Relocation of lower pole renal stones helps improve the stone-free rate during flexible ureteroscopy with a low complication rate.

OBJECTIVE: To compare the efficacy and safety of relocating the lower pole stones to a favorable pole during flexible ureteroscopy with in situ lithotripsy for the treatment of 10-20 mm lower pole stone (LPS). METHODS: This study was a prospective analysis of patient outcomes who underwent an FURS procedure for the treatment of 10-20 mm lower pole renal stones from January 2020 to November 2022. The patients were randomized into a relocation group or in situ group. The LPSs were relocated into a calyx, during lithotripsy in the relocation group was performed, whereas the in situ group underwent FURS without relocation. All the procedures were performed by the same surgeon. The patients' demographic data, stone characteristics, perioperative parameters and outcomes, stone-free rate (SFR), complications, and overall costs were assessed retrospectively. RESULTS: A total of 90 patients were enrolled and analyzed in this study (45 per group) with no significant differences between the two groups in terms of age, gender, BMI, diabetes, hypertension, stone size, number, laterality, composition, and density. The mean operation time, total energy consumption, postoperative stay, and complications were similar between the groups. Both groups had similar SFR at 1 day postoperative follow-up (p = 0.091), while the relocation group achieved significantly higher SFR 3 months later (97.8% vs 84.4%, p = 0.026). The relocation group also had a significantly higher WisQol score than the in situ group (126.98 vs 110.18, p < 0.001). CONCLUSION: A satisfactory SFR with a relatively low complication rate was achieved by the relocation technique during the FURS procedure.

Up-regulation of PRKDC was associated with poor renal dysfunction after renal transplantation: A multi-centre analysis.

Renal transplantation is the only efficacious treatment for end-stage kidney disease. However, some people have developed renal insufficiency after transplantation, the mechanisms of which have not been well clarified. Previous studies have focused on patient factors, while the effect of gene expression in the donor kidney on post-transplant renal function has been less studied. Donor kidney clinical data and mRNA expression status were extracted from the GEO database (GSE147451). Weight gene co-expression network analysis (WGCNA) and differential gene enrichment analysis were performed. For external validation, we collected data from 122 patients who accepted renal transplantation at several hospitals and measured the level of target genes by qPCR. This study included 192 patients from the GEO data set, and 13 co-expressed genes were confirmed by WGCNA and differential gene enrichment analysis. Then, the PPI network contained 17 edges as well as 12 nodes, and four central genes (PRKDC, RFC5, RFC3 and RBM14) were identified. We found by collecting data from 122 patients who underwent renal transplantation in several hospitals and by multivariate logistic regression that acute graft-versus-host disease postoperative infection, PRKDC [Hazard Ratio (HR) = 4.44; 95% CI = [1.60, 13.68]; p = 0.006] mRNA level correlated with the renal function after transplantation. The prediction model constructed had good predictive accuracy (C-index = 0.886). Elevated levels of donor kidney PRKDC are associated with renal dysfunction after transplantation. The prediction model of renal function status for post-transplant recipients based on PRKDC has good predictive accuracy and clinical application.

CircTENM3 inhibites tumor progression via the miR-558/RUNX3 axis in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is currently acknowledged as the second most widespread cancer among men worldwide. Yet, the lack of dependable diagnostic biomarkers and therapeutic targets has presented considerable hurdles to the progression of prostate cancer treatment. Circular RNAs are implicated in the pathogenesis of numerous diseases, positioning them as promising biomarkers for diverse medical conditions. This study aims to uncover a specific circRNA that could serve as a diagnostic and therapeutic target for detecting and treating PCa. METHODS: The change of circTENM3 expression levels in PCa was detected by qPCR. CCK8 assays, EdU assays, Scratch assay and Transwell migration assay conducted to detect the role of circTENM3 in PCa cells in vitro. RIP assay, RNA-pull down and luciferase reporter assay were performed to explore the mechanism of circTENM3. Gain-of-function analysis was performed to reveal the function of circTENM3 in PCa in vivo. RESULTS: The results revealed that the expression level of circTENM3 was significantly down-regulated in PCa. CircTENM3 overexpression alleviated the progression of PCa in vitro. Mechanistically, circTENM3 enhanced RUNX3 levels via miR-558 sponge. Gain-of-function analysis determined that circTENM3 overexpression could inhibit PCa progression in vitro. CONCLUSIONS: Our research offers profound insights into the protective role played by circTENM3 in PCa. CircTENM3 operates as a sponge for miR-558, thereby triggering the elevation of RUNX3 expression, which subsequently curbs the progression of PCa.

Dominant Contribution of NO3 Radical to NO3- Formation during Heavy Haze Episodes: Insights from High-Time Resolution of Dual Isotopes Δ17O and δ18O.

δ18O is widely used to track nitrate (NO3-) formation but overlooks NO3 radical reactions with hydrocarbons (HCs), particularly in heavily emitting hazes. This study introduces high-time resolution Δ17O-NO3- as a powerful tool to quantify NO3- formation during five hazes in three cities. Results show significant differences between Δ17O-NO3- and δ18O-NO3- in identifying NO3- formation. δ18O-NO3- results suggested N2O5 hydrolysis (62.0-88.4%) as the major pathway of NO3- formation, while Δ17O-NO3- shows the NO3- formation contributions of NO2 + OH (17.7-66.3%), NO3 + HC (10.8-49.6%), and N2O5 hydrolysis (22.9-33.3%), revealing significant NO3 + HC contribution (41.7-56%) under severe pollution. Furthermore, NO3- formation varies with temperatures, NOx oxidation rate (NOR), and pollution levels. Higher NO2 + OH contribution and lower NO3 + HC contribution were observed at higher temperatures, except for low NOR haze where higher NO2 + OH contributions were observed at low temperatures (T ← 10 °C). This emphasizes the significance of NO2 + OH in emission-dominated haze. Contributions of NO2 + OH and NO3 + HC relate to NOR as positive (fP1 = 3.0*NOR2 - 2.4*NOR + 0.8) and negative (fP2 = -2.3*NOR2 + 1.8*NOR) quadratic functions, respectively, with min/max values at NOR = 0.4. At mild pollution, NO2 + OH (58.1 ± 22.2%) dominated NO3- formation, shifting to NO3 + HC (35.5 ± 16.3%) during severe pollution. Additionally, high-time resolution Δ17O-NO3- reveals that morning-evening rush hours and high temperatures at noon promote the contributions of NO3 + HC and NO2 + OH, respectively. Our results suggested that the differences in the NO3- pathway are attributed to temperatures, NOR, and pollution levels. Furthermore, high-time resolution Δ17O-NO3- is vital for quantifying NO3 + HC contribution during severe hazes.

AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo.

BACKGROUNDS/AIMS: Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor. METHODS: Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153's activity in vivo. RESULTS: AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206. CONCLUSION: Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells.

Dual inhibition of BRD4 and PI3K by SF2523 suppresses human prostate cancer cell growth in vitro and in vivo.

Bromodomain-containing protein 4 (BRD4) and phosphatidylinositol 3-kinase (PI3K) are both key oncogenic proteins in human prostate cancer. In the current study, we examined the anti-prostate cancer cell activity by SF2523, a BRD4 and PI3K dual inhibitor. We showed that SF2523 potently inhibited survival and proliferation of the primary human prostate cancer cells. SF2523 induced profound apoptosis activation in prostate cancer cells. The dual inhibitor was yet non-cytotoxic to the prostate epithelial cells. At the molecular level, SF2523 downregulated BRD4-regulated genes (cyclin D1, c-Myc and androgen receptor) and almost blocked AKT-S6K1 activation in prostate cancer cells. In vivo, SF2523 intraperitoneal administration at the well-tolerated dose inhibited human prostate cancer xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-regulated genes (cyclin D1, c-Myc and androgen receptor) and AKT-S6K1 activation were inhibited in SF2523-treated tumors. Together, dual inhibition of BRD4 and PI3K by SF2523 suppresses human prostate cancer cell growth in vitro and in vivo.

Sleep correlates of depression and anxiety in an elderly Asian population.

BACKGROUND: Research looking at the association between sleep and psychiatric symptoms in elderly Asian populations is lacking. The present study examines the sleep correlates of depression and anxiety in a sample of cognitively healthy older adults. METHODS: The Geriatric Depression Scale, Geriatric Anxiety Inventory, and the Pittsburgh Sleep Quality Index were administered to a community sample of elderly participants (n = 107; 81 women; Mage = 71.3 years, SD = 5.7) RESULTS: Geriatric Depression Scale and Geriatric Anxiety Inventory scores are both significantly correlated with sleep disturbance. Geriatric Depression Scale scores are uniquely associated with daytime dysfunction, and Geriatric Anxiety Inventory scores are uniquely associated with perceived sleep quality, sleep latency, and global Pittsburgh Sleep Quality Index scores. CONCLUSIONS: Depression and anxiety in a cohort of elderly Asian subjects are associated with a number of sleep-related issues; both are related to a somewhat different profile of sleep problems.

Flexible ureteroscopy with holmium laser lithotripsy: a new choice for intrarenal stone patients.

OBJECTIVE: To evaluate the efficiency and safety of flexible ureteroscopy (FURS) and holmium lithotripsy for intrarenal stones and to stratify the efficiency and safety by stone burdens of ≤20, 20-40, and ≥40 mm. METHODS: Five hundred eighty-two patients with intrarenal stones were treated with FURS and holmium lithotripsy at a single department from August 2008 to October 2013. Stone size was evaluated by calculating the cumulative stone diameter of all intrarenal stones, and stone-free status was defined as the absence of any stone or stone fragment <1 mm in the kidney. RESULTS: Data analysis revealed a mean stone burden of 21.8 ± 7.6 mm. The overall primary stone-free rate (SFR) was 65.3%, which increased to 89.0% 6 months after the first surgery. Complications developed in 6.7% of patients. A significant difference was found between lower-calyx stones and other stones (p < 0.001; p = 0.006), while noncalcium stones had a much higher SFR than calcium stones (p < 0.001; p = 0.04). CONCLUSION: Our study showed that the overall renal SFR with the use of FURS and holmium lithotripsy was satisfactory, with a relatively low complication rate. We believe that FURS with holmium lithotripsy could be a valuable choice for patients with renal stones, especially for patients with a cumulative stone burden ≤40 mm.

GREM1 knockdown regulates the proliferation, apoptosis and EMT of benign prostatic hyperplasia by suppressing the STAT3/c-Myc signaling.

BACKGROUND: Gremlin 1 (GREM1) has been reported to be highly expressed in prostate hyperplasia tissues. However, the role and molecular mechanism of GREM1 in benign prostatic hyperplasia (BPH) is still unclear. METHODS: In this study, expression of GREM1 in BPH-1 cells was detected by western blot assay. Cell counting kit-8 assay was performed to assess cell proliferation. Flow cytometry and western blot were used to assess cell apoptosis and cell cycle. The EMT process was detected by western blot assay and immunofluorescence staining. In addition, colivelin was used as a STAT3 activator and the expressions of STAT3/c-Myc signaling were assessed by western blot assay. RESULTS: The data showed that GREM1 silencing inhibited BPH-1 cell proliferation and promoted cell apoptosis. Moreover, GREM1 silencing repressed the cell cycle progression and the development of EMT. In addition, knockdown of GREM1 suppressed the expression of the STAT3/c-Myc signaling in BPH-1 cells and colivelin treatment rehabilitated this signaling. Moreover, c-Myc overexpression or colivelin reversed the effects of GREM1 silencing on BPH-1 cell proliferation, cell apoptosis, cell cycle, as well as EMT. CONCLUSION: To sum up, GREM1 silencing may alleviate the BPH progress by inhibiting the STAT3/c-Myc signaling.

MKI67 with arterial hypertension predict a poor survival for prostate cancer patients, a real-life investigation.

INTRODUCTION: Prostate cancer is a common urology malignant in males, ranking second globally. The disease is especially severe when diagnosed alongside hypertension. MKI67 is an established marker of neoplastic cell proliferation in humans, but the significance of its prognostic value in patients with prostate cancer and hypertension requires further research. METHODS: In this retrospective analysis, we evaluated 296 hypertensive prostate cancer patients between March 2, 2012, and November 1, 2015. We used Cox regression models and prediction analysis to assess overall survival. Furthermore, we created a nomogram and verified its accuracy using a calibration curve. RESULTS: Of all participants, 101 (34.12%) died. Our multi-factor analysis revealed that MKI67 expression was associated with an increased hazard ratio of death (> fivefold) (Hazard Ratio 5.829, 95% CI 3.349-10.138, p value < 0.01) and progression (twofold) (HR 2.059, 95% CI 1.368-3.102, p value < 0.01). Our Lasso analysis model displayed that several factors, including heart failure, smoking, ACS, serum albumin, Gealson score, prognostic nutritional index, MKI67 expression, surgery, and stage were high risks of prostate cancer. To ensure each covariate's contribution to cancer prognosis, we created a Cox model nomogram, which accurately predicted the risk of death (C-statistic of 0.8289) and had a proper calibration plot for risk assessment. CONCLUSION: MKI67 expression predicts poor outcomes for overall mortality in prostate cancer and hypertension patients. Additionally, our cross-validated multivariate score, which includes MKI67, demonstrated accuracy efficacy of predicting prognosis.

Histone lactylation-related genes correlate with the molecular patterns and functions of cancer-associated fibroblasts and have significant clinical implications in clear cell renal cell carcinoma.

Recent research emphasised the indispensable role of histone lactylation in the activation of hepatic stellate cells. The VHL mutation is extremely common in clear cell renal cell carcinoma, which normally causes a metabolic shift in cancer cells and increases lactate production, eventually creating a lactate-enriched tumour microenvironment. Cancer-associated fibroblasts (CAFs) promote tumour progression, which is also vital in clear cell renal cell carcinoma. Therefore, this study investigated histone lactylation in CAFs and its impact on patient survival. Multiomics technology was employed to determine the role of histone lactylation-related genes in the evolution of CAFs which correlated with the function and molecular signatures of CAFs. The results suggested that TIMP1 was the hub gene of histone lactylation-related genes in clear cell renal cell carcinoma.

LINC00106/RPS19BP1/p53 axis promotes the proliferation and migration of human prostate cancer cells.

Background: Prostate cancer (PCa) is among the most prevalent cancers in males with high biochemical recurrence risk. LINC00106 contributes to the carcinogenesis of Hepatocellular carcinoma (HCC). However, it is unclear how it affects PCa advancement. Here, we studied LINC00106's effects on PCa cells' ability to proliferate, invade, and metastasize. Methods: The data of LINC00106 from The Cancer Genome Atlas (TCGA) in human PCa tissues were analyzed using TANRIC and survival analysis. In order to determine the expression levels of genes and proteins, we also performed reverse transcription-quantitative PCR and western blot analysis. The migration, invasion, colony formation, and proliferation (CCK-8) of PCa cells with LINC00106 knockdown were investigated. The impact of LINC00106 on cell proliferation and invasion was also analyzed in mice. LncRNA prediction software catRAPID omics v2.1 (catRAPID omics v2.0 (tartaglialab.com)) was used to predict proteins that might interact with LINC00106. The interactions were verified via RNA immunoprecipitation and RNA pull-down assays and finally, the interaction between LINC00106 and its target protein and the p53 signaling pathway was studied using a dual-luciferase reporter assay. Results: In PCa, LINC00106 was over-expressed in comparison to normal tissues, and it was linked to an unfavorableprognosis. In vitro and in vivo analyses showed that downregulating LINC00106 decreased PCa cells'ability to proliferate and migrate. A common regulatory axis generated by LINC00106 and RPS19BP1 prevents p53 activity. Conclusion: Our experimental data indicate that LINC00106 functions as an oncogene in the onset of PCa, and the LINC00106/RPS19BP1/P53 axis canserve as a novel therapeutic target for PCa treatment.

Mechanism Study on Radiosensitization Effect of Curcumin in Bladder Cancer Cells Regulated by Filamin A.

Objective: To study the radiosensitization effect of curcumin, a natural product with anti-inflammatory and anti-cancer properties, in bladder cancer cells and identify the specific role of FLNA gene in that process. Methods: CCK-8 method was initially adopted to identify the proper interventional concentration of curcumin. T24 bladder cancer cells were subjected to CCK-8, flow cytometry, and colony formation assay to study the cell biological behaviors under different interventions. γ-H2AX test was performed to test the level of damage in T24 cells. RT-qPCR and Western blot were conducted to measure FLNA mRNA and protein levels. Results: Low-dose curcumin (10, 20 µM) following X-ray exposure resulted in increased DNA damage, augmented apoptosis, and reduced proliferation of T24 cells. Certain radiosensitization was demonstrated when curcumin was applied at 10 µM. Additionally, elevation of FLNA gene and protein levels was also indicated upon combination treatment. Conclusion: Low-dose curcumin has certain radiosensitization effect in bladder cancer, where FLNA plays a certain regulatory role.

Prognostic value and potential biological functions of ferroptosis-related gene signature in bladder cancer.

Bladder cancer (BC), as a genitourinary system tumor, is a highly prevalent tumor type. Ferroptosis is an iron-dependent oxidative cell death mechanism that is becoming increasingly recognized as a promising avenue for cancer therapy. However, further determination of the prospective prognostic value of ferroptosis for BC and investigation of the underlying mechanisms is required. The mRNA expression profiles and associated clinical data were downloaded from public databases such as The Cancer Genome Atlas, Gene Expression Omnibus and the IMvigor210 database. To construct a predictive formula, the least absolute shrinkage and selection operator Cox regression algorithm was used. In addition, a prognostic multigene signature was constructed using previously selected ferroptosis-related genes (FRGs). A total of 28 FRGs were differentially expressed between tumor and normal samples with |log2 fold change| >1 and adjusted P<0.05. A prognostic model was then established and it was validated in the GEO cohort using six genes: Glutamate-cysteine ligase modifier subunit, crystallin α-B, transferrin receptor, zinc finger E-box binding homeobox 1, squalene epoxidase and glucose-6-phosphate dehydrogenase (G6PD). Numerous important pathways involved in the development of the immune system and cancer were indicated to be significantly different between the two risk groups. In addition, it was discovered that G6PD expression subgroups that were associated with immunotherapy response in patients with BC had similar prognostic features to risk score subgroups. In the present study, a gene signature with a prognostic value for ferroptosis in BC was successfully developed and the potential value of G6PD was identified for future research.

Identification of immune subtypes to guide immunotherapy and targeted therapy in clear cell renal cell carcinoma.

Accumulating pieces of evidence suggested that immunotypes may indicate the overall immune landscape in the tumor microenvironment, which were closely related to therapeutic response. The purpose of this study was to classify and define the immune subtypes of clear cell renal cell carcinoma (ccRCC), so as to authenticate the potential immune subtypes that respond to immunotherapy. Transcriptome expression profile and mutation profile data of ccRCC, as well as clinical characteristics used in this study were obtained from TCGA database. There were significant differences in the infiltration of immune cells, immune checkpoints, and antigens between ccRCC and para-cancerous tissues. According to immune components, patients with ccRCC were divided into three immune subtypes, with different clinical and molecular characteristics. Compared with other subtypes, IS2 showed cold immune phenotype, and was associated with better survival. IS1 represented complex immune populations and was associated with poor overall survival (OS) and progression free survival (PFS). Further analysis indicated that expression of immune checkpoints also differed among the three subtypes, and was abnormally up-regulated in IS3. Pathway enrichment analysis indicated that the mTOR signaling pathway was abnormally enriched in IS3, while the TGF_BETA, ANGIOGENESIS and receptor tyrosine kinase signaling pathways were abnormally enriched in IS2. Furthermore, there was an abnormal enrichment of the epithelial-to-mesenchymal transition (EMT) signaling pathway in IS1, which may be associated with a higher rate of metastasis. Finally, SCG2 was screened as a specific antigen of ccRCC, which was not only related to poor prognosis, but also significantly associated with immune cells and immune checkpoints. In conclusion, the immune subtypes of ccRCC may provide new insights into the tumor biology and the precise clinical management of this disease.

Safety and efficacy of prostatic artery embolization for large benign prostatic hyperplasia in elderly patients.

OBJECTIVE: To assess the safety and efficacy of prostatic arterial embolization (PAE) for elderly patients with lower urinary tract symptoms secondary to large benign prostatic hyperplasia. METHODS: Twenty-eight patients (>80 years of age) with prostate volume >80 mL were enrolled from October 2016 to October 2019. PAE was performed using microspheres and functional results were evaluated at 1, 3, 6, and 12 months postoperatively. The following data were recorded: International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urine flow rate (Qmax), post-void residual urine volume, prostate volume and total prostate-specific antigen level. RESULTS: Selective prostatic arterial catheterization and embolization were achieved in 27 of 28 patients. Follow-up data were available for those 27 patients until 12 months postoperatively. Significant improvements were found at all postoperative time points in terms of the mean IPSS, mean QoL score, mean Qmax, mean post-void residual urine volume, mean total prostate-specific antigen level, and mean prostate volume. The overall complication rate was 46.4%. CONCLUSIONS: PAE is an efficacious and safe treatment for elderly patients with large prostate volume; it may offer an effective approach for patients who are not candidates for open or endoscopic surgical procedures because of comorbidities.

Mutation of Klotho rs3752472 protect the kidney from the renal epithelial cell injury caused by CaOx crystals through the Wnt/ß-catenin signaling pathway.

Calcium oxalate (CaOx) is a major contributor to urolithiasis, one of the most common urological diseases. Our previous study has shown that Klotho rs3752472 polymorphism correlates with an increased risk of CaOx-related urolithiasis in human cohorts. This study aims to identify the effect of Klotho rs3752472 polymorphism on the renal epithelium injury caused by CaOx. A rat urolithiasis model was established and validated. Renal function was assessed, and histological examination was performed. The distribution and expression of Klotho in the rat model were detected by immunohistochemical staining and western blotting analysis. A renal epithelial cell line (HK2) was used and intervened by COM crystals with several concentrations and time points. Expression of Klotho and key mediators in Wnt/ß-catenin pathway were assessed by Western blotting analysis. Wide-type and mutated plasmids of Klotho rs3752472 were added in the cell culture, and the activation of Wnt/ß-catenin signaling was tested. Finally, Wide-type and mutated plasmids of Klotho rs3752472 were adoptively transferred to the rat model, and the expression of Klotho was verified. In the rat model, Klotho was mainly distributed in the renal tubular area, which significantly declined in the urolithiasis group. In vitro, COM crystals significantly inhibited the expression of Klotho and induced remarkable renal epithelial cell injury. The mutation of Klotho rs3752472 can notably enhance the expression of Klotho, as well as the protection from renal epithelial cell injury and the inhibition of Wnt/ß-catenin signaling pathway. After adoptively transferred to the rat urolithiasis model, similar results were observed for the mutation of Klotho rs3752472. Klotho was significantly correlated with the renal epithelial cell injury induced by CaOx crystals. Furthermore, the mutation of Klotho rs3752472 can remarkably enhance the expression of Klotho in renal tissues and cells, and subsequently protect the renal epithelial cell from the formation of CaOx crystals through the inhibition of Wnt/ß-catenin signaling pathway.

Castration aggravates insulin resistance, reduces immune function and improves quality of life of prostate cancer patients.

PURPOSE: To investigate the influence of castration on insulin resistance, quality of life and immune function of prostate cancer (PCa) patients. METHODS: A total of 57 PCa patients definitely diagnosed via prostate biopsy underwent bilateral orchiectomy. No patient had history of diabetes mellitus before operation. The hemoglobin, leukocyte count, platelet count, albumin and alkaline phosphatase in the blood before operation and at 1 year after operation were analyzed using a full-automatic biochemistry analyzer, and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the peripheral blood were calculated. RESULTS: The levels of serum testosterone (T) and free testosterone (FT) in PCa patients declined remarkably at 1 month after castration. Compared with those before operation, the levels of serum T and FT were decreased significantly at 1, 2, 4 and 8 months as well as 1 year after castration. The levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were elevated gradually with the prolongation of time after operation. The level of high-density lipoprotein cholesterol (HDL-C) displayed an apparent rising trend from 2 months after surgical castration. The results of flow cytometry indicated that the levels of cluster of differentiation (CD) 4+ and CD4+/CD8+ were lowered markedly, while that of CD8+ was raised significantly in comparison with those before castration (p<0.05) After castration, both fasting blood glucose and fasting insulin were increased obviously in the patients (p<0.05). The 2 h postprandial blood glucose and insulin were raised distinctly at 1 month after castration (p<0.05). The insulin resistance index was increased persistently and prominently (p<0.05). CONCLUSION: The treatment of PCa through castration can aggravate the insulin resistance, reduce the immune function and improve the patient quality of life.

A retrospective study comparing super-mini percutaneous nephrolithotomy and flexible ureteroscopy for the treatment of 20-30 mm renal stones in obese patients.

OBJECTIVE: This study aimed to compare the efficacy and safety of Super-mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopy (F-URS) in the treatment of 20-30 mm renal stones in obese patients. METHODS: We conducted a retrospective analysis of outcomes of patients who underwent SMP and F-URS to treat 20-30 mm renal stones from August 2017 to September 2018. Patients with BMI >30 kg/m2 were enrolled into this study. Forty-eight patients underwent SMP, while 104 patients underwent F-URS by the same surgeon. The patients' demographic data, stone characteristics, perioperative parameters and outcomes, complications, stone-free rate (SFR) and overall costs were retrospectively assessed. RESULTS: No significant differences were found between the two groups in terms of age, gender, BMI, operation side, stone size, number, locations, stone compositions and CT value. The mean operation time was significantly shorter in the SMP group (p < 0.001), while the F-URS group had significantly shorter postoperative stays (p < 0.001) and lower complication rates (p < 0.001). Both groups had similar SFR at a 3-month follow-up (p = 0.190), while the SMP group achieved significant higher SFR 3 days after the operation (p < 0.001). The SMP group had a significantly lower overall cost and fewer stage-2 procedures than the F-URS group. CONCLUSION: SMP and F-URS are equally effective in obese patients with 20-30 mm renal stones. However, F-URS offers the advantage of a lower complication rate, while SMP performed better in terms of operation time, tubeless rate, stage-2 procedures and overall costs.

A pH-Responsive Charge-Reversal Drug Delivery System with Tumor-Specific Drug Release and ROS Generation for Cancer Therapy.

INTRODUCTION: Poor cell uptake and incomplete intracellular drug release are the two major challenges for polymeric prodrug-based drug delivery systems (PPDDSs) in cancer treatment. METHODS: Herein, a PPDDS with pH-induced surface charge-reversal and reactive oxygen species (ROS) amplification for ROS-triggered self-accelerating drug release was developed, which was formed by encapsulating a ROS generation agent (vitamin K3 (VK3)) in pH/ROS dual-sensitive polymetric prodrug (PEG-b-P(LL-g-TK-PTX)-(LL-g-DMA)) based micelle nanoparticles (denoted as PVD-NPs). RESULTS: The surface charge of the PVD-NPs can change from negative to positive for enhanced cell uptake in response to tumor extracellular acidity pH. After internalization by cancer cells, PVD-NPs demonstrate dual drug release in response to intracellular ROS-rich conditions. In addition, the released VK3 can produce ROS under the catalysis by NAD(P)H:quinone oxidoreductase-1, which facilitates tumor-specific ROS amplification and drug release selectively in cancer cells to enhance chemotherapy. CONCLUSION: Both in vitro and in vivo experiments demonstrated that the PVD-NPs showed significant antitumor activity in human prostate cancer.