Clinical evaluation of an artificial intelligence-assisted cytological system among screening strategies for a cervical cancer high-risk population.

BACKGROUND: Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China. METHODS: A total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies. RESULTS: The Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587-0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484-0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606-0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491-0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively). CONCLUSIONS: These results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting.

Nicotinamide deficiency promotes imidacloprid resistance via activation of ROS/CncC signaling pathway-mediated UGT detoxification in Nilaparvata lugens.

Metabolic alternation is a typical characteristic of insecticide resistance in insects. However, mechanisms underlying metabolic alternation and how altered metabolism in turn affects insecticide resistance are largely unknown. Here, we report that nicotinamide levels are decreased in the imidacloprid-resistant strain of Nilaparvata lugens, may due to reduced abundance of the symbiotic bacteria Arsenophonus. Importantly, the low levels of nicotinamide promote imidacloprid resistance via metabolic detoxification alternation, including elevations in UDP-glycosyltransferase enzymatic activity and enhancements in UGT386B2-mediated metabolism capability. Mechanistically, nicotinamide suppresses transcriptional regulatory activities of cap 'n' collar isoform C (CncC) and its partner small muscle aponeurosis fibromatosis isoform K (MafK) by scavenging the reactive oxygen species (ROS) and blocking the DNA binding domain of MafK. In imidacloprid-resistant N. lugens, nicotinamide deficiency re-activates the ROS/CncC signaling pathway to provoke UGT386B2 overexpression, thereby promoting imidacloprid detoxification. Thus, nicotinamide metabolism represents a promising target to counteract imidacloprid resistance in N. lugens.

The clinical and imaging features of eosinophilic cystitis in children: a case series study.

BACKGROUND: Eosinophilic cystitis (EC) is rare in children and remains poorly understood. Our aim was to analyse the clinical and imaging features of eosinophilic cystitis in children. METHODS: A retrospective review of histologically confirmed eosinophilic cystitis between January 2008 and December 2022 was performed, including patient age, sex, symptoms, laboratory examination, radiology, treatment and outcome. RESULTS: Twelve children (two girls, 10 boys; age range: 3-12 years, mean age: 7.2 years) were included in the study. Urinary irritation symptoms (10/12), haematuria (5/12) and hypogastralgia (3/12) were the most common symptoms. Five patients had a history of allergies, six patients had elevated serum IgE, nine patients had elevated peripheral eosinophils and six patients had positive microscopic haematuria. Radiology revealed diffuse homogeneous or inhomogeneous thickening in seven patients, localised thickening in three patients, and solitary tumour-like lesions in the other two patients. Preservation of the mucosal line and bladder wall layering were observed in eleven patients, and perivesical exudation and small vessel dilatation were observed in ten patients. All four patients with delayed scans showed obvious delayed enhancement. One patient showed low signal intensity on T2-W imaging. All patients received antihistamine, antibiotic and/or corticosteroid therapy and two tumour-like patients underwent transurethral resection. Nine patients achieved complete response and three patients achieved partial response. CONCLUSION: The clinical and imaging manifestations of EC in children have relative characteristics; when urologist and radiologist confronted with similar cases, EC should be considered. The final diagnosis depends on pathological biopsy.

Role of the epsilon glutathione S-transferases in xanthotoxin tolerance in Spodoptera litura.

Spodoptera litura, a polyphagous lepidopteran pest, demonstrates a remarkable capacity to adapt to varying host plants by efficiently detoxifying phytochemicals. However, the underlying mechanism for this adaptation is not well understood. Herein, twenty eplison glutathione S-transferase genes (GSTes) were characterized and their roles in phytochemical tolerance were analyzed in S. litura. Most of the GSTe genes were mainly expressed in the larval midgut and fat body. Exposure to the phytochemicals, especially xanthotoxin, induced the expression of most GSTe genes. Molecular docking analysis revealed that xanthotoxin could form stable bonds with six xanthotoxin-responsive GSTes, with binding free energies ranging from -36.44 to -68.83 kcal mol-1. Knockdown of these six GSTe genes increased the larval susceptibility to xanthotoxin. Furthermore, xanthotoxin exposure significantly upregulated the expression of two transcription factor genes CncC and MafK. Silencing of either CncC or MafK reduced the expression of GSTe16, which exhibited the largest change in response to xanthotoxin. Additionally, analysis of the promoter sequence of GSTe16 revealed the presence of seven CncC/Maf binding sites. Luciferase reporter assays showed that CncC and MafK enhanced the expression of GSTe16, leading to the increased xanthotoxin tolerance in S. litura. These findings provide insight into the functions and transcriptional regulatory mechanisms of GSTes, thereby enhancing our understanding of the role of GSTs in the adaptation of lepidopteran pests to phytochemicals.

CYP321A Subfamily P450s Contribute to the Detoxification of Phytochemicals and Pyrethroids in Spodoptera litura.

Although the induction of cytochrome P450 monooxygenases involved in insect detoxification has been well documented, the underlying regulatory mechanisms remain obscure. In Spodoptera litura, CYP321A subfamily members were effectively induced by exposure to flavone, xanthotoxin, curcumin, and λ-cyhalothrin, while knockdown of the CYP321A genes increased larval susceptibility to these xenobiotics. Homology modeling and molecular docking analyses showed that these four xenobiotics could stably bind to the CYP321A enzymes. Furthermore, two transcription factor genes, CncC and MafK, were significantly induced by the xenobiotics. Knockdown of CncC or MafK reduced the expression of four CYP321A genes and increased larval susceptibility to the xenobiotics. Dual-luciferase reporter assays showed that cotransfection of reporter plasmids carrying the CYP321A promoter with CncC and/or MafK-expressing constructs significantly magnified the promoter activity. These results indicate that the induction of CYP321A subfamily members conferring larval detoxification capability to xenobiotics is mediated by the activation of CncC and MafK.

Alternative Splicing and Expression Reduction of P450 Genes Mediating the Oxidation of Chlorpyrifos Revealed a Novel Resistance Mechanism in Nilaparvata lugens.

Cytochrome P450 enzymes metabolize various xenobiotics in insects. Compared to numerous P450s associated with insecticide detoxification and resistance, fewer have been identified to bioactivate proinsecticides in insects. Here we reported that two P450s, CYP4C62 and CYP6BD12, in Nilaparvata lugens could bioactivate chlorpyrifos, an organophosphorus insecticide, into its active ingredient chlorpyrifos-oxon in vivo and in vitro. RNAi knockdown of these two genes significantly reduced the sensitivity to chlorpyrifos and the formation of chlorpyrifos-oxon in N. lugens. Chlorpyrifos-oxon was generated when chlorpyrifos was incubated with the crude P450 enzyme prepared from N. lugens or recombinant CYP4C62 and CYP6BD12 enzymes. The expression reduction of CYP4C62 and CYP6BD12 and alternative splicing in CYP4C62 reduced the oxidation of chlorpyrifos into chlorpyrifos-oxon, which contributed importantly to chlorpyrifos resistance in N. lugens. This study revealed a novel mechanism of insecticide resistance due to the bioactivation reduction, which would be common for all currently used proinsecticides.

Imaging features of juvenile xanthogranuloma.

BACKGROUND: Juvenile xanthogranuloma is rare in children and there are limited data on its imaging features. OBJECTIVE: To analyze the computed tomography (CT) and magnetic resonance imaging (MRI) features of juvenile xanthogranuloma in children. MATERIALS AND METHODS: A retrospective review was performed of clinical and radiographic data of histologically confirmed juvenile xanthogranuloma between January 2009 and June 2020. RESULTS: Fourteen children (4 girls, 10 boys; age range: 1 day to 13 years, mean age: 73 months) were included in the study: 4/14 had CT only, 5/14 had MRI only and 5/14 had CT and MRI. Sites of extracutaneous juvenile xanthogranuloma involvement included subcutaneous soft tissue (8/14), liver (2/14), lungs (2/14), kidney (2/14), nose (2/14), pancreas (1/14), central nervous system (1/14) and greater omentum (1/14), mainly manifested as single or multiple nodules or masses in different organs. On CT, the lesions mainly manifested as an iso-hypo density mass with mild or marked enhancement. On MRI, the lesions mainly manifested as slightly hyperintense on T1 and slightly hypointense on T2, with decreased diffusivity and homogeneous enhancement. Juvenile xanthogranuloma was not included in the imaging differential diagnosis in any case. CONCLUSION: Juvenile xanthogranuloma mainly manifests as single or multiple nodules or masses in different organs. Slight hyperintensity on T1 and slight hypointensity on T2 with decreased diffusivity and homogeneous enhancement are relatively characteristic imaging findings of juvenile xanthogranuloma. Combined with its typical skin lesions and imaging features, radiologists should include juvenile xanthogranuloma in the differential diagnosis when confronted with similar cases.

Long-term exposure to PM2.5 constituents in relation to glucose levels and diabetes in middle-aged and older Chinese.

BACKGROUND: Previous studies have indicated the associations between fine particulate matter (PM2.5) exposure and diabetes or glucose levels. However, evidence linking PM2.5 constituents and diabetes or glucose levels was extensively scarce, particularly in developing countries. This study aimed to investigate the associations of exposure to PM2.5 and its five constituents (black carbon [BC], organic matter [OM], nitrate [NO3-], sulfate [SO42-], and ammonium [NH4+]) with diabetes and glucose levels among the middle-aged and elderly Chinese populations. METHODS: A national cross-sectional sample of participants aged 45+ years was enrolled from 28 provinces across China's mainland. Health examination and questionnaire survey for each respondent were performed during 2011-2012. Diabetes was determined by alternative definitions, and the main definition (MD) was self-report diabetes or antidiabetic medicine use or HbA1c ≥6.5 or fasting glucose ≥7 mmol/L or random glucose ≥11.1 mmol/L. Monthly exposure to PM2.5 mass and its five constituents (BC, OM, NO3-, SO42-, and NH4+) for each participant at residence were estimated using satellite-based spatiotemporal prediction models. Generalized linear models and linear mixed-effects models were used to assess the effects of exposure to PM2.5 and its constituents on diabetes or glucose levels, respectively. Stratification analyses were done by sex and age. RESULTS: We included a total of 17,326 adults over 45 years in this study. The 3-year mean (interquartile range [IQR]) concentrations of PM2.5, BC, OM, NO3-, SO42-, and NH4+ were 47.9 (27.4) µg/m3, 2.9 (2.2) µg/m3, 9.2 (6.6) µg/m3, 10.2 (9.4) µg/m3, 11.0 (5.2) µg/m3, and 7.1 (4.4) µg/m3, respectively. Per IQR rise in exposure to PM2.5 was significantly associated with an increase of 0.133 mmol/L (95% confidence interval, 0.048-0.219) in glucose concentrations. Similar positive associations were observed for BC (0.097 mmol/L [0.012-0.181]), OM (0.160 mmol/L [0.065-0.256]), NO3- (0.145 mmol/L [0.039-0.251]), SO42- (0.111 mmol/L [0.026-0.196]), and NH4+ (0.135 mmol/L [0.041-0.230]). Under different diabetes definitions, PM2.5 mass and selected constituents with the exception of SO42- were all associated with a higher risk of prevalent diabetes. In MD-based analysis, similar positive associations were observed for four constituents, with corresponding odds ratios of 1.180 (1.097-1.270) for PM2.5, 1.154 (1.079-1.235) for BC, 1.170 (1.079-1.270) for OM, 1.200 (1.098-1.312) for NO3-, and 1.123 (1.037-1.215) for NH4+. Stratified analyses showed a significantly higher risk of diabetes in males (1.225 [1.064-1.411]) than females (1.024 [0.923-1.136]) when exposed to PM2.5. Participants under 65 years were generally more vulnerable to diabetes hazards related to PM2.5 constituents exposure. CONCLUSIONS: Exposures to PM2.5 and its constituents (i.e., BC, OM, NO3-, and NH4+) were positively associated with increased risks of prevalent diabetes and elevated glucose levels in middle-aged and older adults.

Highly sensitive electrochemical determination of rutin based on the synergistic effect of 3D porous carbon and cobalt tungstate nanosheets.

Rutin, a flavonoid found in fruits and vegetables, is a potential anticancer compound with strong anticancer activity. Therefore, electrochemical sensor was developed for the detection of rutin. In this study, CoWO4 nanosheets were synthesized via a hydrothermal method, and porous carbon (PC) was prepared via high-temperature pyrolysis. Successful preparation of the materials was confirmed, and characterization was performed by transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin. The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability. PC has a high surface-to-volume ratio and superior conductivity. Moreover, the hydrophobicity of PC allows large amounts of rutin to be adsorbed, thereby increasing the concentration of rutin at the electrode surface. Owing to the synergistic effect of the 3D CoWO4 nanosheets and PC, the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity. The sensor showed a good linear range (5-5000 ng/mL) with a detection limit of 0.45 ng/mL. The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Hsa_circ_0000285 knockdown inhibits the progression of hepatocellular carcinoma by sponging miR-582-3p to regulate CCNB2 expression.

AIM: Hsa_circ_0000285, a novel circular RNA, has been proven to extensively take part in the pathogenesis of numerous tumors. In hepatocellular carcinoma (HCC), very little is known about hsa_circ_0000285 until now. Hence, this research aims to determine hsa_circ_0000285's functional role and underlying mechanisms in HCC. METHODS: The expressions of miR-582-3p, hsa_circ_000028, and cyclin B2 (CCNB2) among the HCC cells and tumor samples were determined by performing western blotting and qRT-PCR analyses. The impacts of hsa_circ_000028 on the proliferative and migratory abilities of HCC cells were examined through the execution of CCK-8 and wound-healing assays. Meanwhile, the expressions of the proteins Bcl-2 and Bax were detected via western blotting. Tumor xenograft models were established to examine how hsa_circ_000028 functions during the mediation of HCC tumor growth in vivo. RNA immunoprecipitation and luciferase reporter experiments were performed for the validation of the interactions of miR-582-3p, hsa_circ_000028, and CCNB2 with each other. RESULTS: Elevated hsa_circ_0000285 and CCNB2 expressions, and a decreased miR-582-3p expression were observed among the HCC cell lines and tumors. Hsa_circ_0000285 bound to miR-582-3p competitively to improve CCNB2 levels. Silencing of hsa_circ_0000285 promoted apoptosis and repressed proliferation and migration among HCC cells. Moreover, silencing hsa_circ_0000285 also impeded the growth of HCC tumors in vivo. Inhibiting hsa_circ_0000285 or CCNB2 reversed the miR-582-3p-knockdown-mediated promotion of malignant HCC cell phenotypes. CONCLUSION: Our study has demonstrated that hsa_circ_0000285 fosters the development of malignant HCC cells phenotypes through the modulation of the miR-582-3p/CCNB2 axis. Thus, these results suggest that hsa_circ_0000285 is a prospective target for HCC treatment.

The effect of application of a Soton ureteroscope on infection after flexible ureteroscopy lithotripsy.

INTRODUCTION: Postoperative infection is still one of the most common complications following flexible ureteroscopy lithotripsy (FURL). However, whether a combination of negative pressure ureteroscopy (and Soton ureteroscopy) is superior to FURL in lithotripsy with regard to intraoperative pressure and possibly the incidence of postoperative infection remains to be validated. AIM: To explore the effect of a Soton ureteroscope on infection following flexible ureteroscope lithotripsy. MATERIAL AND METHODS: Sixty patients with kidney stones were randomly divided equally into study and control groups. The operation duration, stone-free rate, postoperative blood routine, procalcitonin, C-reactive protein, and other data between the two groups were then analysed and compared. RESULTS: There were no statistically significant differences between the study group and the control group regarding the average operation time and the average number of hospitalization days. The mean stone-free rate 1 week after surgery and mean VAS pain score 1 day after surgery for the study group and the control group were 91.3% and 0.27 vs. 76.9% and 0.61, respectively. Notably, the average body temperature after the first day of the operation was 36.4°C in the study group and 36.7°C in the control group. More importantly, concerning postoperative infection index, white blood cells (WBCs), percentage of neutrophils, C-reactive protein, and procalcitonin were all lower in the study group than in the control group. CONCLUSIONS: Compared with flexible ureteroscopy alone, combined use of Soton ureteroscopy is associated with fewer substantially infection following lithotripsy.

Patient selection for ambulatory laparoscopic cholecystectomy: A systematic review.

Background: Currently, there is no consensus on patient selection for ambulatory laparoscopic cholecystectomy (LC). This study is a systematic review of previously published patient selection for ambulatory LC. Methods: A comprehensive search was done in PubMed, Web of Science, Embase and Google Scholar Database up to March 2020 to summarise previously reported medical or surgical selection criteria used for inclusion and exclusion of patients, as well as successful same-day discharge rates and readmission rate after discharge. Results: Fifty-nine studies with a total of 13,219 patients were included in this systematic review. In total, the median same-day discharge rate was 90% (range: 63%-99.4%), and median readmission rate was 2.22% (range: 0%-16.9%). The most considered medical criteria were American Society of Anesthesiologists classification I and II, age <70, and body mass index <35. Surgical criteria varied greatly. The top three accessible exclusion variables were (1) common bile duct stones, cholangitis, or jaundice (27 publications, 45.8%); (2) history of abdominal surgery (12 publications, 20.3%) and (3) history of pancreatitis (9 publications, 15.3%). Conclusion: The results of the current study showed the variable patient selection in different centres, the medical aspect criteria may be expanded under adequate pre-anaesthetic assessment and preparation and the surgical aspect criteria should include more laboratory or imaging parameters to ensure the surgical safety.

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy: Involvement of Single Versus Multiple Sextant Sites.

CONTEXT.­: Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. OBJECTIVE.­: To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. DESIGN.­: We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. RESULTS.­: PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1-3), pT (GG1-2/GG1-3/GG2/GG3), surgical margin status (GG1-3/GG3/GG5), or tumor volume (GG1-2/GG1-3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1-2 versus 3-6/1-3 versus 4-6/1-4 versus 5-6), RP GG (1-3 versus 4-6/1-4 versus 5-6), pT (1-2 versus 3-6/1-3 versus 4-6), pN (1-3 versus 4-6), or tumor volume (1-2 versus 3-6/1-4 versus 5-6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1-2/GG1-3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). CONCLUSIONS.­: Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1-3 cancer.

Limited Adenocarcinoma of the Prostate on Needle Core Biopsy.

CONTEXT.­: Grading small foci of prostate cancer on a needle biopsy is often difficult, yet the clinical significance of accurate grading remains uncertain. OBJECTIVE.­: To assess if grading of limited adenocarcinoma on prostate biopsy specimen is critical. DESIGN.­: We studied 295 consecutive patients undergoing extended-sextant biopsy with only 1-core involvement of adenocarcinoma, followed by radical prostatectomy. RESULTS.­: The linear tumor lengths on these biopsy specimens were: less than 1 mm (n = 114); 1 mm or more or less than 2 mm (n = 82); 2 mm or more or less than 3 mm (n = 35); and 3 mm or more (n = 64). Longer length was strongly associated with higher Grade Group (GG) on biopsy or prostatectomy specimen, higher risk of extraprostatic extension/seminal vesicle invasion and positive surgical margin, and larger estimated tumor volume. When cases were compared based on biopsy specimen GG, higher grade was strongly associated with higher prostatectomy specimen GG, higher incidence of pT3/pT3b disease, and larger tumor volume. Outcome analysis further showed significantly higher risks for biochemical recurrence after radical prostatectomy in patients with 1 mm or more, 2 mm or more, 3 mm or more, GG2-4, GG3-4, GG4, less than 1 mm/GG2-4, less than 1 mm/GG3-4, less than 2 mm/GG3-4, 3 mm or more/GG2-4, or 3 mm or more/GG3-4 tumor on biopsy specimens, compared with respective control subgroups. In particular, 3 mm or more, GG3, and GG4 on biopsy specimens showed significance as independent prognosticators by multivariate analysis. Meanwhile, there were no significant differences in the rate of upgrading or downgrading after radical prostatectomy among those subgrouped by biopsy specimen tumor length (eg, <1 mm [44.7%] versus ≥1/<2 mm [41.5%] versus ≥2/<3 mm [45.7%] versus ≥3 mm [46.9%]). CONCLUSIONS.­: These results indicate that pathologists still need to make maximum efforts to grade relatively small prostate cancer on biopsy specimens.

The Clinical Impact of pT3a Lesions in Patients With pT3b Prostate Cancer Undergoing Radical Prostatectomy.

CONTEXT.­: Seminal vesicle invasion (SVI) by prostate cancer (pT3b disease) has been considered as a key prognostic factor. OBJECTIVE.­: To assess the clinical impact of T3a lesions (ie, extraprostatic extension other than bladder neck invasion [BNI] or SVI [EPE], microscopic bladder neck invasion [mBNI]) in pT3b disease. DESIGN.­: We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients with pT3b disease, with versus without EPE/mBNI. RESULTS.­: Extraprostatic extension/mBNI was found in 219 (88.3%)/48 (19.4%) cases, respectively. Extraprostatic extension was significantly associated with higher preoperative prostate-specific antigen (PSA) level, higher rates of positive surgical margin (pSM) and lymphovascular invasion (LVI), and larger tumor volume. Similarly, mBNI was significantly associated with higher PSA level, higher rates of Grade Group(s) 4-5 or 5, pSM, LVI, and pN1, and larger tumor volume. Significant differences in all of these clinicopathologic features (except lymph node metastasis) between EPE-/mBNI+ or EPE+/mBNI- and EPE+/mBNI+ cases were also observed. Outcome analysis revealed that patients with EPE (P < .001) or mBNI (P < .001) had a significantly higher risk of disease progression than respective controls. Notably, there were significant differences in progression-free survival between EPE-/mBNI+ or EPE+/mBNI- cases and EPE-/mBNI- (P = .001) or EPE+/mBNI+ (P < .001) cases. In multivariate analysis, EPE (hazard ratio [HR] = 6.53, P = .009) and mBNI (HR = 2.33, P = .003), as well as EPE-/mBNI+ or EPE+/mBNI- (HR = 11.7, P = .01) and EPE+/mBNI+ (HR = 25.9, P = .002) versus EPE-/mBNI-, showed significance for progression. CONCLUSIONS.­: From these significant findings, we propose a novel pT3b subclassification: pT3b1 (SVI alone without EPE or mBNI), pT3b2 (SVI with either EPE or mBNI), and pT3b3 (SVI with both EPE and mBNI).

Circ-LTBP1 is involved in doxorubicin-induced intracellular toxicity in cardiomyocytes via miR-107/ADCY1 signal.

Although doxorubicin (DOX) is a broad-spectrum and anthracycline chemotherapeutic agent, cardiotoxicity limits its clinical application. Therefore, it is meant to prevent the clinical side effects of DOX. Human cardiomyocyte-like AC16 cells were treated with DOX to induce intracellular toxicity. AC16 cell viability was determined by Cell Counting Kit 8 and 5-ethynyl-2'-deoxyuridine assays. The tumor necrosis factor-α and interleukin-6 abundances were quantified by matched kits. The apoptosis rate was measured by flow cytometry. Western blot analysis was conducted to measure the protein expression levels in AC16 cells. Oxidative stress was analyzed by measuring superoxide dismutase and malondialdehyde production. The quantitative real-time polymerase chain reaction was conducted to assess the expression levels of circ-latent transforming growth factor-beta binding protein-1 (circ-LTBP1), microRNA-107 (miR-107), and Adenylate cyclase 1 (ADCY1) expression in AC16 cells. The interaction relationship among circ-LTBP1, miR-107, and ADCY1 was verified by dual-luciferase reporter and RNA immunoprecipitation assays. As a result, treatment with DOX induced the proliferation inhibition, inflammation, apoptosis, and oxidative stress in AC16 cells, which were rescued by circ-LTBP1 inhibition or miR-107 upregulation. MiR-107 was confirmed as a target of circ-LTBP1, and inhibition of circ-LTBP1-mediated effects on DOX-stimulated cells were abolished by downregulation of miR-107. Circ-LTBP1 mediated ADCY1 expression by sponging miR-107 in AC16 cells. The upregulation of miR-107 increased cell proliferation and inhibited inflammation, apoptosis, and oxidative stress in DOX-stimulated cells through downregulation of ADCY1. Circ-LTBP1 was found to enhance DOX-induced effects on proliferation inhibition, inflammation, apoptosis, and oxidative stress in AC16 cells through competitively sponging miR-107 and elevating ADCY1.

The Clinical Impact of Unilateral Versus Bilateral Invasion Into the Seminal Vesicle in Patients With Prostate Cancer Undergoing Radical Prostatectomy.

CONTEXT.­: Seminal vesicle involvement by prostate cancer has generally been considered as a key prognosticator. OBJECTIVE.­: To assess the clinical significance of unilateral (Uni) versus bilateral (Bil) seminal vesicle invasion (SVI). DESIGN.­: We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients showing Uni-SVI (n = 139) versus Bil-SVI (n = 109). RESULTS.­: Tumor grade was significantly higher in Bil-SVI cases than in Uni-SVI cases. Additionally, Bil-SVI was significantly associated with a higher incidence of lymphovascular invasion, lymph node metastasis, or positive surgical margin, and larger estimated tumor volume. When the histopathologic features at SVI foci were compared, Grade Group (GG) 3-5/4-5/5 and cribriform morphology were significantly more often seen in Bil-SVI. Outcome analysis revealed that patients with Bil-SVI had a significantly higher risk of disease progression (P < .001) than patients with Uni-SVI. Significantly worse progression-free survival in patients with Bil-SVI was also observed in all subgroups examined, including those with no immediate adjuvant therapy (IAT) (n = 139; P = .01), IAT (n = 109; P = .001), pN0 disease (n = 153; P = .002), or pN1 disease (n = 93; P = .006). In multivariate analysis, Bil-SVI (versus Uni-SVI) showed significance for progression in the entire (hazard ratio [HR] = 1.83, P = .01), IAT (HR = 2.90, P = .006), and pN0 (HR = 2.05, P = .01) cohorts. Meanwhile, tumor grade at SVI (eg, GG4, GG5), as an independent predictor, was significantly associated with patient outcomes. CONCLUSIONS.­: Bil-SVI was found to be strongly associated with worse histopathologic features on radical prostatectomy and poorer prognosis. Pathologists may thus need to report Uni-SVI versus Bil-SVI, along with other histopathologic findings, such as Gleason score, at SVI in prostatectomy specimens.

Angiotensin II induces the expression of periostin to promote foam cell formation in oxLDL-treated macrophages.

A matricellular protein periostin has been documented to promote macrophage recruitment in atherosclerotic lesions. However, the role of periostin in macrophage foam cell formation is still unknown. In this study, we examined the expression and function of periostin in cholesterol homeostasis in macrophages. The role of periostin in mediating Ang II-induced foam cell formation was also investigated. The mechanism by which Ang II induced the expression of periostin was explored. It was found that oxLDL treatment significantly increased the expression and secretion of periostin in THP-1 macrophages. Knockdown of periostin blocked oxLDL-induced lipid accumulation and enhanced cholesterol efflux. In contrast, treatment with recombinant periostin protein enhanced oxLDL-induced macrophage foam cell formation. Ang II caused a time-dependent induction of periostin in THP-1 macrophages, which was ascribed to Twist2-mediated transactivation of periostin. Ang II treatment significantly augmented lipid accumulation in THP-1 macrophages, and knockdown of periostin blocked the effect of Ang II on foam cell formation. Moreover, periostin depletion restored cholesterol efflux in Ang II-treated THP-1 macrophages. Clinically, there was a significant positive correlation between serum periostin and Ang II levels in patients with atherosclerosis. Collectively, we show that periostin is essential for Ang II-induced enhancement of macrophage foam cell formation via suppression of cholesterol efflux.

[Epidemiological and clinicopathological characteristics of prostate cancer in Hunan].

OBJECTIVE: To investigate the epidemiological and clinicopathological characteristics of PCa and provide some strategies for the clinical prevention and treatment of the malignancy. METHODS: This study included 1 594 cases of pathologically diagnosed PCa after radical prostatectomy in Xiangya Hospital of Central South University from January 1, 2010 to December 31, 2020. We collected the basic information about the patients, their main complaints and clinicopathological results, and analyzed the epidemiological and clinicopathological data. RESULTS: The patients were aged from 28 to 93 years, and the number of PCa cases showed an overall upward trend from 2010 to 2020. Urinary system symptoms were most common (62.53%) as initial symptoms, followed by increased PSA (17.82%), PCa, prostate nodule, prostate mass (8.43%) and bone metastasis (2.94%) found at physical examinations, and the cases of PSA elevation among the clinic visitors increased year by year from 2010 to 2020. Gleason score 7 was found in a largest proportion of the PCa patients, and adenocarcinoma was the main pathological type (78.6%). Logistic regression analysis showed that high Gleason score, instead of age and expressions of Ki67, AR and ERG, was an independent risk factor for intraductal carcinoma. CONCLUSION: The incidence of PCa shows an increasing trend, and is more common in those over 50 years old. PSA screening is gradually popularized in China. Intraductal carcinoma, as a major risk factor for aggressive PCa and poor prognosis of the malignancy, is significantly correlated with high Gleason scores.

[Quercetin for the treatment of prostate cancer: Progress in studies].

Prostate cancer (PCa) is a common urinary malignancy, and advanced PCa has a poor prognosis and a high mortality. Drug therapies currently available for this malignancy often cause serious adverse reactions, and therefore new drugs with fewer adverse effects or the potential to reduce the adverse effects of traditional chemotherapeutic drugs are badly needed for the management of PCa. Quercetin, as a natural flavonoid, has been extensively studied in recent years for its anti-cancer effects, as in cell signal transduction, apoptosis promotion, anti-proliferation and -oxidation, and growth inhibition. In fact, quercetin has a variety of biological effects and can inhibit various enzymes involved in cell proliferation and signal transduction pathways. Besides, quercetin is also reported to have potential synergistic effects when used in combination with radiotherapy or chemotherapeutic drugs. This review summarizes the advances in the treatment of PCa with quercetin, focusing on its effects of promoting the apoptosis, inhibiting the proliferation and reducing the invasiveness and migration of tumor cells, and reversing drug resistance, aiming to provide a new theoretical basis and some new ideas for the studies of the treatment of PCa.