The association between computed tomography attenuation value of renal angiomyolipoma associated with tuberous sclerosis complex and response to everolimus.

BACKGROUND: The response to everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML) varies among individuals. This study aims to identify potential factors associated with the response to everolimus. METHOD: We retrospectively examined data encompassing age, gender, tumor size, computed tomography attenuation value (CT value), CT enhancement, and tumor reduction rate in patients with TSC-RAML undergoing everolimus in two previously registered clinical trials. RESULT: A total of 33 participants (29.33 ± 6.63 years old, 20 females) were included. The correlation analysis conducted separately for tumors located in the left and right kidneys revealed significant negative correlations (P < 0.05) between tumor reduction rate and age, as well as tumor size. While significant positive correlations (P < 0.05) were observed between tumor reduction rate and unenhanced CT value as well as CT enhancement. Nonetheless, based on multiple linear regression analysis, unenhanced CT value emerged as the sole-independent predictor of tumor reduction rate among age, gender, tumor size, unenhanced CT value and CT enhancement for both left (coefficient = 0.00319, P < 0.0001) and right kidneys (coefficient = 0.00315, P = 0.0104). Notable reductions were observed in unenhanced CT value (- 3.81 vs - 24.70HU, P < 0.0001) and CT enhancement (48.16 vs 33.56HU, P < 0.0001) following a 3-month administration of everolimus. The decline in both unenhanced CT value and tumor size predominantly occurred within the initial 3 months, subsequently maintaining a relatively stable level throughout the treatment. CONCLUSION: The unenhanced CT value of TSC-RAML showed an independent correlation with the response to everolimus, suggesting its potential as a predictor of everolimus efficacy in patients with TSC-RAML.

New staging criteria predicting m-tor inhibitors treatment effect of renal angiomyolipoma in tuberous sclerosis complex patients.

BACKGROUND: We aimed to launched new staging criteria to predict mTOR inhibitors treatment effect of renal angiomyolipomas (r-AMLs) in TSC patients. METHODS: 40 TSC patients with 69 r-AMLs were divided into two groups based on the efficacy of 6-month mTOR inhibitor treatment. Epidemiological data, therapeutic response, and predictive factors of enrolled patients were collected and analyzed. Age, sex, maximum diameter, maximum cross-sectional area (CSAmax), unenhanced mean CT value, enhanced mean CT value, and added value of enhanced CT of largest r-AML at baseline were assessed as potential influencing factors. Receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) was used to estimate prediction power. RESULTS: After 6 months of mTOR inhibitor treatment, the tumor reduction rates in the two groups were 55.87% and 16.44% (P < 0.001). At the start of treatment, the maximum diameters, CSAmax, added value of enhanced CT of the target lesion in two groups were 7.70 ± 0.73 cm vs. 13.18 ± 1.23 cm(P = 0.028), 57.40 ± 10.76cm2 vs. 167.29 ± 33.09cm2 (P = 0.015), and 62.32 ± 5.03HU vs. 33.06 ± 3.13HU (P = 0.009), respectively. AUCs of CSAmax, added value of enhanced CT, and combination of both were 0.8024, 0.7672, and 0.8116, respectively (P < 0.001). Cut-off values of CSAmax combined with the added value of enhanced CT were 40cm2 and 46HU. AUCs of maximum diameters, combination of maximum diameters and added value of enhanced CT were 0.7600 and 0.8100, respectively (P < 0.001), with cut-off values of 6.6 cm and 46 HU. CONCLUSION: New staging criteria, based on CSAmax and added value of enhanced CT, can predict the treatment efficiency of m-TOR inhibitors for r-AMLs in TSC patients. A simplified version based on maximum diameter and added value of enhanced CT of lesion has also been proposed.

[Intrauterine Device Totally Embedded in the Bladder Wall:Report of One Case].

Intrauterine device(IUD)migrating to the bladder is rare,especially the migration far away from the uterus into the bladder wall.Due to no obvious clinical symptom in the early stage and being far away from the uterus,the IUD totally embedded in the bladder wall is prone to misdiagnosis and delay in treatment.We reported one case of such migration,aiming to improve the clinical management of the IUD totally embedded in the bladder wall.

Is milder psychological stress responsible for more severe erectile dysfunction?

China is a sexually conservative country compared with Western countries. To evaluate the psychological characteristics of Chinese erectile dysfunction (ED) patients, we conducted a cross-sectional study of 153 ED outpatients. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. ED was measured by International Index of Erectile Function (IIEF). Depression and anxiety were evaluated with 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalised Anxiety Disorder Scale (GAD-7) respectively. Most patients (74.5%) were <40 years old. IIEF-5 were significantly correlated with SIEDY scale 3 (r = .16, p = .040) and GAD-7 (p = .15, p = .033). The SIEDY scale 1 increased with age, but the IIEF-5, SIEDY scale 3, PHQ-9 and GAD-7 decreased with age. A negative correlation was observed between ED and psychological stress, which conflicts with many Western-country studies. Younger patients were characterised by milder ED but more psychological stress, while older patients were characterised by worse ED but less psychological stress. Which may be responsible for the conflicting result. Meanwhile, the much younger age distribution among Chinese ED outpatients may indicate that quite a few older ED patients (≥40 years) in China do not seek outpatient service which should merit more attention.

Dysuria due to benign prostatic hyperplasia of the median lobe with ketamine-associated uropathy in a young male.

BACKGROUND: Benign prostatic hyperplasia (BPH) rarely occurs in children or young males. In this case report, a 29-year-old male patient diagnosed with BPH coexisting with ketamine-associated uropathy was reported to investigate the possible relationship between BPH and ketamine-associated uropathy as well as therapeutic strategies. CASE PRESENTATION: A 29-year-old male patient with a 3-year history of ketamine inhalation, complaining of dysuria with frequency and urgency, was admitted. Hydronephrosis, hydroureters, uneven bladder wall thickening and a tumour located in the outlet of the bladder were detected with computed tomography (CT). The patient agreed to cystoscopy under general anaesthesia. A spherical tumour with a diameter of approximately 2 cm was found to originate from the median lobe of the prostate and follicular lesions were diffusely distributed on the right bladder wall. The tumour and follicular lesions in the bladder were resected successfully, and pathology demonstrated BPH and chronic inflammation of the mucous membranes separately. The patient quit ketamine completely during the one-year follow-up. Dysuria was relieved completely and no tumour or follicular neoplasm recurrence was found. CONTRIBUTION: Inflammation in the urothelium, as a direct or indirect consequence of ketamine, may contribute to the development of BPH. Both surgical interventions to remove obstruction and ketamine cessation are necessary approaches.

The impact of everolimus on hematologic parameters in patients with renal angiomyolipoma associated with tuberous sclerosis complex.

BACKGROUND: Everolimus is an effective treatment for renal angiomyolipoma associated with TSC (TSC-RAML). However, its impact on hematologic parameters in TSC-RAML patients remains unclear. METHODS: Hematologic data were collected from TSC-RAML patients undergoing everolimus treatment in two registered clinical trials. Dynamic changes in hematologic parameters during treatment were analyzed. Additionally, we also explored variations in hematologic impact based on gender and age within the patient population. RESULT: A total of 55 patients from the two clinical trials are included in this analysis. Hemoglobin, white blood cells (WBC), lymphocytes, neutrophils, and platelet showed significant decreases during everolimus treatment (P < 0.05). However, the decline in hemoglobin, WBC, and neutrophils attenuated by the 12th month (P ≥ 0.05). Aspartate transaminase (AST), Alanine transferase (ALT), total cholesterol (TC), and triglyceride (TG) increased significantly during everolimus treatment (P < 0.05), and these increases persisted throughout the year-long treatment. Hemoglobin decreased significantly more in male patients (- 15 vs - 6, P = 0.010), and AST showed a more significant increase in males (7.0 vs 3.0, P = 0.041). Platelet counts decreased significantly more in younger patients (≤ 30 years old) compared to older patients (- 50 vs - 14, P = 0.020). CONCLUSION: Everolimus administration in TSC-RAML patients may increase hematologic risks, with male and younger patients potentially exhibiting greater susceptibility to these effects.

The predictive value of PFKFB3 in bladder cancer prognosis.

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to evaluate the prognostic significance of PFKFB3 in bladder cancer (BLCA) patients by analyzing a combination of publicly available databases, clinical patient data, and bladder tumor samples from our hospital. Single-cell and bulk RNA-seq data of bladder cancer, obtained from ENA, GEO, and TCGA databases, were utilized for our analysis. The results indicated that PFKFB3 mRNA expression was markedly elevated in bladder cancer compared to paired normal tissue. Furthermore, BLCA patients with high PFKFB3 expression exhibited a significantly worse prognosis (P < 0.05). To validate these findings, clinical data and immunohistochemistry staining were performed on specimens obtained from 89 BLCA patients who underwent radical cystectomy at either Qingdao University Affiliated Hospital or Peking Union Medical College Hospital. The findings from this verification process confirmed that high expression of PFKFB3 serves as a biomarker for predicting worse prognosis in BLCA patients (OR: 2.462, 95 % CI: 1.202-5.042, P = 0.012). To facilitate clinical application, we developed a nomogram based on four variables, including PFKFB3 expression, to predict the survival of BLCA patients. Importantly, this nomogram demonstrated a low mean prediction error of 0.03. Taken together, our findings suggest that PFKFB3 has the potential to serve as both a prognostic biomarker and a therapeutic target for BLCA patients.

Surgical strategies of complicated pheochromocytomas/paragangliomas and literature review.

Pheochromocytomas (PCC)/paragangliomas (PGL) are catecholamine (CA) -secreting neuroendocrine tumors, which are known as PPGL due to their histological and pathophysiological similarities. In addition to the typical triad of paroxysmal headache, palpitation, and sweating, PPGL may also be accompanied by symptoms and signs involving multiple organs and systems such as the cardiovascular system, digestive system, endocrine system, and nervous system. Currently, surgical resection is the first choice for PPGL. Safe and effective surgical management of complicated PPGL is the goal of clinical work. In this paper, we discuss this hot issue based on complicated PPGL cases, aiming to share our experience of the surgical management strategy of PPGL.

Pure androgen-secreting adrenal tumor (PASAT): A rare case report of bilateral PASATs and a systematic review.

Background: Adult pure androgen-secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown. Methods: A rare case of adult bilateral PASATs was reported, and a systematic literature review of adult PASATs was conducted to summarize the characteristics of PASATs. Results: In total, 48 studies, including 40 case reports and 8 articles, were identified in this review. Analysis based on data of 42 patients (including current case and 41 patients from 40 case reports) showed that average age was 40.48 ± 15.80 years (range of 18-76). The incidence of adult PASAT peaked at 21-30 years old, while that of malignant PASAT peaked at 41-50 years old. Most PASAT patients were female (40/42, 95.23%), and hirsutism was the most common symptom (37/39, 94.87%). Testosterone (T) was the most commonly elevated androgen (36/42, 85.71%), and 26 of 32 tested patients presented increased dehydroepiandrosterone sulfate (DS) levels. In malignancy cases, disease duration was significantly decreased (1.96 vs. 4.51 years, P=0.025), and tumor diameter was significantly increased (8.9 vs. 4.9 cm, p=0.011). Moreover, the androgen levels, namely, T/upper normal range limit (UNRL) (11.94 vs. 4.943, P=0.770) and DS/UNRL (16.5 vs. 5.28, P=0.625), were higher in patients with malignancy. In total, 5 out of 7 patients showed an increase in DS or T in the human chorionic gonadotropin (HCG) stimulation test. Overall, 41 out of 42 patients (including current case) underwent adrenal surgery, and recurrence, metastasis, or death was reported in 5 out of 11 malignant patients even with adjuvant or rescue mitotane chemotherapy. Conclusion: Adult PASAT, which is predominant in women, is characterized by virilism and menstrual dysfunction, especially hirsutism. Elevated T and DS may contribute to the diagnosis of adult PASAT, and HCG stimulation test might also be of help in diagnosis. Patients with malignant PASAT have a shorter disease duration, larger tumor sizes and relatively higher androgen levels. Surgery is recommended for all local PASATs, and Malignancy of PASAT should be fully considered due to the high risk of malignancy, poor prognosis and limited effective approaches.

UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment.

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis. Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms. Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism. Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.

Construction of TSC2 knockout cell line using CRISPR/Cas9 system and demonstration of its effects on NIH-3T3 cells.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder involving multiple organ systems. TSC2 gene plays an important role in the development of TSC. The most common kidney manifestation of TSC is renal angiomyolipoma (RAML). TSC-RAML is more likely to be bilateral multiple tumors and tends to destroy the renal structure and damages renal function severely. As a result, patients with TSC-RAML often miss the opportunity for surgical treatment when TSC-RAML is diagnosed, causing difficulty in obtaining tumor specimens through surgery. Due to this difficulty, model cell lines must be constructed for scientific research. In this paper, TSC2 was knocked out in NIH-3T3 cell lines by CRISPR/Cas9 system. PCR, WB and mTOR inhibitor drug sensitivity test showed that the TSC2 knockout NIH-3T3 cells were successfully constructed. The ability of proliferation and invasion in TSC2 KO NIH-3T3 cells were higher than those in wild type group. The constructed KO cell line lay the foundation for further study of TSC.

A multi­omics study of diagnostic markers and the unique inflammatory tumor micro­environment involved in tuberous sclerosis complex­related renal angiomyolipoma.

Tuberous sclerosis complex (TSC) is a rare disease that threatens multiple organs in the human body. TSC­associated renal angiomyolipoma (TSC­RAML) has potentially life­threatening complications and a generally poor prognosis. The present study aimed to find plasma proteomic diagnostics and disease­associated markers, and explore the tumor microenvironment using multi­omics. To achieve this goal, the plasma proteomics as well as tissue proteomics, bulk and single­cell RNA transcriptome from patients with TSC­RAML were examined and analyzed. The results suggested that plasma proteins such as MMP9 and C­C motif chemokine ligand 5 were able to differentiate TSC­RAML from sporadic angiomyolipoma and renal cyst. A correlation analysis revealed that plasma proteomics were associated with lymphangioleiomyomatosis, TSC­RAML grading and whole­body disease burden. Tissue proteomics of participants with TSC­RAML revealed disturbed small molecule catabolic process, mitochondrial matrix component and actin binding function. Bulk and single­cell RNA sequencing suggested a greater number of tumor­like cells, fibroblasts and mononuclear macrophages within the tumor microenvironment. The above results indicated that TSC­RAML exhibited a characteristic and disease­associated plasma proteomic profile. The unique microenvironment, made up of fibroblasts and mono­macrophages, may promote tumorigenesis and TSC­RAML progression.

The Relationship Between Hematologic Parameters and Erectile Dysfunction.

INTRODUCTION: Certain hematologic parameters related to blood cells, known as the biomarkers that predict cardiovascular disease, might be potential predictors of erectile dysfunction (ED) due to the shared pathophysiology between ED and cardiovascular disease . AIM: To investigate the relationship between ED and these hematologic parameters and the clinical significance of hematologic parameters for the diagnosis of ED. METHODS: A total of 113 male patients diagnosed with ED were included in this study. Blood samples were collected before 10:00 AM for blood cells examination, biochemical tests, and sex hormone analysis. Another 212 healthy controls without ED from the health management center was included as the control group. The relationship between hematologic parameters and ED was assessed by comparing differences in body mass index (BMI), biochemical indexes and hematologic parameters between the 2 groups, and the diagnostic value of hematologic parameters for ED was also examined and compared. MAIN OUTCOME MEASURES: International Index of Erectile Function, hematologic parameters RESULTS: The neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in ED patients were significantly higher than those in healthy controls, whereas the lymphocyte count (LC) was significantly lower than that in healthy controls. After adjusting for age, BMI, uric acid (UA), fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), increases in the NC, NLR, and PLR and a decrease in the LC were shown to be independent risk factors for ED. Receiver operating characteristic (ROC) curve analysis showed that the NLR exhibited better diagnostic performance for ED than the other parameters. CONCLUSION: Increases in the NC, NLR, and PLR and a decrease in the LC significantly increased the risk of ED. The NC, LC, NLR and PLR could contribute to the diagnosis and assessment of ED. Zhangcheng L, Yuxin T, Xiucheng L and Dongjie L, et al. The Relationship Between Hematologic Parameters and Erectile Dysfunction. Sex Med 2021;9:100401.

Is mild erectile dysfunction associated with severe psychological symptoms in Chinese patients with moderate-to-severe chronic prostatitis/chronic pelvic pain syndrome?

This study aimed to assess the association between psychological disorders and erectile dysfunction (ED) in patients with different degrees of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This was a retrospective study conducted from June 2017 to October 2019 and included 182 outpatients. Patients were interviewed using the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) were used for the evaluation of CP/CPPS and ED. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety symptoms and depressive symptoms. The number of patients with mild CP/CPPS and mild ED, mild CP/CPPS and moderate-to-severe ED, moderate-to-severe CP/CPPS and mild ED, and moderate-to-severe CP/CPPS and moderate-to-severe ED was 69 (37.9%), 36 (19.8%), 35 (19.2%), and 42 (23.1%), respectively. The corresponding PHQ-9 scores of the four groups were 6.22, 7.19, 10.69, and 7.71, respectively. The corresponding GAD-7 scores of the four groups were 5.26, 6.31, 8.77, and 6.36, respectively. Among patients with moderate-to-severe CP/CPPS, the PHQ-9 and GAD-7 scores of the moderate-to-severe ED group were significantly lower than those of the mild ED group (P = 0.007 and P = 0.010, respectively). The prevalence of ED and premature ejaculation (PE) in patients with moderate-to-severe CP/CPPS was significantly higher than that in patients with mild CP/CPPS (P = 0.001 and P = 0.024, respectively). Our findings proved that the severity of ED was negatively associated with psychological symptoms in outpatients with moderate-to-severe CP/CPPS.

Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease?

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular diseases (CVDs) share many common risk factors. ED could be a strong independent predictive factor of CVDs. Furthermore, the treatment of ED had been shown to be beneficial for cardiovascular diseases. However, the association between ED and CVDs has been reported scarcely in the literature. AIM: To investigate urologists' perception, diagnosis, and treatment of CVDs in patients with ED. METHODS: The study was conducted as a prospective study from November 2018 through February 2019, including urologists aged 18-64 years. All participants completed a survey of the knowledge of ED via an online questionnaire platform in 7 WeChat groups of urologists. WeChat is the most popular multipurpose messaging and social media in China. MAIN OUTCOME MEASURE: The main outcomes were the answers that urologists chose or filled. RESULTS: 449 urologists were included. Most of participants (375, 83.5%) agreed that CVDs are associated with ED. Only 231 participants (51.4%) thought ED was an independent disorder. The awareness of the association between ED and CVDs is significantly higher among male urologists than their female counterparts. Although 378 (83.6%) participants believed that the progression of these 2 diseases was consistent, only 181 (44.9%) would do conjoined assessment of both CVDs and ED. In addition, most urologists only considered conventional treatment, such as psychological intervention (341, 75.4%) and phosphodiesterase type 5 inhibitor (PDE5i) therapy (318, 70.4%) for their patients, whereas 339 urologists (88.3%) claimed that they would treat CVDs in patients with both ED and CVDs. 344 (76.6%) urologists showed some concerns over PDE5is. CONCLUSION: Urologists' assessment of CVDs in patients with ED was disappointing especially among young and female urologists or those working in underserved areas. Besides, the urologists' treatments of ED were not updated, and their attitudes toward the safety and effectiveness of PDE5is for CVDs were not optimistic. Li D, Li X, Peng A, et al. Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease? Sex Med 2020;8:195-204.

A thermally activated delayed fluorescence exciplex to achieve highly efficient and stable blue and green phosphorescent organic light-emitting diodes.

The development of a thermally activated delayed fluorescence (TADF) exciplex with high energy is of great significance in achieving highly efficient blue, green, and red organic light-emitting diodes (OLEDs) for use in full-color displays and white lighting. Highly efficient and stable blue and green phosphorescent OLEDs were demonstrated by employing a TADF exciplex (energy: 2.9 eV) based on 4-substituted aza-9,9'-spirobifluorenes (aza-SBFs). Blue PhOLEDs demonstrated a maximum current efficiency (CE) of 47.9 cd A-1 and an external quantum efficiency (EQE) of 22.5% at 1300 cd m-2 (2.5 times the values of aza-SBF-based systems), with the best blue PhOLED demonstrating a CE, power efficiency (PE) and EQE of 60.3 cd A-1, 52.7 lm W-1, and 26.2%, respectively. Green PhOLEDs exhibited a CE of 78.1 cd A-1 and EQE of 22.5% at 9360 cd m-2, with the best green PhOLED exhibiting a maximum CE, PE, and EQE of 87.4 cd A-1, 101.6 lm W-1, and 24.5%, respectively. The device operational lifetime was improved over 17-fold compared to reference devices because of the high thermal stability of the materials and full utilization of the TADF exciplex energy, indicating their potential for application in commercial OLEDs.