pathways and products, and redox status were investigated by simulated dough medium. The results showed that yeast was subjected to oxidative stress and damage under both sugar-free and high-fructose conditions. Yeast has a strong ability to metabolize pentose phosphate, trehalose, and tricarboxylic acid under sugar-free conditions. In the high fructose environment, yeast preferentially produced trehalose and glycerol in the early stage and gradually increased the metabolism of pentose phosphate in the later stage. Compared with the low fructose concentration, yeast had stronger pentose phosphate and tricarboxylic acid cycle (TCA) metabolism to ensure nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine triphosphate (ATP) content in higher fructose levels. Therefore, sugar-free and high fructose levels affected the growth of yeast cells and yeast responded to fructose levels by regulating the metabolic carbon flow of glycolysis, pentose phosphate, trehalose, and TCA.

Vitamin D deficiency aggravates growth and metastasis of prostate cancer through promoting EMT in two ß-catenin-related mechanisms.

Increasing evidence has demonstrated that vitamin D deficiency is associated with prostate cancer progression, but its mechanism remains unclear. This study investigated effects of vitamin D deficiency on growth and metastasis of prostate cancer. Nude mice and Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed with vitamin D-deficient (VDD) diets. Prostate cancer growth was aggravated in VDD diet-fed nude mice and TRAMP mice. Invasion and metastasis of prostate cancer were exacerbated in VDD diet-fed TRAMP mice. In vitro experiments showed that calcitriol, an active vitamin D3, inhibited migration and invasion in transforming growth factor (TGF)-ß1 -stimulated and -unstimulated PC-3 and DU145 cells. Mechanistically, calcitriol inhibited epithelial-mesenchymal transition (EMT) in TGF-ß1 -stimulated and -unstimulated DU145 cells. Unexpectedly, calcitriol did not inhibit Smad2/3 phosphorylation in TGF-ß1-stimulated DU145 cells. Instead, calcitriol downregulated expression of proliferation-, metastasis- and EMT-related genes, includes Cyclin D1, MMP7, and Zeb1, by inhibiting interaction between TCF4 and ß-catenin. In addition, calcitriol promoted interaction between cytoplasmic VDR and ß-catenin, reduced ß-catenin phosphorylation and elevated ß-catenin/E-cadherin adherens junction complex formation. We provide novel evidence that vitamin D deficiency aggravates growth and metastasis of prostate cancer possibly through promoting EMT in two ß-catenin-related mechanisms.

p-Phenylenediamine induces epithelial-mesenchymal transition in SV-40 immortalized human urothelial cells via the ERK5/AP-1 signaling.

PURPOSE: To investigate whether p-Phenylenediamine (PPD) could triggered EMT inSV-40 immortalized human urothelial cells (SV-HUC-1), and the regulation role of ERK5/AP-1 during this process. MATERIALS AND METHODS: SV-HUC-1 cells were treated with different concentrations of PPD. MTT assay was employed to detect cell viability. Wound healing and transwell assay were performed to detect migrative and invasive capacity. Western blot and qRT-PCR were utilized for detecting molecular changes. ERK5 specific inhibitor was used to suppress ERK5 signaling. RESULTS: Migration and invasion capacity of SV-HUC-1cells were enhanced after PPD exposure. Expression of epithelial markers E-cadherin and ZO-1 was decreased and expression of mesenchymal markers N-cadherin and vimentin was increased after being cultured with low concentrations of PPD, indicating that PPD induced EMT in PPD-cultured SV-HUC-1 cells. Meanwhile, PPD triggered activation of ERK5signaling and downstream AP-1 was activated, but no obvious influence of PPD on other sub-families of MAPK was detected. After inhibition of ERK5/AP-1, PPD-induced enhancement of migrative and invasive abilities were attenuated and expression of EMT markers was also reversed. CONCLUSION: PPD may be a carcinogen, which could induce EMT in SV-40 immortalized human urothelial cells (SV-HUC-1) via activating ERK5/AP-1 signaling.

High-dose-androgen-induced autophagic cell death to suppress the Enzalutamide-resistant prostate cancer growth via altering the circRNA-BCL2/miRNA-198/AMBRA1 signaling.

Androgen deprivation therapy (ADT) is a gold standard treatment for advanced PCa. However, most patients eventually develop the castration-resistant prostate cancer (CRPC) that progresses rapidly despite ongoing systemic androgen deprivation. While early studies indicated that high physiological doses of androgens might suppress rather than promote PCa cell growth in some selective CRPC patients, the exact mechanism of this opposite effect remains unclear. Here we found that Enzalutamide-resistant (EnzR) CRPC cells can be suppressed by the high-dose-androgen (dihydrotestosterone, DHT). Mechanism dissection suggested that a high-dose-DHT can suppress the circular RNA-BCL2 (circRNA-BCL2) expression via transcriptional regulation of its host gene BCL2. The suppressed circRNA-BCL2 can then alter the expression of miRNA-198 to modulate the AMBRA1 expression via direct binding to the 3'UTR of AMBRA1 mRNA. The consequences of high-dose-DHT suppressed circRNA-BCL2/miRNA-198/AMBRA1 signaling likely result in induction of the autophagic cell death to suppress the EnzR CRPC cell growth. Preclinical studies using in vivo xenograft mouse models also demonstrated that AMBRA1-shRNA to suppress the autophagic cell death can weaken the effect of high-dose-DHT on EnzR CRPC tumors. Together, these in vitro and in vivo data provide new insights for understanding the mechanisms underlying high-dose-DHT suppression of the EnzR CRPC cell growth, supporting a potential therapy using high-dose-androgens to suppress CRPC progression in the future.

Effect of glucose levels on carbon flow rate, antioxidant status, and enzyme activity of yeast during fermentation.

BACKGROUND: The physiological metabolism of yeast has a significant impact on the quality of fermentation products. The present study aimed to investigate yeast metabolism in response to a changing glucose content environment, especially in fermentation products, as well as the change of carbon flow rate, antioxidant status, and yeast enzyme activity. RESULTS: Yeast in a 0 g L-1 glucose level was subjected to carbon starvation stress, cell growth retardation and cell proliferation was significantly inadequate; in the logarithmic growth stage of yeast, at a 30 g L-1 glucose level, the carbon source mainly flowed to tricarboxylic acid cycle and pentose phosphate metabolism, cell division, proliferation, and increased cell growth. In later logarithmic growth period and stable period, carbon flowed into glycerol and trehalose metabolism, to cope with the environmental stress; yeast in 60 and 150 g L-1 glucose levels faced high glucose stress at the beginning, the content of reactive oxygen increased, malondialdehyde content increased, cell damage was reduced through the regulation of superoxide dismutase and catalase enzyme activities, and most of the carbon flowed into the metabolic pathway of ethanol, glycerol, and trehalose to cope with high glucose stress, the pentose phosphate pathway showed a large late influx, and NADPH also started to increase rapidly after 24 h. CONCLUSION: Yeast was stressed in a high-sugar environment and ensured the activity of yeast by preferentially increasing the metabolic intensity of trehalose, glycerol, and glycolytic metabolism, weakening tricarboxylic acid metabolism, and first weakening and then increasing pentose phosphate metabolism. © 2022 Society of Chemical Industry.

Application of a new position in endoscopic combined intrarenal surgery: modified prone split-leg position.

BACKGROUND: Endoscopic combined intrarenal surgery (ECIRS) is well established as a minimally invasive procedure for the treatment of multiple urolithiasis. The position is the key to the perfect combination of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). Galdakao-modified supine Valdivia (GMSV) and prone split-leg positions are widely used. However, both positions have their own advantages and disadvantages. This study aimed to evaluate the effect of ECIRS in the treatment of multiple urolithiasis in the modified prone split-leg position. PATIENTS AND METHODS: A total of 96 patients with multiple urolithiasis underwent ECIRS in modified prone split-leg position from September 2017 to January 2021. Relevant demographic and clinical data were analysed retrospectively. Clinical outcomes, such as the stone free rate, complications and postoperative hospital stay were evaluated. The chi-square test was used to compare categorical variables and Student's t test was applied for continuous variables of the treatment groups. RESULTS: The mean renal stone size was 32.5 ± 10.7 mm and renal stone surface area was 712.2 ± 264.8 mm2. The mean ureteral stones size was 24.8 ± 12.3 mm. The mean surgical time was 82.2 ± 38.3 min. The incidence of complications was 16.7%, and they were mainly grade 1 and grade 2. No complications occurred above grade 3. The stone was completely removed in 75 (78.1%) patients in a single operation. The risk factors affecting the stone-free rate of ECIRS were analysed, and only the number of involved calyces by stone was found to be significant (p = 0.01). CONCLUSION: ECIRS is safe and effective in the treatment of multiple renal calculi or multiple renal calculi with ipsilateral ureteral calculi in the modified prone split-leg position. The modification of the prone split-leg position makes the retrograde operation more convenient, which is conducive to the combination of RIRS and PCNL.

Analysis of predictors of adherent perinephric fat and its impact on perioperative outcomes in laparoscopic partial nephrectomy: a retrospective case-control study.

BACKGROUND: Adherent perinephric fat (APF), characterized by inflammatory fat surrounding the kidney, can limit the isolation of renal tumors and increase the operative difficulty in laparoscopic partial nephrectomy (LPN). The aim of this study was to investigate the predictors of APF and its impact on perioperative outcomes during LPN. METHODS: A total of 215 consecutive patients undergoing LPN for renal cell carcinoma (RCC) from January 2017 to June 2019 at our institute were included. We divided these patients into two groups according to the presence of APF. Radiographic data were retrospectively collected from preoperative cross-sectional imaging. The perioperative clinical parameters were compared between the two groups. Univariate and multivariate analyses were performed to evaluate the predictive factors of APF. RESULTS: APF was identified in 41 patients (19.1%) at the time of LPN. Univariate analysis demonstrated that APF was significantly correlated with the male gender (P = 0.001), higher body mass index (P = 0.002), lower preoperative estimated glomerular filtration rate (P = 0.004), greater posterior perinephric fat thickness (P < 0.001), greater perinephric stranding (P < 0.001), and higher Mayo Adhesive Probability (MAP) score (P < 0.001). The MAP score (P < 0.001) was the only variable that remained an independent predictor for APF in multivariate analysis. We found that patients with APF had longer operative times (P < 0.001), warm ischemia times (P = 0.001), and greater estimated blood loss (P = 0.003) than those without APF. However, there were no significant differences in surgical approach, transfusion rate, length of postoperative stay, complication rate, or surgical margin between the two groups. CONCLUSIONS: Several specific clinical and radiographic factors including the MAP score can predict APF. The presence of APF is associated with an increased operative time, warm ischemia time, and greater estimated blood loss but has no impact on other perioperative outcomes in LPN.

Melatonin Inhibits Migration and Invasion in LPS-Stimulated and -Unstimulated Prostate Cancer Cells Through Blocking Multiple EMT-Relative Pathways.

PURPOSE: Gram-negative bacteria are usually found in prostate cancer (PCa) tissues. This study aims to investigate the role of lipopolysaccharide (LPS), a glycolipid compound found in the outer membrane of gram-negative bacteria, on the migration and invasion of PCa cells, and to evaluate the protective effect of melatonin. MATERIALS AND METHODS: DU145, PC-3 and LNCaP cells were incubated with LPS in the presence or absence of melatonin. Wound healing and Transwell assays were used to analyze migration and invasion of PCa cells. RT-PCR and Western blotting were used to assess the mRNA and protein levels, respectively. Co-IP was used to analyze ß-catenin ubiquitination. RESULTS: Our results showed that LPS promoted migration and invasion of PCa cells. In addition, LPS stimulated inflammatory reaction and induced epithelial-mesenchymal transition (EMT) in PCa cells by activating several TLR4 downstream pathways. Specifically, LPS promoted NF-κB/IL-6/STAT3 signal transduction. In addition, LPS upregulated phosphorylation levels of cytoplasmic AKTSer473 and GSK-3ßSer9. Moreover, LPS induced phosphorylation of GSK-3ßSer9 in the "disruption complex", and then inhibited phosphorylation and ubiquitination of cytoplasmic ß-catenin, leading to ß-catenin nuclear translocation. Interestingly, melatonin inhibited invasion and migration not only in LPS-stimulated but also in LPS-unstimulated PCa cells. Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3ß and ß-catenin pathways. CONCLUSION: This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.

Diallyl trisulfide inhibited tobacco smoke-mediated bladder EMT and cancer stem cell marker expression via the NF-κB pathway in vivo.

OBJECTIVE: This study examined the effect of the NF-κB pathway on tobacco smoke-elicited bladder epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) marker expression in vivo. The effect of diallyl trisulfide (DATS) treatment was also examined. METHODS: BALB/c mice were exposed to tobacco smoke and treated with an NF-κB inhibitor and DATS. Western blotting, quantitative real-time PCR, and immunohistochemical staining were used to detect the changes of relevant indices. RESULTS: Phosphorylated inhibitor of kappa-B kinase alpha/beta expression and p65 and p50 nuclear transcription were increased by tobacco smoke exposure, whereas inhibitor of kappa-B expression was decreased. In addition, tobacco smoke reduced the expression of epithelial markers but increased that of mesenchymal and CSC markers. Our study further demonstrated that tobacco smoke-mediated EMT and CSC marker expression were attenuated by inhibition of the NF-κB pathway. Moreover, DATS reversed tobacco smoke-induced NF-κB pathway activation, EMT, and the acquisition of CSC properties in bladder tissues. CONCLUSIONS: These data suggested that the NF-κB pathway regulated tobacco smoke-induced bladder EMT, CSC marker expression, and the protective effects of DATS.

Benzidine promotes the stemness of bladder cancer stem cells via activation of the Sonic hedgehog pathway.

Substantial evidence suggests that cancer stem cells (CSCs) are the main cause of the initiation, progression and recurrence of tumors. Benzidine has been identified as a risk factor for bladder cancer. The aim of the present study was to investigate the effects of benzidine on bladder CSCs (BCSCs) and the possible mechanism underlying its action. The bladder cancer cell lines UM-UC-3 and EJ were maintained in serum-free medium and cells forming three-dimensional spheres were characterized as BCSCs. The sphere-forming cells were exposed to different concentrations of benzidine and vismodegib, and western blotting was performed to evaluate the expression of markers associated with CSCs and the Sonic hedgehog (SHH) signaling pathway. Flow cytometry was used to detect the distribution of cells in different phases of the cell cycle, and immunofluorescence staining was used to detect the protein expression of CD44. The results revealed that the levels of BCSC markers, namely CD133, CD44, aldehyde dehydrogenase 1-A1, Nanog and octamer-binding transcription factor-4, in the cell spheres were markedly elevated compared with those in cells cultured in serum-supplemented medium. Furthermore, benzidine increased the expression of BCSC markers and promoted the sphere-forming ability of the cells. In addition, it was observed that benzidine activated the SHH pathway, while inhibition of the Shh pathway using vismodegib diminished the promoting effects of benzidine on BCSCs. The findings of the present study indicate that benzidine promoted the stemness of BCSCs via activation of the SHH pathway, which may support further exploration of the molecular basis of the association between benzidine exposure and bladder oncogenesis.

The changes of brain functional networks in young adult smokers based on independent component analysis.

Intrinsic functional connectivity (FC) networks, including the default mode network (DMN), central executive network (CEN), and salience network (SN), have been implicated in nicotine addiction. However, litter evidence exists about the abnormalities in the three networks in young adult smokers. Forty-eight young adult smokers and 49 age- and gender-matched non-smokers were recruited in the present study. Resting-state functional magnetic resonance imaging (fMRI) data were analyzed by a combination of independent component analysis (ICA) and dual regression to identify potential differences of FC patterns in the DMN, CEN, and SN. Compared to non-smokers, young adult smokers showed enhanced FC of the left posterior cingulate cortex (LPCC), right medial prefrontal cortex (RMPFC) and right precuneus within the DMN network, of the right dorsolateral prefrontal cortex (DLPFC) within the right CEN, and of the left anterior insula (LAI) within the SN. We also found increased FC between the DMN, CEN and key node of the SN (anterior insula, AI). Correlation analysis showed that the increased FC within the networks was significantly correlated with smoking behaviors (pack-years, smoking duration, FTND, first smoking age, and number of cigarettes per day). Our findings may provide additional evidence for conceptualizing the framework of nicotine addiction as a disease of intercommunicating brain networks.

ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

Several epidemiological studies reported that chronic arsenic exposure increased risk of prostate cancer. This study aimed to investigate whether chronic NaAsO2 exposure elevates stemness and chemoresistance in prostate cancer cells. DU145 (wild-type p53) and PC-3 (p53-null) cells were exposed to NaAsO2 (2 µmol/L) for 30 generations. IC50s to docetaxel and cisplatin were increased in NaAsO2-exposed DU145 and PC-3 cells. The number of tumor spheres was elevated in NaAsO2-exposed DU145 and PC-3 cells. Nanog, SOX-2 and ALDH1A1, three markers of cancer stemness, were upregulated in NaAsO2-exposed PC-3 spheres. Moreover, NaAsO2-exposed DU145 and PC-3 cells were arrested in G2/M phase. Histone H2AX phosphorylation on Ser139, an indicator for DNA double-strand break, was upregulated in NaAsO2-exposed DU145 and PC-3 cells. ATM phosphorylation on Ser1981, a key sensor of genotoxic stress, was rapidly elevated in NaAsO2-exposed DU145 cells. Phosphor-p53, a downstream molecule of ATM signaling, and p21, a direct target of p53, were upregulated in NaAsO2-exposed DU145 cells. Unexpectedly, p21 was also elevated in NaAsO2-exposed p53-null PC-3 cells. Antioxidant NAC alleviated NaAsO2-induced ATM phosphorylation, cell cycle arrest, and subsequent stemness enhancement and chemoresistance in both DU145 and PC-3 cells. These results suggest that ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

Pleomorphic rhabdomyosarcoma of the spermatic cord and a secondary hydrocele testis: A case report.

BACKGROUND: Pleomorphic rhabdomyosarcoma (RMS) of the spermatic cord is a group of rare neoplasms, and a secondary hydrocele testis occasionally occurs. The misdiagnosis of paratesticular mass may lead to a therapeutic delay. CASE SUMMARY: A 79-year-old man presented to our clinic complaining of a 1-mo history of painless scrotal swelling. Physical examination revealed approximately a 15 cm × 10 cm × 5 cm inguinal mass with limited mobility. Contrast-enhanced magnetic resonance imaging showed a hydrocele testis, several enlarged inguinal lymph nodes, and a heterogeneously enhanced lesion with a relatively well-defined margin in the left inguinal region. Due to the imaging findings, he was diagnosed with pleomorphic RMS and received a wide resection of the mass, an inguinal incision with a high section of the left spermatic cord, and a left radical orchiectomy. He experienced local relapse 1 mo postoperatively and received radiotherapy and anlotinib hydrochloride-based immunotherapy as adjuvant therapy. The patient died 3 mo after the surgery. CONCLUSION: The optimal interventions for advanced-stage pleomorphic RMS patients should be investigated by more preclinical studies and clinical trials. Physicians need to be aware of the occurrence of pleomorphic RMS in unusual locations, especially when accompanied by a hydrocele testis.

Electrophysiological Evidence of Event-Related Potential Changes Induced by 12 h Abstinence in Young Smokers Based on the Flanker Study.

The cognitive control processes may be disrupted by abstinence in smokers, which may be helpful in the development and maintenance of addictive behavior. The purpose of this study was to measure the performance of cognitive task after 12 h of smoking abstinence by using event-related potentials (ERPs), including the error-related negativity (ERN) and the error positivity (Pe). In Eriksen flanker task, electroencephalography (EEG) signals of 24 smokers were recorded in two conditions: satiety and 12 h abstinence. In the behavioral data, both conditions exhibited more errors and more time on the incongruent trials than congruence. Meantime, the Minnesota Nicotine Withdrawal Scale (MNWS) score was increased during abstinence. Smokers showed reduced ERN and Pe after 12 h of abstinence, compared with satiety condition. The results indicate that the diminished error processing in young smokers after 12 h of abstinence. It may be related to increased withdrawal symptoms. In conclusion, the disrupted neurophysiological indexes in the general behavior monitoring system may be caused by abstinence. The results of this study may provide us with new ideas about the effects of short-term abstinence on brain cognitive neuroscience and be helpful for the solution of relapse.

Calcitriol inhibits lipopolysaccharide-induced proliferation, migration and invasion of prostate cancer cells through suppressing STAT3 signal activation.

Increasing evidence suggests that infection promotes the initiation and progression of prostate cancer. This study investigated the effects of lipopolysaccharide (LPS), a major component of Gram-negative bacilli, on proliferation, migration and invasion of prostate cancer cells and the protective effects of 1α,25(OH)2D3 (calcitriol). PC-3 and DU145 cells were stimulated with LPS (2.0 µg/mL) in the presence or absence of 1α,25(OH)2D3 (100 nM). Our results shown that 1α,25(OH)2D3 reduced the proportion of S phase cells in LPS-stimulated PC-3 and DU145 cells, and down-regulated the nuclear protein levels of Cyclin D1 and PCNA in LPS-stimulated PC-3 cells. In addition, 1α,25(OH)2D3 inhibited migration and invasion, as determined by wound healing and transwell assay, in LPS-stimulated PC-3 and DU145 cells. Of interest, we observed that 1α,25(OH)2D3 inhibits NF-κB activation and subsequent synthesis and secretion of IL-6 and IL-8 by promoting VDR and NF-κB p65 interaction. Surprisingly, 1α,25(OH)2D3 blocks nuclear translocation of pSTAT3 by promoting physical interaction between VDR and pSTAT3 (Tyr705) in LPS-stimulated PC-3 and DU145 cells. These results suggest that 1α,25(OH)2D3 inhibits LPS-induced proliferation, migration and invasion in prostate cancer cells by directly and indirectly blocking STAT3 signal transduction.