FV-MViT: Mobile Vision Transformer for Finger Vein Recognition.

In addressing challenges related to high parameter counts and limited training samples for finger vein recognition, we present the FV-MViT model. It serves as a lightweight deep learning solution, emphasizing high accuracy, portable design, and low latency. The FV-MViT introduces two key components. The Mul-MV2 Block utilizes a dual-path inverted residual connection structure for multi-scale convolutions, extracting additional local features. Simultaneously, the Enhanced MobileViT Block eliminates the large-scale convolution block at the beginning of the original MobileViT Block. It converts the Transformer's self-attention into separable self-attention with linear complexity, optimizing the back end of the original MobileViT Block with depth-wise separable convolutions. This aims to extract global features and effectively reduce parameter counts and feature extraction times. Additionally, we introduce a soft target center cross-entropy loss function to enhance generalization and increase accuracy. Experimental results indicate that the FV-MViT achieves a recognition accuracy of 99.53% and 100.00% on the Shandong University (SDU) and Universiti Teknologi Malaysia (USM) datasets, with equal error rates of 0.47% and 0.02%, respectively. The model has a parameter count of 5.26 million and exhibits a latency of 10.00 milliseconds from the sample input to the recognition output. Comparison with state-of-the-art (SOTA) methods reveals competitive performance for FV-MViT.

The novel transcriptomic signature of angiogenesis predicts clinical outcome, tumor microenvironment and treatment response for prostate adenocarcinoma.

Angiogenesis plays the critical roles in promoting tumor progression, aggressiveness, and metastasis. Although few studies have revealed some angiogenesis-related genes (ARGs) could serve as prognosis-related biomarkers for the prostate cancer (PCa), the integrated role of ARGs has not been systematically studied. The RNA-sequencing data and clinical information of prostate adenocarcinoma (PRAD) were downloaded from The Cancer Genome Atlas (TCGA) as discovery dataset. Twenty-three ARGs in total were identified to be correlated with prognosis of PRAD by the univariate Cox regression analysis, and a 19-ARG signature was further developed with significant correlation with the disease-free survival (DFS) of PRAD by the least absolute shrinkage and selection operator (LASSO) Cox regression with tenfold cross-validation. The signature stratified PRAD patients into high- and low-ARGs signature score groups, and those with high ARGs signature score were associated with significantly poorer outcomes (median DFS: 62.71 months vs unreached, p < 0.0001). The predicting ability of ARGs signature was subsequently validated in two independent cohorts of GSE40272 & PRAD_MSKCC. Notably, the 19-ARG signature outperformed the typical clinical features or each involved ARG in predicting the DFS of PRAD. Furthermore, a prognostic nomogram was constructed with three independent prognostic factors, including the ARGs signature, T stage and Gleason score. The predicted results from the nomogram (C-index = 0.799, 95%CI = 0.744-0.854) matched well with the observed outcomes, which was verified by the calibration curves. The values of area under receiver operating characteristic curve (AUC) for DFS at 1-, 3-, 5-year for the nomogram were 0.82, 0.83, and 0.83, respectively, indicating the performance of nomogram model is of reasonably high accuracy and robustness. Moreover, functional enrichment analysis demonstrated the potential targets of E2F targets, G2M checkpoint pathways, and cell cycle pathways to suppress the PRAD progression. Of note, the high-risk PRAD patients were more sensitive to immune therapies, but Treg might hinder benefits from immunotherapies. Additionally, this established tool also could predict response to neoadjuvant androgen deprivation therapy (ADT) and some chemotherapy drugs, such as cisplatin, paclitaxel, and docetaxel, etc. The novel ARGs signature, with prognostic significance, can further promote the application of targeted therapies in different stratifications of PCa patients.

Inherited Mutations in Chinese Men With Prostate Cancer.

BACKGROUND: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. PATIENTS AND METHODS: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. RESULTS: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1-11.1), BRCA2 (OR, 15.3; 95% CI, 10.0-23.2), MSH2 (OR, 15.8; 95% CI, 4.2-59.6), and PALB2 (OR, 5.9; 95% CI, 2.7-13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34-3.58] and 2.47 [95% CI, 1.23-4.96], respectively) but similar benefit from docetaxel. CONCLUSIONS: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.

[Changes in the penis size of prostate cancer patients after radical prostatectomy and its influencing factors].

OBJECTIVE: To investigate the changes in the size of the penis after radical prostatectomy (RP) and the possible influencing factors. METHODS: This study included 45 cases of RP for PCa performed by the same surgeon from January to June 2019. Before and at 2 weeks after surgery, we measured the stretched penile length (SPL), flaccid penile length (FPL) and penile circumference of the patients. We conducted an IIEF-5 questionnaire investigation on the preoperative characteristics of the patients and their attitudes towards postoperative penile rehabilitation. We also analyzed the factors associated with the postoperative changes in the size of the penis. RESULTS: Compared with the baseline, the postoperative SPL (ï¼»9.72 ± 1.87ï¼½ vs ï¼»7.80 ± 1.57ï¼½ cm, P = 0), FPL (ï¼»6.26 ± 1.14ï¼½ vs ï¼»5.13 ± 1.10ï¼½ cm, P = 0) and penile circumference (ï¼»7.69 ± 0.83ï¼½ vs ï¼»7.26 ± 0.78ï¼½ cm, P = 0.012) were decreased significantly, by (1.92 ± 0.12) cm, (1.13 ± 0.09) cm and (0.43 ± 0.08) cm, respectively. The age of the patients was significantly correlated with the change of the FPL (P = 0.042), but not the other factors with the change of the penile size. Twenty-six (57.7%) cases of severe and moderate ED were observed in the patients postoperatively. Those with better preoperative sexual function took a more positive attitude towards penile rehabilitation and treatment postoperatively (n = 3, 75.0%). CONCLUSIONS: The penile size of the PCa patient is decreased markedly after radical prostatectomy, with a significant correlation between the patient's age and the postoperative change of the flaccid penile length. The patients with better preoperative sexual function are more likely to seek penile rehabilitation and treatment postoperatively.

Targeting CPT1B as a potential therapeutic strategy in castration-resistant and enzalutamide-resistant prostate cancer.

BACKGROUND: Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism. METHODS: CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data. A tissue microarray was constructed with 60 samples of prostate cancer and immunohistochemically stained for CPT1B. Castration-resistant prostate cancer (CRPC) cell lines 22RV1 and C4-2 in which CPT1B expression had been stably knocked down were established; and cell proliferation, cell cycle distribution, and invasion were investigated by Cell Counting Kit-8 (CCK-8) and colony formation assays, flow cytometry, and Transwell assays, respectively. To examine the impact of androgen receptor (AR) inhibition on CPT1B expression, JASPAR CORE was searched to identify AR-binding sites in CPT1B. Dual luciferase and ChIP assays were performed to confirm CPT1B activity and AR binding, respectively. Differentially expressed genes (DEGs) in prostate cancer underwent gene set enrichment analysis (GSEA). Enzalutamide-resistant C4-2 cells were generated and the mechanism of enzalutamide resistance and downstream signaling pathway changes of CPT1B to C4-2 was explored through CCK-8 test. RESULTS: CPT1B expression was upregulated in human prostate cancer compared with normal prostate tissue and was associated with poor disease-free survival and overall survival. Silencing of CPT1B resulted in downregulated cell proliferation, reduced S-phase distribution, and lower invasive ability, whereas the opposite was observed in CRPC cells overexpressing CPTB1. DEGS in prostate cancer were correlated with G-protein-coupled receptor signaling, molecular transducer activity, and calcium ion binding. AR may regulate CPT1B expression and activity via specific binding sites, as confirmed by dual luciferase and ChIP assays. The CCK-8 experiment demonstrated that CPT1B overexpression in C4-2 cells did not significantly increase the ability of enzalutamide resistance. However, overexpression of CPT1B in C4-2R cells significantly increased the enzalutamide resistance. Upregulation of CPT1B expression increased AKT expression and phosphorylation. CONCLUSIONS: CPT1B is upregulated in prostate cancer and is correlated with poor prognosis, indicating its potential as a biomarker. AR inhibits the transcription of CPT1B. In the CRPC cell line, overexpression of CPT1B alone cannot promote enzalutamide resistance, but in the drug-resistant line C4-2R, overexpression of CPT1B can promote the resistance of C4-2R to enzalutamide.

Prognostic Value of Germline DNA Repair Gene Mutations in De Novo Metastatic and Castration-Sensitive Prostate Cancer.

BACKGROUND: Germline DNA damage repair gene mutations (gDDRm) have been found in approximately 12% of patients with metastatic prostate cancer (mPCa). Previous studies of the clinical impact of gDDRm have mainly been in the setting of metastatic castration-resistant prostate cancer (mCRPC). This study aimed to determine the prognostic value of gDDRm in de novo metastatic and castration-sensitive prostate cancer (mCSPC). MATERIALS AND METHODS: We retrospectively collected the records of 139 consecutive men with de novo mCSPC who initially received systemic therapies following guidelines. This included 128 patients who underwent genetic testing at our center and 11 patients referred to our center after being identified as gDDRm carriers. Time to mCRPC was collected. Kaplan-Meier and log-rank analysis were used to analyze the association between gDDRm and clinical outcomes. Survival outcomes were adjusted using multivariable Cox regression models. RESULTS: Of the 139 patients with de novo mCSPC, 28 gDDRm carriers were identified. Median time progressing to mCRPC was significantly shorter in patients carrying gDDRm than in those without mutations (8.3 vs 13.2 months; hazard ratio [HR], 2.37; p < .001). Moreover, median progression time was almost halved in BRCA2 carriers (6.3 vs. 13.2 months; HR, 3.73; p < .001). Subgroup analysis revealed that the presence of gDDRm indicated poor therapy response regardless of disease volume and prostate-specific antigen nadir within the first 7 months. Presence of gDDRm remained independently associated with increased risk of progression to mCRPC in multivariate analysis (adjusted HR, 1.98; p = .006). CONCLUSION: Our study suggested that positive gDDRm status predicted rapid progression to castration resistance in patients with de novo mCSPC. We propose identifying gDDRm status at the time of diagnosis for mCSPC patients, considering it is the first step of tailoring individualized treatment. In addition, DNA repair genes were a good therapeutic target for poly (ADP-ribose) polymerase inhibitors, and our results call for more frontline targeted therapy trials in gDDRm carriers to prolong the progression time. IMPLICATIONS FOR PRACTICE: Results of this study suggested that positive germline DNA damage repair gene mutation (gDDRm) status predicted earlier progression to castration resistance in patients with de novo metastatic and castration-sensitive prostate cancer (mCSPC). These findings indicated the importance of intense therapy for some subgroups of mCSPC, especially for mCSPC harboring gDDRm with low-volume disease. Moreover, gDDRm was a good therapeutic target for poly (ADP-ribose) polymerase inhibitors, and these findings call for more molecular marker driven trials moving to the mTNPC setting.

Low-serum prostate-specific antigen level predicts poor outcomes in patients with primary neuroendocrine prostate cancer.

BACKGROUND: The rarities of primary neuroendocrine prostate cancer (NEPC) and primary adenocarcinoma with neuroendocrine differentiation (NE differentiation) mean that their clinical characteristics have not been fully elucidated. MATERIALS AND METHODS: A total of 449 patients with NEPC, including 352 cases of pure NEPC and 97 cases of NE differentiation, together with 408 629 cases of prostate adenocarcinoma at diagnosis were retrieved from the Surveillance, Epidemiology, and End Results program (2010-2015). Clinical parameters and prognoses were compared between patients with different histological types of NEPC using the χ2 test and Kaplan-Meier analysis, respectively. The prognostic value of prostate-specific antigen (PSA) in NEPC and adenocarcinoma was evaluated using Cox regression and the Kaplan-Meier method. RESULTS: Pure NEPC had higher rates of visceral metastases (brain, lung, and liver: 4.58%, 26.72%, and 36.64%, respectively) but a lower rate of bone metastasis (65.65%) compared with NE differentiation and prostate adenocarcinoma. Moreover, patients diagnosed with pure NEPC had a poorer outcome (median survival time: 10 months) compared with patients with NE differentiation (26 months) and prostate adenocarcinoma (median survival time not reached). Using PSA 4.1 to 10 ng/mL as the reference, the adjusted hazard ratios (HRs) for PSA lower than or equal to 4.0 ng/mL were 2.24 (95% confidence interval [CI]: 1.11-4.55, P = .025) in the NE differentiation group and 1.57 (95% CI: 1.11-2.23, P = .011) in the pure NEPC group. CONCLUSIONS: Patients with NE differentiation had different clinical characteristics and a better prognosis than patients with pure NEPC. In addition, low-serum PSA levels were associated with a poorer prognosis in patients with either NEPC or NE differentiation.

The Value of 99mTc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients.

BACKGROUND: This study evaluated the effect of technetium-99m (99mTc)-labeled prostate-specific membrane antigen (PSMA)-based image-guided surgery on the oncologic outcomes for patients with primary or recurrent prostate cancer (PCa). METHODS: This study retrospectively analyzed 54 consecutive patients with PCa who underwent 99mTc-labeled PSMA-based image-guided surgery between January 2016 and September 2017. These patients received a radical prostatectomy (RP) with pelvic lymph node dissection (PLND) or salvage lymph node dissection (sLND). The resected specimens were compared with findings of postoperative histologic analysis. The responses to the treatment were recorded during the follow-up period. RESULTS: In 31 patients, PSMA single-photon emission computerized tomography (SPECT) and computed tomography (CT) could find 52 suspicious lymph node metastases (LNMs). With the help of PSMA SPECT/CT, 12 patients with recurrence received sLND, 19 primary PCa patients received RP with extended PLND, and 23 primary PCa patients received RP with standard PLND. The findings showed that PSMA SPECT/CT could detect LNMs with high sensitivity and specificity. In six patients, PSMA SPECT/CT could find more LNMs that were not found by MRI and help to modify the extent of lymphadenectomy. At the latest follow-up evaluation, 39 patients showed a biochemical response (BR), 9 patients showed a biochemical recurrence (BCR) after BR, and 6 patients never exhibited BR. The patients who received RP with standard PLND or extended PLND had a better prostate-specific antigen (PSA) response than the patients who received sLND. The patients with pelvic LNMs also had a better PSA response than the patients with retroperitoneal LNMs. CONCLUSIONS: This study showed that 99mTc-PSMA SPECT/CT-guided surgery can remove more LNMs than conventional imaging with high sensitivity and specificity and delay disease progression in PCa patients.

[Attitudes of prostate cancer patients towards postoperative penile rehabilitation and their influencing factors].

OBJECTIVE: To investigate the attitudes of prostate cancer (PCa) patients towards postoperative penile rehabilitation and their influencing factors. METHODS: Seventy-nine PCa patients underwent radical prostatectomy from January through June 2017 and all received a questionnaire investigation before surgery on IIEF-5 and their attitudes towards postoperative penile rehabilitation. We analyzed the reasons for the patients' rejection of postoperative penile rehabilitation. RESULTS: Totally 56 (71%) of the patients accepted and the other 23 (29%) refused postoperative penile rehabilitation. The factors influencing their attitudes towards penile rehabilitation mainly included age (P = 0.023), income (P = 0.040), tumor stage (P = 0.044), and preoperative sexual activity (P = 0.004). The patients who accepted penile rehabilitation had significantly higher IIEF-5 scores than those who refused it (14.75 ± 0.88 vs 8.48 ± 1.16, P = 0.000 2). During the follow-up period, only 29 (36.7%) of the patients bought the vacuum erection device but not the other 50 (63.3%). The tumor stage (P = 0.004), income (P < 0.01) and preoperative androgen-deprivation therapy (P = 0.039) significantly influenced the patients' decision on the purchase of the device. Relevant admission education achieved a 45% decrease in the number of the patients unwilling to accept penile rehabilitation for worrying about its negative effect on cancer treatment, a 25% decrease in those rejecting penile rehabilitation because of age, and a 20% decrease in those refusing it due to the tumor stage. The cost of treatment was an important reason for the patients' rejection of postoperative penile rehabilitation. CONCLUSIONS: The tumor stage and income are the main factors influencing PCa patients' decision on postoperative penile rehabilitation. Relevant admission education and reduced cost of rehabilitation are important for popularization of postoperative penile rehabilitation in PCa patients.

HIC1 loss promotes prostate cancer metastasis by triggering epithelial-mesenchymal transition.

Metastatic disease is the leading cause of death due to prostate cancer (PCa). Although the hypermethylated in cancer 1 (HIC1) gene has been observed to be epigenetically modified in PCa, its intrinsic role and mechanism in PCa metastasis still remain uncertain. Here, we show that hypermethylation of the HIC1 promoter markedly reduces its suppressive function in metastatic PCa tissues as compared with primary and adjacent normal prostate tissues, and is associated with poor patient survival. PCas in cancer-prone mice homozygous for a prostate-targeted Hic1 conditional knockout showed stronger metastatic behaviour than those in heterozygous mice, as a result of epithelial-mesenchymal transition (EMT). Moreover, impairment of HIC1 expression in PCa cells induced their migration and metastasis through EMT, by enhancing expression of Slug and CXCR4, both of which are critical to PCa metastasis; the CXCL12-CXCR4 axis promotes EMT by activating the extracellular signal-regulated kinase (ERK) 1/2 pathway. Taken together, our results suggest that evaluation of HIC1-CXCR4-Slug signalling may provide a potential predictor for PCa aggressiveness. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Abiraterone acetate for metastatic castration-resistant prostate cancer after docetaxel failure: A randomized, double-blind, placebo-controlled phase 3 bridging study.

OBJECTIVES: To evaluate the efficacy and safety of abiraterone acetate-prednisone versus placebo-prednisone in Asian metastatic castration-resistant prostate cancer patients who have failed docetaxel-based chemotherapy. METHODS: In this double-blind, phase 3 study from China, 214 patients were randomized (2:1) to abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily and placebo plus prednisone 5 mg twice daily in 28-day treatment cycles. RESULTS: Abiraterone acetate-prednisone treatment significantly decreased prostate-specific antigen progression risk by 49%, with longer median time to prostate-specific antigen progression of 5.55 months versus 2.76 months in the placebo-prednisone group (hazard ratio 0.506, P = 0.0001, primary end-point). There was a strong trend for improved overall survival in the abiraterone acetate-prednisone group, with a 40% decrease in the risk of death (hazard ratio 0.604, P = 0.0597); however, median survival was not reached in either group because of the short follow-up period (12.9 months) and limited number of observed death events. The prostate-specific antigen response rate was higher in the abiraterone-prednisone group (49.7%) than in the placebo-prednisone group (14.1%). A total of 37.1% patients in this group had pain progression events compared with 50.7% in the placebo-prednisone group. Abiraterone-prednisone significantly decreased the risk of pain progression by 50% (hazard ratio 0.496, P = 0.0014). The incidence of adverse events was similar between the two groups; the most common adverse events being anemia (25.9% for abiraterone-prednisone vs 22.5% for placebo-prednisone), hypokalemia (25.9% and 11.3%), bone pain (23.8% and 21.1%), hypertension (16.1% and 12.7%) and increased aspartate aminotransferase (14.7% and 15.5%), respectively. CONCLUSIONS: Abiraterone-prednisone significantly delays disease and pain progression, and prostate-specific antigen, with a favorable benefit-risk ratio in Asian metastatic castration-resistant prostate cancer patients in the post-docetaxel setting.

Visceral fat accumulation is associated with different pathological subtypes of renal cell carcinoma (RCC): a multicentre study in China.

OBJECTIVE: To investigate whether visceral obesity is associated with certain histological subtypes of renal cell carcinoma (RCC) ina multicentre Chinese cohort. PATIENTS AND METHODS: A kidney tumour database was created using three tertiary centres in China; 487 patients were enrolled presenting with localised RCC and complete computer tomography(CT)/magnetic resonance imaging (MRI) information. A single-slice CT image was used to measure the area of visceral and subcutaneous adipose tissues in each patient. Statistical methods were used to analyse clear-cell RCC (ccRCC) and non-clear-cell RCC (non-ccRCC) as they relate to visceral fat area (VFA) and other risk factors, such as age, gender, tumour size, diabetes, hypertension, total fat area (TFA) and body mass index (BMI). RESULTS: In all, 418 patients had a ccRCC subtype and 69 had a non-ccRCC subtype. For all the patients with RCC, the mean VFA was 102 cm2, while mean BMI was 24 kg/m2. The mean VFA was greater in ccRCC than non-ccRCC patients by 25 cm2. There were significant differences in the mean VFA and TFA between patients with ccRCC and those with non-ccRCC.Multivariate analysis showed that the presence ofVFA was more important than the effects of BMI and Type 2 diabetes on pathology prediction. In patients with a normal BMI, those with a higher quartile of VFA were more likely to develop ccRCC than those with a low VFA. CONCLUSIONS: Increased visceral fat was found to be associated with ccRCC and the significance of VFA outweighed the effects of BMI and Type 2 diabetes for the prediction of RCC pathology in multivariate analyses. As a result, VFA could constitute a primary explanation for the link between obesity and ccRCC.

A Phase II trial of dosage escalation of sorafenib in Asian patients with metastatic renal cell carcinoma.

AIM: To investigate the role of sorafenib dosage escalation in Asian patients with metastatic renal cell carcinoma that had progressed after routine dosages. PATIENTS & METHODS: Sorafenib dosage escalation to 600 or 800 mg twice a day was offered to 41 patients with metastatic renal cell carcinoma who had progressed on normal dosages. Clinical outcome, toxicity and favorable clinical covariables for progression-free survival (PFS) were evaluated. RESULTS: The median PFS with dosage-escalated therapy was 7 months. Drug-related adverse events were tolerable. The pre-escalation Karnofsky performance status, serum calcium concentration, neutrophil/lymphocyte ratio, PFS and the highest toxicity grade at the routine dosage were associated with a longer PFS in the dosage-escalation period. CONCLUSION: Sorafenib dosage escalation was efficacious and tolerable in Asian patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (no. ChiCTR-ONRC-12002088).

Role of gut microbiota in the pathogenesis of castration-resistant prostate cancer: a comprehensive study using sequencing and animal models.

CRPC remains a significant challenge in prostate cancer research. We aimed to elucidate the role of gut microbiota and its specific mechanisms in CRPC using a multidisciplinary approach. We analyzed 16S rRNA sequencing data from mouse fecal samples, revealing substantial differences in gut microbiota composition between CRPC and castration-sensitive prostate cancer mice, particularly in Firmicutes and Bacteroidetes. Functional analysis suggested different bacteria may influence CRPC via the α-linolenic acid metabolism pathway. In vivo, experiments utilizing mouse models and fecal microbiota transplantation (FMT) demonstrated that FMT from healthy control mice could decelerate tumor growth in CRPC mice, reduce TNF-α levels, and inhibit the activation of the TLR4/MyD88/NF-κB signaling pathway. Transcriptome sequencing identified crucial genes and pathways, with rescue experiments confirming the gut microbiota's role in modulating CRPC progression through the TLR4/MyD88/NF-κB pathway. The activation of this pathway by TNF-α has been corroborated by in vitro cell experiments, indicating its role in promoting prostate cancer cell proliferation, migration, and invasion while inhibiting apoptosis. Gut microbiota dysbiosis may promote CRPC development through TNF-α activation of the TLR4/MyD88/NF-κB signaling pathway, potentially linked to α-linolenic acid metabolism.

Antibiotic Resistance and Genetic Profiles of Vibrio parahaemolyticus Isolated from Farmed Pacific White Shrimp (Litopenaeus vannamei) in Ningde Regions.

To better understand the antibiotic resistance, virulence genes, and some related drug-resistance genes of Vibrio parahaemolyticus in farmed pacific white shrimp (Litopenaeus vannamei) in Ningde regions, Fujian province, we collected and isolated a total of 102 strains of V. parahaemolyticus from farmed pacific white shrimp in three different areas of Ningde in 2022. The Kirby-Bauer disk method was used to detect V. parahaemolyticus resistance to 22 antibiotics, and resistant genes (such as quinolones (qnrVC136, qnrVC457, qnrA), tetracyclines (tet A, tetM, tetB), sulfonamides (sulI, sulII, sulIII), aminoglycosides (strA, strB), phenicols (cat, optrA, floR, cfr), ß-lactams (carB), and macrolides (erm)) were detected by using PCR. The findings in this study revealed that V. parahaemolyticus was most resistant to sulfamoxazole, rifampicin, and erythromycin, with resistance rates of 56.9%, 36.3%, and 33.3%, respectively. Flufenicol, chloramphenicol, and ofloxacin susceptibility rates were 97.1%, 94.1%, and 92.2%, respectively. In all, 46% of the bacteria tested positive for multi-drug resistance. The virulence gene test revealed that all bacteria lacked the tdh and trh genes. Furthermore, 91.84% and 52.04% of the isolates were largely mediated by cat and sulII, respectively, with less than 5% resistance to aminoglycosides and macrolides. There was a clear mismatch between the antimicrobial resistance phenotypes and genotypes, indicating the complexities of V. parahaemolyticus resistance.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

[Hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib].

OBJECTIVE: To explore the hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib. METHODS: A total of 136 patients with advanced renal cell carcinoma were treated with sunitinib at our hospital from 2008 to 2011. There were 91 males and 45 females with an average age of 55.5 years. They received sunitinib in repeated 6-week cycles consisting of 4 weeks of sunitinib 50 mg per day followed by 2 weeks of treatment (schedule 4/2). The hematologic toxicities, collected at baseline and 14, 28, 42 (after a 2-week rest period) days, were graded according to the National Cancer Institute common terminology criteria for adverse events version 3.0. The paired Wilcoxon test was used to evaluate the kinetics of hematologic adverse effects at days 14, 28, and 42 post-treatment. RESULTS: The hematologic toxicities included leukopenia (n = 91, 66.9%), neutropenia (n = 95, 69.8%), lymphopenia (n = 58, 46.2%), thrombopenia (n = 89, 65.4%) and hypohemoglobinemia (n = 48, 35.3%). Among them, 31 cases (22.8%) had the high-grade (including grades 3 and 4) toxicity of thrombopenia. There were depressions in hematopoietic cell populations including leukocytes, neutrophils, and platelets at days 14, 28 and 42 versus the baseline level (all P < 0.05). The median hemoglobin level transiently increased at days 14 and 28 (both P < 0.01) and returned to the level of baseline at days 42 (P = 0.754). CONCLUSIONS: The incidence of hematologic adverse effects of sunitinib slightly varies with what have been observed in previous studies. And the incidence of high-grade toxicity of thrombocytopenia is higher than that reported in studies conducted in the US and Europe.

[Exploratory analysis of the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma].

OBJECTIVE: To explore the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma (RCC) . METHODS: A total of 136 patients with advanced RCC were treated with sunitinib from 2008 to 2011. There were 91 males and 45 females with an average age of 56 years. Their 6-week therapy cycle was 4 weeks of sunitinib 50 mg daily followed by 2-week off-treatment (schedule 4/2). The median follow-up time was 15 months. Correlation between toxicities and overall survival (OS) was evaluated in a Cox model using log-transformed levels after adjusting for MSKCC model.Log-rank test and Cox proportional hazard model were used to assess the value of drug toxicity as the prognostic factors. RESULTS: The increased hemoglobin on cycle 1 day 14 (HR:0.950, 95%CI:0.923-0.978) and the increased lymphocytes on cycle 1 days 28 and 42 (HR:0.405, 95%CI:0.203-0.809, HR:0.394, 95%CI:0.179-0.867) were significantly associated with OS (P adj = 0.001, 0.014 and 0.022 respectively). Hypertension class III/IV (HR:0.066, 95%CI:0.008-0.582), and the number of neutrophils screening and lymphocyte count ratio (HR:2.537, 95%CI:1.182-5.404) were the survival prognosis independent predictors. CONCLUSION: Early hematopoietic toxicities may potentially predict the outcomes of advanced RCC after a therapy of sunitinib.

Nucleophosmin 1 cooperates with BRD4 to facilitate c-Myc transcription to promote prostate cancer progression.

Nucleophosmin 1 (NPM1) is a multifunctional protein that promotes tumor progression in various cancers and is associated with a poor prognosis of prostate cancer (PCa). However, the mechanism by which NPM1 exerts its malignant potential in PCa remains elusive. Here, we showed that NPM1 is overexpressed in PCa cell lines and tissues and that the dysregulation of NPM1 promotes PCa proliferation. We also demonstrated that NPM1 transcriptionally upregulates c-Myc expression in PCa cells that is diminished by blockade of bromodomain-containing protein 4 (BRD4). Furthermore, we detected a correlation between NPM1 and c-Myc in patient PCa specimens. Mechanistically, NPM1 influences and cooperates with BRD4 to facilitate c-Myc transcription to promote PCa progression. In addition, JQ1, a bromodomain and extra-terminal domain (BET) inhibitor, in combination with NPM1 inhibition suppresses PCa progression in vitro and in vivo. These results indicate that NPM1 promotes PCa progression through a c-Myc -mediated pathway via BRD4, and blockade of the NPM1-c-Myc oncogenic pathway may be a therapeutic strategy for PCa.

Prospective clinical sequencing of 1016 Chinese prostate cancer patients: uncovering genomic characterization and race disparity.

Although there is a well-known disparity in prostate cancer (PC) incidence and mortality between Chinese and Western patients, the underlying genomic differences have been investigated only sparsely. This clinicogenomic study was conducted to reveal the genomic mutations contributing to the PC disparity across ethnicities and investigate the mutational profile of Chinese PC patients. A total of 1016 Chinese PC patients were prospectively enrolled and subjected to targeted sequencing, resulting in usable sequencing data for 41 genes from 859 patients. Genomic data retrieved from The Cancer Genome Atlas (TCGA; locoregional PC), Memorial Sloan Kettering Cancer Center [MSKCC; metastatic castration-sensitive PC (mCSPC)], and Stand Up To Cancer [SU2C; metastatic castration-resistant PC (mCRPC)] cohorts were used as comparators representing Western men. Genomic mutations were analyzed using an integrated bioinformatic strategy. A comparison of the disease stages revealed that mutations in tumor protein 53 (TP53), androgen receptor (AR), forkhead box A1 (FOXA1), and genes involved in the cell cycle pathway were enriched in mCRPC. Mutations in adenomatous polyposis coli (APC) gene were found to be more prevalent in patients with visceral metastasis. Genomic differences between Western and Chinese men were mainly observed in castration-sensitive PC, with tumors from Chinese men having more FOXA1 (11.4% vs. 4.2%) but fewer TP53 (4.8% vs. 13%) mutations in locoregional PC and harboring fewer TP53 (11% vs. 29.2%), phosphatase and tensin homolog (PTEN; 2.5% vs. 10.3%), and APC (1.7% vs. 7.4%) mutations in the mCSPC stage than those of Western men. Patients of both ethnicities with mCRPC had similar mutational spectra. Furthermore, FOXA1 class-2 was less common than FOXA1 class-1 and showed no enrichment in metastasis, contrary to the findings in the Western cohort. Our study provides a valuable resource for a better understanding of PC in China and reveals the genomic alterations associated with PC disparity across races.