Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs.

Increasing evidence suggests that autophagy plays a major role during renal fibrosis. Transcription factor EB (TFEB) is a critical regulator of autophagy- and lysosome-related gene transcription. However, the pathophysiological roles of TFEB in renal fibrosis and fine-tuned mechanisms by which TFEB regulates fibrosis remain largely unknown. Here, we found that TFEB was downregulated in unilateral ureteral obstruction (UUO)-induced human and mouse fibrotic kidneys, and kidney-specific TFEB overexpression using recombinant AAV serotype 9 (rAAV9)-TFEB in UUO mice alleviated renal fibrosis pathogenesis. Mechanically, we found that TFEB's prevention of extracellular matrix (ECM) deposition depended on autophagic flux integrity and its subsequent blockade of G2/M arrest in tubular cells, rather than the autophagosome synthesis. In addition, we together RNA-seq with CUT&Tag analysis to determine the TFEB targeted gene ATP6V0C, and revealed that TFEB was directly bound to the ATP6V0C promoter only at specific site to promote its expression through CUT&Run-qPCR and luciferase reporter assay. Interestingly, TFEB induced autophagic flux integrity, mainly dependent on scaffold protein ATP6V0C-mediated autophagosome-lysosome fusion by bridging with STX17 and VAMP8 (major SNARE complex) by co-immunoprecipitation analysis, rather than its mediated lysosomal acidification and degradation function. Moreover, we further investigated the underlying mechanism behind the low expression of TEFB in UUO-induced renal fibrosis, and clearly revealed that TFEB suppression in fibrotic kidney was due to DNMT3a-associated TFEB promoter hypermethylation by utilizing methylation specific PCR (MSP) and bisulfite-sequencing PCR (BSP), which could be effectively recovered by 5-Aza-2'-deoxycytidine (5A-za) to alleviate renal fibrosis pathogenesis. These findings reveal for the first time that impaired TFEB-mediated autophagosome-lysosome fusion disorder, tubular cell G2/M arrest and renal fibrosis appear to be sequentially linked in UUO-induced renal fibrosis and suggest that DNMT3a/TFEB/ATP6V0C may serve as potential therapeutic targets to prevent renal fibrosis.

Analysis of risk factors affecting the postoperative drainage after a laparoscopic partial nephrectomy: a retrospective study.

Purpose: Laparoscopic partial nephrectomy (LPN) remains the most commonly used measure for treating localized renal cell cancer (RCC) with an increasing incidence of RCC ever since the 1990s. This study aimed to identify risk factors that affect the postoperative time of drainage and total drainage volume after LPN. Method: The clinical data of 612 RCC patients who received LPN from January 2012 to December 2022 in our hospital, including the postoperative drainage time and total drainage volume, were retrospectively analyzed. Univariable and multivariable linear regression and correlation analyses were used to identify the correlations between 21 factors, which include gender, age, history of alcohol consumption, family history of RCC, body weight, body mass index (BMI), and operation time, postoperative drainage time, and total drainage volume. Results: The mean time of drainage was 3.52 ± 0.71 days (range: 2 to 8 days), with an average total drainage volume of 259.83 ± 72.64 mL (range: 50 to 620 mL). Both univariable and multivariable linear regression analyses revealed several statistically significant associations. Gender (p = 0.04), age (p = 0.008), smoking history (p < 0.001), diabetes (p = 0.032), operation time (p = 0.014), and BMI (p = 0.023) were identified as significant factors associated with the time of drainage. On the other hand, age (p = 0.008), smoking history (p < 0.001), diabetes (p = 0.006), and BMI (p = 0.016) emerged as independent risk factors influencing the total drainage volume. Conclusion: The duration of postoperative drainage was found to be associated with gender, age, smoking history, diabetes, operation time, and BMI. In contrast, the total drainage volume was primarily influenced by age, smoking history, diabetes, and high BMI following LPN. For patients with these conditions, meticulous attention to hemostasis and bleeding control is crucial during the perioperative period.

Frailty as a risk marker of adverse lower urinary symptom outcomes in patients with benign prostatic hyperplasia undergoing transurethral resection of prostate.

Purpose: Lower urinary symptoms (LUTS) may persist in a proportion of patients with benign prostatic hyperplasia (BPH) following transurethral resection of prostate (TURP), which is a major cause of reduced quality-of-life. We aimed to investigate the effect of frailty on LUTS in patients with BPH treated with TURP. Methods: We longitudinally evaluated LUTS and health-related quality-of-life (HRQOL) in patients with BPH treated with TURP from February 2019 and January 2022 using International Prostate Symptom Score (IPSS) and Short Form-8 (SF-8), respectively. Patients were divided into frail and non-frail groups according to the Fried phenotype (FP). The primary purpose was comparing the outcomes of LUTS and HRQOL between two groups. Secondary purposes were investigating the frailty as a preoperative predictor of postoperative adverse LUTS outcomes following TURP using logistic regression analysis. A 1:2 propensity score matching (PSM) was performed to reduce the effects of selection bias and potential confounders. Results: Of the 567 patients enrolled, 495 (87.3%) patients were non-frail (FP = 0-2), and the remaining 72 (12.7%) patients were classified into the frail group. There were no significant differences in body mass index (BMI), urine white blood cell (UWBC), creatinine, prostate-specific antigen (PSA) and prostate volume in both groups at baseline (all p > 0.05). However, patients with frailty were older, higher comorbidity rates, lower peak flow rates and lower HRQOL. In the frail group, although LUTS and HRQOL at 6 months following TURP improved significantly compared to those at baseline, it did not show a significant improvement compared with the non-frail group (both p < 0.001). Moreover, multivariable logistic regression analysis demonstrated that preoperative frailty was significantly associated with poor LUTS improvement in both the entire cohort and PSM subset (both p < 0.05), whereas age and comorbidities were not after PSM analysis. Conclusion: In patients with frail or non-frail, TURP for BPH provides overall good results. However, frail individuals are at higher risk of postoperative adverse LUTS outcomes. Frailty has the potential to be a strong objective tool for risk stratification and should be considered during the perioperative evaluation.

Hypertension Resolution after Laparoscopic Adrenal Tumor Resection in Patients of Adrenal Incidentaloma with Normal Hormone Levels.

INTRODUCTION: Postoperative hypertension resolution among patients with adrenal incidentalomas and normal hormone levels was unknown. Identifying the predictive factors was beneficial to the management of adrenal incidentalomas. METHODS: We conducted a retrospective cohort study, recruiting patients undergoing laparoscopic adrenal tumor resection for adrenal incidentaloma with hypertension and normal hormone levels. Demographic, clinical, treatment, and laboratory data were collected and compared. We used univariable and multivariable logistic regression methods to identify the predictive factors of postoperative hypertension resolution. RESULTS: Of the 171 patients in our study, 130 (76.0%) patients performed a resolution of hypertension, and 57 (33.3%) patients had a significant reduction. Multivariate logistic regression analysis showed that the male sex (odds ratio (OR) 0.305, 95% confidence interval (CI): 0.098-0.948, p = 0.040), body mass index (BMI) (OR 0.973, 95% CI: 0.670-0.938, p = 0.007), aldosterone and plasma renin activity ratio (APR) in erect position (OR 1.206, 95% CI: 1.042-1.397, p = 0.012), and preoperative systolic pressure (OR 1.044, 95% CI: 1.009-1.080, p = 0.014), were significantly associated with the outcomes of hypertension resolution. DISCUSSION/CONCLUSION: Adrenal incidentalomas patients with hypertension and normal hormone levels would perform hypertension resolution after laparoscopic adrenal tumor resection, especially for females with low BMI, high preoperative systolic blood pressure, and high APR (erect position).

Multi-Scale Superpixel-Guided Structural Profiles for Hyperspectral Image Classification.

Hyperspectral image classification has received a lot of attention in the remote sensing field. However, most classification methods require a large number of training samples to obtain satisfactory performance. In real applications, it is difficult for users to label sufficient samples. To overcome this problem, in this work, a novel multi-scale superpixel-guided structural profile method is proposed for the classification of hyperspectral images. First, the spectral number (of the original image) is reduced with an averaging fusion method. Then, multi-scale structural profiles are extracted with the help of the superpixel segmentation method. Finally, the extracted multi-scale structural profiles are fused with an unsupervised feature selection method followed by a spectral classifier to obtain classification results. Experiments on several hyperspectral datasets verify that the proposed method can produce outstanding classification effects in the case of limited samples compared to other advanced classification methods. The classification accuracies obtained by the proposed method on the Salinas dataset are increased by 43.25%, 31.34%, and 46.82% in terms of overall accuracy (OA), average accuracy (AA), and Kappa coefficient compared to recently proposed deep learning methods.

Qualification of Necroptosis-Related lncRNA to Forecast the Treatment Outcome, Immune Response, and Therapeutic Effect of Kidney Renal Clear Cell Carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) is considered as a highly immune infiltrative tumor. Necroptosis is an inflammatory programmed cell death associated with a wide range of diseases. Long noncoding RNAs (lncRNAs) play important roles in gene regulation and immune function. lncRNA associated with necroptosis could systematically explore the prognostic value, regulate tumor microenvironment (TME), etc. Method: The patients' data was collected from TCGA datasets. We used the univariate Cox regression (UCR) to select prediction lncRNAs that are related to necroptosis. Meanwhile, risk models were constructed using LASSO Cox regression (LCR). Kaplan-Meier (KM) analysis, accompanied with receiver operating characteristic (ROC) curves, was performed to assess the independent risk factors of different clinical characteristics. The evaluated factors are age, gender, disease staging, grade, and their related risk score. Databases such as Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSEA) were used to search the probable biological characteristics that could influence the risk groups, containing signaling pathway and immue-related pathways. The single-sample gene set enrichment analysis (ssGSEA) was chosen to perform gene set variation analysis (GSVA), and the GSEABase package was selected to detect the immune and inflammatory infiltration profiles. The TIDE and IC50 evaluation were used to estimate the effectiveness of clinical treatment on KIRC. Results: Based on the above analysis, we have got a conclusion that patients who show high risk had higher immune infiltration, immune checkpoint expression, and poorer prognosis. We identified 19 novel prognostic necroptosis-related lncRNAs, which could offer opinions for a deeper study of KIRC. Conclusion: The risk model we constructed makes it possible to predict the prognosis of KIRC patients and offers directions for further research on the prognostication and treatment strategies for KIRC.

A Multilayer Nanofibrous Mat for the Topical Chemotherapy of the Positive Margin in Bladder Cancer.

Treatment of positive margins after solid tumor resection remains a significant challenge for clinicians. Owing to unique structural features, electrospun nanofibrous mats are promised to be an implantable antitumor system through the delivery of active agents in a controlled manner. In this study, we utilized sequential electrospinning to fabricate a multilayer mat in which gemcitabine (GEM) and cisplatin (CDDP) were electrospun individually in distinct layers. By designing the structure, the multilayer mat could deliver antitumor agents sustainedly and prolong the release of GEM, which is loaded in the inner layer. In vitro assays show that the multilayer mats effectively inhibit bladder cancer (BC) cells and elevate apoptosis. In animal models of BC, the implantable drug-loaded fibrous mat can effectively treat positive margins and prevent local recurrence. Moreover, the local delivery of GEM and CDDP significantly lowers liver toxicity compared with systemic chemotherapy. In summary, a multilayer nanofibrous mat is developed for the localized and controlled delivery of GEM, dramatically improving the treatment of residual tumors and preventing BC recurrence. Impact statement The designed multilayer nanofibrous mats can achieve two chemotherapeutic drugs (gemcitabine and cisplatin) co-loading and time-programmed sustained release, significantly improving our previous study. The antitumor effect of the drug-loaded mat in vivo and in vitro was sufficiently demonstrated. We expect to bring a new strategy of topical chemotherapy for treating positive surgical margins in bladder cancer.

Tislelizumab in combination with gemcitabine plus cisplatin chemotherapy as first-line adjuvant treatment for locally advanced or metastatic bladder cancer: a retrospective study.

BACKGROUND: Combining immune checkpoint inhibitors with chemotherapy can synergistically improve antitumor activity and are generally well tolerated. Recently, the efficacy and safety of combination therapy has been demonstrated for many cancers, including urothelial carcinomas. The aim of this retrospective pilot study was to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line adjuvant treatment for locally advanced or metastatic bladder cancer. METHODS: We conducted a retrospective analysis of 31 patients with locally advanced or metastatic bladder cancer from December 2020 to January 2022 with an Eastern Cooperative Oncology Group performance status of 0/1. Of the 31 patients, 14 patients received tislelizumab (200 mg i.v. every 3 weeks, Q3W) plus 21 days cycles of chemotherapy (gemcitabine, 1000 mg/m2 i.v. on days 1 and 8 of each cycle + cisplatin, 70 mg/m2 i.v. on day 2 of each cycle) (TGC) treatment and 17 patients received gemcitabine plus cisplatin chemotherapy (GC) treatment. All patients treated with bladder cytoreductive surgery and were treated for four 21 days cycles until disease progression or intolerable treatment-related adverse events (TRAEs). The objective progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and TRAEs were recorded and reviewed. RESULTS: As of the cut-off date (March 25, 2022), PFS, OS, ORR, DCR, CBR and TRAEs were evaluated in 14 patients receiving combination therapy and 17 patients in the chemotherapy alone group. The median PFS was 36.0 [95% confidence interval (CI) 33.1-38.9] weeks in the TGC group and 29.0 (95% CI 25.4-32.6) weeks in the GC group [hazard ratio (HR) 0.15 (95% CI 0.04-0.55)]. In the GC group, the median OS was 48.0 (95% CI 39.7-56.3) weeks; the median OS was not yet mature for the TGC group [HR 0.26 (95% CI 0.07-0.94)]. Treatment with TGC resulted in improved DCR (TGC 71.4%; GC 65.0%) and CBR (TGC 64.3%; GC 52.9%) compared with GC. However, although higher incidences of grade ≥ 3 TRAEs were observed with TGC compared with GC (35.7% vs 23.5%), the difference was not statistically significant (p = 0.47). CONCLUSION: This study suggested that TGC provided survivors of locally advanced or metastatic bladder cancer with encouraging antitumor activity and was generally well tolerated.

Successful management of the stone inside Allium bulbar urethral stent: A very interesting and rare case.

The stone inside the Allium bulbar urethral stent for treatment of urethral stenosis is an exceedingly rare disease. Herein, we report a case of the stone inside the Allium bulbar urethral stent(BUS) for treating urethral stricture in a 48-year-old Chinese male patient. The patient underwent a cystoscopy and URS for the stone inside BUS. The patient had only a symptom of urodynia. Urination of the patient is unobstructed after removing BUS and the urethral stricture of the patient was cured.

Clinicopathological factors associated with pathological upgrading from biopsy to prostatectomy in patients with ISUP grade group ≤2 prostate cancer.

We performed this study to investigate pathological upgrading from biopsy to prostatectomy and clinicopathological factors associated with grade group (GG) upgrading in patients with International Society of Urological Pathology (ISUP) GG 1 and 2 prostate cancer (PCa) in a Chinese cohort. We included patients diagnosed with PCa with ISUP GG 1 and 2 at biopsy, who underwent RP at our institution. Pre- and postoperative clinical variables were examined. Univariate and multivariate logistic regression analyses were conducted to identify independent factors associated with GG upgrading. Patients in GG upgraded group had higher total prostate-specific antigen (tPSA; median: 14.43 ng ml-1 vs 10.52 ng ml-1, P = 0.001) and PSA density (PSAD; median: 0.45 ng ml-2 vs 0.27 ng ml-2, P < 0.001) than those in GG nonupgraded group. Patients in upgraded group had a higher ratio for Prostate Imaging-Reporting and Data System (PI-RADS) score >3 (86.4% vs 67.9%, P < 0.001). Those with GG 1 in biopsy were more likely to experience GG upgrading after RP than those with GG 2 (71 vs 54, P = 0.016). Independent preoperative factors predicting GG upgrading were PI-RADS score >3 (odds ratio [OR]: 2.471, 95% confidence interval [CI]: 1.132-5.393; P = 0.023), higher PSAD (P = 0.001), and GG in biopsy (OR: 0.241, 95% CI: 0.123-0.471; P < 0.001). The histopathological analyses of RP specimens revealed that perineural invasion (PNI; OR: 1.839, 95% CI: 1.027-3.490; P = 0.041) was identified as an independent factor associated with GG upgrading. Our results revealed that GG in the biopsy, PSAD, PI-RADS score >3, and PNI were independent factors of GG upgrading. These factors should be considered for patients with ISUP grade ≤2 PCa.

Standardized Incidence Rate, Risk and Survival Outcomes of Second Primary Malignancy Among Renal Cell Carcinoma Survivors: A Nested Case-Control Study.

PURPOSE: Second primary malignancy (SPM) is challenging for treatment and long-term survival. We sought to investigate the standardized incidence rate (SIR), risk factors, and survival outcomes for SPM after renal cell carcinoma (RCC) treatment. METHOD: A nested case-control study was designed, we identified all T1-4N0-1M0 RCC patients diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database and followed them for SPM diagnosis for up to 13 years. Patients with SPM diagnosis ≥6 months after treatment of primary T1-4N0-1M0 RCC were identified as the case cohort and SPM-free patients were the control cohort. SIRs and the excess risk were calculated. A competing risks and Cox model were used to evaluate the risk factors of SPM and overall survival (OS). RESULTS: A cohort of 6,204 RCC patients with SPM were matched with a control group of 31,020 RCC patients without SPM. The median time-to-SPM interval was 54.5 months in RCC patients with SPM diagnosis. Besides, an SPM of T3/4 or/and M1 stage diagnosis was positively associated with a longer time-to-SPM interval. SIR of SPM increased by follow-up time and decreased with age at diagnosis (Pfor all <0.001). SPM in the kidney had the highest SIR (54.6, P <0.001) among all SPMs. Prostate cancer (29.8%) in males and breast cancer (23.5%) in females were the most common SPM. Older age, black ethnicity, male sex, higher family income, papillary RCC, and lower TNM stage were significant risk factors for SPM diagnosis. The proportion of deaths from SPM exceeds that of deaths from RCC 3 years after the first RCC treatment. Patients with SPM and early time-to-SPM interval shortens the OS compared with SPM-free patients. The 5-year OS was 85.9% and 58.9% from the first RCC and the SPM diagnosis, respectively. Besides, patients with low-grade/early-stage SPM could benefit from aggressive surgical treatment for solid tumors. CONCLUSIONS: Collectively, our study described the epidemiological characteristics of SPM among RCC survivors and identified the independent predictors of the SPM diagnosis and its survival outcomes. This study highlights the importance of patient education and follow-up after the surgery for RCC.

Cause-Specific Mortality Among Survivors From T1N0M0 Renal Cell Carcinoma: A Registry-Based Cohort Study.

OBJECTIVE: More T1N0M0 renal cell carcinoma (RCC) is detected and the prognosis has improved, but, the current focus on non-RCC-related mortality is superficial. We investigated cause-specific mortality and its temporal patterns after an RCC diagnosis. METHODS: In the Surveillance, Epidemiology, and End Results-18 database, patients with T1N0M0 RCC treated with partial nephrectomy (PN) or radical nephrectomy (RN) during 2000-15 were identified. Standardized mortality ratios (SMRs) for cause of death were calculated. Risk predictors for each cause-specific mortality were investigated using the Fine and Gray sub-distribution model. RESULTS: In all, 68,612 eligible patients were pooled. A total of 14,047 (20.5%) patients had died (cardiovascular disease [CVD], 28.3%; other non-cancer-related diseases, 20.3%; RCC, 18.7%; other cancer types, 16.3%; non-disease events, 16.1%) during follow-up. Heart disease, diabetes mellitus, and cerebrovascular disease were the primary causes of non-RCC-related mortality within 1 year after the diagnosis. The greatest proportion of death (39.0%) occurred within 1-5 years after the diagnosis, mostly due to RCC itself, followed by heart disease. However, >5 years after the diagnosis, heart disease became the leading cause of death. Compared with the general US population, a 21% (SMR, 1.21; 95%CI 1.19-1.23) increased risk of all-mortality was observed; RCC patients had a higher risk of heart disease-related death within 5-10 years (SMR, 1.10; 95%CI 1.04-1.17) and >10 years (1.12; 1.02-1.22) after the diagnosis. Older age and RN increased the death risk of CVD and RCC-specific mortality. Although a larger tumor diameter increased the risk of RCC-specific death, this was not a significant predictor for CVD. Moreover, for T1N0M0 RCC tumors of diameter >4 cm, there was no significant difference in CVD incidence for RN vs. PN. CONCLUSIONS: RCC-specific mortality is a common challenge for the prognosis. Importantly, a large proportion and higher SMRs of other non-RCC-related diseases (especially CVD) should not be disregarded for the better holistic management of survivors of local RCC. Targeted prevention strategies for non-RCC-related death could lead to significant reductions in mortality for RCC survivors.

Optimize the management of urological tube-related emergencies during the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: To introduce and determine the value of optimized strategies for the management of urological tube-related emergencies with increased incidence, complexity and operational risk during the global spread of coronavirus disease 2019 (COVID-19). METHODS: All emergent urological patients at Tongji Hospital, Wuhan, during the period of January 23 (the beginning of lockdown in Wuhan) to March 23, 2020, and the corresponding period in 2019 were recruited to form this study's COVID-19 group and control group, respectively. Tongji Hospital has the most concentrated and strongest Chinese medical teams to treat the largest number of severe COVID-19 patients. Patients in the control group were routinely treated, while patients in the COVID-19 group were managed following the optimized principles and strategies. The case incidence for each type of tube-related emergency was recorded. Baseline characteristics and management outcomes (surgery time, secondary complex operation rate, readmission rate, COVID-19 infection rate) were analyzed and compared across the control and COVID-19 periods. RESULTS: The total emergent urological patients during the COVID-19 period was 42, whereas during the control period, it was 124. The incidence of tube-related emergencies increased from 53% to 88% (P<0.001) during the COVID-19 period. In particular, the incidence of nephrostomy tube-related (31% vs. 15%, P=0.027) and single-J stent-related problems (19% vs. 6%, P=0.009) increased significantly. The mean surgery times across the two periods were comparable. The number of secondary complex operations increased from 12 (18%) to 14 (38%) (P=0.028) during the COVID 19-period. The number of 2-week postoperative readmission decreased from 10 (15%) to 1 (3%) (P=0.049). No participants contracted during the COVID-19 period. CONCLUSIONS: Urological tube-related emergencies have been found to have a higher incidence and require more complicated and dangerous operations during the COVID-19 pandemic. However, the optimized management strategies introduced in this study are efficient, and safe for both urologists and patients.

[Corrigendum] Mutation of TGF­ß receptor II facilitates human bladder cancer progression through altered TGF­ß1 signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 1B on p. 1552, the MCF­7 and T24, and the A549 and ScaBER data panels, respectively, appeared to be strikingly similar. After having re­examined the original data, the authors have realized that these pairings of data panels were indeed duplicates of each other. Essentially, errors were made in the labelling of the data panels pertaining to the separate experiments, and in the compilation of the published version of Fig. 1. The authors, however, were willing to repeat the affected experiments, and obtained results that were consistent with those of the experiments that had been originally performed. Consequently, the revised version of Fig. 1 is shown below, showing the new data for Fig. 1B. The results from the flow cytometric analysis demonstrated the abnormally high expression level of TGF­ß receptor II in T24 cells. The authors confirm that these data support the main conclusions presented in their paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum. They also apologise to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 43: 1549­1559, 2013; DOI: 10.3892/ijo.2013.2065].

Effects of SARS-CoV-2 infection on male sex-related hormones in recovering patients.

BACKGROUND: A novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causing the pandemic of coronavirus disease 2019 (COVID-19), may attack testes by angiotensin-converting enzyme 2. OBJECTIVE: To assess whether SARS-CoV-2 infection can affect sex-related hormones and testicular function in recovering patients. MATERIALS AND METHODS: The patients were separately classified according to the duration of viral shedding (long-term positive vs normal-term group, with the former cases having a duration > 50 days) and disease severity (moderate vs severe group). Differences in sex-related hormone levels were compared between groups and linear regression analysis was used to compare the associations of testosterone (T) and estradiol with various clinical and laboratory factors. RESULTS: A total of 39 COVID-19-infected patients were included in this study. The mean T level was in the normal reference range while the mean estradiol level was above the normal limit. There were no significant differences between the long-term positive and normal-term groups in T (P = .964), follicle-stimulating hormone (FSH; P = .694), luteinizing hormone (LH; P = .171), prolactin (PRL; P = .836), or T/LH (P = .512). However, estradiol was higher in the normal-term group than the long-term positive group (P < .001). Moreover, there were also no significant differences between the moderate and severe groups in sex-related hormones, duration of viral shedding, or serum biochemical or inflammation indicators. Additionally, regression analyses showed that there were no associations between the T level and the clinical and laboratory factors, while estradiol was negatively associated with the duration of viral shedding. CONCLUSION: In males infected with SARS-CoV-2, most sex-related hormones (T, FSH and LH levels) remain within the normal reference ranges after recovery from COVID-19, and no significant associations were observed between T level and disease duration or severity. At present, there is insufficient evidence to show that SARS-CoV-2 causes hypogonadism and sterility, but the potential risk should not be ignored.

The Delivery Materials with Chemotherapy Drugs for Treatment of the Positive Margin in Solid Tumors.

The positive surgical margins in solid tumors has been a disturbing issue for clinicians. Chemotherapy is an important method to deal with the positive margin. However, systemic chemotherapy is required for long-term administration and has great side effects on health, which cause great pain to the patients. Local administration of slow-release materials provides an opportunity to improve the situation. In this study, we utilized electrospinning technology to create the drug sustained-release materials with nanofibrous structure, which were made from polylactic acid and a certain proportion of chemotherapy drugs (gemcitabine and cisplatin). In vitro release behavior of the drug sustained-release materials were explored by the high-performance liquid chromatography. The antitumor efficacy of the drug sustained-release materials was preliminarily verified in prostate cancer and breast cancer in vitro. Through animal models of breast cancer, the drug sustained-release materials in the treatment of the positive margin has been well documented in vivo, and we also found that the drug sustained-release materials could definitely reduce the liver damage and myelosuppression compared with systemic chemotherapy. In summary, the experimental results showed that the local administration of the drug sustained-release materials could effectively inhibit the growth of the positive incision margins and definitely reduce the partial side effects associated with systemic chemotherapy.

Identify the Risk Factors of COVID-19-Related Acute Kidney Injury: A Single-Center, Retrospective Cohort Study.

Background: The kidney is a target organ that could be infected by SARS-CoV-2, and acute kidney injury (AKI) was associated with a higher risk of COVID-19 patients' in-hospital death. However, no published works discussed about the risk factors of COVID-19 related AKI. Methods: We conducted a retrospective cohort study, recruiting COVID-19 inpatients from the Sino-French branch of Tongji Hospital. Demographic, clinical, treatment, and laboratory data were collected and compared. We used univariable and multivariable logistic regression methods to identify the risk factors of COVID-19-related AKI. Results: Of the 116 patients in our study, 12 (10.3%) were recognized as AKI, including 5 (4.3%) in-hospital AKI. Multivariable regression showed increasing odds of COVID-19-related AKI associated with COVID-19 clinical classification (OR = 8.155, 95% CI = 1.848-35.983, ref = non-critical, p = 0.06), procalcitonin more than 0.1 ng/mL (OR = 4.822, 95% CI = 1.095-21.228, p = 0.037), and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (OR = 13.451, 95% CI = 1.617-111.891, p = 0.016). Conclusions: COVID-19-related AKI was likely to be related to multiorgan failure rather than the kidney tropism of SARS-CoV-2. The potential risk factors of COVID-19 clinical classification, procalcitonin more than 0.1 ng/mL, and eGFR <60 mL/min/1.73 m2 could help clinicians to identify patients with kidney injury at an early stage.

Epidemiological and clinical course of 483 patients with COVID-19 in Wuhan, China: a single-center, retrospective study from the mobile cabin hospital.

During the COVID-19 outbreak, the mobile cabin hospital has effectively isolated and treated patients diagnosed as mild-moderate disease. However, a detailed clinical course has not been well described. We included 483 patients who were isolated and treated from Feb 6, 2020, to Feb 15, 2020, including definite outcome (discharge or deterioration). Sixty-two patients were transferred to severe cases, of whom were trasfered to designated hospital for intensive care. By March 9, 2020, all patients were discharged without dead. The mobile cabin hospital provides feasible strategy of isolation of mild-moderate cases and timely intervention during the virus outbreak.

Multiple Patterns of Perirenal Fat Invasion Are Associated With a Poorer Prognosis Compared With Isolated Invasion: A Proposal for a Revision of T3aN0M0 TNM Staging System.

Objectives: Currently, renal cell carcinoma (RCC) presenting with perisinus fat invasion (PSI) and/or perinephric fat invasion (PFI) is merged as one entity, pathological T3a (pT3a); however, the combination of PFI and PSI (PFI+PSI) may not be associated with equivalent prognosis compared with either PFI or PSI alone (PFI/PSI). Here, we analyzed the prognostic significance of PFI+PSI vs. PFI/PSI in pT3aN0-1M0-1 RCC. Method: We identified 5,290 patients with pT3aN0-1M0-1 RCC, treated by nephrectomy, from the Surveillance, Epidemiology and End Results database, between 2010 and 2016. Cox proportional hazards regression and Fine and Gray competing risks regression were fitted to assess risks of survival outcomes, respectively. 1:1 propensity score method was used to minimize differences in the covariates' distributions. Results: Among all patients, 746 patients (14.1%), 2,569 patients (48.5%) and 1,975 patients (37.3%) experienced PFI+SI, PFI, and PSI, respectively, and 3,952 patients (74.7%) without diseases of lymphnode (N1) and/or distant metastasis (M1). PFI alone compared with PSI alone showed a comparable overall survival (OS) and cancer-special survival (CSS), either PFI or PSI alone experienced a better OS and CSS than PFI+PSI. In patients with pT3aN0M0 RCC, PFI+PSI compared with the PFI/PSI was significantly associated with worse OS with hazard ratio (HR) [95% confidence interval (CI)]: 1.38 [1.12-1.69], p = 0.002 and 1.41 [1.06-1.87], p = 0.017 for unmatched data and matched data, respectively, and higher RCC-special mortality (HR [95%CI]: 1.55 [1.21-1.99], p = 0.001 and 1.70 [1.19-2.43], p = 0.004 for unmatched data and matched data, respectively). However, in pT3aN1/M1 RCC patients, PFI+PSI was not significantly associated with RCC-special mortality (HR [95%CI]: 1.02 [0.85-1.23], p = 0.800 and 0.99 [0.79-1.24], p = 0.920 for unmatched data and matched data, respectively) in comparison with PFI/PSI. In addition, invasion type was not an independent risk factor for patient's prognostication in the pT3a RCC with diseases of N1 and/or M1 (all p > 0.5). Conclusion: Multiple invasion patterns (PFI+PSI) are associated with inferior survival relative to PFI/PSI alone in patients with pT3aN0M0 RCC; however, these effects are masked in patients with metastatic disease. These results warrant consideration in the development of the next edition of the tumor-node-metastasis staging system, to improve risk stratification.

Minimally invasive adrenalectomy results in equivalent perioperative outcomes versus open adrenalectomy for adrenal mass larger than 6 cm: A retrospective propensity score-matched study.

INTRODUCTION: The indication for choosing the minimally invasive approach for large adrenal mass remains controversial. This study is to assess perioperative outcomes after minimally invasive adrenalectomy (MIA) versus open adrenalectomy (OA) for adrenal mass ≥ 6 cm. MATERIALS AND METHODS: A cohort of 173 patients underwent adrenalectomy for adrenal mass ≥ 6 cm in our urology center between May 2005 and April 2018 was included. MIA was performed in 96 patients, whereas 77 patients underwent OA. We performed a retrospective propensity score-matched study to compare MIA versus OA. RESULTS: After propensity score-matched, 58 matched pairs of patients identified from each group. There were no significant differences between the groups in postoperative morbidity (p = 0.146), operative time (p = 0.163), intraoperative hypertension (p = 0.248) and drainage time (p = 0.188). Estimated blood loss, the rate of blood transfusions postoperative hospital stay was less in MIA group (p < 0.0001; p = 0.007; p < 0.0001). Total expense was significantly more in the MIA group [49379.28 (38496.69, 68008.69) CNY vs 39951.48 (30666.33, 50292.03) CNY, p = 0.001]. CONCLUSIONS: MIA results in equivalent perioperative outcomes compared with OA and is an effective and safe surgical method for patients with an adrenal mass more than 6 cm in diameter.