Sarcomatoid renal pelvis carcinoma: Experience of treatment at a single-institution.

OBJECTIVES: Sarcomatoid renal pelvis carcinoma (SRPC) is a rare variant of RPC. We aimed to summarize the clinicopathological features and prognostic factors of SRPC. METHODS: In this retrospective study, we collected data from 24 patients with SRPC who were treated at the Department of Urology, Affiliated Hospital of Qingdao University between 2008 and 2021. The clinicopathological features of the patients were obtained from their medical records to evaluate the diagnosis, prognostic factors, and response to systemic therapy. RESULTS: Immunohistochemical staining revealed that cytokeratin was expressed in 19 patients with SRPC, while vimentin was expressed in all patients. Computer tomography showed these tumors as low-density (n = 12) or mixed-density masses, with or without necrotic areas (n = 12). All patients showed different degrees of enhancement on computed tomography. Lymph node metastasis was present in 6 patients and distant metastasis in 5. The median survival of all patients was 28 months. Patients without metastasis had a median survival of 46 months compared with 18 months in those with metastasis (P < 0.05). Necrosis had no significant influence on prognosis (P > 0.05). The median survival of patients with and without hydronephrosis was 18 and 104 months (P < 0.05). Among patients without metastasis, those without hydronephrosis survived longer than those with hydronephrosis (104 vs 18 months, P < 0.05), and necrosis had no effect on prognosis. In patients with metastasis, necrosis and hydronephrosis had no effect on prognosis (P > 0.05). CONCLUSION: The prognosis of SRPC is poor, and the clinical stage, particularly the presence of distant metastasis, has a significant impact on prognosis.

External validation of a four-tiered grading system for chromophobe renal cell carcinoma.

This study aimed to validate the prognostic value of a four-tiered grading system recently proposed by Avulova et al. and to explore the prognostic ability of another four-tiered classification grading system in which there is a separate Grade 3 for tumor necrosis. Grading of chromophobe renal cell carcinoma (ChRCC) by the Fuhrman system is not feasible because of the inherent nuclear atypia in ChRCC. We collected relevant data of 263 patients with ChRCC who had undergone surgery in our hospital from 2008 to 2020. The Kaplan-Meier method was used to calculate the survival rate and Cox proportional hazard regression models to assess associations with cancer-specific survival and distant metastasis-free survival by hazard ratios (HRs) and 95% confidence intervals (CIs). Ten patients died from ChRCC, and 12 developed metastases. The 5 year CSS rates were 95.9%. Grades 2 (HR = 10.9; CI 1.11-106.4; P = 0.04), 3 (HR = 33.6, CI 3.32-339.1; P = 0.003), and 4 (HR = 417.4, CI 35.0-4976.2; P < 0.001) in a four-tiered grading system were significantly associated with CSS in a multivariate setting. However, the difference in CSS between Grades 2 and 3 was not significant (HR = 2.14, 95% CI 0.43-10.63; P = 0.35). The HRs of the associations between an exploratory grading system that includes a separate Grade 3 for tumor necrosis and CSS were as follows: Grade 2, 10.2 (CI 1.06-97.9, P = 0.045); Grade 3, 11.4 (CI 1.18-109.6, P = 0.04); and Grade 4, 267.9 (CI 27.6-2603.3, P < 0.001). Similarly, Grades 2 and 3 did not differ significantly. The four-tiered grading system studied is useful for predicting death from ChRCC and metastasis. However, Grade 3 did not more accurately predict risk of death and metastasis than did Grade 2. This was also true for the novel exploratory grading system that classifies tumors with necrosis into a separate Grade 3.

Toxic effects of environmental concentration Bisphenol AF exposure on the survival, growth and reproduction of adult male Oryzias curvinotus.

Bisphenol AF (BPAF) is a novel environmental endocrine disruptor, and is widely detected in the aquatic environment, which is a potential threat to the health of fish. In this study, male Oryzias curvinotus were exposed to environmental concentrations (0.93 and 9.33 µg/L) of BPAF for 21 days. The effects of BPAF on survival, growth, reproduction, liver and testis histology, and gene transcriptional profiles of O. curvinotus were investigated. The results showed that the survival rate of male O. curvinotus slight decrease with increasing BPAF concentration, and there was no significant effect on body length, body weight, and K-factor. BPAF (9.33 µg/L) caused significant changes in testicular structure and reduced spermatid count in O. curvinotus. Changes in transcript levels of some antioxidant-related genes in gills and liver following BPAF exposure, imply an effect of BPAF on the immune system. After BPAF exposure, chgs and vtgs were up-regulated, validating the estrogenic effect of BPAF. In the hypothalamic - pituitary - gonadal axis (HPG) results, erα, erγ and cyp19a1b were all up-regulated in the brain, and the 0.93 µg/L BPAF group was more up-regulated than the 9.33 µg/L BPAF group. In testis, BPAF significantly up-regulated the mRNA expression level of cyp17a1 and cyp11b, while significantly down-regulated mRNA expression level of cyp11a, and cyp19a1 was significantly down-regulated only in the 0.93 µg/L BPAF group. In conclusion, environmental levels of BPAF have adverse effects on the survival and reproduction of O. curvinotus, and the potential toxic effects of environmental levels of BPAF cannot be ignored.

Urogenital microbiota-driven virulence factor genes associated with recurrent urinary tract infection.

Urinary tract infections (UTIs) are a common health issue affecting individuals worldwide. Recurrent urinary tract infections (rUTI) pose a significant clinical challenge, with limited understanding of the underlying mechanisms. Recent research suggests that the urobiome, the microbial community residing in the urinary tract, may play a crucial role in the development and recurrence of urinary tract infections. However, the specific virulence factor genes (VFGs) driven by urobiome contributing to infection recurrence remain poorly understood. Our study aimed to investigate the relationship between urobiome driven VFGs and recurrent urinary tract infections. By analyzing the VFGs composition of the urinary microbiome in patients with rUTI compared to a control group, we found higher alpha diversity in rUTI patients compared with healthy control. And then, we sought to identify specific VFGs features associated with infection recurrence. Specifically, we observed an increased abundance of certain VGFs in the recurrent infection group. We also associated VFGs and clinical data. We then developed a diagnostic model based on the levels of these VFGs using random forest and support vector machine analysis to distinguish healthy control and rUIT, rUTI relapse and rUTI remission. The diagnostic accuracy of the model was assessed using receiver operating characteristic curve analysis, and the area under the ROC curve were 0.83 and 0.75. These findings provide valuable insights into the complex interplay between the VFGs of urobiome and recurrent urinary tract infections, highlighting potential targets for therapeutic interventions to prevent infection recurrence.

Characteristics and survival of primary urothelial carcinoma of the prostate: A multi-center retrospective study of 18 cases.

OBJECTIVES: To explore the features, treatment, and outcomes of primary urothelial carcinoma of the prostate (PUCP) in a multicenter study. METHODS: The clinical and imaging features, pathological findings, treatment, and outcomes of patients diagnosed with PUCP from January 2011 to April 2022 at three institutions were collected and analyzed. The Kaplan-Meier method and log-rank test were used to assess survival rates of the overall group and survival differences between groups according to TNM stage. RESULTS: The study cohort comprised 18 patients with PUCP of mean age 72.4±7.8 years. Dysuria and urinary frequency were the most common symptoms (77.8 %). Sixteen (88.9 %) patients had normal serum total PSA concentrations. Most patients showed abnormalities on urinalysis. MRI was the most accurate diagnostic imaging method (88.9 %). As to immunohistochemistry findings, GATA-3 (81.8 %) and P63 (84.6 %) were positive in most examined patients; however, no lesions were positive for PSA. Three (17.6 %) patients with T1N0M0 and T2N0M0 tumors underwent radical cystectomy. Eleven (64.7 %) patients which almost all had T4 tumors received systematic therapy, most of them receiving chemotherapy with gemcitabine and cisplatin, and radiotherapy. The median overall survival was 42 months, and the median progression-free survival 25 months, the latter being significantly longer in patients with T1-2 than in those with T3-4 disease (p=0.035). CONCLUSION: PUCP, a rare but highly aggressive type of prostate cancer, should be considered in men with abnormalities on MRI and normal serum PSA concentrations. Positive GATA-3, P63, and negative PSA are typical immunohistochemistry features. Radical cystectomy and systematic therapies can be effective.

Identification and validation of a ferroptosis-related signature for prediction of the prognosis and tumor microenvironment in patients with chromophobe renal cell carcinoma.

BACKGROUND: Ferroptosis is a novel form of regulated cell death that is different from other forms, which has an important role in tumor growth inhibition. The purpose of this study was to construct and validate a prognostic signature related to ferroptosis in chromophobe renal cell carcinoma (ChRCC) and to explore its role in immune cell infiltration and systemic therapy. METHODS: The gene expression profiles of ChRCC patients obtained from The Cancer Genome Atlas (TCGA) database were used to identify differentially expressed prognostic ferroptosis-related genes (FRGs) by univariate Cox proportional hazards analyses. Ferroptosis molecular subtypes were obtained by consensus clustering analysis. The FRG-based signature in the training set was established by least absolute shrinkage and selection operator analysis and verified in the testing set. The association between molecular subtypes and the prognostic signature and immune microenvironment was explored to predict responses to immunotherapy. Immunohistochemistry was used to verify expression of the FRG-based signature externally. RESULTS: ChRCC patients were divided into two FRG subtypes. Two FRGs (TFRC and SLC7A11) were identified to construct the prognostic signature. The high-risk group and cluster 2 had worse overall survival than the low-risk group and cluster 1, respectively. The low-risk group and cluster 1 had higher levels of immune cell infiltration and expression of MHC and immune checkpoint molecules than the high-risk group and cluster 2. The risk score was a predictor of overall survival and had a good predictive ability, which was verified in the testing set and evaluated by ROC and calibration curves. The high-risk group had a higher tumor mutation burden. The different sensitivities of targeted drugs in patients with different risks were evaluated. External immunohistochemical analysis showed that TFRC and SLC7A11 were highly expressed in tumor tissues compared with para-cancer normal tissues, and the expression level was significantly associated with a more advanced stage and worse cancer-specific survival. CONCLUSIONS: An FRG signature was identified and validated to predict the clinicopathological features and prognosis of ChRCC. A significant association between the signature and immune cell infiltration, immune checkpoint expression, and drug response is helpful to guide comprehensive treatment of ChRCC.

Role of Human Monocarboxylate Transporter 1 (hMCT1) and 4 (hMCT4) in Tumor Cells and the Tumor Microenvironment.

In recent years, the abnormal glucose metabolism of tumor cells has attracted increasing attention. Abnormal glucose metabolism is closely related to the occurrence and development of tumors. Monocarboxylate transporters (MCTs) transport the sugar metabolites lactic acid and pyruvate, which affect glucose metabolism and tumor progression in a variety of ways. Thus, research has recently focused on MCTs and their potential functions in cancer. The MCT superfamily consists of 14 members. MCT1 and MCT4 play a crucial role in the maintenance of intracellular pH in tumor cells by transporting monocarboxylic acids (such as lactate, pyruvate and butyrate). MCT1 and MCT4 are highly expressed in a variety of tumor cells and are involved the proliferation, invasion and migration of tumor cells, which are closely related to the prognosis of cancer. Because of their important functions in tumor cells, MCT1 and MCT4 have become potential targets for cancer treatment. In this review, we focus on the structure, function and regulation of MCT1 and MCT4 and discuss the developed inhibitors of MCT1 and MCT4 to provide more comprehensive information that might aid in the development of strategies targeting MCTs in cancer.

Systemic therapies for high-volume metastatic hormone-sensitive prostate cancer: a network meta-analysis.

BACKGROUND: We compared the effectiveness of currently available systemic therapies for high-volume metastatic hormone-sensitive prostate cancer (mHSPC) and aimed to establish the optimal treatment regimen. MATERIAL AND METHODS: We searched multiple databases for randomized controlled trials (RCTs) that evaluated the efficacy of systemic therapy in patients with high-volume mHSPC. Bayesian network meta-analysis was used to indirectly compare overall survival (OS) and progression-free survival (PFS) of various systemic therapies. RESULTS: Eleven RCTs (6708 participants) finally met the eligibility criteria. Compared with androgen deprivation therapy (ADT) alone, rezvilutamide (REZ) [hazard ratio (HR) = 0.58, 95% confidence interval (CI): 0.44-0.77], abiraterone (ABI) (HR = 0.61, 95% CI: 0.53-0.71), apalutamide (APA) (HR = 0.70, 95% CI: 0.56-0.88), enzalutamide (ENZ) (HR = 0.65, 95% CI: 0.53-0.80), docetaxel (DOC) (HR = 0.72, 95% CI: 0.63-0.84), darolutamide (DAR) + DOC (HR = 0.49, 95% CI: 0.39-0.62), and ABI + DOC (HR = 0.52, 95% CI: 0.38-0.71) significantly improved OS in patients with high-volume mHSPC. Compared with DOC, no advantages were observed for doublet therapies, including REZ, ABI, APA, and ENZ on the basis of ADT, whereas DAR + DOC (HR = 0.68, 95% CI: 0.57-0.82) and ABI + DOC (HR = 0.72, 95% CI: 0.55-0.95) was associated with better OS. The ranking analysis showed that triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT) had the greatest improvement in OS, followed by REZ + ADT. All the regimens showed improved PFS in patients with high-volume mHSPC. Compared with DOC, significant differences were detected for DAR + DOC, ABI + DOC, ENZ + DOC, REZ, and ENZ. According to the ranking analysis, triplet therapy ranked first, followed by ENZ and REZ. CONCLUSIONS: REZ + ADT were the highest ranked doublet therapy for improvement in OS of patients with high-volume mHSPC, second only to triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT).

Impact of BMI on the Survival of Renal Cell Carcinoma Patients Treated with Targeted Therapy: A Systematic Review and Meta-Analysis.

It is unclear whether obese renal cell carcinoma (RCC) patients treated with targeted therapy have better survival. We conducted this meta-analysis to assess the prognostic significance of body mass index (BMI) in RCC patients treated with targeted therapy. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science by November 17, 2021. We calculated effect outcomes using random-effects and fixed-effects models. Fifteen articles were identified. We found that RCC patients treated with targeted therapy with BMI over 25 obtained better overall survival (OS) (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.58-0.82, I2 = 75.5%, p < 0.001) and progression-free survival (PFS) (HR = 0.71, 95%CI = 0.55-0.92, I2 = 69.7%, p = 0.006) than patients with BMI below 25. Obese (BMI over 30) patients had remarkably better OS (HR = 0.77, 95%CI = 0.70-0.85, I2 = 0.0%, p = 0.439) and PFS (HR = 0.86, 95%CI = 0.77-0.97, I2 = 0.0%, p = 0.934) than patients with BMI below 25. Overweight (BMI over 25 but below 30) patients also had better OS (HR = 0.86, 95%CI = 0.79-0.93, I2 = 17.7%, p = 0.295) and PFS (HR = 0.82, 95%CI = 0.74-0.90, I2 = 0.0%, p = 0.904) than patients with BMI below 25. When using BMI as continuous variable, patients with high BMI also obtained significantly better OS (HR = 0.92, 95%CI = 0.88-0.96, I2 = 0.0%, p = 0.806). Therefore, higher BMI was associated with greater OS and PFS in RCC patients treated with targeted therapy.

Primary seminal vesicle adenocarcinoma with a history of seminal vesicle cyst: A case report and review of literature.

BACKGROUND: Primary seminal vesicle adenocarcinoma is a rare malignancy that is difficult to diagnose. CASE SUMMARY: A 54-year-old man with an 18-year history of a seminal vesicle cyst presented with worsening hematospermia that had persisted for one month. Dynamic contrast-enhanced computed tomography and pelvic magnetic resonance imaging indicated a mass with a cystic-solid component. Robot-assisted seminal vesicle tumor resection was performed, and primary seminal vesicle adenocarcinoma was confirmed pathologically. The patient received pelvic radiotherapy for six weeks, and to date, no evidence of recurrence has been found. CONCLUSION: Seminal vesicle cysts should be monitored long-term. Seminal vesicle adenocarcinoma presents with non-specific symptoms and can be diagnosed by immunohistochemistry.

Development and validation of a preoperative nomogram to predict lymph node metastasis in patients with bladder urothelial carcinoma.

PURPOSE: Predicting lymph node metastasis (LNM) in patients with bladder urothelial carcinoma (BUC) before radical cystectomy aids clinical decision making. Here, we aimed to develop and validate a nomogram to preoperatively predict LNM in BUC patients. METHODS: Patients with histologically confirmed BUC, who underwent radical cystectomy and bilateral lymphadenectomy, were retrospectively recruited from two institutions. Patients from one institution were enrolled in the primary cohort, while those from the other were enrolled in the external validation cohort. Patient demographic, pathological (using transurethral resection of the bladder tumor specimens), imaging, and laboratory data were recorded. Univariate and multivariate logistic regression analyses were performed to explore the independent preoperative risk factors and develop the nomogram. Internal and external validation was conducted to assess nomogram performance. RESULTS: 522 and 215 BUC patients were enrolled in the primary and external validation cohorts, respectively. We identified tumor grade, infiltration, extravesical invasion, LNM on imaging, tumor size, and serum creatinine levels as independent preoperative risk factors, which were subsequently used to develop the nomogram. The nomogram showed a good predictive accuracy, with area under the receiver operator characteristic curve values of 0.817 and 0.825 for the primary and external validation cohorts, respectively. The corrected C-indexes, calibration curves (after 1000 bootstrap resampling), decision curve analysis results, and clinical impact curves demonstrated that the nomogram performed well in both cohorts and was highly clinically applicable. CONCLUSION: We developed a nomogram to preoperatively predict LNM in BUC, which was highly accurate, reliable, and clinically applicable.

First principles terahertz spectroscopy of molecular crystals: the crucial role of periodic boundary conditions benchmarked with experimental L-ascorbic acid spectra.

The terahertz (THz) region vibration spectral signatures of molecular crystals can usually be ascribed to the low-frequency vibrational modes related to weak intermolecular interactions, e.g. van der Waals (vdW) interactions or hydrogen bonding. These interactions collectively dictate the compositional units deviating from their equilibrium configurations. The collective movements are intrinsically long-range, and hence the boundary conditions used for theoretical calculation can affect the corresponding potential energy gradients and alter the vibrational features. In this work, we constructed a series of finite-sized cluster models with varying sizes and an extended periodic crystal model for L-ascorbic acid (L-AA) crystals. Density functionals with both semi-local contributions and nonlocal vdW terms, implemented with either atom-centered Gaussian basis or plane waves, were tested. By comparing first principles calculations with experimental time-domain spectra (TDS), we found that the non-local vdW functional opt-B88 combined with a periodic boundary condition is capable of assigning all the experimental features in the 0.2-1.6 THz region. Calculations with cluster models failed in this task. Even worse, the deficiency of the cluster models varied with cluster sizes, and did not converge as the cluster size grew. Our results demonstrate that an appropriate periodic boundary condition is essential to correctly assign and analyze the THz vibration spectra of molecular crystals.

Granulomatous prostatitis after bacille Calmette-Guérin instillation resembles prostate carcinoma: A case report and review of the literature.

BACKGROUND: Bacille Calmette-Guérin (BCG) instillation is recommended in patients with non-muscle-invasive bladder cancer who have intermediate-risk and high-risk tumors. However, granulomatous prostatitis is a rare complication induced by BCG instillation, which can easily be misdiagnosed as prostate cancer. Here, we report a case of granulomatous prostatitis that resembled prostate cancer. CASE SUMMARY: A 64-year-old Chinese man with bladder cancer received BCG instillation. Three days later, he stopped BCG instillation and received anti-infective therapy due to the urinary tract infection. Three months after BCG restart, he had rising total prostate-specific antigen (PSA) (9.14 ng/mL) and decreasing free PSA/total PSA (0.09). T2-weighted images of magnetic resonance imaging (MRI) showed a 28 mm × 20 mm diffuse low signal abnormality in the right peripheral zone, which was markedly hyperintense on high b-value diffusion-weighted MRI and hypointense on apparent diffusion coefficient map images. Considering Prostate Imaging Reporting and Data System score of 5 and possibility of prostate cancer, a prostate biopsy was conducted. Histopathology showed typical features of granulomatous prostatitis. The nucleic acid test for tuberculosis was positive. He was finally diagnosed with BCG-induced granulomatous prostatitis. Thereafter, he stopped BCG instillation and received anti-tuberculosis treatment. During 10 mo follow-up, he had no evidence of tumor recurrence or symptoms of tuberculosis. CONCLUSION: Temporarily elevated PSA and high followed by low signal abnormality on diffusion-weighted MRI are important indicators of BCG-induced granulomatous prostatitis.

Prognostic value of the sarcomatoid component in bladder cancer: A propensity score matching study.

Sarcomatoid carcinoma of the bladder is rare, and little is known about the prognostic impact of the proportion of sarcomatoid components of the bladder. The present study aimed to assess the prognostic value of the proportion of sarcomatoid components with regard to death and recurrence rates in patients with bladder cancer (BC), and to validate the worse survival results of sarcomatoid carcinomas of the bladder using propensity score matching. Patients with sarcomatoid carcinoma of the bladder who were treated at the Affiliated Hospital of Qingdao University between August 2010 and May 2021 were included in the study. A 1:2 propensity score matching system based on age, sex and pathological T stage was used for sarcomatoid and non-sarcomatoid carcinoma matching. Finally, 114 patients with BC were included. Patients with sarcomatoid carcinoma had worse 5-year cancer-specific survival (CSS) (69.1 vs. 86.9%; log-rank P=0.008) and recurrence-free survival (RFS) (64.1 vs. 83.6%; log-rank P=0.001) rates compared with patients with non-sarcomatoid carcinoma, as had the subgroup with muscle invasion. Multivariate analysis revealed sarcomatoid carcinoma as an independent prognostic factor. Patients with a low proportion of sarcomatoid components (1-50%) had a better prognosis than patients with a high proportion (>50%), and no significant difference was found compared with the non-sarcomatoid group. Overall, a proportion of sarcomatoid components >50% was a predictor of CSS and RFS. Sarcomatoid components markedly increased the risk of death and recurrence in muscle-invasive BC, but not in non-muscle-invasive BC. A higher proportion of sarcomatoid components was significantly associated with poorer survival.

Prognostic Factors of Adrenocortical Carcinoma: Experience from a Regional Medical Center in Eastern China.

Objective: This study aimed to summarize and analyze the clinical and pathological features and prognostic risk factors of adrenocortical carcinoma (ACC). Methods: We retrospectively analyzed clinical and pathological data and the prognoses of 39 adult ACC patients confirmed by pathologic diagnosis at the Affiliated Hospital of Qingdao University between August 2009 and October 2021. Kaplan-Meier curves and univariate and multivariate Cox regression models were used to analyze correlations between clinical and pathological parameters and prognosis. A nomogram prediction model was constructed for overall survival (OS) based on the independent prognostic factors and externally validated it with The Cancer Genome Atlas (TCGA) dataset. Results: The mean age of the patient cohort was 53.87 ± 11.1 years (range: 29-80 years), which included 17 men and 22 women. The 1-, 2-, and 5-year OS rates were 83.7%, 64.4%, and 59.8%, respectively; the recurrence-free survival (RFS) rates at the same time points were 76.1%, 45.8%, and 23.5%, respectively. Kaplan-Meier curves showed that patients with poor OS were associated with M1 stage (P = 0.008), late ENSAT stage (P = 0.017), presence of venous tumor thrombus (P = 0.015), Ki67 >20% (P = 0.006), R1/R2 status (P = 0.018), and poorly differentiated tumors (P = 0.047). Patients with late ENSAT stage (P = 0.017), combined with venous tumor thrombus (P = 0.008), Ki67 >20% (P = 0.022) were more likely to have tumor recurrence. However, age, gender, BMI, tumor diameter, clinical symptoms and postoperative treatment were not correlated with OS or RFS (P > 0.05). Univariate and multivariate COX analyses showed that Ki67 >20% (P = 0.013) and R1/2 status (P = 0.040) were independent risk factors for OS, while only Ki67 >20% (P = 0.032) was an independent risk factor for RFS. A nomogram for predicting OS was constructed based on the above factors, and the area under the receiver characteristic curve (ROC)-1, 3, and 5-year survival were 0.8, 0.825 and 0.902, respectively. The C-index of the predicted nomogram was 0.813 and a high C-index value of 0.846 could still be achieved in the external validation of TCGA. Conclusion: ACC is a rare and deadly endocrine malignancy with a high rate of recurrence. High Ki67 index (>20%) and R1/R2 resection status were independent risk factors for poor prognosis in ACC patients. A novel nomogram with a relatively good accuracy was established to assist clinicians in assessing the risk of OS in patients with ACC.

Equol exerts a protective effect on postmenopausal osteoporosis by upregulating OPG/RANKL pathway.

BACKGROUD: Estrogen deficiency is the leading cause of postmenopausal osteoporosis(PMOP) and phytoestrogens soy isoflavones (SI) have been shown to improve PMOP. Equol (Eq), an in vivo metabolite of phytoestrogens soy isoflavones (SI), has a more stable structure and stronger biological activity than its parent compound and has the greatest estrogenic activity. However, there are few studies on the therapeutic effect of Eq on PMOP. PURPOSE: To explore the therapeutic effect and mechanisms of Eq on POMP. METHODS: Osteoblast-like cells ROS1728 were cultured with different doses of Eq, estradiol (E2), separately. The effect of Eq on the proliferation, apoptosis, cell cycle of osteoblasts were detected by CCK-8 and flow cytometry, and the expression of OPG/RANK/RANKL signaling pathway of osteoblasts was detected by Quantitative real-time PCR (qRT-PCR) and Western blot (WB), and RNA silencing technology were carried out to explore the receptors through which Eq plays a role. Then PMOP rat model was established and treated by Eq or E2 to further verification of the effect and mechanism of Eq on PMOP. RESULT: Eq promoted the proliferation and inhibited the apoptosis of osteoblasts and increased the proportion of osteoblasts in the S phase and G2/M phase in a dose-dependent manner. Mechanistically, Eq treatment upregulated the expression of OPG and OPG/RANKL ratio in osteoblasts and this regulatory effect was mainly mediated through the ERß receptor. Furthermore, in vivo study, Eq improved microstructure and BMD of the femur of PMOP rat model, which imitated the osteoprotective effect of E2. Moreover, the Eq or E2 treatment increased serum levels of Ca, 1,25(OH)2D3, bone Gla-protein(BGP), and Type I procollagen (PC1), and reduced serum levels of phosphorus (P), parathyroid hormone(PTH), pyridinol (PYD), tartrate-resistant acid phosphatase (TRAP) and urinary level of deoxypyridinoline (DPD) in the treatment OVX group compared with the untreated OVX group. Meanwhile, Eq or E2 markedly induced the mRNA and protein expression of OPG and OPG/RANKL ratio. CONCLUSION: Eq can combine with ERß and exert a protective effect on PMOP by upregulating OPG/RANKL pathway.

S-Equol enhances osteoblastic bone formation and prevents bone loss through OPG/RANKL via the PI3K/Akt pathway in streptozotocin-induced diabetic rats.

Background: This study aimed to explore whether S-Equol delays diabetes-induced osteoporosis and the molecular mechanisms underlying its therapeutic effects. Materials and methods: Thirty-five male Sprague-Dawley rats were randomized into five groups. The diabetic osteoporosis (DOP) group and three S-Equol treatment groups were intraperitoneally injected with streptozotocin (STZ) to develop a DOP model. After the 12-week intervention, bone transformation indicators were detected using an enzyme-linked immunosorbent assay kit; bone mineral density (BMD) and bone microstructure were obtained using dual-energy X-ray absorptiometry and microCT; morphological changes in the bone tissue were investigated using HE staining; bone morphogenetic proteins were detected using immunohistochemical staining. ROS17/2.8 cells were cultured in vitro, and Cell Counting Kit-8 was used to test the protective effects of S-Equol in osteoblastic cells in a high-fat and high-glucose environment. Furthermore, the expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), estrogen receptor ß(ERß), phosphorylated Akt (pAKT)/protein kinase B (AKT), and osteocalcin (OC) in bone tissue and ROS17/2.8 cells was assessed using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. To determine whether ERß and phosphatidylinositol 3' -kinase (PI3K)/AKT signaling pathways are involved in the process, LY294002 (PI3K signaling pathway inhibitor) and small interfering RNA targeting ERß mRNA (si-ERß) were used to verify the function of the ERß-mediated PI3K/AKT pathway in this process. Results: After the 12-week intervention, S-Equol enhanced BMD, improved bone microarchitecture in DOP rats (P < 0.05), and improved markers of bone metabolism (P < 0.05). In vitro, 10-6 mmol/L S-Equol was selected to significantly protect osteoblasts from high- and high-glucose environments (P < 0.05). Gene expression of OPG, ERß, pAKT/AKT, and OC was upregulated compared to the DOP group, and RANKL was downregulated compared to the DOP group (P < 0.05) both in bone tissue and osteoblastic cells. The promotion of OPG and pAKT/AKT is mediated by LY294002 and siERß. Conclusion: S-Equol binds to ERß to regulate OPG/RANKL via the PI3K/AKT pathway and improve DOP. Our results demonstrate the potential role of S-Equol in the treatment of DOP by targeting ERß. Thus, S-Equol may have the potential to be an adjuvant drug for treating DOP.

Testis and epididymis-unusual sites of metastatic gastric cancer: A case report and review of the literature.

BACKGROUND: Although gastric cancer is one of the most prevalent cancers worldwide, cases of gastric cancer metastasis to the male reproductive system are rare. Here, we report a case involving testicular and epididymal gastric cancer metastases. CASE SUMMARY: A 75-year-old Chinese man complained of experiencing a palpable painful mass in the right scrotum for 6 mo. He had undergone distal gastrectomy with chemotherapy for pT3N3aMx poorly differentiated gastric adenocarcinoma 9 mo before. Physical examination revealed a moderate right hydrocele and a painful mass in the right testis and epididymis. Serum tumor biomarkers were all normal except for elevated beta-human chorionic gonadotropin levels. Computed tomography urography and B-ultrasound imaging revealed a moderate right hydrocele and a mixed solid-cystic mass in the right testicular and epididymal area. Thus, the patient underwent right radical orchiectomy. Immunohistochemical analysis revealed that the tumor cells were positive for pancytokeratins and caudal related homeodomain transcription 2. Metastatic, poorly differentiated gastric adenocarcinoma of the testis and epididymis was confirmed by pathology. He continued to undergo chemotherapy at the department of oncology of our hospital. Mesenteric lymph node metastases were found at the postoperative 1-mo follow-up. CONCLUSION: Palpable, painful scrotal mass, history of gastric cancer, and imaging features may indicate testicular and epididymal metastatic gastric cancer.

Reciprocal positive regulation between BRD4 and YAP in GNAQ-mutant uveal melanoma cells confers sensitivity to BET inhibitors.

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations. Here, we identified a causal link between Gq activating mutations and hypersensitivity to bromodomain and extra-terminal (BET) inhibitors. BET inhibitors transcriptionally repress YAP via BRD4 regardless of Gq mutation status, independently of Hippo core components LATS1/2. In contrast, YAP/TAZ downregulation reduces BRD4 transcription exclusively in Gq-mutant cells and LATS1/2 double knockout cells, both of which are featured by constitutively active YAP/TAZ. The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.

Genome insights from the identification of a novel Pandoraea sputorum isolate and its characteristics.

In this study, we sequenced a bacteria isolate Pandoraea sp. 892iso isolated from a Phytophthora rubi strain which is an important plant pathogenic oomycete, identified through genome and combined the data with existing genomic data from other 28 the genus of Pandoraea species. Next, we conducted a comparative genomic analysis of the genome structure, evolutionary relationships, and pathogenic characteristics of Pandoraea species. Our results identified Pandoraea sp. 892iso as Pandoraea sputorum at both the genome and gene levels. At the genome level, we carried out phylogenetic analysis of single-copy, gene co-linearity, ANI (average nucleotide identity) and AAI (average amino acid identity) indices, rpoB similarity, MLSA phylogenetic analysis, and genome-to-genome distance calculator calculations to identify the relationship between Pandoraea sp. 892iso and P. sputorum. At the gene level, the quorum sensing genes ppnI and ppnR and the OXA-159 gene were assessed. It is speculated that Pandoraea sp. 892iso is the endosymbiont of the Oomycetes strain of Phytophthora rubi.