Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation.

Objective: Bazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC. Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD's active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an "herb-ingredient-target" network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer. Results: BZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the "herb-ingredient-target" network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles. Conclusion: BZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations.

Robot-assisted radical cystectomy vs open radical cystectomy in patients with bladder cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Even though there isn't enough clinical evidence to demonstrate that robot-assisted radical cystectomy (RARC) is preferable to open radical cystectomy (ORC), RARC has become a widely used alternative. We performed the present study of RARC vs ORC with a focus on oncologic, pathological, perioperative, and complication-related outcomes and health-related quality of life (QOL). METHODS: We conducted a literature review up to August 2022. The search included PubMed, EMBASE and Cochrane controlled trials register databases. We classified the studies according to version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). The data was assessed by Review Manager 5.4.0. RESULTS: 8 RCTs comparing 1024 patients were analyzed in our study. RARC was related to lower estimated blood loss (weighted mean difference (WMD): -328.2; 95% CI -463.49--192.92; p < 0.00001), lower blood transfusion rates (OR: 0.45; 95% CI 0.32 - 0.65; p < 0.0001) but longer operation time (WMD: 84.21; 95% CI 46.20 -121.72; p < 0.0001). And we found no significant difference in terms of positive surgical margins (P = 0.97), lymph node yield (P = 0.30) and length of stay (P = 0.99). Moreover, no significant difference was found between the two groups in terms of survival outcomes, pathological outcomes, postoperative complication outcomes and health-related QOL. CONCLUSION: Based on the present evidence, we demonstrated that RARC and ORC have similar cancer control results. RARC is related to less blood loss and lower transfusion rate. We found no difference in postoperative complications and health-related QOL between robotic and open approaches. RARC procedures could be used as an alternate treatment for bladder cancer patients. Additional RCTs with long-term follow-up are needed to validate this observation.

Up-regulated serum lactate dehydrogenase could become a poor prognostic marker in patients with bladder cancer by an evidence-based analysis of 2,182 patients.

Background: A growing number of studies have considered serum lactate dehydrogenase (LDH) as an indicator of bladder cancer (BC) prognosis. However, a meta-analysis of the serum LDH's influence on BC prognosis is still missing. Methods: PubMed, EMBASE, Web of Science and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between high-LDH and low-LDH patients. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3) for overall survival (OS) in patients with BC. Results: Six studies involving 2,182 patients were selected according to predefined eligibility criteria. The results showed that serum LDH level was significantly associated with OS (HR = 1.86, 95%CI = 1.54-2.25, p<0.0001) in BC. Sensitivity analysis showed the stability of the results. Subgroup analysis revealed that the levels of serum LDH had a significant impact on the OS of BC patients among different groups including publication time, research country, sample size, tumor stage, LDH cut-off value, therapy and follow-up time (all HR>1 and p<0.05), revealing that the ability of serum LDH is not affected by other factors. Conclusion: Our findings indicated that a high level of serum LDH was associated with inferior OS in patients with BC. However, caution must be taken before recommendations are given because this interpretation is based upon very few clinical studies and a small sample.

Analysis of lncRNAs profiles associated with ferroptosis can predict prognosis and immune landscape and drug sensitivity in patients with clear cell renal cell carcinoma.

Ferroptosis is a novel kind of iron- and reactive oxygen-induced cell death, investigation into ferroptosis-associated long noncoding RNAs (FALs) in clear cell renal cell carcinoma (ccRCC) is scarce. The goal of the research was to look at FALs' possible predictive significance, as well as their interaction with the immune microenvironment and therapeutic responsiveness of ccRCC. The Cancer Genome Atlas database was employed to retrieve RNA sequencing data from 530 individuals with ccRCC. Patients with ccRCC were randomly assigned to one of two groups: training or testing. Pearson's correlation analysis through the identified ferroptosis-related genes was implemented to screen for FALs. Finally, a FALs signature composed of eight lncRNAs was discovered for predicting survival outcomes in ccRCC patients. ccRCC patients in the training, testing, and overall cohorts were separated into low-risk and high-risk groups based on their risk score. The FALs signature was identified to be an independent factor for overall survival in the multivariate Cox analysis (hazard ratio = 1.013, 95% confidence interval = 1.008-1.018, p < 0.001). A clinically prognostic nomogram was created depending on the FALs signature and clinical characteristics. The nomogram provides greater clinical practicability and may reliably estimate patients' overall survival. The FALs signature may additionally precisely represent ccRCC's immunological environment, immunotherapy reaction, and drug sensitivity. The eight FALs and their signature provide precise and reliable methods for evaluating the clinical effects of in ccRCC patients, and they could be biological markers and targets for therapy.

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.

Wiskott-Aldrich syndrome gene as a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.

Introduction: The abnormal expression of the Wiskott-Aldrich syndrome protein (WASP) encoded by the Wiskott-Aldrich syndrome (WAS) gene has been implicated in tumor invasion and immune regulation. However, prognostic implications of WAS and its correlation tumor infiltrating in renal clear cell carcinoma (ccRCC) is not clear cut. Methods: The correlation between WAS expression, clinicopathological variables and clinical outcomes were evaluated using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER), UALCAN, Gene Expression Profiling Interaction Analysis (GEPIA), Kaplan-Meier (KM) plotter and other databases. Furthermore, we assessed the transcription expression of WAS in renal cancer tissues, various renal carcinoma cell lines and human renal tubular cells (HK2) using quantitative polymerase chain reaction (qPCR). A comprehensive analysis of multiple databases including TIMER, GEPIA, TISIDB, ESTIMATE algorithm, and CIBERSORT algorithm were performed to determine the correlation between WAS and tumor infiltrating immune cells in ccRCC. Results: The results displayed an increase in WAS mRNA level in ccRCC compared to normal tissue. WAS protein level was found highly expressed in cancer tissues, particularly within renal tumor cells via the human protein atlas (HPA). Interestingly, we found that elevated WAS expression was significantly positively correlated with the infiltration of CD8+ T cells, B cells, Monocytes, Neutrophils, Macrophages, T cell regulation, NK cells, and Dendritic cells in ccRCC. Bioinformatics demonstrated a strong correlation between WAS expression and 42 immune checkpoints, including the T cell exhaustion gene PD-1, which is critical for exploring immunotherapy for ccRCC. We revealed that patients with high WAS expression were less sensitive to immunotherapy medications. Conclusion: In conclusion, our study identified that WAS was a prognostic biomarker and correlated with immune infiltrates in ccRCC.

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.

The prognosis and safety of continuous saline bladder irrigation in patients after transurethral resection of bladder tumors: a systematic review and meta-analysis of comparative study.

The prognosis and safety of continuous saline bladder irrigation (CSBI) after transurethral resection of bladder tumor (TURB) as an alternative method needs to be explored. A literature review and meta-analysis were performed by searching PubMed, EMBASE, Cochrane Library databases and original references of the included articles. PRISMA checklists were followed. We used the GRADEpro GDT to assess the certainty of evidence from the results of our meta-analysis. A total of eight articles including 1600 patients were studied. The results indicated that patients received CSBI after TURB had no statistical differences compared to the control group in the recurrence-free survival and progression-free survival. However, the CSBI group showed significant improvements compared to the control group in terms of the number of recurrences during follow-up and the period to first recurrence except for the number of tumor progression during follow-up. Furthermore, patients treated with CSBI did not show an inferior effect than those treated with immediate intravesical chemotherapy (IC) in respects of recurrence-free survival, progression-free survival, the number of recurrences during follow-up, the number of tumor progression during follow-up and the period to first recurrence. But the immediate IC group had a higher incidence than the CSBI group in terms of macrohematuria, micturition pain, frequency of urination, dysuria, retention and local toxicities. Patients treated with CSBI after TURB showed a significant improvement compared to the control group in terms of the number of recurrences during follow-up and the period to first recurrence. However, compared to immediate IC, CSBI did not show an inferior effect except for lower incidence of adverse reactions.PROSPERO registration number CRD42021247088.

The efficacy and safety of medication for treating overactive bladder in patients with Parkinson's disease: a meta-analysis and systematic review of randomized double-blind placebo-controlled trials.

INTRODUCTION AND HYPOTHESIS: The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD). METHODS: Papers containing predefined key terms were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases up to December 2021 to collect randomized double-blind placebo-controlled trials (RCTs). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Two reviewers independently assessed the risk of bias using the modified Jadad scale and Cochrane risk-of-bias tool. The GRADEpro GDT was employed to evaluate the strength of evidence based on the findings of this meta-analysis. RESULTS: We eventually included four RCTs involving 313 patients (163 patients in the medication group and 150 patients in the placebo group). Of these, the therapeutic agent in two RCTs was mirabegron (121 and 106 patients and controls, respectively, representing 3/4 -2/3 of the patients). The results showed that the number of micturition episodes per 24 h (MD -1.33; 95% CI -2.30 to -0.36; p = 0.007), the number of nocturia episodes per 24 h (MD -0.33; 95% CI -0.58 to -0.08; p = 0.009) and the number of urinary incontinence episodes per 24 h (MD -0.72; 95% CI -1.32 to -0.12; p = 0.02) were significantly lower in the medication group than in the placebo group. The OAB symptom score (MD -2.84; 95% CI -4.67 to -1.00; p = 0.002) and quality of life score (MD 15.15; 95% CI 12.33 to 17.96; p < 0.0001) of the medication group were significantly improved compared with those of the placebo group. However, no significant difference in the daily frequency of urinary urgency episodes was identified between the medication group and the placebo group (MD -0.79; 95% CI -1.71 to 0.14; p = 0.09). There were no significant differences between the two groups in terms of drug-related adverse events (OR 1.69; 95% CI 0.41 to 6.99; p = 0.47), especially in PD patients receiving mirabegron therapy. CONCLUSIONS: Medication was effective for OAB symptoms in patients with PD, and patients tolerated adverse events well.

The Efficacy and Safety of Acupuncture in Treating Stress Urinary Incontinence in Women from a Meta-Analysis of Four Randomized Controlled Trials.

PURPOSE: To verify the efficacy and safety of acupuncture in treating stress urinary incontinence (SUI) in women in a single treatment cycle lasting at least 6 weeks. METHODS: A preferred reporting items for systematic reviews and meta-analyses (PRISMA) summary was followed correctly. Through the use of EMBASE, Cochrane Library databases, and PubMed (until July 2021), we looked for randomized controlled trials. In addition, the included articles' original references were looked up as well. RESULTS: Totally, we analyzed four studies including 690 patients. Compared with the sham acupuncture group, this analysis verified that acupuncture was critically better result in decreasing mean urine leakage (p = 0.04), 1-hour pad test (p = 0.04), 72-hour incontinence episodes (p < 0.00001), International Consultation on Incontinence Questionnaire-Short Form scores (p = 0.0005) and improving patient self-evaluation (All p < 0.05). However, two groups had no statistical significance in improving pelvic floor muscle strength. In the matter of safety, mainly adverse events, especially with respect to pain, both groups showed no statistical difference. CONCLUSIONS: Acupuncture is more beneficial to patients with stress urinary incontinence in women with no critical difference in the incidence of advent events than sham acupuncture.

A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia.

Lower urinary tract symptoms (LUTS) secondary to benign prostrate hyperplasia (BPH) are common geriatric diseases, and its incidence rises with age. The treatment of BPH and LUTS is becoming a burden for health care. The meta-analysis was performed to evaluate the efficacy and safety of combination therapy (tamsulosin plus tadalafil) compared with tamsulosin alone in treatment of males with LUTS/BPH. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were utilized to conduct this study. There were several databases available for literature retrieval, including Medline, Embase, PubMed, Scopus, Web of Science databases, and Cochrane Controlled Trials Register. To improve the comprehensiveness of the search, related references were also searched. Finally, six randomized controlled trials including 441 patients were included. The combination therapy had significant improvements in total International Prostate Symptom Score (p < .0001), quality of life score (p = .003), maximum urine flow rate (p < .00001), and International Index of Erectile Function (p < .00001) compared with the tamsulosin monotherapy, but there was no obvious difference in postvoid residual volume (p = .06). In terms of safety, the combination group had comparable rates of discontinuation due to adverse events (p = .19) than the monotherapy group except for pain symptoms (p < .0001). The combination of tamsulosin and tadalafil provided a preferable therapeutic effect compared with the tamsulosin alone in treating males with BPH/LUTS, and both therapy regimens were well tolerated by the patients.

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.

The efficacy of peripheral nerve block on postoperative catheter-related bladder discomfort in males: A systematic review and meta-analysis.

Objective: To determine the efficacy of peripheral nerve block (PNB) in preventing postoperative catheter-related bladder discomfort (CRBD). Methods: Up to July 1, 2022, the PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched, and all articles that met the PICOS (Patient, Intervention, Comparator, Outcome, Study design) criteria were enrolled. The included trials were evaluated using the Cochrane Collaboration's tool. Patients in the block group received bilateral PNB, while those in the non-block group did not need any additional procedure or simply achieved "sham block". CRBD was quantified using the visual analog scale (VAS) score, which was questioned and recorded at 0-1 h, 1-2 h, 4-8 h, 8-12 h and 12-24 h intervals. The incidences of CRBD, moderate to severe CRBD and postoperative nausea and vomiting (PONV) were meta-analysed. Results: Six trials with a total of 544 patients were considered. First, the block group had a lower incidence of CRBD than the non-block group at 0-1 h (OR 0.22; 95% CI, 0.18-0.08; P < 0.0001), 1-2 h (OR 0.14; 95% CI, 0.08-0.26; P < 0.00001), 4-8 h (OR 0.27; 95% CI, 0.13 to 0.58; P < 0.0008) and 8-12 h (OR 0.51; 95% CI, 0.30 to 0.87; P = 0.01). Second, the block group showed a lower incidence of moderate to severe CRBD than the non-block group at 0-1 h, 1-2 h and 4-8 h, and the ORs were 0.12 (95% CI, 0.03 to 0.49; P = 0.003), 0.17 (95% CI, 0.08 to 0.37; P < 0.00001) and 0.29 (95% CI, 0.15 to 0.55; P = 0.0002),respectively. Finally, the block group was significantly associated with a decreased incidence of PONV (OR, 0.14; 95% CI, 0.05 to 0.39; P = 0.0002). Conclusion: This meta-analysis suggested that PNB markedly reduced the incidence and severity of early postoperative CRBD and decreased the occurrence of PONV.

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 and Safety of Acupuncture in Treating Stress Urinary Incontinence in Women from a Meta-Analysis of Four Randomized Controlled Trials

Abstract Purpose: To verify the efficacy and safety of acupuncture in treating stress urinary incontinence (SUI) in women in a single treatment cycle lasting at least 6 weeks. Methods: A preferred reporting items for systematic reviews and meta-analyses (PRISMA) summary was followed correctly. Through the use of EMBASE, Cochrane Library databases, and PubMed (until July 2021), we looked for randomized controlled trials. In addition, the included articles’ original references were looked up as well. Results: Totally, we analyzed four studies including 690 patients. Compared with the sham acupuncture group, this analysis verified that acupuncture was critically better result in decreasing mean urine leakage (p = 0.04), 1-hour pad test (p = 0.04), 72-hour incontinence episodes (p < 0.00001), International Consultation on Incontinence Questionnaire-Short Form scores (p = 0.0005) and improving patient self-evaluation (All p < 0.05). However, two groups had no statistical significance in improving pelvic floor muscle strength. In the matter of safety, mainly adverse events, especially with respect to pain, both groups showed no statistical difference. Conclusions: Acupuncture is more beneficial to patients with stress urinary incontinence in women with no critical difference in the incidence of advent events than sham acupuncture (AU)

The Efficacy and Safety of Holmium Laser Enucleation of Prostate Compared With Bipolar Technologies in Treating Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials.

We performed a systematic review and meta-analysis on efficacy and safety of holmium laser enucleation of prostate compared with bipolar technologies in treating benign prostatic hyperplasia. We analyzed several databases such PubMed, Embase, and Web of Science. Two reviewers independently reviewed studies for consistent criteria and extracted relevant data. Reviewers independently assessed the risk of bias and strength of the evidence for the body of the literature. Ten randomized controlled trials including 1,157 participants were included in this meta-analysis. The holmium laser group had favorable perioperative outcomes in this study. The holmium laser group identified shorter catheterization duration and shorter hospital stay duration than the bipolar technologies group. Efficiency outcomes, such as International Prostate Symptom Score, peak urinary flow rate, quality of life, postvoid residual urine volume, and international index of erectile function reported no obvious differences between the holmium laser and bipolar technologies groups at the 6 to 12 months follow-up. Bipolar technologies and holmium laser groups shared equivalent effectiveness and safety in treatments for benign prostate hyperplasia. Holmium lasers identified lower catheter times, shorter hospital stays, and lesser risk of hemorrhage than bipolar technologies.

Two novel lncRNAs AF111167.2 and AL162377.1 targeting miR-21-5p mediated down expression of SYDE2 correlates with poor prognosis and tumor immune infiltration of ccRCC.

Advanced clear cell Renal Cell Carcinoma (ccRCC) is notoriously known for its poor prognosis. Synapse defective protein 1 homolog 2 encoded by the SYDE2 gene is a Rho GTPase-activating protein whose functional tumorigenic significance is still unclear. Recent pan-cancer analysis using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) data showed the potential tumor-suppressing effects of SYDE2 in ccRCC. Subsequently, the TCGA, GTEx data, and human protein atlas were employed to assess the correlation between the SYDE2 expression, clinical data, and overall survival (OS) in ccRCC patients. Furthermore, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) contributing to SYDE2 down expression were identified by expression, relationship, and survival analysis. Eventually, two novel lncRNAs, AL162377.1 and AF111167.2, targeting the miR-21-5p axis, were identified in the SYDE2 upstream non-coding RNAs (ncRNAs)-related pathway in ccRCC. The expression level of SYDE2 highly depends on the tumor immune cell infiltration and immune checkpoint expression. In summary, these data demonstrated that lncRNAs/miRNAs-mediated down-regulation of SYDE2 is related to the tumor immune infiltration. Hence, giving an insight into the prognosis of ccRCC.

Decreased Preoperative Serum AGR as a Diagnostic Marker of Poor Prognosis after Radical Surgery of Upper Urinary Tract and Bladder Cancers from a Pooled Analysis of 9,002 Patients.

A growing number of studies have regarded the preoperative serum albumin-to-globulin ratio (AGR) as a prognostic indicator of urothelial carcinoma (UC) following radical surgery. However, a pooled analysis of AGR's effect on UC prognosis was still insufficient. Up to January 2022, a systematic search was conducted using PubMed, Embase, Web of Science, and Cochrane Library. Stata SE software was applied in this study. The reviewers collected the hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and metastasis-free survival (MFS). A total of 9,002 patients from 12 retrospective studies were included in this analysis. The results showed that preoperative serum AGR was significantly associated with the OS (HR = 1.85, 95%CI = 1.43 to 2.39), CSS (HR = 2.38, 95%CI = 1.69 to 3.34), RFS (HR = 1.64, 95%CI = 1.29 to 2.08), PFS (HR = 2.16, 95%CI = 1.43 to 3.27), and MFS (HR = 3.00, 95%CI = 1.63 to 5.53) of patients with UC following radical surgery. Sensitivity analysis indicated the stability of the results. Subgroup analysis revealed that preoperative low AGR was seen as a risk factor for OS (HR = 1.90, 95%CI = 1.34 to 2.69), CSS (HR = 2.13, 95%CI = 1.40 to 3.26), and RFS (HR = 1.60, 95%CI = 1.24 to 2.07) in upper tract urothelial carcinoma (UTUC), but it was only a risk factor for CSS (HR = 2.95, 95%CI = 1.14 to 7.60) in bladder cancer (BC). Besides, preoperative AGR cut - value ≤ 1.4 could not be deemed as a stable prognostic indicator for RFS (HR = 2.07, 95%CI = 0.71 to 6.04) in UC. However, the predictive ability of AGR cut - value > 1.4 was stable. All in all, preoperative low AGR was considered as a risk factor for UC. AGR level can be regarded as a prognostic indicator for OS, CSS, and RFS in UTUC but only for CSS in BC. AGR greater than 1.4 can be a great cut-off value for predicting the prognosis of UC patients with radical operation.

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.