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Mutants in the gene encoding mitochondrion-associated protein LRPPRC were found to be associated with French Canadian Type Leigh syndrome, a human disorder characterized with neurodegeneration and cytochrome c oxidase deficiency. LRPPRC interacts with one of microtubule-associated protein family MAP1S that promotes autophagy initiation and maturation to suppress genomic instability and tumorigenesis. Previously, although various studies have attributed LRPPRC nuclear acid-associated functions, we characterized that LRPPRC acted as an inhibitor of autophagy in human cancer cells. Here we show that liver-specific deletion of LRPPRC causes liver-specific increases of YAP and P27 and decreases of P62, leading to an increase of cell polyploidy and an impairment of autophagy maturation. The blockade of autophagy maturation and promotion of polyploidy caused by LRPPRC depletion synergistically enhances diethylnitrosamine-induced DNA damage, genome instability, and further tumorigenesis so that LRPPRC knockout mice develop more and larger hepatocellular carcinomas and survive a shorter lifespan. Therefore, LRPPRC suppresses genome instability and hepatocellular carcinomas and promotes survivals in mice by sustaining Yap-P27-mediated cell ploidy and P62-HDAC6-controlled autophagy maturation.

This study assesses the feasibility and effectiveness of using a three-dimensional (3D) printing model for preoperative planning in the treatment of full staghorn stones, specifically in the selection of the most optimal calyx for puncture. Twelve patients were enrolled in this trial. A preoperative CT taken in prone position was performed on each of the patients. 3D models were reconstructed using digital imaging and 3D printers. Three identical models were printed for each patient. Three puncture sites from the upper-, middle-, and lower-pole calyces of the kidney models were selected for simulation of percutaneous nephrolithotomy. The stone-free rates were recorded after each of the simulations. The puncture site that yielded the maximum SFR was translated to the patient for the actual procedure. CT was performed postoperatively on both patients and simulation models. The SFR of patients and simulation models was compared. Correlation analysis and consistency analysis suggested that there was a high degree of consistency between patients and 3D-printed models. The Pearson product-moment correlation coefficient r for the postoperative stone volume of the patients (PoSVP) and postoperative stone volume of the models (PoSVM) was 0.972 (P < 0.001, 95% CI = 0.900–0.992). The Bland–Altman plot of PoSVP to PoSVM showed an icon of 95% consistency 205.8(− 725.5 ~ 1137.1), and 100% of the points were within the 95% limits of agreement. 3D-printed models can potentially be used for preoperative planning in the treatment of full staghorn stones, especially in the selection of the most optimal calyx for puncture.

This work proposed KidneyRegNet, a novel deep registration pipeline for 3D CT and 2D U/S kidney scans of free breathing, which comprises a feature network, and a 3D–2D CNN-based registration network. The feature network has handcrafted texture feature layers to reduce the semantic gap. The registration network is an encoder-decoder structure with loss of feature-image-motion (FIM), which enables hierarchical regression at decoder layers and avoids multiple network concatenation. It was first pretrained with a retrospective dataset cum training data generation strategy and then adapted to specific patient data under unsupervised one-cycle transfer learning in onsite applications. The experiment was performed on 132 U/S sequences, 39 multiple-phase CT and 210 public single-phase CT images, and 25 pairs of CT and U/S sequences. This resulted in a mean contour distance (MCD) of 0.94 mm between kidneys on CT and U/S images and MCD of 1.15 mm on CT and reference CT images. Datasets with small transformations resulted in MCDs of 0.82 and 1.02 mm, respectively. Large transformations resulted in MCDs of 1.10 and 1.28 mm, respectively. This work addressed difficulties in 3DCT-2DUS kidney registration during free breathing via novel network structures and training strategies.

Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets. Mitofusin 2 (MFN2) suppressed disease progression and improved prognosis for patients with clear cell renal cell carcinoma (ccRCC) possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.

Renal calyceal neck atresia is a rare disorder. There is no clear guidance for standard treatment of this condition. The Memokath™ 045 temperature-controlled memory alloy stent is commonly used in the treatment of urethral strictures, but it has not been used for treating calyceal neck atresia. We present a case of a 44-year-old female patient with left lumbar pain who underwent two stages of treatment to resolve calyceal neck atresia located at the upper calyx of her left kidney. The first procedure was transurethral ureteroscopy combined with percutaneous recanalization of the left upper calyx calyceal neck atresia. One 6 F internal stent and one 8 F internal stent were placed, and she was discharged with a left nephrostomy tube. After her urinary tract infection was fully resolved, the patient returned for the second procedure of percutaneous upper renal calyx calyceal neck metal stent implantation. The temporary stents and nephrostomy tube were successfully removed. Our findings suggest that the Memokath™ 045 temperature-controlled memory alloy stent is an effective choice for treating calyceal neck atresia.

This study evaluates the consistency between intrarenal pelvic pressures (IPP) and intracaliceal pressures (ICP) and explores the impacts of irrigation flow rate (IFR) and ureteral access sheath (UAS) position on ICP using a novel Flexible Ureteroscope Pressure Measurement System. Six pigs with 12 kidneys were included in this study under general anesthesia. The IPP and ICP were measured using the Flexible Ureteroscopic Pressure Measurement System under varying UAS positions and IFRs. The 12/14Fr UAS was sequentially placed in the upper, middle, and lower segments of the porcine ureters. The irrigation pump was set to cumulative flow rates of 20, 30, 40, and 50 mL/min. Hemodynamic parameters were monitored using the Edwards Lifesciences monitoring system. The experiment was successfully completed in 10 kidneys. One kidney failed due to issues with UAS placement, and another was penetrated by the UAS. No significant difference was observed between the middle calyx ICP and IPP. ICP in the upper and lower calyces was higher than IPP, with the discrepancy being minor at 20 or 30 mL/min IFR but significant at higher IFRs of 40 and 50 mL/min. The ICP increased with higher IFRs and when the UAS was set in the low ureteral segment. Under the same IFR and UAS position, ICP varied among the three calyces (lower calyx > upper calyx > middle calyx). The Edwards Lifesciences monitoring system accurately measured hemodynamic parameters, which remained stable even at an IFR of 50 mL/min. The Flexible Ureteroscopic Pressure Measurement System can be used to measure the IPP and ICP. These pressures were not consistent across different IFRs and UAS positions. The highest ICP was observed in the lower calyx.

RASSF1A (Ras association domain family 1 isoform A) is a tumor suppressor and frequently inactivated by promoter hypermethylation in hepatocellular carcinoma (HCC). Autophagy is to degrade misfolded or aggregated proteins and dysfunctional organelles. Autophagy defects enhance oxidative stress and genome instability to promote tumorigenesis. Activating autophagy flux by increasing levels of the RASSF1A-interacting microtubule-associated protein 1 S (MAP1S) leads to suppression of HCC in addition to extending lifespans. Here we tested whether RASSF1A itself functions as a HCC suppressor and activates autophagy similarly as MAP1S does. We show that RASSF1A deletion leads to an acceleration of diethylnitrosamine-induced HCC and a 31% reduction of median survival times in mice. RASSF1A enhances autophagy initiation by suppressing PI3K-AKT-mTOR through the Hippo pathway-regulatory component MST1 and promotes autophagy maturation by recruiting autophagosomes on RASSF1A-stabilized acetylated microtubules through MAP1S. RASSF1A deletion causes a blockade of autophagy flux. Therefore, RASSF1A may suppress HCC and improve survival by activating autophagy flux.

Background The effectiveness of metallic stents in treating ureteral strictures following surgery and radiotherapy for gynecological tumors is currently uncertain. We aimed to investigate the efficacy and safety of thermo-expandable metallic stent (Memokath) in the treatment of ureteral stricture after radiotherapy for gynecological tumors. Methods In this descriptive cross-sectional study, 27 patients with ureteral stricture were treated with Memokath stent after gynecological tumor radiotherapy with or without chemotherapy that was admitted to our hospital from August 2021 to August 2023. Clinical data on efficacy, safety, and complications during stent insertion and indwelling were analyzed. Results The successful insertion of thirty-three stents in twenty-seven patients studied. The stenosis length was 10.14 ± 6.76 cm, and the hospitalization was 4.43 ± 1.83 days. One patient has died from the primary disease carrying a patency stent. The Kaplan-Meier graph showed that the cumilative patency rate of patients with thermo-expandable metallic stent were 92.4% (SD = 5.2%) in eight months, 77.4% (9.1%) in 12 months and 67.7% (SD = 12%) in 29 months, while the cumilative survival rate was 87.5% (SD = 11.5%) in 29 months. The stent patency was 81.48% and later complications of stent indwelling were 5/27, including refractory urinary tract infection (UTI) in three cases, stent migration, and stent intolerance respectively. The creatinine levels, hydronephrosis degree, and glomerular filtration rate improved after the operation, and the first two indicators were statistically significant. Conclusion Memokath stent is a safe and effective treatment for ureteral stricture after surgery and radiotherapy with or without chemotherapy for gynecological tumors.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors in the urinary system. Surgical intervention is the preferred treatment for ccRCC, but targeted biological therapy is required for postoperative recurrent or metastatic ccRCC. Autophagy is an intracellular degradation system for misfolded/aggregated proteins and dysfunctional organelles. Defective autophagy is associated with many diseases. Mul1 is a mitochondrion‐associated E3 ubiquitin ligase and involved in the regulation of divergent pathophysiological processes such as mitochondrial dynamics, and thus affects the development of various diseases including cancers. Whether Mul1 regulates ccRCC development and what is the mechanism remain unclear. Histochemical staining and immunoblotting were used to analyze the levels of Mul1 protein in human renal tissues. Statistical analysis of information associated with tissue microarray and The Cancer Genome Atlas (TCGA) database was conducted to show the relationship between Mul1 expression and clinical features and survival of ccRCC patients. Impact of Mul1 on rates of cell growth and migration and autophagy flux were tested in cultured cancer cells. Herein we show that Mul1 promoted autophagy flux to facilitate the degradation of P62‐associated protein aggresomes and adipose differentiation‐related protein (ADFP)‐associated lipid droplets and suppressed the growth and migration of ccRCC cells. Levels of Mul1 protein and mRNA were significantly reduced so that autophagy flux was likely blocked in ccRCC tissues, which is potentially correlated with enhancement of malignancy of ccRCC and impairment of patient survival. Therefore, Mul1 may promote autophagy to suppress the development of ccRCC. MuL1 is a mitochondrion‐associated E3 ubiquitin ligase involved in the regulation of divergent pathophysiological processes such as mitochondrial dynamics and mitophagy, and thus affects the development of various diseases including cancer. Herein we show that Mul1 promoted autophagy flux to facilitate degradation of P62‐associated protein aggresomes and adipose differentiation‐related protein (ADFP)‐associated lipid droplets and suppressed the growth and migration of ccRCC cells.

To deliver insoluble natural compounds into colon cancer cells in a controlled fashion. Curcumin (CM)-silk fibroin (SF) nanoparticles (NPs) were prepared by solution-enhanced dispersion by supercritical CO (SEDS) (20 MPa pressure, 1:2 CM:SF ratio, 1% concentration), and their physicochemical properties, intracellular uptake efficiency, in vitro anticancer effect, toxicity, and mechanisms were evaluated and analyzed. CM-SF NPs (<100 nm) with controllable particle size were prepared by SEDS. CM-SF NPs had a time-dependent intracellular uptake ability, which led to an improved inhibition effect on colon cancer cells. Interestingly, the anticancer effect of CM-SF NPs was improved, while the side effect on normal human colon mucosal epithelial cells was reduced by a concentration of ~10 μg/mL. The anticancer mechanism involves cell-cycle arrest in the G /G and G /M phases in association with inducing apoptotic cells. The natural compound-loaded SF nanoplatform prepared by SEDS indicates promising colon cancer-therapy potential.