Calcium oxalate crystal-induced kidney injury (COC-KI) is characterized by excessive oxidative stress and inflammation. Nanozymes can partially mitigate COC-KI through superoxide dismutase (SOD)- and catalase (CAT)-like activities, but their therapeutic efficacy is often compromised by the coexisting peroxidase (POD)- and oxidase (OXD)-like activities, which may paradoxically generate reactive oxygen species (ROS). Additionally, the lack of targeted delivery remains another challenge. To overcome these limitations together, metal-organic framework (MOF)-based nanozyme PCN222-Mn (PM), which exhibits prominent SOD- and CAT-like activities with negligible POD/OXD-like activities, was chosen for the treatment of COC-KI. To achieve precise renal targeting, we functionalized PM with hyaluronic acid (HA), yielding PCN222-Mn@HA (PMH). Both in vitro and in vivo studies demonstrated that PMH effectively accumulated in injured renal tubular epithelial cells (RTECs) and provided superior protection against COC-KI. Mechanistic investigation via RNA sequencing revealed that PMH exerted its renoprotective effects primarily by suppressing NF-κB signaling, which in turn downregulated the expression of NLRP3 and MCP-1, thereby inhibiting inflammasome activation and macrophage recruitment. Collectively, this work proposes a novel and effective targeted nanozyme strategy for the treatment of COC-KI.

Clear cell renal cell carcinoma (ccRCC) remains a therapeutic challenge due to tyrosine kinase inhibitor (TKI) resistance and an immunosuppressive tumor microenvironment (TME). To avoid the limitations of systemic nanotherapeutics, which often suffer from inadequate tumor accumulation, we developed a pH-activatable injectable gelatin methacryloyl (GelMA) hydrogel (termed SUN/CuONPs@GelMA) for localized co-delivery of sunitinib and copper oxide nanoparticles. The photocrosslinkable GelMA matrix enables minimally invasive intratumoral administration and sustained drug retention. Unlike ferroptosis, which is frequently migigated by the antioxidant defenses inherent in ccRCC, cuproptosis circumvents this resistance by targeting mitochondrial metabolism. In the weakly acidic TME (pH 5.3-7), CuONP assemblies dissolve to release CuO nanoparticles and Cu2+, triggering dual mechanisms: (1) cuproptosis via mitochondrial proteotoxicity and the depletion of iron-sulfur cluster protein, and (2) Fenton-like reaction-mediated reactive oxygen species (ROS) generation and the release of damage-associated molecular patterns (DAMPs). Concurrently, sunitinib inhibits angiogenesis and synergizes with copper-driven immunomodulation to reprogram macrophages toward tumor-suppressive M1 phenotypes. In vitro and in vivo studies demonstrated potent tumor growth inhibition, migration suppression, and prolonged survival in ccRCC. The SUN/CuONPs@GelMA platform overcomes TKI resistance through the synergy of cuproptosis and immunotherapy. This localized co-delivery strategy provides a multi-mechanistic approach for the treatment of advanced ccRCC. STATEMENT OF SIGNIFICANCE: Systemic treatments for advanced clear cell renal cell carcinoma (ccRCC) are restricted by tyrosine kinase inhibitor (TKI) resistance, systemic toxicity, and an immunosuppressive tumor microenvironment (TME). We herein report a pH-activatable, injectable photocrosslinkable GelMA hydrogel for localized co-delivery of sunitinib and copper nanoparticles, enabling minimally invasive delivery, sustained drug retention, and reduced systemic toxicity. This hydrogel triggers cuproptosis via acidic TME-responsive copper release, and synergizes with sunitinib to reverse TKI resistance, suppress tumor progression and migration, reprogram immunosuppressive macrophages to antitumor phenotypes, and extend preclinical survival. This work establishes a combinatorial ccRCC therapeutic platform, providing a promising translational strategy for advanced ccRCC management.

Background:Percutaneous nephrolithotomy (PCNL) is a mainstream minimally invasive strategy for renal calculi. Despite widespread use, residual calculi after PCNL remain a key clinical challenge. Precise preoperative evaluation of renal collecting system anatomy and rational planning of the percutaneous access route are critical for improving stone-free rates. This study aimed to explore whether morphological features of the target calyx can predict stone clearance from a non-target puncture calyx and establish a model for assessing residual stone risk. Methods:A retrospective study was conducted including 105 PCNL cases (67 stone-free, 38 with residual stones) with distinct puncture and target calyces between January 2023 and June 2025. Three-dimensional (3D) models were reconstructed from preoperative computed tomography (CT) urography to measure spatial anatomical parameters. Patient characteristics, stone features, and 3D metrics were entered into binary logistic regression to screen independent predictors and construct a nomogram. Model performance was evaluated using receiver operating characteristic (ROC), calibration curves, decision curve analysis (DCA), and internal validation (n=29). Results:Three independent predictors were identified: punctured calyx length-to-width ratio [odds ratio (OR) =6.89, P=0.020], inter-calyceal axis angle (OR =0.929, P<0.001), and target calyx length-to-width ratio (OR =8.925, P=0.003). The model showed excellent discrimination with an area under the curve (AUC) of 0.905, sensitivity of 86.8%, and specificity of 80.6% at the optimal cutoff of 0.291. The Hosmer-Lemeshow test indicated good calibration (χ2=12.467, P=0.132). Calibration and DCA confirmed favorable accuracy and clinical utility. Internal validation yielded an AUC of 0.829, verifying model stability and reliability. Conclusions:A predictive model combining calyceal length-to-width ratios and inter-calyceal axis angle can effectively predict stone clearance in the target calyx. This model provides a valuable reference for optimizing calyx selection and improving stone-free outcomes in PCNL.

BackgroundPrimary aldosteronism (PA) and pheochromocytoma (PHEO) are both causes of secondary hypertension. Since these two diseases have different pathogeneses, the coexistence of PA and PHEO is very rare and poses challenges in diagnosis and treatment.Case presentationA 65-year-old woman developed paroxysmal hypertension two years ago, accompanied by palpitation, dizziness, headache, and vomiting, and she had a poor response to conventional antihypertensive drugs. Contrast-enhanced computed tomography showed a nodule in the medial limb of the right adrenal gland. A mildly elevated aldosterone to renin ratio and an unsuppressed captopril challenge test met the diagnostic criteria for primary aldosteronism. Normetanephrine was elevated in plasma catecholamine testing. Adrenal venous sampling (AVS) demonstrated bilateral aldosterone excess. Right adrenalectomy was performed after multidisciplinary discussion and resulted in rapid clinical improvement. Postoperative pathology revealed coexistence of a cortical aldosterone-producing nodule (APN), a micro-pheochromocytoma and multiple aldosterone-producing micronodules (multiple APM) in adrenal cortex. A KCNJ5 mutation was found in the APN, representing the first report of this gene mutation in APN in cases coexisting PA and PHEO.ConclusionsWe report a rare case of concurrent PA and micro-pheochromocytoma. This case highlights the importance of early identification and diagnosis, and it provides experience regarding the diagnostic and treatment protocol for such a rare condition. Pathological findings and the KCNJ5 mutation in APN provide directions for subsequent research on the pathogenesis of concomitant PA and PHEO.

Rationale:Heart failure (HF) is slightly more common in primary aldosteronism (PA) than in essential hypertension, but early-onset HF remains rare. In such cases, underlying genetic cardiomyopathies should be considered. Autonomously secreted aldosterone and activation of the renin-angiotensin-aldosterone system can lead to extremely high aldosterone levels, worsening cardiac function and creating major therapeutic challenges.Patient concerns:A 39-year-old male presented with progressive chest tightness and shortness of breath for 4 months. He had a 7-year history of hypertension and persistent hypokalemia. Electrocardiogram revealed a markedly reduced left ventricular ejection fraction of 18.3%.Diagnosis and interventions:The patient was diagnosed with PA based on elevated plasma aldosterone concentration, an increased aldosterone-to-renin ratio, and a positive captopril challenge test. Computed tomography and adrenal vein sampling indicated unilateral PA. After initial HF management, the patient underwent laparoscopic adrenalectomy for PA treatment.Outcomes:According to the primary aldosteronism surgical outcome consensus criteria for postoperative evaluation of PA, complete biochemical remission (normalization of aldosterone-to-renin ratio and potassium) and partial clinical remission (stable blood pressure with reduced antihypertensive medication) were achieved 1 month postoperatively and have been maintained since. At the 8-month follow-up, his left ventricular ejection fraction had improved to 45.4% and BNP levels normalized. Whole-exon sequencing revealed a missense mutation of the dystrophin (DMD) gene. Certain DMD mutations are linked to X-linked dilated cardiomyopathy with absent or subclinical skeletal muscle involvement. Sanger sequencing confirmed the hemizygous mutation in the proband. The final diagnosis was poorly controlled PA with early-onset HF, potentially influenced by a coexisting DMD gene missense mutation that may modify both the onset and severity of PA-related HF.Lessons:Early recognition and surgical treatment of PA with early-onset HF can substantially improve cardiac function, even in the presence of genetic susceptibility to cardiomyopathy. This case underscores the need to consider underlying cardiac genetic disorders in PA patients with atypical or early-onset HF and raises the hypothesis that the identified DMD variant may serve as a potential genetic modifier of HF severity in the context of PA.

Objective Kidney stone disease (nephrolithiasis), characterized by calcium oxalate (CaOx) deposition, often leads to chronic kidney disease. Recent studies suggest that copper metabolism and oxidative stress play roles in kidney stone pathogenesis. Cuproptosis, a regulated cell death pathway driven by copper, is hypothesized to be implicated in nephrolithiasis. This study aimed to assess the therapeutic potential of tetrathiomolybdate (TTM), a copper chelator, in reducing copper-induced toxicity and oxidative stress in nephrocalcinosis models. Methods Forty C57BL/6 mice were divided into four groups: control, TTM, glyoxylate-induced CaOx, and glyoxylate with TTM. TTM was administered intraperitoneally for 10 days, and kidney function, copper levels, and crystal deposition were assessed. In vitro, human renal epithelial cells (HK-2) treated with CaOx monohydrate were analyzed for reactive oxygen species levels, protein expression, and gene regulation under the TTM treatment. Results The TTM treatment significantly improved kidney function, reduced copper content, and decreased CaOx crystal deposition in vivo. In vitro, TTM reduced reactive oxygen species, LDH, and malondialdehyde levels in CaOx monohydrate-treated HK-2 cells, while decreasing Cu+ level and reversing altered protein expression associated with cuproptosis. A transcriptomic analysis identified four TTM-regulated copper metabolism-related genes: cyclin D1 (Ccnd1), ceruloplasmin (Cp), lysyl oxidase (Lox), and lox like 2 (Loxl2). Conclusions TTM mitigates copper-induced toxicity and oxidative stress by modulating cuproptosis-related genes, offering a promising therapeutic approach for nephrolithiasis.

The molecular complexity of bladder cancer restricts reliance on single-feature or single-gene targeted therapies, necessitating integrated individualized treatments and multi-gene interventions. In this study, we introduced the CRISPR/dCas9-SAM system to BCa treatment, known for its high specificity, low off-target effects, and reduced genetic toxicity, making it ideal for multiplexed gene activation at minimal cost-just 20 nucleotides per target. However, despite its potential in complex gene therapy and cellular engineering, challenges persist due to safety concerns associated with viral vectors and the risk of off-target effects during in vivo delivery, necessitating the development of new vectors. Herein, we reported pH-sensitive hollow mesoporous silica nanoparticles modified with PLZ4 ligands (PLZ4-Lip@AMSN/CRISPR/dCas9-SAM, PLACS NPs) for precise targeting of bladder tumors and co-delivery of CRISPR/dCas9-SAM system. With good stability and high plasmid loading capacity, they efficiently co-delivered dCas9-VP64, MS2-P65-HSF1, and sgRNA. Compared to Lipofectamine 3000, these nanoparticles exhibited superior lysosomal escape capability, significantly enhancing transfection efficiency in bladder cancer cells. Moreover, PLACS NPs simultaneously activated the expression of four target genes, inhibiting proliferation and migration, and promoting apoptosis in bladder cancer cells. In vivo, they achieved efficient gene editing at tumor sites, significantly inhibiting bladder tumor growth. Real-time imaging revealed their substantial accumulation and prolonged retention at bladder tumor sites without significant liver targeting and major organ damage, showcasing good specificity and biosafety. This study overcomes in vivo delivery challenges of multi-component CRISPR/dCas9 systems, enabling precise gene editing and anti-tumor effects, presenting an innovative strategy for targeted therapy in bladder cancer treatment. STATEMENT OF SIGNIFICANCE: This study introduces a newly-developed approach to address key challenges in bladder cancer gene therapy, namely low gene upregulation efficiency, limited targeting specificity, and inefficient nucleic acid delivery. By integrating the CRISPR/dCas9-SAM system, we achieve highly specific gene activation with minimal off-target effects, enabling the addition of treatment targets with just 20 nucleotides per target. To improve bladder cancer targeting, we developed PLACS NPs, a mesoporous silica nanoparticle system that enhances plasmid delivery, transfection efficiency, and endosomal escape. This system shows good tumor targeting and significant anti-tumor effects in bladder cancer, without significant liver targeting and major organ toxicity, offering promising therapeutic potential and broad clinical applications.

Acute Kidney Injury (AKI) is a significant medical condition characterized by the abrupt decline in kidney function.Low-intensity pulsed ultrasound (LIPUS), a non-invasive therapeutic technique employing low-intensity acoustic wave pulses, has shown promise in promoting tissue repair and regeneration. A novel LIPUS system was developed and evaluated in rat AKI models, focusing on its effects on glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum creatinine (SCr), and the Notch1-Akt-eNOS signaling pathway. The results demonstrated that LIPUS treatment improved GFR, BUN, SCr levels, and renal pathology in AKI rats. In vitro experiments using HUVEC cells revealed that LIPUS stimulation promoted angiogenesis, cell migration mechanically-dependent calcium ion influx, which was partially attenuated by TRPV1 knockdown. RNA sequencing analysis indicated LIPUS-induced activation of the Notch pathway, phosphorylation of Akt and eNOS. Furthermore, inhibition or genetic silencing of Notch1 abolished the beneficial effects of LIPUS on angiogenesis, renal function, and Akt-eNOS phosphorylation in both cells and AKI rats. These findings suggest that LIPUS-induced calcium influx promotes Akt-eNOS phosphorylation, nitric oxide (NO) production, angiogenesis, and improved renal function in AKI via Notch1-Akt-eNOS signaling, positioning LIPUS as a promising therapeutic strategy for AKI by targeting vascular regeneration.

Abstract Background Previous observational studies have indicated a potential link between insomnia and bladder cancer, yet the underlying causal relationship remains uncertain. The current study employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate this association. Methods A two-sample MR analysis was conducted utilizing publicly available summary data from genome-wide association studies (GWAS) on insomnia and bladder cancer. Various regression methods including the inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode methods were employed for the MR analysis. The presence of pleiotropy and heterogeneity in the MR results was also assessed. Furthermore, additional sensitivity tests were performed to mitigate potential biases. Results No significant causal relationship was detected between insomnia and bladder cancer using IVW method (OR = 0.761, 95% CI 0.996–1.005; P = 0.76). Similarly, the IVW model did not reveal any causal effect of bladder cancer on the risk of insomnia (OR = 1.47, 95% CI 0.772–2.799; P = 0.24). Consistent results were obtained from the other four methods employed. There was no evidence of horizontal pleiotropy or heterogeneity in our MR analysis (P > 0.05). The sensitivity analyses further supported the reliability of the estimated causal effects. Conclusions This study presents no evidence for a causal relationship between insomnia and bladder cancer.

One of the challenges in the diagnosis and management of primary aldosteronism (PA), the most common type of secondary hypertension with curative potential, is the modification of antihypertensive medications. We seek to explore whether these medications can be continued during the diagnostic process of PA to minimize the duration and risks associated with medication adjustments. We searched PubMed for eligible original literature between 1990 and 2024 using the following keywords: (screening) AND (primary aldosteronism); (confirmatory) AND (primary aldosteronism); (adrenal vein sampling) AND primary aldosteronism). Some recent studies support the feasibility of PA-related tests and even adrenal vein sampling (AVS) without the need to discontinue antihypertensive medications in certain cases. In this review, we propose a management approach that considers the specific effects of antihypertensive medications on the RAAS axis and the patient's disease phenotype. Based on this, we suggest a strategy that enables the diagnosis of PA in certain patients without discontinuing their antihypertensive medications.

Background: Previous epidemiological observational studies have potentially associated psoriasis with bladder cancer, but the results are inconsistent, and the causality remains unknown. The present study aimed to examine whether there are causal associations between psoriasis and bladder cancer using bidirectional two-sample Mendelian randomization (MR) analysis. Materials and Methods: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) data for individuals diagnosed with psoriasis and bladder cancer. The inverse variance weighted (IVW) method was the primary method. The complementary methods used included the weighted median, MR-Egger, weighted mode, and simple mode methods. Heterogeneity and pleiotropy of the MR results were detected. Moreover, leave-one-out sensitivity analysis was also employed to evaluate the robustness and validity of the findings. Results: No significant causal association was detected between psoriasis incidence and the risk of bladder cancer using the IVW method (OR = 0.999, 95% CI 0.977-1.022; P = 0.956). Similarly, the IVW model revealed no evidence of a causal relationship between bladder cancer and the risk of psoriasis (OR = 0.979, 95%CI = 0.873-1.098; P = 0.716). The results of the complementary methods were consistent with those of the IVW method. There was no notable horizontal pleiotropy or heterogeneity (P > 0.05) in our MR analysis. The results of sensitivity analysis confirmed that the MR estimates were not driven by single-nucleotide polymorphisms (SNPs). Conclusion: This study does not support a causal relationship between psoriasis and bladder cancer.

Background Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal tumors and is associated with a unfavorable prognosis. Disulfidptosis is a recently identified form of cell death mediated by disulfide bonds. Numerous studies have highlighted the significance of immune checkpoint genes (ICGs) in ccRCC. Nevertheless, the involvement of disulfidptosis-related immune checkpoint genes (DRICGs) in ccRCC remains poorly understood.Methods The mRNA expression profiles and clinicopathological data of ccRCC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. The associations between disulfidptosis-related genes (DRGs) and immune checkpoint genes (ICGs) were assessed to identify DRICGs. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were conducted to construct a risk signature.Results A total of 39 differentially expressed immune-related candidate genes were identified. A prognostic signature was constructed utilizing nine DRICGs (CD276, CD80, CD86, HLA-E, LAG3, PDCD1LG2, PVR, TIGIT, and TNFRSF4) and validated using GEO data. The risk model functioned as an independent prognostic indicator for ccRCC, while the associated nomogram provided a reliable scoring system for ccRCC. Gene set enrichment analysis indicated enrichment of phospholipase D, antigen processing and presentation, and ascorbate and aldarate metabolism-related signaling pathways in the high-risk group. Furthermore, the DRICGs exhibited correlations with the infiltration of various immune cells. It is noteworthy that patients with ccRCC categorized into distinct risk groups based on this model displayed varying sensitivities to potential therapeutic agents.Conclusions The novel DRICG-based risk signature is a reliable indicator for the prognosis of ccRCC patients. Moreover, it also aids in drug selection and correlates with the tumour immune microenvironment in ccRCC.

The risk of thermal damage increases with the introduction of high-power lasers during holmium laser lithotripsy. This study aimed to quantitatively evaluate the temperature change of renal calyx in the human body and the 3D printed model during high-power flexible ureteroscopic holmium laser lithotripsy and map out the temperature curve. The temperature was continuously measured by a medical temperature sensor secured to a flexible ureteroscope. Between December 2021 and December 2022, willing patients with kidney stones undergoing flexible ureteroscopic holmium laser lithotripsy were enrolled. High frequency and high-power settings (24 W, 80 Hz/0.3 J and 32 W, 80 Hz/0.4 J) were performed for each patient with room temperature (25 °C) irrigation. In the 3D printed model, we studied more holmium laser settings (24 W, 80 Hz/0.3 J, 32 W, 80 Hz/0.4 J and 40 W, 80 Hz/0.4 J) with warmed (37 °C) and room temperature (25 °C) irrigation. Twenty-two patients were enrolled in our study. With 30 ml/min or 60 ml/min irrigation, the local temperature of the renal calyx did not reach 43 °C in any patient under 25 °C irrigation after 60 s laser activation. There were similar temperature changes in the 3D printed model with the human body under the irrigation of 25 °C. Under the irrigation of 37 °C, the temperature rise slowed down, but the temperature in the renal calyces was close to or even exceeded the 43 °C at the setting of 32 W, 30 ml/min and 40 W, 30 ml/min after continuing laser activation. In the irrigation of 60 ml/min, the temperature in the renal calyces can still be maintained within a safe range after continuous activation of a holmium laser up to 40 W. However, continuous activation of 32 W or higher power holmium laser in the renal calyces for more than 60 s in the limited irrigation of 30 ml/min can cause excessive local temperature, in such situation room temperature perfusion at 25 ℃ may be a relatively safer option.

Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cell (TEC) inflammatory and oxidative injury. This study is aimed at exploring potential therapeutic lipid components in kidney stones because lipids are involved in the development of several diseases and indicate the risk of kidney stones. Serum specimens were collected from 35 kidney stone patients and 35 normal controls. The lipid components in serum were measured, and differences were analyzed. The documented biological importance was comprehensively reviewed to identify lipids that differed significantly between the two groups to find potential agents associated with kidney stones. CaOx nephrocalcinosis mouse model was established to examine the therapeutic effects of specific lipids on CaOx deposition and CaOx-induced oxidative renal injury. Several lipids with significantly different levels were present in the serum of patients with stones and normal controls. Resolvin D1 (RvD1) (4.93-fold change, P < 0.001) and protectin D1 (PD1) (5.06-fold change, P < 0.001) were significantly decreased in the serum of patients with kidney stones, and an integrative review suggested that these factors might be associated with inflammatory responses, which is a crucial mechanism associated with stone damage. The administration of RvD1 and PD1 significantly inhibited kidney CaOx deposition and suppressed CaOx-induced renal tubular cell inflammatory injury and necrosis in a CaOx nephrocalcinosis mouse model. Furthermore, RvD1 and PD1 facilitated the expression of the oxidative indicator superoxide dismutase 2 (SOD2), inhibited NADPH oxidase 2 (NOX2) expression, and diminished intracellular reactive oxygen species (ROS) levels. This study preliminarily elucidated the role of lipids in kidney stones. The inhibitory effects of RvD1 and PD1 on oxidative damage induced by CaOx deposition provide a promising perspective for kidney stone treatment strategies.

Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of human kidney cancer with a high probability of metastasis. To understand the molecular processing essential for ccRCC tumorigenicity, we conducted an integrative in silico analysis of The Cancer Genome Atlas (TCGA) ccRCC dataset and clustered randomly interspersed short palindromic repeats (CRISPR) screening dataset of ccRCC cell lines from Depmap. We identified spindle pole body component 24 homolog (SPC24) as an essential gene for ccRCC cell lines with prognostic significance in the TCGA database. Targeting SPC24 by CRISPR/Cas9-mediated gene knockout attenuated ccRCC proliferation, metastasis, and in vivo tumor growth. Furthermore, we found that SPC24 regulates metastasis genes expression in a SRY-box transcription factor 2 (SOX2)-dependent manner. The anti-proliferative effects of SPC24 knockout were strengthened with SOX2 knockdown. Collectively, our findings suggest SPC24 has a pivotal function in promoting ccRCC progression, providing a new insight for the treatment of ccRCC.

Background: Transurethral split of the prostate (TUSP) is effective in treating benign prostatic hyperplasia (BPH). However, there is still a lack of research focusing on the optimal target population for TUSP. This study aimed to compare the efficacy of TUSP in patients with different prostate volumes or ages. Methods: The study was a multicenter retrospective study. The outcomes of TUSP in BPH patients with different prostate volumes or different ages were compared. A total of 439 patients were included in the study. Patients were divided into two groups according to prostate volume, with a cut-off value of 50 mL. Similarly, the cut-off value for the age groups was 70 years. Baseline patient characteristics and perioperative outcomes were recorded. Follow-up was performed at 1, 6, and 12 months after surgery. Results: The mean age of the patients was 73.4 years, and the mean prostate volume was 51.2 mL. At 12-month follow-up after TUSP treatment, the patients' International Prostate Symptom Scores (IPSS), quality of life (QoL) scores, and postvoid residual (PVR) volumes decreased significantly, while peak urinary flow rate (Qmax) increased significantly. Intraoperative hemoglobin (Hb) reduction was significantly lower in the small volume group than in the large volume group. The incidence of postoperative urinary urgency and transient incontinence was lower in the small volume group. IPSS score, PVR, and Qmax in the small volume group showed more remarkable changes at several time points compared to the preoperative period. Postoperative pain scores were higher in the small volume group than in the large volume group. There were no differences between the two groups in terms of long-term complications. The younger group showed greater variation in PVR and Qmax at some time points but less variation in QoL than the older group. Conclusions: TUSP is overall safe and effective in treating BPH. This study showed differences in the outcomes of TUSP in treating different prostate volumes or ages of BPH patients. The optimal surgical approach for BPH patients might be selected clinically based on a combination of prostate volume or patient age.

The clear cell renal cell carcinoma (ccRCC) microenvironment consists of many different cell types and structural components that play critical roles in cancer progression and drug resistance, but the cellular architecture and underlying gene regulatory features of ccRCC have not been fully characterized. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to generate transcriptional and epigenomic landscapes of ccRCC. We identified tumor cell-specific regulatory programs mediated by four key transcription factors (TFs) (HOXC5, VENTX, ISL1, and OTP), and these TFs have prognostic significance in The Cancer Genome Atlas (TCGA) database. Targeting these TFs via short hairpin RNAs (shRNAs) or small molecule inhibitors decreased tumor cell proliferation. We next performed an integrative analysis of chromatin accessibility and gene expression for CD8+ T cells and macrophages to reveal the different regulatory elements in their subgroups. Furthermore, we delineated the intercellular communications mediated by ligand-receptor interactions within the tumor microenvironment. Taken together, our multiomics approach further clarifies the cellular heterogeneity of ccRCC and identifies potential therapeutic targets.

Abstract Rationale: The emphysematous prostatic abscess is a rare but potentially life-threatening clinical condition. The early diagnosis is difficult due to nonspecific symptoms. Patient concerns: A 72-year-old man with poorly controlled diabetes mellitus was admitted to hospital because of dysuria and acute urine retention. He had a refractory fever after admission. Diagnoses: The diagnosis of emphysematous prostatic abscess was confirmed by culture of catheterized urine and pelvic CT. Interventions: We tried to give antimicrobial treatment and control of blood glucose at first, but the infection could not be controlled by antibiotic therapy and control of blood glucose. TRUS-guided aspiration was performed, but obviously not adequate for abscess drainage and the abscess progressed. TUR was then performed and the infection was gradually controlled. Outcomes: Pelvic CT scan 1 month after discharge showed complete resolution of the EPA. Lessons: Given the poor conservative treatment effect of emphysematous prostatic abscesses, CT or TRUS should be performed in the patients with suspected diagnosis. Early and appropriate drainage with proper antibiotic therapy is important to achieve a favorable outcome.

Background Transurethral resection of the prostate (TURP) was considered the golden standard to treat benign prostatic hyperplasia (BPH) for decades. However, TURP was associated with low efficiency to alleviate the lower urinary tract symptoms (LUTS) and a significantly higher risk of bladder neck contracture (BNC) for patients with small-volume BPH. Our study aims to compare the therapeutic effect of a transurethral split of the prostate (TUSP) with TURP for patients with small-volume BPH (<30 mL). Methods In this study, 101 small-volume BPH patients were randomly divided into two groups (TUSP and TURP group). The patient’s baseline characteristics and perioperative outcomes were recorded. The follow-up was done at six months, one year and two years after surgical treatment. Results No significant differences were observed between the two groups for the baseline characteristics, including age, prostate volume, prostate-specific antigen (PSA) level, concurrent disease, post-void residual (PVR), maximum urinary flow rate (Qmax), international prostate symptoms score (IPSS), and quality of life (QoL) score. The operative time and hemoglobin decrease were significantly lower in the TUSP group compared to the TURP group. However, no significant differences were observed between both groups for catheterization time, postoperative hospital stay, and incidence of transurethral resection syndrome (TURS). However, of the late complications, the incidence of BNC in the TUSP group was significantly lower than the TURP group. No significant differences were found between both groups for other complications, including postoperative bleeding, micturition urgency, micturition frequency, micturition pain, urinary tract infection, recatheterization, transient incontinence, and continuous incontinence. Follow-up results showed that the IPSS of the TUSP group was significantly lower than the TURP group, while the Qmax of the TUSP group was significantly higher than the TURP group. Conclusions This study shows that TUSP may be an efficient and safe treatment for small-volume BPH (<30 mL) with a lower incidence of postoperative BNC and better longtime clinical outcomes than TURP. It suggested that TUSP could be an ideal treatment choice for small-volume BPH.