SMG5 Inhibition Restrains Hepatocellular Carcinoma Growth and Enhances Sorafenib Sensitivity.

Hepatocellular carcinoma (HCC) has a pathogenesis that remains elusive with restricted therapeutic strategies and efficacy. This study aimed to investigate the role of SMG5, a crucial component in nonsense-mediated mRNA decay (NMD) that degrades mRNA containing a premature termination codon (PTC), in HCC pathogenesis and therapeutic resistance. We demonstrated an elevated expression of SMG5 in HCC and scrutinized its potential as a therapeutic target. Our findings revealed that SMG5 knockdown not only inhibited the migration, invasion, and proliferation of HCC cells but also influenced sorafenib resistance. Differential gene expression analysis between the control and SMG5 knockdown groups showed an upregulation of MAT1A in the latter. High expression of MAT1A, a catalyst for S-adenosylmethionine (SAM) production, as suggested by TCGA data, was indicative of a better prognosis for HCC. Further, an enzyme-linked immunosorbent assay showed a higher concentration of SAM in SMG5 knockdown cell supernatants. Furthermore, we found that exogenous SAM supplementation enhanced the sensitivity of HCC cells to sorafenib alongside changes in the expression of Bax and Bcl 2, apoptosis-related proteins. Our findings underscore the important role of SMG5 in HCC development and its involvement in sorafenib resistance, highlighting it as a potential target for HCC treatment.

Efficacy of collagenase Clostridium histolyticum combination therapies for Peyronie's disease: a systematic review and meta-analysis.

INTRODUCTION: Peyronie's disease (PD) is a common penile disorder characterized by the formation of fibrous noncompliant hard nodules in the tunica albuginea of the penis. Collagenase Clostridium histolyticum (CCH) is an injectable drug that treats PD by enzymatically degrading plaque interstitial collagen. CCH has been used in patients with varying curvature, as well as in the acute and stable phases of the disease, through a variety of treatment regimens and combinations. We carried out a systematic review and meta-analysis to assess the efficacy of CCH combination therapies for PD. METHODS: We selected 4 observational comparative studies and 3 randomized controlled trials including 532 participants from the PubMed, Embase, and Cochrane databases (until December 2023) to evaluate the efficacy of CCH combination therapies for PD. The primary outcome was clinical efficacy as evaluated by improvement in penile curvature and penile length, as well as by scores on the Peyronie's Disease Questionnaire (PDQ) for symptom bother, penile pain, and psychological symptoms. Continuous data were represented by mean difference (MD) and 95% CI. All data were analyzed by Review Manager version 5.3. RESULTS: For penile length (MD, 0.81 cm; 95% CI, 0.17-1.45; P = .01), PDQ symptom bother (MD, -1.02; 95% CI, -1.83 to -0.21; P = .01), and PDQ penile pain (MD, -0.93; 95% CI, -1.50 to -0.36; P = .001), CCH combination therapy showed significantly greater improvements vs CCH monotherapy. However, in the other indicators, penile curvature and PDQ psychological symptoms, there was no significant difference between the therapies. CONCLUSION: This meta-analysis supports that CCH combination therapies can partially increase penile length and ameliorate symptom bother and penile pain to some extent. However, CCH combination therapies still need to be evaluated through more high-quality research.

The Effect of Distraction Techniques on Pain, Fear, and Anxiety in Children Undergoing Circumcision: A Meta-Analysis of Randomized Controlled Trials.

Circumcision is a common pediatric operation, and distraction technique can be used as an adjunct analgesic method during the perioperative period. The study aims to explore the effect of distraction techniques on reducing pain, fear, and anxiety in children undergoing circumcision. The PubMed, ClinicalTrials.gov, and Embase databases were searched for articles published from January 1, 2000, to December 31, 2023. Only randomized controlled trials (RCTs) were included. Meta-analysis and forest plots were carried out using Review Manager 5.4.1 software, and outcomes were reviewed by two authors independently. We used the Risk of Bias assessment form (ROB2) developed by the Cochrane Collaboration to assess the quality of included studies. PRISMA 2020 guidelines were used in this article to achieve the quantitative and qualitative synthesis of data. A total of seven RCTs were included. The intervention group consisted of 417 patients, while the control group had 245 patients. The meta-analysis and sensitivity analysis results showed that the distraction technique could significantly relieve pain (MD -1.3, 95% confidence interval [CI]: [-1.61 to -0.99], p < .00001), fear (SMD -1.04, 95%CI -1.68 to -0.4, p = .001), and anxiety (SMD -1.07, 95%CI [-1.64 to -0.51], p = .0002). Similarly, therapeutic play significant could significantly relieve fear (MD -0.4, 95%CI [-0.71 to -0.1], p = .01) and anxiety (SMD -1.31, 95%CI [-2.59 to -0.04], p = .04), virtual reality (VR) could significantly relieve anxiety (SMD -0.67, 95%CI [-0.98 to -0.37], p < .0001). Distraction techniques can alleviate perioperative pain, fear, and anxiety in children undergoing circumcision.

Testicular Torsion in Jiaodong Peninsula: A 14-Year Multicenter Retrospective Study.

BACKGROUND: To investigate the correlation between temperature and testicular torsion in Jiaodong Peninsula which has temperate continental monsoon climate and is represented by Yantai and its surrounding areas. METHODS: A retrospective analysis was conducted by reviewing clinical data of 292 patients who were admitted and surgically confirmed to have testicular torsion in the Yantai Yuhuangding hospital medical complex between January 1, 2009, and August 31, 2022. Male patients who underwent circumcision (foreskin) were allocated to the control group. Temperature data were obtained from the China Meteorological Data Service Center. Chi-squared test or Fisher's exact test and one-way analysis of variance were employed to compare patient characteristics and climatic variables among the different groups. Pearson's correlation analysis was used to analyze the association between monthly average ambient temperature and monthly cumulative number of cases. Moreover, a logistic regression model was utilized to identify the independent factors of testicular torsion. RESULTS: The mean age of patients with testicular torsion was 16.8 years. The number of cases was the highest in autumn. The temperature was the highest in summer and the lowest in winter (p < 0.01). Furthermore, the temperature difference (TD) in autumn was the highest in the four seasons groups (p < 0.01). The patients were divided into the high TD and low TD groups according to the mean TD (7.62 ◦C) on the admission day. The high TD group had a higher number of patients than the low TD group, and the temperature was lower in the former group than in the latter group (p < 0.01). A roughly negative correlation was observed between ambient temperature and the number of cases (Pearson's r = -0.228, 95% confidence interval (CI): -0.366 to -0.079, p = 0.003). Logistic regression analysis revealed that the independent risk factor for testicular torsion was TD on admission day (odds ratio, 1.82; 95% CI, 1.28-2.59; p < 0.001). CONCLUSIONS: To some extent, external temperature can affect the body surface temperature of patients and then induce testicular torsion. We concluded that testicular torsion easily occurs in the season in which the temperature drops and the TD is high.

Testicular Torsion in Jiaodong Peninsula: A 14-Year Multicenter Retrospective Study

Background: To investigate the correlation between temperature and testicular torsion in Jiaodong Peninsula which has temperate continental monsoon climate and is represented by Yantai and its surrounding areas. Methods: A retrospective analysis was conducted by reviewing clinical data of 292 patients who were admitted and surgically confirmed to have testicular torsion in the Yantai Yuhuangding hospital medical complex between January 1, 2009, and August 31, 2022. Male patients who underwent circumcision (foreskin) were allocated to the control group. Temperature data were obtained from the China Meteorological Data Service Center. Chi-squared test or Fisher’s exact test and one-way analysis of variance were employed to compare patient characteristics and climatic variables among the different groups. Pearson’s correlation analysis was used to analyze the association between monthly average ambient temperature and monthly cumulative number of cases. Moreover, a logistic regression model was utilized to identify the independent factors of testicular torsion. Results: The mean age of patients with testicular torsion was 16.8 years. The number of cases was the highest in autumn. The temperature was the highest in summer and the lowest in winter (p < 0.01). Furthermore, the temperature difference (TD) in autumn was the highest in the four seasons groups (p < 0.01). The patients were divided into the high TD and low TD groups according to the mean TD (7.62 ◦C) on the admission day. The high TD group had a higher number of patients than the low TD group, and the temperature was lower in the former group than in the latter group (p < 0.01). A roughly negative correlation was observed between ambient temperature and the number of cases (Pearson’s r = −0.228, 95% confidence interval (CI): −0.366 to −0.079, p = 0.003) (AU)

Targeted delivery of a PD-1-blocking scFv by CD133-specific CAR-T cells using nonviral Sleeping Beauty transposition shows enhanced antitumour efficacy for advanced hepatocellular carcinoma.

BACKGROUND: CD133 is considered a marker for cancer stem cells (CSCs) in several types of tumours, including hepatocellular carcinoma (HCC). Chimeric antigen receptor-specific T (CAR-T) cells targeting CD133-positive CSCs have emerged as a tool for the clinical treatment of HCC, but immunogenicity, the high cost of clinical-grade recombinant viral vectors and potential insertional mutagenesis limit their clinical application. METHODS: CD133-specific CAR-T cells secreting PD-1 blocking scFv (CD133 CAR-T and PD-1 s cells) were constructed using a sleeping beauty transposon system from minicircle technology, and the antitumour efficacy of CD133 CAR-T and PD-1 s cells was analysed in vitro and in vivo. RESULTS: A univariate analysis showed that CD133 expression in male patients at the late stage (II and III) was significantly associated with worse progression-free survival (PFS) (P = 0.0057) and overall survival (OS) (P = 0.015), and a multivariate analysis showed a trend toward worse OS (P = 0.041). Male patients with advanced HCC exhibited an approximately 20-fold higher PD-L1 combined positive score (CPS) compared with those with HCC at an early stage. We successfully generated CD133 CAR-T and PD-1 s cells that could secrete PD-1 blocking scFv based on a sleeping beauty system involving minicircle vectors. CD133 CAR-T and PD-1 s cells exhibited significant antitumour activity against HCC in vitro and in xenograft mouse models. Thus, CD133 CAR-T and PD-1 s cells may be a therapeutically tractable strategy for targeting CD133-positive CSCs in male patients with advanced HCC. CONCLUSIONS: Our study provides a nonviral strategy for constructing CAR-T cells that could also secrete checkpoint blockade inhibitors based on a Sleeping Beauty system from minicircle vectors and revealed a potential benefit of this strategy for male patients with advanced HCC and high CD133 expression (median immunohistochemistry score > 2.284).

A systematic review and meta-analysis of efficacy and safety comparing greenlight laser vaporization with transurethral resection of the prostate for benign prostatic hyperplasia with prostate volume less than 80 ml.

We conducted a meta-analysis to evaluate the efficacy and safety of photo selective vaporisation of the prostate (PVP) with the GreenLight Laser versus transurethral resection of the prostate (TURP) for the treatment of small-volume benign prostatic hyperplasia (BPH). As of July 2022, relevant literature in online databases such as Cochrane Library, PubMed, and Embase was searched, including studies published on or before that date, and there were 9 studies in total, including 5 RCTs and 4 non-RCTs. In total 1525 patients were included to compare the efficacy of PVP and TURP in treating BPH. The Cochrane Collaboration criteria were used to evaluate the risk of bias. The software was used for random effect meta-analysis with RevMan 5.3. Data extraction included: clinical baseline characteristics, perioperative parameters, complication rates, International Prostate Symptom Score (IPSS), prostate specific antigen (PSA), post-void residual urine (PVR), maximum flow rate (Qmax), and quality of life (QoL). The pooled analysis showed that PVP was associated with reduced blood loss, blood transfusion, clot retention, catheterization time, definitive catheter removal, and hospital stay, but was associated with longer operative time and more severe dysuria (all p < 0.05). The results of this meta-analysis show that PVP as a technique for the treatment of benign prostatic hyperplasia with a volume of less than 80 cc has similar efficacy to standard TURP in IPSS, PSA, PVR, Qmax and QoL, and is an effective alternative. It outperformed TURP in terms of blood transfusion, catheterization time and hospital stay, while TURP is superior to PVP in terms of operation time.

The role of three-dimensional model in preoperative communication before partial nephrectomy and postoperative management.

Objective: To investigate the role of the three-dimensional (3D) image reconstruction technique in preoperative communication before partial nephrectomy (PN) and postoperative follow-up. Methods: A retrospective study was performed with 158 renal cancer patients treated with PN at our center from May 1, 2017 to April 30, 2019. 81 patients (group A) had preoperative communication using the 3D reconstruction technique, while 77 patients (group B) did not. The surgeon explained the anatomical structure, tumor characteristics, and surgical approach in detail to the two groups of patients. Each patient completed a questionnaire. The loss to follow-up rate over a 3-year period was counted for both groups, and non-cancer-related serious complications such as renal failure and cardio-cerebrovascular disease were observed. This research did not include patients who returned for follow-up care owing to associated complications such as postoperative chronic kidney disease. Comparisons between two groups were performed using the Mann-Whitney U test and chi-square test. Results: All patients showed no statistically significant differences in basic clinical parameters, such as age, gender, body mass index, tumor size, and R.E.N.A.L. score (P â€‹> â€‹0.05). In group A, patients were significantly more likely to experience understanding of renal anatomy (P â€‹= â€‹0.001), characteristics of renal cell carcinoma (P â€‹= â€‹0.003), surgical approach (P â€‹= â€‹0.007), and relief of preoperative anxiety (P â€‹= â€‹0.013). The follow-up adherence at 3 years postoperatively in group A and group B was 21 cases and 10 cases, respectively (P â€‹= â€‹0.041). In addition, glomerular filtration rate < 60 â€‹mL/min/1.73 â€‹m2 or serum creatinine > 186 â€‹µmol/L at 3 years after surgery occurred in 5 patients in group A and 13 in group B (P â€‹= â€‹0.034), and a systolic blood pressure rise greater than 20 â€‹mmHg occurred in 9 patients in group A and 18 in group B (P â€‹= â€‹0.041). Conclusions: The use of 3D reconstruction techniques for preoperative communication can successfully improve patients' perception and comprehension of kidney tumors and PN, as well as help to prevent serious postoperative non-cancer-related complications.

Gravity-driven rattan-based catalytic filter for rapid and highly efficient organic pollutant removal.

Metal organic frameworks hold great promise as heterogeneous catalysts in sulfate radical (SO4∙-) based advanced oxidation. However, the aggregation of powdered MOF crystals and the complicated recovery procedure largely hinder their large-scale practical applications. It is important to develop eco-friendly and adaptable substrate-immobilized metal organic frameworks. Based on the hierarchical pore structure of the rattan, gravity-driven metal organic frameworks loaded rattan-based catalytic filter was designed to degrade organic pollutants by activating PMS at high liquid fluxes. Inspired by the water transportation of rattan, ZIF-67 was in-situ grown uniformly on the rattan channels inner surface using the continuous flow method. The intrinsically aligned microchannels in the vascular bundles of rattan acted as reaction compartments for the immobilization and stabilization of ZIF-67. Furthermore, the rattan-based catalytic filter exhibited excellent gravity-driven catalytic activity (up to 100 % treatment efficiency for a water flux of 10173.6 L·m-2·h-1), recyclability, and stability of organic pollutant degradation. After ten cycles, the TOC removal of ZIF-67@rattan was 69.34 %, maintaining a stable mineralisation capacity for pollutants. The inhibitory effect of the micro-channel promoted the interaction between active groups and contaminants, increasing the degradation efficiency and improving the stability of the composite. The design of a gravity-driven rattan-based catalytic filter for wastewater treatment provides an effective strategy for developing renewable and continuous catalytic systems.

PIMREG is a prognostic biomarker involved in immune microenvironment of clear cell renal cell carcinoma and associated with the transition from G1 phase to S phase.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the world and affects human health seriously. PIMREG is a mitotic regulator which is essential to the metaphase-to-anaphase transition in cell cycle. Although PIMREG plays a crucial role in the malignant progression of tumors, there are few reports on its role in ccRCC. Methods: The transcriptional expression profile and clinical data of PIMREG were downloaded from TCGA database and verified by qRT-PCR. Kaplan-Meier plotter was used to analyze the effect of PIMREG on overall survival (OS), disease specific survival (DSS) and progression-free interval (PFI) of patients with ccRCC. Univariable and multivariable Cox regression analysis were used to determine the independent prognostic factors of ccRCC. The effects of PIMREG on cell migration and invasion were detected by wound healing assay and transwell invasion assay, and CCK-8 assay, colony formation assay and cell cycle assay were used to detect the effect of PIMREG on cell proliferation. In addition, the changes in cell cycle related proteins were detected by western blot. Results: PIMREG was highly expressed in human ccRCC and was positively correlated with pathologic stage, TNM stage and histologic grade. In addition, patients with high expression of PIMREG had a poor prognosis. Univariable and multivariable Cox regression analysis identified that PIMREG was an independent prognostic factor of ccRCC. Additionally, PIMREG was also closely related to immune cell infiltration. Experiments in vitro identified that the knockdown of PIMREG could significantly inhibit the proliferation, migration and invasion abilities of ccRCC. The expression of cyclin D1, CDK4 and CDK6 was also significantly reduced after PIMREG knockdown. Conclusions: PIMREG plays a vital role in the development of ccRCC and may become a potential therapeutic target in the future.

Comprehensive Analysis of Transcriptomic Profiles Identified the Prediction of Prognosis and Drug Sensitivity of Aminopeptidase-Like 1 (NPEPL1) for Clear Cell Renal Cell Carcinoma.

Aminopeptidase-like 1 (NPEPL1) is a member of the aminopeptidase group that plays a role in the development and progression of various diseases. Expression of NPEPL1 has been reported to be involved in prostate, breast, and colorectal cancers. However, the role and mechanism of NPEPL1 in clear cell renal cell carcinoma (ccRCC) are unclear. The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases were used to predict the relationship between clinicopathological features and NPEPL1 expression. Changes in immune status and drug sensitivity with NPEPL1 expression were analyzed by the "CIBERSORT" function in R software. The results found that NPEPL1 expression was upregulated in ccRCC tissues, with expression progressively increasing with ccRCC stage and grade. Patients with high NPEPL1 expression presented with a poor prognosis across different clinicopathological features. Univariate and multivariate Cox regression analyses indicated that aberrant NPEPL1 expression was an independent risk factor for ccRCC. The nomogram showed that NPEPL1 expression improved the accuracy of predicting the prognosis of ccRCC patients. The Gene Ontology (GO) term enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that NPEPL1 may be involved in the development of ccRCC through the voltage-gated calcium channel complex, channel activity, cAMP signaling pathway, and oxytocin signaling pathway. The coexpression analysis found that NPEPL1 altered tumor characteristics by interacting with related genes. The "CIBERSORT" analysis showed that elevated NPEPL1 expression was followed by an enrichment of regulatory T cells and follicular helper T cells in the microenvironment. The drug sensitivity analysis found patients with high NPEPL1 expression had a higher benefit from axitinib, cisplatin, and GSK429286A. In conclusion, upregulation of NPEPL1 expression was involved in ccRCC prognosis and treatment. NPEPL1 could be used as a therapeutic target to guide clinical dosing.

The efficacy of intravaginal electrical stimulation (IVES) in treating female with urinary incontinence symptom from meta-analysis of nine randomized controlled trials.

Background: Urinary incontinence (UI) is a common disease in the middle-aged and elderly women, and physical therapy has gradually become the mainstream treatment of UI. We conducted a meta-analysis to evaluate the efficacy of intravaginal electrical stimulation (IVES) in the treatment of UI. Methods: From January 2006 to December 2021, we finally selected nine randomized controlled trials (RCTs) including 657 participants from PubMed, EMBASE, and Cochrane databases to evaluate the efficacy of IVES in the treatment of female UI. Continuous data were represented by mean difference and 95% CI, while dichotomous data were represented by odds ratio and 95% CI. All the data were analyzed by the Review Manager Version 5.4. Results: Compared with the control group, there were significant improvements in urine pad test (P = 0.01), urinary incontinence frequency (P = 0.04), some indicators in the incontinence quality of life questionnaire and King's health questionnaires, and subjective feeling of cure (P = 0.009) in the IVES group. However, in other indicators reflecting UI, there was no significant difference between the IVES group and the control group. In addition, subgroup analysis showed that IVES and IVES combined with training could significantly reduce the weight of the urine pad, which reflected the improvement of urine leakage. Conclusion: This meta-analysis proved that IVES can partially improve the symptoms of female patients with UI compared with the control group. However, it still needs to be further evaluated through more high-quality research in the future.

Distal end of Double-J ureteral stent position on ureteral stent-related symptoms: A systematic review and meta-analysis.

Background: Most patients suffer from ureteral stent-related symptoms (USRS) caused by indwelling ureteral stents. Nevertheless, various medications to alleviate discomfort as well as novel stents are continually being developed, and in recent years, some researchers have believed that proper intravesical stent placement can relieve USRS. Objective: To determine appropriate intravesical ureteral stent position may alleviate USRS. Methods: Up to May 1, 2022, the PubMed, Embase, Scopus and Web of Science databases were thoroughly searched, and two independent reviewers included relevant studies that met the PICO (Patient, Intervention, Comparison, Outcome) criteria. Studies methodological quality were assessed by ROB2 and ROBINS-I. Ureteral stent symptom questionnaire (USSQ), international prostate symptom score (IPSS) and quality of life (QoL) was used to quantify the USRS. According to intravesical ureteral stent position, Group A was defined as the contralateral group, that is distal end of ureteral stent crossed the bladder midline, whereas Group B was classified as ipsilateral group, meaning stent end did not cross the midline. Results: Six studies incorporating a total of 590 patients were eligible. In terms of USSQ score, the meta-analysis showed that contralateral group was associated with a significant increase in USSQ total (MD, 17.55; 95% CI, 12.04 to 23.07; P < 0.001), urinary symptoms (MD, 2.74; 95% CI, 0.48 to 5.01; P = 0.02), general health (MD, 4.04; 95% CI, 2.66 to 5.42; P < 0.001), work performance (MD, 1.36; 95% CI, 0.75 to 1.98; P < 0.001) and additional problems (MD, 0.89; 95% CI, 0.47 to 1.32; P < 0.001) scores while not associated with a significant increase in body pain (MD, 3.13; 95% CI, -0.19 to 6.44; P = 0.06) and sexual matters (MD, 1.01; 95% CI, -0.03 to 2.06; P = 0.06). As for IPSS, although no significant differences in IPSS total (MD, 2.65; 95% CI, -0.24 to 5.54; P = 0.07) or voiding symptoms (MD, -0.84; 95% CI, -3.16 to 1.48; P = 0.48) scores were found, ipsilateral group was associated with a significant decrease in storage symptoms (MD, 1.92; 95% CI, 0.91 to 2.93; P = 0.0002). Furthermore, ipsilateral group was linked to a significant decrease in QoL score (MD, 1.00; 95% CI, 0.18 to 1.82; P = 0.02). Conclusion: This meta-analysis proven that correct intravesical stent position was critical, and patients with stents crossing the midline experienced more severe USRS than those who did not. Further high-quality randomized controlled trials are needed to corroborate our findings.

The Efficacy and Safety of HoLEP for Benign Prostatic Hyperplasia With Large Volume: A Systematic Review and Meta-Analysis.

This meta-analysis was to evaluate the efficacy and safety of holmium laser enucleation of prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with large volume. PubMed, Embase, and Cochrane Library databases (until March 2022) were used to search related randomized controlled trials. A total of 11 studies including 1,258 patients were involved. HoLEP could significantly decrease the length of hospital stay and accelerate recovery. In subanalysis, HoLEP had better perioperative outcomes than bipolar transurethral resection of the prostate (B-TURP) and bipolar transurethral enucleation of the prostate (BPEP). The improvement in operative time and enucleation time was better in thulium laser enucleation of the prostate (ThuLEP) than HoLEP. In the follow-up period, the HoLEP decreased post-void residual urine (PVR) in short-term intervals and improved patients' maximum flow rate (Qmax) and prostate-specific antigen (PSA) in mid- and long-term intervals. In subanalysis, HoLEP presented significant improvements in Qmax, PSA, and quality of life (QoL) than B-TURP, and HoLEP could also improve Qmax than ThuLEP after 6 months of surgery. The HoLEP reduced the risk of postoperative bleeding compared with other surgeries in safety. In our study, we confirmed the advantages of HoLEP in treating BPH when the prostate size was larger than 80 mL, which indicated that HoLEP could be the best choice for treatment of large volume of prostate.

Generation of Urothelial Cells from Mouse-Induced Pluripotent Stem Cells.

Background and Objectives: The search for a suitable alternative for urethral defect is a challenge in the field of urethral tissue engineering. Induced pluripotent stem cells (iPSCs) possess multipotential for differentiation. The in vitro derivation of urothelial cells from mouse-iPSCs (miPSCs) has thus far not been reported. The purpose of this study was to establish an efficient and robust differentiation protocol for the differentiation of miPSCs into urothelial cells. Methods and Results: Our protocol made the visualization of differentiation processes of a 2-step approach possible. We firstly induced miPSCs into posterior definitive endoderm (DE) with glycogen synthase kinase-3ß (GSK3ß) inhibitor and Activin A. We investigated the optimal conditions for DE differentiation with GSK3ß inhibitor treatment by varying the treatment time and concentration. Differentiation into urothelial cells, was directed with all-trans retinoic acid (ATRA) and recombinant mouse fibroblast growth factor-10 (FGF-10). Specific markers expressed at each stage of differentiation were validated by flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) assay, immunofluorescence staining, and western blotting Assay. The miPSC-derived urothelial cells were successfully in expressed urothelial cell marker genes, proteins, and normal microscopic architecture. Conclusions: We built a model of directed differentiation of miPSCs into urothelial cells, which may provide the evidence for a regenerative potential of miPSCs in preclinical animal studies.

Robot-assisted versus conventional laparoscopic partial nephrectomy for renal hilar tumors: Parenchymal preservation and functional recovery.

OBJECTIVE: To determine whether robot-assisted laparoscopic partial nephrectomy (RALPN) can benefit patients in terms of functional recovery in the treatment of renal hilar tumors compared to conventional laparoscopic partial nephrectomy (CLPN). METHODS: Between January 2019 and July 2021, patients with hilar tumors who underwent partial nephrectomy (PN) were acquired at our center and were classified into RALPN and CLPN groups. Ipsilateral parenchymal volume (IPV) and glomerular filtration rate (GFR) were determined independently 3-5 days before and 3 months after PN using contrast-enhanced computed tomography and nuclear renal scans. Pearson correlation was used to determine the link between ipsilateral GFR preservation and IPV preserved. Concurrently, multivariable analysis was employed to determine characteristics associated with functional recovery. RESULTS: A total of 96 patients with hilar tumors were studied, of which 41 received RALPN and 55 received CLPN. Excisional parenchymal volume was 27 and 37 cm3 (p = 0.005) in RALPN and CLPN groups, respectively, and IPV preserved was 77% and 68% (p < 0.001). Furthermore, the ipsilateral GFR preserved was 77.7% and 75.3%, respectively (p = 0.003). On Pearson correlation, ipsilateral GFR preservation was linked with IPV preserved (r = 0.36, p < 0.001). According to a multivariate study, baseline GFR, IPV preserved, and surgical procedures (RALPN vs. CLPN) were significant factors influencing functional recovery. CONCLUSION: Our study suggests that RALPN, rather than CLPN, can achieve better functional recovery in the treatment of hilar tumors due to its ability to win more IPV preserved. RALPN should be recommended as the first-line treatment for hilar tumors, but randomized controlled trials are required to validate our findings.

Meta-Analysis of the Safety and Efficacy of α-Adrenergic Blockers for Pediatric Urolithiasis in the Distal Ureter.

Objective: Pediatric urolithiasis is a common condition, and medical expulsive therapy has grown to be accepted by many parents. We carried out a meta-analysis to identify the efficacy and safety of α-adrenergic blockers for the treatment of pediatric urolithiasis. Methods: We identified related articles from the PubMed, Embase, and Cochrane Library databases. All published randomized controlled trials (RCTs) describing the use of α-adrenergic blockers and placebo treatment for pediatric distal urolithiasis were involved. The outcomes included stone expulsion rate, stone expulsion time, pain episodes, need for analgesia, adverse events, and related subgroup analyses. Results: A total of nine RCTs were involved in our study, including 586 patients. We found that α-adrenergic blockers could significantly increase the rate of stone expulsion [odds ratio (OR), 3.49; 95% confidence interval (CI), 2.38-5.12; p < 0.00001], reduce the stone expulsion time [mean difference (MD), -5.15; 95% CI, -8.51 to -1.80; p = 0.003], and decrease pain episodes (MD, -1.02; 95% CI, -1.33 to -0.72; p < 0.00001) and analgesia demand (MD, -0.92; 95% CI, -1.32 to -0.53; p < 0.00001) but had a higher incidence of side effects (MD, 2.83; 95% CI, 1.55 to 5.15; p = 0.0007). During subgroup analyses, different medications (tamsulosin, doxazosin, and silodosin) also exhibited better efficiencies than placebo, except for doxazosin, which showed no difference in expulsion time (MD, -1.23; 95% CI, -2.98 to 0.51; p = 0.17). The three kinds of α-adrenergic blockers also appeared to be better tolerated, except for tamsulosin with its greater number of adverse events (MD, 2.85; 95% CI, 1.34 to 6.03; p = 0.006). Silodosin led to a better expulsion rate than tamsulosin (OR, 0.42; 95% CI, 0.20 to 0.92; p = 0.03). In addition, α-adrenergic blockers increased the stone expulsion rate regardless of stone size and decreased the expulsion time of stones measuring <5 mm (MD, -1.71; 95% CI, -2.91 to -0.52; p = 0.005), which was not the case for stones measuring >5 mm in expulsion time (MD, -3.61; 95% CI, -10.17 to 2.96; p = 0.28). Conclusion: Our review suggests that α-adrenergic blockers are well-tolerated and efficient for treating pediatric distal urolithiasis. We also conclude that silodosin is the best choice of drug, offering a better expulsion rate, but it remains to be evaluated further by future studies.

Efficacy and Adverse Events of PD-1 Inhibitors in Patients With Advanced Urothelial Carcinoma From a Real-World Experience.

Background: Programmed death 1 (PD-1) inhibitors-tislelizumab, toripalimab, camrelizumab, and sintilimab-are used for advanced urothelial carcinoma (UC) in China. To date, the efficacy and adverse events (AEs) of these PD-1 inhibitors have been poorly reported for advanced UC. Methods: We reviewed 118 patients treated with PD-1 inhibitors for advanced UC from July 2019 to October 2021 at Yantai Yuhuangding Hospital. Patient data were obtained from hospital records and telephone follow-ups. The safety and efficacy of PD-1 inhibitors were assessed by RESIST and Common Terminology Criteria for Adverse Events (version 4.0), respectively. Results: During a median follow-up period of 6 months, 112 patients (95%) experienced AEs; of these, 104 (88%) were grade 1-2 AEs, and 60 (51%) were grade 3-4 AEs. The most common AE was anemia, and no patients died as a result of treatment. A subanalysis according to treatment method (PD-1 inhibitor vs. PD-1 inhibitor plus chemotherapy) was performed. The incidence of grade 1-2 AEs was not different between the groups (85% vs. 94%), but combination therapy significantly increased grade 3-4 AEs (32% vs. 89%). Monotherapy and combination therapy also did not differ with regard to immune-related AEs of grades 1-2 (13% vs. 22%) or grades 3-4 (1% vs. 6%). In efficacy, complete response was not observed, but 33 patients (28%) had partial response, 30 (25%) had stable disease, and 47 had progressive disease (40%). The overall response and disease control rates were 28% and 53%, respectively. The preliminary efficacy of disease control was better with combination therapy versus monotherapy (78 vs. 43%). Conclusion: PD-1 inhibitors show promising tolerance and efficacy in advanced UC. PD-1 inhibitors combined with chemotherapy offered better disease control but had more grade 3-4 AEs. The clinical use of combination therapy warrants caution.

Systematic Review and Meta-Analysis of 16 Randomized Controlled Trials of Clinical Outcomes of Low-Intensity Extracorporeal Shock Wave Therapy in Treating Erectile Dysfunction.

We conducted a meta-analysis to evaluate the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). From July 2011 to June 2021, we finally selected 16 randomized controlled trials (RCTs) including 1,064 participants to evaluate the efficacy of LI-ESWT in the treatment of ED from PubMed, EMBASE, and Cochrane databases. The data are analyzed by Review Manager Version 5.4. Fifteen articles mentioned International Index of Erectile Function (IIEF), in the follow-up of 1 month (mean difference [MD] = 3.18, 95% confidence interval [CI] = [1.38, 4.98], p = .0005), 3 months (MD = 3.01, 95% CI = [2.04, 3.98], p < .00001), and 6 months (MD = 3.20, 95% CI = [2.49, 3.92], p < .00001). After treatment, the improvement of IIEF in the LI-ESWT group was better than that in the control group. Besides, eight of the 16 trials provided data on the proportion of patients with baseline Erectile Hardness Score (EHS) ≤ 2 improved to EHS ≥ 3. The LI-ESWT group was also significantly better than the placebo group (odds ratio [OR] = 5.07, 95% CI = [1.78, 14.44], p = .002). The positive response rate of Questions 2 and 3 of the Sexual Encounter Profile (SEP) was not statistically significant (SEP2: OR = 1.27, 95% CI = [0.70, 2.30], p = .43; SEP3: OR = 4.24, 95% CI = [0.67, 26.83], p = .13). The results of this meta-analysis suggest that treatment plans with an energy density of 0.09 mJ/mm2 and pulses number of 1,500 to 2,000 are more beneficial to IIEF in ED patients. In addition, IIEF improvement was more pronounced in patients with moderate ED after extracorporeal shockwave therapy.

CircITGB6 promotes ovarian cancer cisplatin resistance by resetting tumor-associated macrophage polarization toward the M2 phenotype.

BACKGROUND: Platinum resistance is a major challenge in the clinical treatment of advanced ovarian cancer (OC). Accumulating evidence shows that the tumor-promotive M2 macrophage is linked to the limiting chemotherapy efficacy of multiple malignancies including OC. Circular RNAs (circRNAs) are a novel class of non-coding RNAs which function as the critical regulator in biological process of cancer. However, their impact on macrophage polarization and chemoresistance of OC remain unclear. METHODS: Platinum-resistant circRNAs were screened using circRNA deep sequencing and validated using in situ hybridization in OC tissues with or without platinum resistance. The role of circITGB6 in inducing cisplatin (CDDP) resistance was evaluated by clone formation, immunofluorescence and annexin V assays in vitro, and by intraperitoneal tumor model in vivo. The mechanism underlying circITGB6-mediated tumor-associated macrophage (TAM) polarization into M2 phenotype was investigated using RNA pull-down, luciferase reporter, electrophoretic mobility shift, RNA binding protein immunoprecipitation (RIP), ELISA and immunofluorescence assays. RESULTS: We identified that a novel circRNA, circITGB6, robustly elevated in tumor tissues and serums from patients with OC with platinum resistance, was correlated with poor prognosis. circITGB6 overexpression promoted an M2 macrophage-dependent CDDP resistance in both vivo and vitro. Mechanistic research determined that circITGB6 directly interacted with IGF2BP2 and FGF9 mRNA to form a circITGB6/IGF2BP2/FGF9 RNA-protein ternary complex in the cytoplasm, thereby stabilizing FGF9 mRNA and inducing polarization of TAMs toward M2 phenotype. Importantly, blocking M2 macrophage polarization with an antisense oligonucleotide targeting circITGB6 markedly reversed the circITGB6-induced CDDP resistance of OC in vivo. CONCLUSIONS: This study reveals a novel mechanism for platinum resistance in OC and demonstrates that circITGB6 may serve as a potential prognostic marker and a therapeutic target for patients with OC.