Association between smoking and alcohol drinking and benign adrenal tumors: a Mendelian randomization study.

BACKGROUND: In recent years, the detection rate of adrenal tumors has increased, but it is unclear whether smoking and alcohol drinking are risk factors for benign adrenal tumors. The objective of this study is to employ Mendelian randomization (MR) analysis to explore the causal relationship between smoking, alcohol drinking and susceptibility to benign adrenal tumors. METHODS: We acquired large-scale data from publicly accessible databases on genome-wide association studies (GWAS) pertaining to smoking, alcohol drinking and benign adrenal tumors. A total of 11 sets of instrumental variables (IVs) and 281 associated single nucleotide polymorphic (SNP) loci were identified. The Mendelian randomization analyses were conducted using inverse variance weighting (IVW), MR-Egger regression and weighted median estimation (WME) methods, in addition to sensitivity analyses. RESULTS: There is no causal relationship between smoking status, alcohol drinking status, alcohol intake frequency, alcohol taken with meals, alcohol consumption and benign adrenal tumors, while pack years of smoking and cigarettes per day are risk factors for benign adrenal tumors. The IVW analysis revealed that both the pack years of smoking and cigarettes per day were positively associated with an increased risk of benign adrenal tumors (OR = 2.853, 95%CI = 1.384-5.878, p = 0.004; OR = 1.543, 95%CI = 1.147-2.076, p = 0.004). Two SNPs (rs8042849 in the analysis of pack years of smoking and rs8034191 in the analysis of cigarettes per day) significantly drove the observed causal effects. CONCLUSION: Two-sample Mendelian randomization analysis showed a causal effect between smoking but not alcohol consumption and benign adrenal tumors.

Comparison of DNA methylation and cytology tests in urine to detect upper tract urothelial carcinoma: A paired-design diagnostic study.

OBJECTIVES: To evaluate the diagnostic efficacy of a DNA methylation test, compare that test with cytology alone, fluorescence in situ hybridization (FISH) alone, and cytology plus FISH, and explore reasons that may influence the accuracy of liquid biopsy. METHODS: We included 37 patients and 12 negative control individuals between April 2019 and May 2022. All patients had undergone radical nephroureterectomy, nephrectomy, diagnostic ureteroscopy, or tissue biopsy. Urine samples were collected for DNA methylation testing, cytology, and FISH. Test performance was calculated, and receiver operating characteristic curves were drawn for comparison. RESULTS: Median patient age was 66 years, and κ = 0.576 (P < .001) for the DNA methylation test and tissue pathology. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the DNA methylation test were 76%, 100%, 100%, and 74%, respectively, compared with 31%, 100%, 100%, and 50%, respectively, for cytology. The sensitivity, specificity, PPV, and NPV of cytology plus FISH were 66%, 100%, 100%, and 67%, respectively. The area under the curve (AUC) of the DNA methylation test was 0.879 (P < .001), and the AUC of cytology plus FISH was 0.828 (P < .001). CONCLUSIONS: The test performance of DNA methylation was satisfactory. The DNA methylation test for the detection of upper tract urothelial carcinoma demonstrated better sensitivity than did cytology alone or cytology with FISH, but the accuracy of the combined tests was still acceptable. Further prospective studies with larger samples are needed to confirm the clinical value of this promising method.

Chronic kidney disease and functional impairment in a longitudinal study of older adults in China.

OBJECTIVES: To examine the associations of chronic kidney disease (CKD) with dynamic functional impairment among older Chinese adults. DESIGN: This was a prospective longitudinal study. SETTING: Data were derived from the Chinese Longitudinal Healthy Longevity Study. PARTICIPANTS: All adults aged ≥60 years were potentially eligible. This study included 2970 participants. PRIMARY OUTCOME MEASURES: CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Functional performances included instrumental activities of daily living (IADL) and basic activities of daily living (BADL), which were measured using six daily activities, including eating, dressing, transferring, using the toilet, bathing and continence, and eight daily activities, including visiting neighbours, shopping, cooking, washing clothes, walking 1 km, lifting 5 kg, crouching and standing up three times and taking public transportation, respectively. RESULTS: This study included 2970 participants, including 988 (33.60%) participants with CKD. Participants with CKD had higher IADL scores than those without CKD (ß=0.895, 95% CI: 0.761 to 1.029). Furthermore, there was a significant linear trend in the association of CKD severity with the IADL score (p<0.001). Similarly, CKD was significantly associated with higher BADL scores (ß=0.067, 95% CI: 0.017 to 0.118). However, only participants with moderate and advanced CKD had a higher BADL score (ß=0.088 and 0.152, 95% CI: 0.006 to 0.171 and 0.019 to 0.286, respectively). CONCLUSIONS: CKD was associated with worse functional impairment. Furthermore, there was a significant linear trend in the association of the severity of CKD with the IADL score. However, only participants with moderate and advanced CKD had higher BADL scores.

Identification of disulfidptosis-related subtypes and development of a prognosis model based on stacking framework in renal clear cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor with an unsatisfactory prognosis. This study aims to identify the expression patterns of disulfidptosis-related genes (DRGs), develop a prognostic model, and predict immunological profiles. METHODS: First, we identified differentially expressed DRGs in TCGA-KIRC cohort and analyzed their mutational profiles, methylation levels, and interaction networks. Subsequently, we identified disulfidptosis-associated molecular subtypes and investigated their prognostic and immunological characteristics. Simultaneously, a disulfidptosis-related prognostic signature (DRPS) was developed using a two-stage stacking framework consisting of 5 machine learning models. The effect of DRPS on immune cell infiltration levels was explored using seven different algorithms, and the status and function of T cells for distinct risk-score groups were evaluated based on T cell exhaustion and dysfunction scores. Additionally, the study also examined differences in clinical characteristics and therapy efficacy between high- and low-risk groups. RESULTS: We found two disulfidptosis-associated clusters, one of which had a poor prognosis and was linked to high immune cell infiltration but impaired T cell function. DRPS showed excellent predictive performance in all four cohorts and could accurately identified disulfidptosis-related molecular subtypes. The DRPS-based risk score was positively associated with poor prognosis, malignant pathological features, high immune cell infiltration levels, and T cell exhaustion or dysfunction, and better respond to immunotherapy and targeted therapy. Additionally, we have identified a close association between ISG20 and disulfidptosis as well as tumor immunity. CONCLUSION: Our study identified distinct disulfidptosis-related subtypes in ccRCC patients, and constructed the highly accurate and robust DRPS based on an ensemble learning framework, which has critical reference value in clinical decision-making and individualized treatment. And this work also revealed ISG20 exhibits promising potential as a therapeutic target for ccRCC.

Role of Tim-3 in COVID-19: a potential biomarker and therapeutic target.

T cell immunoglobulin and mucin domain containing protein 3 (Tim-3), an immune checkpoint, is important for maintaining immune tolerance. There is increasing evidence that Tim-3 is aberrantly expressed in patients with COVID-19, indicating that it may play an important role in COVID-19. In this review, we discuss the altered expression and potential role of Tim-3 in COVID-19. The expression of Tim-3 and its soluble form (sTim-3) has been found to be upregulated in COVID-19 patients. The levels of Tim-3 on T cells and circulating sTim-3 have been shown to be associated with the severity of COVID-19, suggesting that this protein could be a potential biomarker of COVID-19. Moreover, this review also highlights the potential of Tim-3 as a therapeutic target of COVID-19.

ITIH5, as a predictor of prognosis and immunotherapy response for P53-like bladder cancer, is related to cell proliferation and invasion.

p53-like bladder cancer (BLCA) is a bladder cancer subtype that is resistant to cisplatin-based chemotherapy. The ideal treatment modality for such tumors remains poorly defined, and immunotherapy seems to be a potential approach. Therefore, it is significant to understand the risk stratification of p53-like BLCA and identify novel therapeutic targets. ITIH5 is a member of the inter-α-trypsin inhibitory (ITI) gene family, and the effect of ITIH5 on p53-like BLCA remains elusive. In this study, TCGA data and in vitro experiments were used to explore the prognostic value of ITIH5 for p53-like BLCA and its effect on tumor cell proliferation, migration, and invasion. The impact of ITIH5 on the level of immune cell infiltration was explored using seven different algorithms, and the predictive value of ITIH5 on the efficacy of immunotherapy for p53-like BLCA was explored in combination with an independent immunotherapy cohort. The results showed that patients with high ITIH5 expression had a better prognosis, and overexpression of ITIH5 could inhibit the proliferation, migration, and invasion of tumor cells. Two or more algorithms consistently showed that ITIH5 promoted the infiltration of antitumor immune cells, such as B cells, CD4+ T cells, and CD8+ T cells. In addition, ITIH5 expression was positively correlated with the expression levels of many immune checkpoints, and the high ITIH5 expression group showed better response rates to PD-L1 and CTLA-4 therapies. In short, ITIH5 is a predictor of prognosis and the immunotherapy response for p53-like BLCA and is correlated with tumor immunity.

Segmental ureterectomy for high-risk ureteral carcinoma: a preliminary report.

BACKGROUND: EAU guidelines strongly recommend kidney sparing surgery (KSS) as the primary treatment option for the low-risk UTUC patients. While there are few reports involving the KSS treated for the high-risk counterparts, especially the ureteral resection. OBJECTIVE: To evaluate the effectiveness and safety of the segmental ureterectomy (SU) for the patients with high-risk ureteral carcinoma. MATERIALS AND METHODS: We included 20 patients from May 2017 to December 2021 who underwent segmental ureterectomy (SU) in Henan Provincial People's Hospital. The overall survival (OS) and progression free survival (PFS) were evaluated. Besides, the ECOG scores and postoperative complications were also included. RESULTS: As of December 2022, the mean OS was 62.1months (95%CI:55.6-68.6months) and the mean PFS was 45.0months (95%CI:35.9-54.1months). The median OS and median PFS were not reached. The 3-year OS rate was 70% and the 3-year PFS rate was 50%. The percentage of Clavien I and II complications was 15%. CONCLUSION: For the selected patients with high-risk ureteral carcinoma, the efficacy and safety of segmental ureterectomy were satisfactory. But we still need to conduct prospective or randomized study to validate the value of SU in patients with high-risk ureteral carcinoma.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

Correlation between mesenchymal circulating tumor cells and prognosis of urologic malignancies: a single-center retrospective analysis.

OBJECTIVE: To evaluate the correlation of circulating tumor cells (CTCs) and mesenchymal CTCs (M-CTCs) with clinical characteristics and survival of patients with urologic malignancies. METHODS: The clinical data of 52 patients with urinary system malignancy in Henan Provincial People's Hospital were retrospectively analyzed (40 cases of renal malignant tumor, 7 cases of prostate cancer, 3 cases of urothelial carcinoma, 1 case of testis cancer, and 1 case of penile cancer). The CTC counts of patients were collected, and the expression of epithelial-mesenchymal transition phenotype in CTCs was evaluated. The relationship of different types of CTC counts with tumor stage, location, size, metastasis, and differentiation, as well as their effect on progression-free survival (PFS) were analyzed. RESULTS: We detected CTCs in all patients with urinary system malignancy. The positive rates of epithelial CTCs (E-CTC), M-CTCs, and epithelial/mesenchymal CTCs (E/M-CTCs) were 34.62%, 26.92% and 94.23%, respectively. Total CTCs (T-CTCs), M-CTCs and E/M-CTCs were correlated with distant metastasis (Z=-3.052, -3.574, -2.898; all P<0.005). M-CTC count was correlated with lymph node metastasis (Z=-3.125; P=0.002). Furthermore, the presence of T-CTCs ≥13.5, M-CTC ≥0.5 or E/M-CTCs ≥9.5 per 5 ml of blood was correlated with worse PFS in patients with urinary system malignancy. CONCLUSIONS: M-CTC and E/M-CTC counts correlate with the prognosis of patients with urinary system malignancy. Higher M-CTC and E/M-CTC counts are risk factors for worse prognosis in patients with urinary system malignancies. All in all, M-CTC count is a valuable tumor biomarker for urologic malignancies.

Diagnostic performance of 99mTc-HYNIC-PSMA SPECT/CT for biochemically recurrent prostate cancer after radical prostatectomy.

Objectives: 99mTc-HYNIC-PSMA is a novel technetium-99m-labeled small-molecule inhibitor of prostate-specific membrane antigen (PSMA) for detection of prostate cancer. The present study investigated the diagnostic yield of 99mTc-HYNIC-PSMA Single photon emission computed tomography (SPECT)/CT in 147 patients with biochemically recurrent prostate cancer after radical prostatectomy. Methods: 147 patients with biochemical relapse after radical prostatectomy were finally eligible for this retrospective analysis. The median prostate-specific antigen (PSA) level was 8.26 ng/mL (range, 0.22-187.40 ng/mL). Of the 147 patients, 72 patients received androgen deprivation therapy (ADT) at least 6 months before the 99mTc-HYNIC-PSMA SPECT/CT. All patients underwent planar whole-body scans and subsequent SPECT/CT of the thoracic and abdominal regions after intravenous injection of 705 ± 70 MBq of 99mTc-HYNIC-PSMA. Images were evaluated for the presence and location of PSMA-positive lesions, in which SUVmax were also measured. Detection rates were stratified according to PSA levels, ADT and Gleason scores. The relationships between SUVmax and clinical characteristics were analyzed using univariate and multivariable linear regression models for patients with positive findings. Results: Of the 147 patients, 99mTc-HYNIC-PSMA SPECT/CT revealed at least one positive lesion in 118 patients with a high detection rate (80.3%). The detection rates were 48.6% (17/35), 85.1% (40/47), 92.1% (35/38), and 96.3% (26/27) at PSA levels of greater than 0.2 to 2, greater than 2 to 5, greater than 5 to 10, and greater than 10 ng/mL, respectively. PSMA SPECT/CT indicated local recurrence, lymph node metastases, bone metastases, and visceral metastases in 14 (9.5%), 73 (49.7%), 48 (32.7%) and 3 (2.0%) patients. The detection rates of local recurrence and metastasis increased with increasing PSA levels. The detection rate was higher in patients treated with ADT than those without (90.3% vs. 70.7%; P =0.0029). In patients with Gleason scores ≥8, detection rate was slightly higher than those with ≤7 (81.7% vs. 78.5%), but not statistically significant (P = 0.6265). Multivariable linear regression analysis showed a significant correlation of PSA levels and ADT with SUVmax (P=0.0005 and P=0.0397). Conclusions: 99mTc-HYNIC-PSMA SPECT/CT offers high detection rates for biochemically recurrent prostate cancer after radical prostatectomy. The detection rate and SUVmax were positively correlated with PSA levels and ADT.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

LncRNA PGM5-AS1 Inhibits the Progression of Bladder Cancer by Regulating miR-587/SLIT3 Axis.

Bladder cancer (BC), as one of the most common urological malignant tumor types worldwide, places a considerable burden on the economy and patients' health. Long non-coding RNA PGM5-AS1 has been shown to be downregulated in BC, however, its exact function in BC remains unclear. This study aimed to determine the influence of PGM5-AS1 on BC and its related mechanisms. The expression of PGM5-AS1, miR-587, and slit guided ligand 3 (SLIT3) in BC tissues and cells was detected using real-time quantitative polymerase chain reaction and Western blotting. In vitro functional experiments, including CCK-8, Transwell, and Western blotting, were used to assess BC cell proliferation, migration, and the expression of apoptosis-related proteins (Bax and Bcl-2). A xenograft tumor experiment was conducted to test the role of PGM5-AS1 in BC cell growth in vivo. In addition, the relationship between PGM5-AS1, miR-587, and SLIT3 was verified using luciferase reporter and RIP assays. PGM5-AS1 and SLIT3 were expressed at low levels in BC, whereas miR-587 exhibited the opposite trend. PGM5-AS1 overexpression significantly inhibited BC cell proliferation and migration, promoted apoptosis in vitro, and alleviated tumor growth in vivo. miR-587 has been shown to be a target of PGM5-AS1, and miR-587 overexpression can reverse the inhibitory effect of PGM5-AS1 upregulation on BC cell growth. Furthermore, miR-587 directly targeted SLIT3 and negatively regulated its expression. PGM5-AS1 inhibited BC cell proliferation and migration while facilitating apoptosis through the miR-587/SLIT3 pathway. PGM5-AS1 represses BC development via the miR-587/SLIT3 axis, indicating that PGM5-AS1 may be a candidate biomarker and target for BC treatment.

Identification of prognostic and immunotherapy-related eRNA ID2-AS1 in bladder cancer.

AbstractEnhancer RNAs (eRNAs) can participate in enhancer regulation and target gene transcription, thus affecting the occurrence and development of tumors. In this study, we identified eRNAs closely related to bladder cancer (BLCA). Gene expression profiles and clinical information from The Cancer Genome Atlas (TCGA) database were used in this study. The Atlas of Noncoding RNAs in Cancer (TANRIC) co-expression data was also studied to evaluate correlations between the inferred levels of eRNA and its predicted target genes. Moreover, we evaluated differences in tumor microenvironment between high and low ID2-AS1 expression groups, and predicted the response of high- and low-expression groups to immune checkpoint inhibitor (ICI) treatment. Finally, we analyzed the prognostic value of ID2-AS1 in different tumors. ID2-AS1 and ID2 were identified as eRNAs and target genes related to the prognosis of BLCA. Low ID2-AS1 levels were associated with advanced age, low overall survival, high histological grade, and late BLCA staging. ID2-AS1 appeared to regulate epithelial mesenchymal transition, mitotic spindle assembly, and angiogenesis, thereby affecting BLCA progression. The ID2-AS1 high-expression group had better ICI treatment response. In addition, ID2-AS1 also had prognostic value in other cancers. ID2-AS1 helps predict prognostic and immunotherapeutic effects in BLCA.

Identification and Verification of Immune Subtype-Related lncRNAs in Clear Cell Renal Cell Carcinoma.

Background: According to clinical study results, immune checkpoint blockade (ICB) treatment enhances the survival outcome of patients with clear cell renal cell carcinoma (ccRCC). Previous research has divided ccRCC patients into immune subtypes with distinct ICB response rates. However, the study on the association between lncRNAs and ccRCC immune subtypes is lacking. Methods: Differentially expressed lncRNAs/mRNAs between two major immune subgroups were calculated. A weighted gene co-expression network analysis (WGCNA) was conducted to establish the lncRNA-mRNA co-expression network and select the key lncRNAs. Then, prognostic lncRNAs were selected from the network by the bioinformatics method. Next, the risk-score was estimated by lncRNA expression and their coefficients. Finally, a nomogram based on lncRNAs and clinical parameters was created to predict the prognosis of ccRCC. Results: LncRNAs and mRNAs associated with ccRCC immune subtypes were identified. The lncRNAs and mRNAs from a gene module closely linked to the immune subtype were used to construct a network. The KEGG pathways enriched in the network were related to immune system activation processes. These 8 lncRNAs (AL365361.1, LINC01934, AC090152.1, PCED1B-AS1, LINC00426, AC007728.2, AC243829.4, and LINC00158) were found to be positively correlated with immune cells of the tumor microenvironment. The C-index of the nomogram was 0.777, and the calibration curve data suggests that the nomogram has a high degree of discriminating capacity. Conclusion: In summary, we discovered core lncRNAs linked with immune subtypes and created corresponding lncRNA-mRNA networks. These lncRNAs are anticipated to have predictive significance for ccRCC and may provide insight into novel biomarkers for the disease.

Comparison Between Percutaneous Kyphoplasty and Percutaneous Vertebroplasty in Terms of Efficacy in Osteoporotic Vertebral Compression Fractures: A Meta-analysis.

Background and Aim: Osteoporotic vertebral compression fractures (OVCFs) are acknowledged to be common fractures, especially in the elderly population. Minimally invasive percutaneous methods of treatment for these fractures such as kyphoplasty (KP) and vertebroplasty (VP) have been valid and effective tools for decreasing clinical problems, which are associated with more beneficial effects compared with traditional methods such as open surgery or conservative treatment. Hence, we conducted the current meta-analysis in order to gather updated evidence for the systematic assessment of clinical and radiographic outcomes of KP compared with VP. Methods: We searched articles published based on the electronic databases, including PubMed, EMBASE, and Cochrane Library. Publications of studies comparing KP with VP in the treatment of OVCFs were collected. After rigorous and thorough review of study quality, we extracted the data on the basis of eligible trials, which analyzed the summary hazard ratios (HRs) of the end points of interest. Results: Our inclusion criteria involved a total of 6 studies. In total, data from 644 patients, 330 who received VP and 284 who received KP, were included in the review. There was no significant difference in either group in terms of visual analog scale (VAS) scores (MD = 0.17; 95% CI, -0.39 to 0.73; P = .56), risk of cement leakage (odds ratio [OR] = 1.31; 95% CI, 0.62 to 2.74; P = .47) or Oswestry Disability Index (ODI) scores (MD = 0.51; 95% CI, -1.87 to 2.88; P = .68). Nevertheless, the injected cement volume (MD = -0.52; 95% CI, -0.88 to -0.15; P = .005) in the VP group was linked to a markedly lower statistically significant trend compared with the KP group. Conclusion: This meta-analysis evaluated acceptable efficacy levels across the involved trials. VP injected cement volume had several advantages in this meta-analysis. Yet, no significant differences were observed in terms of VAS scores, ODI scores, or cement leakage when KP was compared to VP therapy. Given the combined results of our study, the optimal treatment for patients with OVCFs should be determined by further high-quality multicenter randomized controlled trials with longer follow-up and larger sample sizes.

Classification of Muscle Invasive Bladder Cancer to Predict Prognosis of Patients Treated with Immunotherapy.

Background: Recently, immunotherapies have been approved for advanced muscle invasive bladder cancer (MIBC) treatment, but only a small fraction of MIBC patients could achieve a durable drug response. Our study is aimed at identifying tumor microenvironment (TME) subtypes that have different immunotherapy response rates. Methods: The mRNA expression profiles of MIBC samples from seven discovery datasets (GSE13507, GSE31684, GSE32548, GSE32894, GSE48075, GSE48276, and GSE69795) were analyzed to identify TME subtypes. The identified TME subtypes were then validated by an independent dataset (TCGA-MIBC). The subtype-related biomarkers were discovered using computational analyses and then utilized to establish a random forest predictive model. The associations of TME subtypes with immunotherapy therapeutic responses were investigated in a group of patients who had been treated with immunotherapy. A prognostic index model was constructed using the subtype-related biomarkers. Two nomograms were built by the subtype-related biomarkers or the clinical parameters. Results: Two TME subtypes, including ECM-enriched class (EC) and immune-enriched class (IC), were found. EC was associated with greater extracellular matrix (ECM) pathways, and IC was correlated with immune pathways, respectively. Overall survival was significantly greater for tumors classified as IC, whereas the EC subtype had a worse prognosis. A total of nine genes (AKAP12, APOL3, CXCL13, CXCL9, GBP4, LRIG1, PEG3, PODN, and PTPRD) were selected by computational analyses to construct the random forest model. The area under the curve (AUC) values for this model were 0.827 and 0.767 in the testing and external validation datasets, respectively. Therapeutic response rates were greater in IC patients than in EC patients (28 percent vs. 18 percent). Patients with a high prognostic index had a poorer prognosis than those with a low prognostic index. The nomogram constructed from nine genes and stage achieved a C-index of 0.71. Conclusion: The present investigation defined two distinct TME subtypes and developed models to assess immunotherapeutic treatment outcomes.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Guanylate-binding Protein 2 Expression Is Associated With Poor Survival and Malignancy in Clear-cell Renal Cell Carcinoma.

BACKGROUND/AIM: Clear-cell renal cell carcinoma (ccRCC) is a common recalcitrant cancer. However, little is known about biomarkers of ccRCC. In the present study, we investigated the role of guanylate-binding protein 2 (GBP2), an interferon-induced GTPase, in ccRCC and its potential as a biomarker of this disease. MATERIALS AND METHODS: GBP2 expression was analyzed using the Gene Expression Omnibus, The Cancer Genome Atlas, and Human Protein Atlas databases. Univariate and multivariate Cox-regression analyses were used to investigate the prognostic value of GBP2 in ccRCC. In addition, quantitative real-time polymerase chain reactions, western blotting, and immunohistochemistry were performed to confirm the expression of GBP2 in tissues from patients with ccRCC who had undergone radical nephrectomy at the Department of Urology, the First Affiliated Hospital of Chongqing Medical University (Chongqing, P. R. China). Cell-function assays were performed to investigate the effect of GBP2 on Caki-1 human kidney-cancer cells. RESULTS: Bioinformatics and in vitro experiments showed that the expression of GBP2 was up-regulated in ccRCC tissues and cells and was positively correlated with the malignant clinicopathological parameters of the disease. Univariate and multivariate Cox-regression analyses showed that GBP2 expression was an independent risk factor for the prognosis of ccRCC. Cell-function assays showed that GBP2 expression promoted the proliferation, migration, and invasion of Caki-1 cells through the WNT/ß-catenin signaling pathway. CONCLUSION: The present results indicate that GBP2 expression may serve as a prognostic biomarker for ccRCC.

p53 inhibition attenuates cisplatin-induced acute kidney injury through microRNA-142-5p regulating SIRT7/NF-κB.

Renal tubular epithelial cell apoptosis is the main mechanism of cisplatin-induced acute kidney injury. The role of microRNAs (miRNAs) in the apoptosis of renal tubular epithelial cells has been suggested, but the underlying mechanism has not been fully elucidated. We used microarray analysis to identify miR-142-5p involved in cisplatin-induced acute kidney injury. miR-142-5p was down-regulated in human renal tubular epithelial (HK-2) cells with cisplatin treatment. Notably, the overexpression of miR-142-5p attenuated the cisplatin-induced HK-2 cell apoptosis and inhibition of miR-142-5p aggravated cisplatin-induced HK-2 cell apoptosis. During cisplatin treatment, p53 was activated. The inhibition of p53 by pifithrin-α attenuated the cisplatin-induced kidney injury and up-regulated miR-142-5p expression. We also identified the Sirtuin7 (SIRT7) as a target of miR-142-5p. Furthermore, we demonstrated that the inhibition of SIRT7 prevented cisplatin-induced HK-2 cell apoptosis and decreased the expression of nuclear factor kappa B (NF-κB). Our data revealed that p53 inhibition could attenuate cisplatin-induced acute kidney injury by up-regulating miR-142-5p to repress SIRT7/NF-κB. These findings may provide a novel therapeutic target of cisplatin-induced acute kidney injury.

Revealing potential lipid biomarkers in clear cell renal cell carcinoma using targeted quantitative lipidomics.

BACKGROUND: The high drug resistance and metabolic reprogramming of clear cell renal cell carcinoma (ccRCC) are considered responsible for poor prognosis. In-depth research at multiple levels is urgently warranted to illustrate the lipid composition, distribution, and metabolic pathways of clinical ccRCC specimens. METHODS: In this project, a leading-edge targeted quantitative lipidomic study was conducted using 10 pairs of cancerous and adjacent normal tissues obtained from ccRCC patients. Accurate lipid quantification was performed according to a linear equation calculated using internal standards. Qualitative and quantitative analyses of lipids were performed with multiple reaction monitoring analysis based on ultra-performance liquid chromatography (UPLC) and mass spectrometry (MS). Additionally, a multivariate statistical analysis was performed using data obtained on lipids. RESULTS: A total of 28 lipid classes were identified. Among them, the most abundant were triacylglycerol (TG), diacylglycerol (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Cholesteryl ester (CE) was the lipid exhibiting the most considerable difference between normal samples and tumor samples. Lipid content, chain length, and chain unsaturation of acylcarnitine (CAR), CE, and DG were found to be significantly increased. Based on screening for variable importance in projection scores ≥1, as well as fold change limits between 0.5 and 2, 160 differentially expressed lipids were identified. CE was found to be the most significantly upregulated lipid, while TG was observed to be the most significantly downregulated lipid. CONCLUSION: Based on the absolute quantitative analysis of lipids in ccRCC specimens, it was observed that the content and change trends varied in different lipid classes. Upregulation of CAR, CE, and DG was observed, and analysis of changes in the distribution helped clarify the causes of lipid accumulation in ccRCC and possible carcinogenic molecular mechanisms. The results and methods described herein provide a comprehensive analysis of ccRCC lipid metabolism and lay a theoretical foundation for cancer treatment.