LASS2 enhances chemosensitivity to cisplatin by inhibiting PP2A-mediated ß-catenin dephosphorylation in a subset of stem-like bladder cancer cells.

BACKGROUND: The benefits of first-line, cisplatin-based chemotherapy for muscle-invasive bladder cancer are limited due to intrinsic or acquired resistance to cisplatin. Increasing evidence has revealed the implication of cancer stem cells in the development of chemoresistance. However, the underlying molecular mechanisms remain to be elucidated. This study investigates the role of LASS2, a ceramide synthase, in regulating Wnt/ß-catenin signaling in a subset of stem-like bladder cancer cells and explores strategies to sensitize bladder cancer to cisplatin treatment. METHODS: Data from cohorts of our center and published datasets were used to evaluate the clinical characteristics of LASS2. Flow cytometry was used to sort and analyze bladder cancer stem cells (BCSCs). Tumor sphere formation, soft agar colony formation assay, EdU assay, apoptosis analysis, cell viability, and cisplatin sensitivity assay were used to investigate the functional roles of LASS2. Immunofluorescence, immunoblotting, coimmunoprecipitation, LC-MS, PCR array, luciferase reporter assays, pathway reporter array, chromatin immunoprecipitation, gain-of-function, and loss-of-function approaches were used to investigate the underlying mechanisms. Cell- and patient-derived xenograft models were used to investigate the effect of LASS2 overexpression and a combination of XAV939 on cisplatin sensitization and tumor growth. RESULTS: Patients with low expression of LASS2 have a poorer response to cisplatin-based chemotherapy. Loss of LASS2 confers a stem-like phenotype and contributes to cisplatin resistance. Overexpression of LASS2 results in inhibition of self-renewal ability of BCSCs and increased their sensitivity to cisplatin. Mechanistically, LASS2 inhibits PP2A activity and dissociates PP2A from ß-catenin, preventing the dephosphorylation of ß-catenin and leading to the accumulation of cytosolic phospho-ß-catenin, which decreases the transcription of the downstream genes ABCC2 and CD44 in BCSCs. Overexpression of LASS2 combined with a tankyrase inhibitor (XAV939) synergistically inhibits tumor growth and restores cisplatin sensitivity. CONCLUSIONS: Targeting the LASS2 and ß-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients.

Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand.

Chiral boronic esters are a class of versatile building blocks. We describe herein an asymmetric nickel-catalyzed borylative coupling of terminal alkenes with nonactivated alkyl halides. The success of this asymmetric reaction is ascribed to the application of a chiral anionic bisoxazoline ligand. This study provides a three-component strategy to access α- and ß-stereogenic boronic esters from easily accessible starting materials. This protocol is characterized by mild reaction conditions, wide substrate scope and high regio- and enantioselectivity. We also showcase the value of this method in simplifying the synthesis of several drug molecules. Mechanistic studies suggest that the generation of enantioenriched boronic esters bearing an α-stereogenic center results from a stereoconvergent process, while the enantioselectivity-controlling step in the generation of boronic esters with a ß-stereocenter is switched to the olefin migratory insertion step due to coordination of an ester group.

Fluorinated alcohol mediated N,N'-dialkylation of amino acid derivatives via cascade [1,5]-hydride transfer/cyclization for concise synthesis of tetrahydroquinazoline.

Structurally diverse amino acids and their ester derivatives were conveniently N,N'-dialkylated via a TFE-promoted cascade condensation/[1,5]-hydride transfer/cyclization for straightforward construction of pharmeutically significant tetrahydroquinazolines incorporating various amino acids, which featured broad substrate scope, the use of TFE as a sole solvent, additive-free and mild conditions.

Reoperation on patients with obstructive sleep apnea-hypopnea syndrome after failed uvulopalatopharyngoplasty.

The goals of this study were to explore the reasons after failed uvulopalatopharyngoplasty (UPPP) in some patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), and to observe the efficacy of the second surgery. Twenty-three OSAHS patients with failed UPPP were included in the study. Routine physical exams, electronic endoscopy, computed tomography scan and polysomnography after nasopharyngeal tube insertion were performed to assess the site of upper airway obstruction, and corresponding appropriate surgical treatment was carried out based on the diagnosis. Comprehensive evaluation of the 23 patients revealed that the sites of obstruction after failed UPPP were as follows: 7 cases predominantly in the oropharyngeal area, 2 cases in the nasal, nasopharyngeal and oropharyngeal area, 5 cases predominantly in the glossopharyngeal area and 9 cases in the oropharyngeal and glossopharyngeal areas. Correspondingly, 7 cases underwent improved UPPP alone, 2 cases underwent adenoidectomy or nasal expansion and improved UPPP, 5 cases underwent glossopharyngeal surgery alone and 9 cases underwent improved UPPP and glossopharyngeal surgery. Follow-up for more than 12 months showed that there were four cured cases, 12 cases with marked improvement, and 7 cases with treatment failure. The success rate was 69.6%. After undergoing UPPP, OSAHS patients may still have oropharyngeal airway obstruction. By performing a detailed preoperative assessment on the patient's airway condition and clarifying the site of obstruction, performing the second surgical treatment can still achieve a relatively satisfactory treatment outcome.

Localization of glossopharyngeal obstruction using nasopharyngeal tube versus Friedman tongue position classification in obstructive sleep apnea hypopnea syndrome.

Assessing the severity of glossopharyngeal obstruction is important for the diagnosis and therapy of obstructive sleep apnea hypopnea syndrome (OSAHS). The polysomnography (PSG) with nasopharyngeal tube insertion (NPT-PSG) has shown good results in assessing glossopharyngeal obstruction. The objective of this study was to compare NPT-PSG with Friedman tongue position (FTP) classification which was also used to evaluate the glossopharyngeal obstruction. One hundred and five patients with OSAHS diagnosed by PSG were included in the study. All the patients were successfully examined by NPT-PSG. Based on the grade of FTP classification, 105 patients were divided into four groups. The differences of the general clinical data, PSG and NPT-PSG results were analyzed among the four groups. And the coincidence of diagnosing glossopharyngeal obstruction of two methods was calculated. There was no significant difference among the four groups in general clinical data and PSG results. However, NPT-PSG results were significantly different among the four groups. Following with the increasing FTP, apnea hypopnea index increased and lowest saturation of blood oxygen decreased. There were 38 patients with and other 38 patients without glossopharyngeal obstruction diagnosed by both methods. The coincidence of two methods was 72.4 %. NPT-PSG is an easy and effective method in assessing the severity of glossopharyngeal obstruction. The coincidence between the NPT-PSG and FTP classification is good. But in some special OSAHS patients such as glossoptosis, unsuccessful uvulopalatopharyngoplasty or suspicious pachyglossia, NPT-PSG is better than FTP classification.

Lingua-epiglottis position predicts glossopharyngeal obstruction in patients with obstructive sleep apnea hypopnea syndrome.

The objective of the study was to investigate the relationship between lingua-epiglottis position and glossopharyngeal obstruction in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). One hundred and four patients with OSAHS diagnosed by polysomnography (PSG) were enrolled. Lingua-epiglottis position was visualized using endoscopy and classified into three types. Spiral CT imaging of the upper respiratory tract was performed to measure the cross-sectional area and inner diameter of the glossopharyngeal airway. The PSG was repeated after nasopharyngeal tube insertion (NPT-PSG). The NPT-PSG results, CT-measured data and incidence of stenosis were compared among the different lingua-epiglottis position groups. Obstructive sleep apnea hypopnea syndrome patients with different lingua-epiglottis positions had similar demographics. As lingua-epiglottis position type varied from type I to type III, cross-sectional area and inner diameter of the glossopharyngeal area decreased, glossopharyngeal airway stenosis rate increased, and apnea hypopnea index measured by NPT-PSG increased. The lowest oxygen saturation decreased. Lingua-epiglottis position was significantly related to glossopharyngeal obstruction. Lingua-epiglottis position should be used in clinical practice for the preliminary assessment of glossopharyngeal obstruction.

Synthetic techniques for thermodynamically disfavoured substituted six-membered rings.

Six-membered rings are ubiquitous structural motifs in bioactive compounds and multifunctional materials. Notably, their thermodynamically disfavoured isomers, like disubstituted cyclohexanes featuring one substituent in an equatorial position and the other in an axial position, often exhibit enhanced physical and biological activities in comparison with their opposite isomers. However, the synthesis of thermodynamically disfavoured isomers is, by its nature, challenging, with only a limited number of possible approaches. In this Review, we summarize and compare synthetic methodologies that produce substituted six-membered rings with thermodynamically disfavoured substitution patterns. We place particular emphasis on elucidating the crucial stereoinduction factors within each transformation. Our aim is to stimulate interest in the synthesis of these unique structures, while simultaneously providing synthetic chemists with a guide to approaching this synthetic challenge.

Inflammatory myofibroblastic tumor of the adrenal gland: A case report.

Inflammatory Myofibroblastic Tumor (IMT) occurring in the adrenal gland is extremely rare, and pathologic examination is the gold standard for confirming the diagnosis. We report a case of IMT of adrenal origin in a patient whose diagnosis was confirmed by pathological examination after surgical resection of the tumor. Although previous studies have reported an overall favorable prognosis for IMT, regular and long-term follow-up is necessary.

Malignant melanoma located in the ureter and gallbladder: A case report and literature review.

RATIONALE: Melanoma is one of a common cutaneous malignancy. Currently, metastatic malignant melanoma is difficult to be diagnosed through imaging examinations. Furthermore, the incidence of metastatic melanoma affecting the gallbladder and ureter is exceptionally rare. PATIENT CONCERNS: A 54-year-old female was admitted to the hospital with a half-month history of left lower back pain. Correlative examination revealed an occupying lesion in the mid-left ureter and the neck of the gallbladder. DIAGNOSES: The patient was initially diagnosed with gallbladder cancer and left ureteral carcinoma based on imaging. Following 2 operations, immunohistochemical staining confirmed the presence of metastatic melanoma involving both the gallbladder and ureter. INTERVENTION: After multidisciplinary consultation and obtaining consent from the patient and her family, the patient underwent left radical nephroureterectomy, radical cholecystectomy, laparoscopic partial hepatectomy (Hep IV, Hep V), and lymph node dissection of hepatoduodenal ligament. OUTCOMES: One month after treatment, the patient imaging showed no disease progression, and at 6 months of follow-up, the patient was still alive. LESSONS: It is difficult to distinguish metastatic melanoma from carcinoma in situ by imaging. In addition, metastatic malignant melanoma lacks specific clinical manifestations and is prone to misdiagnosis, which emphasizes the highly aggressive nature of malignant melanoma.

Identification of potential biomarkers for progression and prognosis of renal clear cell carcinoma by comprehensive bioinformatics analysis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common pathological type of renal cell carcinoma (RCC), and effective biomarkers will improve diagnosis and treatment. OBJECTIVE: This study investigated NPEPL1 expression in ccRCC through public databases and clinical samples and assessed its correlation with clinicopathological features and patient prognosis. METHOD: Data from The Cancer Genome Atlas and clinical specimens were gathered, NPEPL1 expression levels were analyzed; a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NPEPL1; and clinicopathological data was used to study the correlations between expression and clinical parameters. NPEPL1's prognostic value was appraised using a Kaplan-Meier (K-M) survival curve, Cox regression analysis, and a nomogram model; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differently expressed genes between tissues with high and low NPEPL1 expression were used to estimate the underlying mechanisms involved. RESULTS: NPEPL1 was significantly higher-expressed in ccRCC tissue. ROC analysis showed that NPEPL1 had noteworthy diagnostic efficacy. NPEPL1 expression was closely related to clinicopathological parameters, such as T and M stage. K-M analysis showed that overall survival was significantly shortened with high NPEPL1 expression. Cox regression analysis showed that NPEPL1 expression was an independent risk factor predicting overall survival. The nomogram showed a significantly high clinical value in predicting the 1-, 3-, and 5-year survival probabilities in ccRCC. GO and KEGG enrichment analysis suggested that NPEPL1 may promote the occurrence and development of ccRCC via the Ras signaling and other pathways. CONCLUSION: NPEPL1 expression in ccRCC was higher than that in normal kidney tissues and was significantly associated with advanced clinical stage and poor prognosis. Therefore, NPEPL1 is a promising prognostic biomarker.

Development of a stemness-related prognostic index to provide therapeutic strategies for bladder cancer.

Bladder cancer (BC) is a heterogeneous disease with varying clinical outcomes. Recent evidence suggests that cancer progression involves the acquisition of stem-like signatures, and assessing stemness indices help uncover patterns of intra-tumor molecular heterogeneity. We used the one-class logistic regression algorithm to compute the mRNAsi for each sample in BLCA cohort. We subsequently classified BC patients into two subtypes based on 189 mRNAsi-related genes, using the unsupervised consensus clustering. Then, we identified nine hub genes to construct a stemness-related prognostic index (SRPI) using Cox regression, LASSO regression and Random Forest methods. We further validated SRPI using two independent datasets. Afterwards, we examined the molecular and immune characterized of SRPI. Finally, we conducted multiply drug screening and experimental approaches to identify and confirm the most proper agents for patients with high SRPI. Based on the mRNAsi-related genes, BC patients were classified into two stemness subtypes with distinct prognosis, functional annotations, genomic variations and immune profiles. Using the SRPI, we identified a specific subgroup of BC patients with high SRPI, who had a poor response to immunotherapy, and were less sensitive to commonly used chemotherapeutic agents, FGFR inhibitors, and EGFR inhibitors. We further identified that dasatinib was the most promising therapeutic agent for this subgroup of patients. This study provides further insights into the stemness classification of BC, and demonstrates that SRPI is a promising tool for predicting prognosis and therapeutic opportunities for BC patients.

A computed tomography urography-based machine learning model for predicting preoperative pathological grade of upper urinary tract urothelial carcinoma.

OBJECTIVES: Development and validation of a computed tomography urography (CTU)-based machine learning (ML) model for prediction of preoperative pathology grade of upper urinary tract urothelial carcinoma (UTUC). METHODS: A total of 140 patients with UTUC who underwent CTU examination from January 2017 to August 2023 were retrospectively enrolled. Tumor lesions on the unenhanced, medullary, and excretory periods of CTU were used to extract Features, respectively. Feature selection was screened by the Pearson and Spearman correlation analysis, least absolute shrinkage and selection operator algorithm, random forest (RF), support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost). The logistic regression (LR) was used to screen for independent influencing factors of clinical baseline characteristics. Machine learning models based on different feature datasets were constructed and validated using algorithms such as LR, RF, SVM, and XGBoost. By computing the selected features, a radiomics score was generated, and a diverse feature dataset was constructed. Based on the training set, 16 ML models were created, and their performance was evaluated using the validation set for metrics including sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC), and others. RESULTS: The training set consisted of 98 patients (mean age: 64.5 ± 10.5 years; 30 males), whereas the validation set consisted of 42 patients (mean age: 65.3 ± 9.78 years; 17 males). Hydronephrosis was the best independent influence factor (p < 0.05). The RF model had the best performance in predicting high-grade UTUC, with AUC of 0.914 (95% Confidence Interval [95%CI] 0.852-0.977) and 0.903 (95%CI 0.809-0.997) in the training set and validation set, and accuracy of 0.878 and 0.857, respectively. CONCLUSIONS: An ML model based on the RF algorithm exhibits excellent predictive performance, offering a non-invasive approach for predicting preoperative high-grade UTUC.

Recurrence/prognosis estimation using a molecularly positive surgical margin-based model calls for alternative curative strategies in pIIIA/N2 NSCLC.

Stage pIIIA/N2 non-small cell lung cancer (NSCLC) is primarily treated by complete surgical resection combined with neoadjuvant/adjuvant therapies. However, up to 40% of patients experience tumor recurrence. Here, we studied 119 stage pIIIA/N2 NSCLC patients who received complete surgery plus adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). The paired tumor and resection margin samples were analyzed using next-generation sequencing (NGS). Although all patients were classified as negative resection margins by histologic methods, NGS revealed that 47.1% of them had molecularly positive surgical margins. Patients who tested positive for NGS-detected residual tumors had significantly shorter disease-free survival (DFS) (P = 0.002). Additionally, metastatic lymph node ratio, erb-b2 receptor tyrosine kinase 2 (ERBB2) mutations, and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations were also independently associated with DFS. We used these four features to construct a COX model that could effectively estimate recurrence risk and prognosis. Notably, mutational profiling through broad-panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.

Robot-assisted radical cystectomy with intracorporeal urinary diversion: an updated systematic review and meta-analysis of its differential effect on effectiveness and safety.

BACKGROUND: Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion (iRARC) is increasingly being used in recent years. Whether iRARC offers advantages over open radical cystectomy (ORC) remains controversial. This study aimed to compare the difference of perioperative outcomes, oncological outcomes and complications between iRARC and ORC. METHODS: The PubMed, Embase, Cochrane Library, Web of Science and CNKI databases were searched in July 2023 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were identified to be eligible if they compared perioperative outcomes, oncological outcomes and complications in patients who underwent iRARC with ORC. RESULTS: Twenty-two studies involving 7020 patients were included. Compared to ORC, iRARC was superior for estimated blood loss [estimated blood loss (EBL) weighted mean difference (WMD): -555.52; 95% CI, -681.64 to -429.39; P <0.001], blood transfusion rate [odds ratio (OR): 0.16; 95% CI, 0.09-0.28; P <0.001], length of hospital stay [length of hospital stay (LOS) WMD: -2.05; 95% CI, -2.93 to -1.17; P <0.001], Clavien-Dindo grades ≥III complication rate [30 days: OR: 0.57; 95% CI 0.44-0.75; P <0.001; 90 days: OR: 0.71; 95% CI 0.60-0.84; P <0.001], and positive surgical margin [positive surgical margin (PSM) OR: 0.65; 95% CI 0.49-0.85; P =0.002]. However, iRARC had a longer operative time [operative time (OT) WMD: 68.54; 95% CI 47.41-89.67; P <0.001] and a higher rate of ureteroenteric stricture [ureteroenteric stricture (UES) OR: 1.56; 95% CI 1.16-2.11; P =0.003]. Time to flatus, time to bowel, time to regular diet, readmission rate, Clavien-Dindo grades less than III complication rate for iRARC were similar to that for ORC. Interestingly, the results of subgroup analysis revealed no difference in EBL between iRARC and ORC when the diversion type was neobladder. When the ileal conduit was selected as the diversion type, the LOS was similar in both procedures. CONCLUSION: Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion appears to be superior to open radical cystectomy in terms of effectiveness and safety. However, attention should be paid to the occurrence of ureteroenteric stricture during follow-up.

Treatment of obstructive sleep apnea hypopnea syndrome caused by glossoptosis with tongue-base suspension.

The objective of the study was to evaluate a surgical method to treat patients with obstructive sleep apnea hypopnea syndrome (OSAHS) caused by suspected glossoptosis. Seventy-eight patients with OSAHS caused by suspected glossoptosis were non-randomly divided into two groups. The 45 patients in the first group received uvulopalatopharyngoplasty (UPPP) and tongue-base suspension (Repose). The 33 patients in the second group received UPPP alone. Follow-up was conducted over 6 months, and polysomnography was used to determine the effects of treatment. Follow-up results revealed that the apnea-hypopnea index (AHI) and ESS scores of the patients from both groups were substantially decreased compared to the corresponding values before surgery. The lowest oxygen saturation (LaSo2) of both groups was improved, compared to the level before surgery. The degree of improvement in patients treated with UPPP + Repose was significantly greater than that seen in patients treated with UPPP alone. In the UPPP + Repose group, 17 patients were cured, 23 showed marked improvement, and 5 did not improve. In the UPPP alone group, 1 patient was cured, 16 showed marked improvement, and 16 did not improve. The marked improvement rates of the two groups were 88.9 and 51.5 %, respectively, a significant difference. Patients who show glossopharyngeal obstruction during sleep, and have normal glossopharyngeal airway morphology when awake, should be suspected to have glossoptosis. Repose surgery is an effective operation for the patients with OSAHS suspected glossoptosis.

Diagnostic and therapeutic effects of fluorescence cystoscopy and narrow-band imaging in bladder cancer: a systematic review and network meta-analysis.

BACKGROUND: This review aims to compare the efficacies of fluorescence cystoscopy, narrow-band imaging (NBI), and white light cystoscopy in the treatment and diagnosis of bladder cancer. METHODS: The authors searched PubMed, EMbase, Web of Science, and the Cochrane Library from January 1990 to April 2022. A total of 26 randomized controlled studies and 22 prospective single-arm studies were selected. Most patients had nonmuscle-invasive bladder cancer. The study protocol has been registered at PROSPERO. RESULTS: In the pairwise meta-analysis, 5-aminolevulinic acid (5-ALA) reduced the short-term and long-term recurrence rates of bladder cancer compared with white light cystoscopy (WLC); however, no statistical difference was observed in intermediate-term recurrence rates (RR=0.79, 95% CI: 0.57-1.09). Hexaminolevulinic acid and NBI reduced short-term, intermediate-term, and long-term recurrence rates. The sensitivity of 5-ALA, hexaminolevulinic acid, NBI, and WLC for bladder cancer were 0.89 (95% CI: 0.81-0.94), 0.96 (95% CI: 0.92-0.98), 0.96 (95% CI: 0.92-0.98), and 0.75 (95% CI: 0.70-0.79), respectively; however, only NBI had the same specificity as WLC (0.74 vs. 0.74). Compared with WLC, 5-ALA improved the detection rate of carcinoma in situ and Ta stage bladder cancer but had no advantage in T1 stage tumors (OR=2.39, 95% CI:0.79-7.19). Hexaminolevulinic acid and NBI improved the detection rates of all nonmuscular-invasive bladder cancers. In the network meta-analysis, there was no significant difference in either recurrence or detection rates between 5-ALA, hexaminolevulinic acid, and NBI. CONCLUSION: Fluorescence cystoscopy and NBI are advantageous for treating and diagnosing patients with nonmuscle-invasive bladder cancer.

Prognostic nutritional index combined with NLR to construct a survival prediction model and decision analysis of patients with muscle-invasive bladder cancer after surgery.

OBJECTIVES: To build a nomogram prediction model, assess its predictive ability, and perform a survival decision analysis on patients with muscle-invasive bladder cancer (MIBC) to study risk factors affecting overall survival (OS). METHODS: A retrospective analysis was performed on the clinical information of 262 patients with MIBC who underwent radical cystectomy (RC) at the Urology Department of the Second Affiliated Hospital of Kunming Medical University between July 2015 and August 2021. The final model variables that were included were chosen using single-factor stepwise Cox regression, optimal subset regression, and LASSO regression + cross-validation with the minimum AIC value. The next step was to do a multivariate Cox regression analysis. The establishment of a nomogram model by fitting and the screening out of independent risk factors impacting the survival of patients with MIBC having radical resection. Receiver Activity Characteristic curves, C-index, and a calibration plot evaluated the prediction accuracy, validity, and clinical benefit of the model. The 1-, 3-, and 5-year survival rates were then computed for each risk factor using a Kaplan-Meier survival analysis. RESULTS: 262 eligible patients in total were enrolled. With a median follow-up of 32 months, the follow-up period ranged from 2 to 83 months. 171 cases (65.27%) survived while 91 cases (34.73%) perished. Age (HR = 1.06 [1.04; 1.08], p = 0.001), preoperative hydronephrosis (HR = 0.69 [0.46, 1.05], p = 0.087), T stage (HR = 2.06 [1.09, 3.93], p = 0.027), lymphovascular invasion (LVI, HR = 1.73 [1.12, 2.67], p = 0.013), prognostic nutritional index (PNI, HR = 1.70 [1.09, 2.63], p = 0.018), and neutrophil-to-lymphocyte ratio (NLR, HR = 0.52 [0.29, 0.93)], p = 0.026) were independent risk factor for the survival of bladder cancer patients. Create a nomogram based on the aforementioned findings, and then draw the 1-year, 3-year, and 5-year OS receiver operating characteristic curves by the nomogram. The AUC values were 0.811 (95% CI [0.752, 0.869]), 0.814 (95% CI [0.755, 0.873]), and 0.787 (95% CI [0.708, 0.865]), respectively, and the calibration plot matched the predicted value well. The 1-year, 3-year, and 5-year decision curve analyses were higher than the ALL line and None line at threshold values of >5%, 5%-70%, and 20%-70% indicating that the model has good clinical applicability. The calibration plot for the Bootstrap 1000-time resampled validation model was similar to the actual value. Patients with preoperative combination hydronephrosis, higher T-stage, combined LVI, low PNI, and high NLR had worse survival, according to Kaplan-Meier survival analysis for each variable. CONCLUSIONS: This study might conclude that PNI and NLR were separate risk factors that affect a patient's OS after RC for MIBC. The prognosis of bladder cancer may be predicted by PNI and NLR, but additional confirmation in randomized controlled trials is required.

Comparative Efficacy of Different Drugs for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Bayesian Network Meta-Analysis.

Background: Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are common in middle-aged and elderly men. The current drugs for treating this disease include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and ß3-adrenoceptor agonists (B3As). However, direct comparative studies analyzing different therapies are limited; therefore, we conducted a network meta-analysis (NMA) to evaluate the efficacy of different drug regimens for treating BPH/LUTS. Methods: The PubMed, EMbase, Web of Science, and Cochrane Library databases were searched to collect randomized controlled trials (RCTs) of different drug treatments for BPH/LUTS from January 2000 to April 2021. The NMA was performed using R 4.1 software. Results: Fifty-five RCTs were included among a total of 1639 trials. ① ABs + PDE5-Is, ABs + B3As, ABs + MRAs, ABs, and PDE5-IS were superior to the placebo in improving the total International Prostate Symptom Score (IPSS), IPSS-Voiding, and IPSS-storage. ② For increasing the maximum flow rate (Qmax), ABs + PDE5-Is, ABs + MRAs, and ABs were more effective than the placebo. ③ Regarding reducing post-void residual urine (PVR), none of the six treatment plans had significant effects. Conclusion: Combination therapy showed greater efficacy than monotherapy, and ABs + PDE5-Is was the most successful treatment for improving the overall IPSS score. ABs are a primary therapeutic measure to increase Qmax, and ABs + PDE5-I may be a more suitable choice for enhancing Qmax. The combination of MRA and AB+ MRA may lead to an increase in PVR. Systematic Review Registration: [website], identifier [registration number].

Comparison of Radiofrequency Ablation Versus Cryoablation For T1 Renal Tumors: An Evidence-Based Analysis of Comparative Outcomes.

Objective: To discuss the differences in the effectiveness and security for T1 renal tumors by radiofrequency ablation (RFA) and cryoablation (CA). Methods: We systematically searched the Cochrane Library, PubMed, Embase, CNKI databases, and Science databases, and the date was from the above database establishment to August 2021. Controlled trials on RFA and CA for T1 renal tumors were included. The meta-analysis was conducted with the Review Manager 5.4 software. Results: A total of ten studies with 2,367 patients were included in the analysis. There were no significant differences in complications (odds ratio [OR], 1.23; 95% CI, 0.80 to 1.90; p=0.35), primary technique efficacy rate (OR, 1.01; 95% CI, 0.33 to 3.14; p=0.98), changes in serum creatinine (weighted mean difference [WMD], 0.53; 95% CI, -0.50 to 1.57; p=0.31), or 5-year survival rate (hazard ratio [HR], 1.11; 95% CI, 0.41 to 3.00; p=0.84) among patients undergoing RFA and CA. However, compared with patients who underwent RFA, patients who underwent CA had a lower Local recurrence (OR: 2.25; 95% CI: 1.38 to 3.67; p = 0.001). Conclusion: The analysis demonstrated that in the treatment of T1 renal tumors, CA may be associated with lower local recurrence rates. However, no differences were observed in terms of primary technique efficacy rate, 5-year survival rate, changes in serum creatinine, and complication rate between groups. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier PROSPERO (CRD42021295160).

Modular access to substituted cyclohexanes with kinetic stereocontrol.

Substituted six-membered cyclic hydrocarbons are common constituents of biologically active compounds. Although methods for the synthesis of thermodynamically favored, disubstituted cyclohexanes are well established, a reliable and modular protocol for the synthesis of their stereoisomers is still elusive. Herein, we report a general strategy for the modular synthesis of disubstituted cyclohexanes with excellent kinetic stereocontrol from readily accessible substituted methylenecyclohexanes by the implementation of chain-walking catalysis. Mechanistically, the initial introduction of a sterically demanding boron ester group adjacent to the cyclohexane is key to guiding the stereochemical outcome. The synthetic potential of this methodology has been highlighted in late-stage modification of complex bioactive molecules and in comparison with current cross-coupling techniques.