NMR Relaxation of Gas Adsorbed in Microporous Material.

NMR relaxometry has been widely applied to characterize fluid confined in porous media because of its versatility, chemical selectivity, and noninvasive nature. Here we extend its usage to gas adsorbed in microporous materials by establishing a new quantitative model based on the molecular level NMR relaxation mechanism revealed by the molecular simulation of a prototypical adsorption system, CH4 adsorbed in ZIF-8. The model enables new NMR relaxometry-based characterization methods for thermodynamic, dynamic, and structural properties of adsorption systems, as demonstrated and validated by the experiments where the adsorption capacity and self-diffusivity of H2, CH4, and small alcohols adsorbed in ZIF-8 are deduced from the NMR relaxation data. The findings can serve for a better understanding of the composition-structure-properties relationships of a wide range of adsorption systems which is essential for the development and application of new functional microporous materials.

Association of mitochondrial DNA copy number with chronic kidney disease in older adults.

BACKGROUND: Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk. PATIENTS AND METHODS: In a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR < 60 mL/min/1.73 m2 or ICD-10 codes (patients = 3831 (26.5%)). Participants had peripheral blood levels of mtDNA-CN calculated from probe intensities of the Axiom CAS Array. RESULTS: The risk of CKD prevalence decreased with mtDNA-CN per 1-SD increment, independent of established risk factors for older CKD (odds ratio [OR] per SD 0.90, 95% confidence interval [CI] 0.86, 0.93, P < 0.001), and has comparable strength of association with these established risk factors. Furthermore, the progression of kidney function was stratified according to the worsening of eGFR categories. The risk of kidney function progression to a more severe stage gradually decreased as the mtDNA-CN increased (P trend < 0.001). Non-CKD participants in the highest quartile of mtDNA-CN had a lower risk of developing CKD compared to the lowest quartile within 2 years of follow-up, reducing the risk of CKD by 36% (95% CI 0.42, 0.97; P = 0.037). CONCLUSIONS: Based on the analysis of the largest sample to date investigating the association between mtDNA-CN and CKD in older adults, higher levels of mtDNA-CN were found to be associated with a lower risk of CKD, suggesting that a reduced level of mtDNA-CN is a potential risk factor for CKD.

CYP2C19 Loss-of-Function Variants Associated With Long-Term Ischemic Stroke Events During Clopidogrel Treatment in the Chinese Population.

This study aims to determine whether CYP2C19 loss-of-function (LoF) variants were associated with long-term ischemic stroke risk in Chinese primary care patients treated with clopidogrel. Patients treated with clopidogrel were ascertained from Chinese electronic medical records linked with a biobank for a retrospective cohort study. Their medical information was examined for the period from January 2018 to December 2021. Two CYP2C19 major loss of function variants (*2:rs4244285 and *3: rs4986893) were genotyped. The clinical outcome was ischemic stroke event. Cox regression analysis was used to evaluate the association between the occurrence of ischemic stroke events and CYP2C19 LoF variants. Covariates included age, gender, body mass index, prior ischemic stroke, transient ischemic attack, hypertension, diabetes mellitus, hyperlipoidemia, smoke status, aspirin use, proton-pump inhibitor use, and statin use. Of the 1,141 patients included in the clopidogrel therapy cohort, 61.9% carried at least one CYP2C19 LoF variant. During a median follow-up period of 12 months, 103 patients (9.0%) had an ischemic stroke. After adjusting for other risk factors, carriers of CYP2C19 LoF variants had significantly higher risk of ischemic stroke compared with non-carriers (hazard ratio: 1.64, 95% confidence interval: 1.06-2.53, P = 0.025). This pharmacogenetic study of clopidogrel provides novel insights into the association between the CYP2C19 LoF variant and long-term stroke risk. We established that there is still a need for CYP2C19 genotype-guided personalized antiplatelet therapy in those who have returned to the primary care setting for clopidogrel prescription.

CAS Array: design and assessment of a genotyping array for Chinese biobanking.

Background: Chronic diseases are becoming a critical challenge to the aging Chinese population. Biobanks with extensive genomic and environmental data offer opportunities to elucidate the complex gene-environment interactions underlying their aetiology. Genome-wide genotyping array remains an efficient approach for large-scale genomic data collection. However, most commercial arrays have reduced performance for biobanking in the Chinese population. Materials and methods: Deep whole-genome sequencing data from 2 641 Chinese individuals were used as a reference to develop the CAS array, a custom-designed genotyping array for precision medicine. Evaluation of the array was performed by comparing data from 384 individuals assayed both by the array and whole-genome sequencing. Validation of its mitochondrial copy number estimating capacity was conducted by examining its association with established covariates among 10 162 Chinese elderly. Results: The CAS Array adopts the proven Axiom technology and is restricted to 652 429 single-nucleotide polymorphism (SNP) markers. Its call rate of 99.79% and concordance rate of 99.89% are both higher than for commercial arrays. Its imputation-based genome coverage reached 98.3% for common SNPs and 63.0% for low-frequency SNPs, both comparable to commercial arrays with larger SNP capacity. After validating its mitochondrial copy number estimates, we developed a publicly available software tool to facilitate the array utility. Conclusion: Based on recent advances in genomic science, we designed and implemented a high-throughput and low-cost genotyping array. It is more cost-effective than commercial arrays for large-scale Chinese biobanking.

Sacral neuromodulation for overactive bladder using the InterStim and BetterStim systems.

This study aimed to evaluate differences in the clinical outcomes of different sacral neuromodulation systems (InterStim and BetterStim) used in the treatment of overactive bladder. Data from a previously established database of sacral neuromodulation in China (the InterStim system) and a 2020 clinical trial of the BetterStim system were screened. Patients with overactive bladder undergoing stage II implanted pulse generator implantation were selected for analysis and divided into InterStim and BetterStim system groups. Voiding diaries and subjective scores obtained preoperatively, after stage I tined-lead implantation (experience period), and after stage II implanted pulse generator implantation were compared between the two groups. This study included 113 patients with overactive bladder (43, InterStim system group; 70, BetterStim system group). Voiding diaries and subjective scores significantly improved in both the InterStim and BetterStim system groups over the treatment period. Specifically, the urination frequency (all P < 0.001), average voiding volume (all P < 0.001), and average urinary leakage (InterStim, P < 0.05; BetterStim, P < 0.01) in both groups significantly improved at different periods during treatment. At the same time, the urgency perception scale (P < 0.001) and OAB-related quality of life score (InterStim, P < 0.05; BetterStim, P < 0.01) also significantly improved. There was no significant difference in urination frequency at baseline between the two groups (P = 0.169). Urination frequency was significantly higher in the BetterStim system group than in the InterStim group during the experience period and at follow-up (P = 0.031, P = 0.006). There was no significant difference in the number of urinary leakages between the different systems at baseline (P = 0.662), although this was higher in the InterStim system group during the experience period (P = 0.016), and the difference disappeared at the last follow-up (P = 0.565). There were significant differences in baseline urgency perception scale (P = 0.001) and OAB-related quality of life score (P < 0.001) between the two groups; however, these differences were not maintained at follow-up (P = 0.81, P = 0.479). Both sacral neuromodulation systems are safe and effective in treating overactive bladder. The InterStim system may be more beneficial for patients with dry overactive bladder. Satisfactory outcomes may be achieved with the BetterStim system in patients with wet overactive bladder. However, further studies are required to confirm this finding.

Acute effect of sacral neuromodulation on video-urodynamic parameters of neurogenic lower urinary tract dysfunction in a patient with vesicoureteral reflux: a case report.

Neurogenic lower urinary tract dysfunction (NLUTD) is a common urological disease that causes long-term complications and severely reduces patient's quality of life. Sacral neuromodulation has proven to be an effective treatment for NLUTD. However, most previous studies have focused mainly on the efficacy and safety of sacral neuromodulation in the treatment of NLUTD and less on the changes in urodynamic parameters in patients before and after sacral neuromodulation. This study aimed to evaluate the effect of short-term sacral neuromodulation on the results of video-urodynamic parameters in a 63-year-old woman with NLUTD with vesicoureteral reflux. The patient was admitted to the Department of Urology of Beijing Hospital in January 2021 and examined using video-urodynamics. In the same month, the patient underwent the first stage of sacral neuromodulation, with an experience period of 2 weeks. After the experience period ended, video-urodynamics was performed again in February 2021. By comparing the two video-urodynamic results, the effect of short-term sacral neuromodulation on the anatomy and physiology of the lower urinary tract was determined. After 2 weeks of sacral neuromodulation treatment, video-urodynamic parameter analysis showed that while the urine storage period of the patient significantly improved, the voiding period was not significantly changed. This was specifically reflected in the improvement of bladder compliance, safe capacity of the bladder, and significant reduction in vesicoureteral reflux. The improvement of the safe capacity of the bladder effectively helped the patient to control the number of intermittent catheterizations within an acceptable range, which greatly improved her quality of life. Therefore, the patient underwent permanent sacral neuromodulation implantation in February 2021. This study suggests that short-term sacral neuromodulation can significantly improve lower urinary tract function and reduce vesicoureteral reflux in patients with NLUTD with vesicoureteral reflux. In short, we believe that sacral neuromodulation may be a good choice for patients with NLUTD.

CGN Correlates With the Prognosis and Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma.

This study aimed to screen and verify the important prognostic genes related to clear cell renal cell carcinoma (ccRCC) and further analyze their relationship with the immune microenvironment. Gene expression profiles from the TCGA-KIRC, GSE46699, GSE36895, and GSE16449 datasets were utilized to explore differentially co-expressed genes in ccRCC. We screened 124 differentially co-expressed genes using a weighted gene co-expression network and differential gene expression analyses. Univariate and multivariate Cox survival analyses revealed that the expressions of genes CGN, FECH, UCHL1, and WT1 were independently related to the overall survival of ccRCC patients. Kaplan-Meier survival analysis was performed, and CGN was found to have the strongest correlation with the prognosis of ccRCC patients and was consequently selected for further analyses and experimental verification. The results showed that NK cell activation, resting dendritic cells, resting monocytes, and resting mast cells were positively correlated with CGN expression; CD4+ memory activated T cells, regulatory T cells, and M0 macrophages were negatively correlated with CGN expression. Finally, using western blotting and reverse transcription polymerase chain reaction, we verified that the CGN protein level was down-regulated in ccRCC samples, which was consistent with the mRNA levels. CGN was thus identified as diagnosis and prognosis biomarker for ccRCC and is related to the immune microenvironment.

Phase dual-resolution networks for a computer-generated hologram.

The computer-generated hologram (CGH) is a method for calculating arbitrary optical field interference patterns. Iterative algorithms for CGHs require a built-in trade-off between computation speed and accuracy of the hologram, which restricts the performance of applications. Although the non-iterative algorithm for CGHs is quicker, the hologram accuracy does not meet expectations. We propose a phase dual-resolution network (PDRNet) based on deep learning for generating phase-only holograms with fixed computational complexity. There are no ground-truth holograms employed in the training; instead, the differentiability of the angular spectrum method is used to realize unsupervised training of the convolutional neural network. In the PDRNet algorithm, we optimized the dual-resolution network as the prototype of the hologram generator to enhance the mapping capability. The combination of multi-scale structural similarity (MS-SSIM) and mean square error (MSE) is used as the loss function to generate a high-fidelity hologram. The simulation indicates that the proposed PDRNet can generate high-fidelity 1080P resolution holograms in 57 ms. Experiments in the holographic display show fewer speckles in the reconstructed image.

N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma.

Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| > 0.7, p < 0.001) and univariable Cox regression analysis (p < 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC.

TNFSF13B and PPARGC1A expression is associated with tumor-infiltrating immune cell abundance and prognosis in clear cell renal cell carcinoma.

Growing evidence suggests that the tumor microenvironment (TME) plays crucial roles in tumor progression and treatment efficacy in clear cell renal cell carcinoma (ccRCC), which typically has a poor prognosis due to high relapse and metastasis rates. We comprehensively analyzed ccRCC RNA-sequencing data from The Cancer Genome Atlas (TCGA) database to identify candidate prognostic TME-related genes involved in ccRCC. We used the ESTIMATE and CIBERSORT algorithms to estimate the proportions of immune cells, stromal cells, and tumor-infiltrating immune cells (TICs) in the TME in ccRCC samples from 539 patients. By examining the intersection of the differentially expressed genes (DEGs) obtained by Cox regression analysis and protein-protein interaction network, we identified five overlapping DEGs (IGLL5, MZB1, HSD11B1, TNFSF13B, and PPARGC1A). Further analysis revealed that TNFSF13B expression was elevated in ccRCC tumor tissues and negatively associated with overall survival. PPARGC1A expression exhibited the opposite patterns. Immunohistochemical analysis of 35 paired ccRCC and adjacent normal tissues confirmed the in-silico results. Gene set enrichment analysis revealed that genes in the groups with high TNFSF13B and PPARGC1A expression were enriched mainly in immune-related activities. In the group with low PPARGC1A expression, genes were enriched in metabolic pathways. CIBERSORT analysis of TIC proportions revealed that Tregs and CD8 T-cell abundance correlated positively with TNFSF13B expression, but negatively with PPARGC1A expression. These findings demonstrate that TNFSF13B and PPARGC1A are prognostic predictors and possible therapeutic targets in ccRCC.

An effective N6-methyladenosine-related long non-coding RNA prognostic signature for predicting the prognosis of patients with bladder cancer.

BACKGROUND: Bladder cancer (BLCA) typically has a poor prognosis due to high relapse and metastasis rates. A growing body of evidence indicates that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play crucial roles in the progression of BLCA and the treatment response of patients with BLCA. Therefore, we conducted a comprehensive RNA-seq analysis of BLCA using data from The Cancer Genome Atlas (TCGA) to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for BLCA. METHODS: Consensus clustering analysis was used to investigate clusters of BLCA patients with varying prognoses. The least absolute shrinkage and selection operator Cox regression were used to develop the m6A-RLPS. The ESTIMATE and CIBERSORT algorithms were used to evaluate the immune composition. RESULTS: A total of 745 m6A-related lncRNAs were identified using Pearson correlation analysis (|R| > 0.4, p < 0.001). Fifty-one prognostic m6A-related lncRNAs were screened using univariate Cox regression analysis. Through consensus clustering analysis, patients were divided into two clusters (clusters 1 and 2) with different overall survival rates and tumor stages based on the differential expression of the lncRNAs. Enrichment analysis demonstrated that terms related to tumor biological processes and immune-related activities were increased in patient cluster 2, which was more likely to exhibit low survival rates. Nine m6A-related prognostic lncRNAs were finally determined and subsequently used to construct the m6A-RLPS, which was verified to be an independent predictor of prognosis using univariate and multivariate Cox regression analyses. Further, a nomogram based on age, tumor stage, and the m6A-RLPS was generated and showed high accuracy and reliability with respect to predicting the survival outcomes of BLCA patients. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. CONCLUSIONS: We established a novel m6A-RLPS with a favorable prognostic value for patients with BLCA. We believe that this prognostic signature can provide new insights into the tumorigenesis of BLCA and predict the treatment response in patients with BLCA.

Association between Diabetes Complications and the Triglyceride-Glucose Index in Hospitalized Patients with Type 2 Diabetes.

BACKGROUND: Triglyceride-glucose (TyG) index is a convenient indicator of insulin resistance. It has been shown to be associated with macrovascular and microvascular complications in nonhospitalized diabetic patients. However, whether TyG index is a risk factor of diabetes vascular complications in hospitalized type 2 diabetic patients is unclear. We sought to explore the association between TyG index and the risk of macrovascular and microvascular complications in a large Chinese cohort of hospitalized patients. METHOD: A total of 4,721 patients with type 2 diabetes (T2D) who were hospitalized in the Department of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University were enrolled between January 2015 and November 2020. TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Measures of macrovascular complications included brachial-ankle pulse wave velocity (ba-PWV) and ankle-brachial index (ABI), whilst urine microalbumin (MAU), chronic kidney disease (CKD), and diabetic retinopathy (DR) were evaluated for microvascular complications. Logistic regressions were used to examine the association between TyG index and diabetes complications. RESULTS: In univariate logistic regressions, higher TyG index was significantly (p < 0.002) associated with increased odds of MAU (OR = 1.39, 95% CI: [1.22~1.59]) and ABI (OR = 1.31, 95% CI: [1.10-1.57]) but not CKD, DR, or ba-PWV. After controlling for confounders such as age, sex, and body mass index (BMI), TyG index remained strongly (p < 0.002) associated with MAU and ABI. These associations were more pronounced (p < 0.001) in patients with poor glycemic control or in the elderly. CONCLUSION: Hospitalized patients with an elevated TyG index were at a higher risk of lower limb vascular stenosis and nephric microvascular damage. Close monitoring of TyG index in patients with younger age or poor glycemic control could potentially reduce the burden of diabetes complications and prevent readmission.

Young age increases the risk of lymph node positivity but improves prognosis in patients with bladder cancer treated via cystectomy: a population-based study.

BACKGROUND: Age and lymph node positivity are significant prognostic indicators in patients with bladder cancer. This study aimed to investigate the impact of age on lymph node positivity and bladder cancer outcomes. METHODS: Patients with bladder cancer who underwent cystectomy with at least one lymph node examined between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Cochran-Armitage trend tests and logistic regression analyses were used to evaluate the association between age and lymph node positivity in all T stages. Multivariate Cox regression analysis was used to analyze the effect of age on overall survival (OS) and cancer-specific survival (CSS). RESULTS: Overall, 13,251 patients were identified, 648 of whom were under 50 years of age (4.89%). Lymph node positivity was negatively associated with increasing age in each stage except in non-invasive-muscular bladder cancer. In the multivariable analysis, age was an independent prognostic factor for OS and CSS in both the overall cohort and the lymph node positivity group. CONCLUSIONS: In patients with bladder cancer undergoing cystectomy, young age at diagnosis is associated with a higher risk of lymph node positivity and superior outcomes. These findings may guide clinicians in selecting suitable treatments, determining the aggressiveness of lymph node involvement, and predicting survival outcomes in patients of different ages.

Predictive Nomogram and Risk Factors for Lymph Node Metastasis in Bladder Cancer.

Lymph node metastasis (LNM) is an important prognostic factor for bladder cancer (BCA) and determines the treatment strategy. This study aimed to determine related clinicopathological factors of LNM and analyze the prognosis of BCA. A total of 10,653 eligible patients with BCA were randomly divided into training or verification sets using the 2004-2015 data of the Surveillance, Epidemiology, and End Results database. To identify prognostic factors for the overall survival of BCA, we utilized the Cox proportional hazard model. Independent risk factors for LNM were evaluated via logistic regression analysis. T-stage, tumor grade, patient age and tumor size were identified as independent risk factors for LNM and were used to develop the LNM nomogram. The Kaplan-Meier method and competitive risk analyses were applied to establish the influence of lymph node status on BCA prognosis. The accuracy of LNM nomogram was evaluated in the training and verification sets. The areas under the receiver operating characteristic curve (AUC) showed an effective predictive accuracy of the nomogram in both the training (AUC: 0.690) and verification (AUC: 0.704) sets. In addition, the calibration curve indicated good consistency between the prediction of deviation correction and the ideal reference line. The decision curve analysis showed that the nomogram had a high clinical application value. In conclusion, our nomogram displayed high accuracy and reliability in predicting LNM. This could assist the selection of the optimal treatment for patients.

Survival in Patients With Metastatic Prostate Cancer Undergoing Radiotherapy: The Importance of Prostate-Specific Antigen-Based Stratification.

OBJECTIVES: To explore the effectiveness of radiotherapy in mPCa patients with different PSA stratifications based on the cancer database of a large population. BACKGROUND: Screening criteria for patients with metastatic prostate cancer, who are candidates for radiotherapy, are rarely reported. PATIENTS AND METHODS: We identified 22,604 patients with metastatic prostate cancer in the Surveillance, Epidemiology, and End Results database and divided them into a radiotherapy group and a control group. Patients with metastatic prostate cancer were divided into subgroups according to their levels of prostate-specific antigen to evaluate the efficacy of radiotherapy. They were also divided into six subgroups according to their prostate-specific antigen levels. We used multivariate Cox analysis to evaluate overall survival and cancer-specific survival. After 1:1 propensity score matching, Kaplan-Meier analysis was used to explore the difference in overall survival and cancer-specific survival in the radiotherapy and control group. RESULTS: In all, 5,505 patients received radiotherapy, compared to 17,099 in the control group. In the multivariate Cox analysis, radiotherapy improved overall survival (hazard ratio [HR]: 0.730, 95% confidence interval [CI]: 0.636-0.838; P<0.001) and cancer-specific survival (HR: 0.764, 95% CI: 0.647-0.903; P=0.002) in patients with a PSA level of 4-10 ng/mL. Similar results were obtained by Kaplan-Meier analysis after 1:1 propensity score matching. In patients with prostate-specific antigen levels between 4-10 ng/mL, the overall survival (P<0.001) and cancer-specific survival (P<0.05) in the radiotherapy group was significantly better than those in the control group. CONCLUSION: The result of this large population-based study shows that rigorous selection of appropriate metastatic prostate cancer patients for radiotherapy can benefit prognosis significantly. This can be the basis for future prospective trials.

Effect of myeloid ecotropic viral integration site (MEIS) family genes on tumor microenvironment remodeling and its potential therapeutic effect.

BACKGROUND: The myeloid ecotropic viral integration site (MEIS) family of genes is related to the occurrence, development, and outcome of many cancers. However, its role in the immune and tumor microenvironment (TME) is unclear. This study explored the relationship between the expression of MEIS genes and patient survival, immune subtypes, TME, tumor stem cell correlation, and drug sensitivity in cancer. METHODS: We used The Cancer Genome Atlas pan-cancer data to analyze the expression of the MEIS family genes. Kaplan-Meier analysis and univariate Cox proportional hazard regression model were used to detect the relationship between gene expression and overall survival. Analysis of variance was used to explore the relationship between the MEIS family and the immune components in the tumor, and the ESTIMATE algorithm was used to calculate the proportion and level of tumor-infiltrating immune cells. Spearman and Pearson's correlation tests were carried out to detect the relationship between MEIS and the characteristics of tumor stem cells and drug sensitivity. RESULTS: The MEIS family of genes shows different expression profiles in different cancers, with substantial inter- and intra-cancer heterogeneity. Among them, MEIS3 was upregulated in most cancers, whereas MEIS2 was downregulated. The change in MEIS gene expression was usually related to overall survival, but whether a member of the MEIS family was a risk factor or a protective factor was cancer-dependent. Immune component analysis suggested that the role of MEIS genes in promoting or inhibiting cancer may be related to different degrees of immune silencing. Further, there were varying degrees of correlation between MEIS gene expression and cancer cell stemness characteristics. It was also found that MEIS genes, especially MEIS1 and MEIS2, may be related to chemotherapy resistance. CONCLUSIONS: We explored the expression, prognostic relationship, molecular characteristics, and effects on immunity and TME of the MEIS gene family in cancer. Our results suggest that MEIS members should be studied as independent entities in different types of cancer. The MEIS gene family may be a potential target for cancer therapy, but further experiments are needed to confirm this.

Variable- versus constant-frequency sacral neuromodulation in black-zone overactive bladder patients: a study protocol for a multicenter, prospective, randomized, blind, self-controlled trial.

BACKGROUND: The curative effect of sacral neuromodulation (SNM), used to treat overactive bladder (OAB) patients, is definite. However, some patients still have recurrent symptoms after SNM and unsatisfactory symptom improvement after repeated adjustments of the stimulation parameters combined with oral drugs. These are referred to as black-zone OAB patients. The described SNM is the standard method, which involves a constant-frequency stimulation (CFS) of the patient's specific sacral nerve. A new treatment strategy, which combines the advantages of high-frequency and low-frequency stimulations to generate variable-frequency stimulation (VFS), has not yet undergone a formal randomized clinical trial. Therefore, we designed this clinical trial to evaluate the efficacy and safety of VFS-SNM and CFS-SNM in the treatment of black-zone OAB patients. METHODS: We designed a multicenter, prospective, randomized, blinded, self-controlled trial with a 12-week follow-up period. The trial randomly divides the enrolled patients into CFS-SNM and VFS-SNM groups. The main evaluation index is the comparative effectiveness of VFS-SNM and CFS-SNM at the last follow-up. The secondary evaluation indices include the change in the OAB symptom score, the quality of life (QOL) score, and the visual analog scale compared with the baseline period at each follow-up time point. DISCUSSION: Previous studies and our pre-experimental results suggest that black-zone OAB patients may benefit from VFS-SNM. Twelve weeks of VFS-SNM are effective in 40%, and the non-inferior cutoff value is 10% (80% power, 0.05 significance level, 20% loss to follow up). Thus, the calculated sample size is 37 cases each for CFS and VFS groups. The trial is expected to be carried out in 18 centers, but centers will be added or removed as appropriate depending on specific implementation conditions. Clinical researchers at each center will be responsible for screening qualified participants. This is the first randomized controlled trial to comprehensively evaluate the efficacy and safety of VFS-SNM in black-zone OAB patients, which will provide high-quality clinical evidence and may provide new clinical options for such patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000036677, registration date: 24 August 2020.

Nomograms to predict individual prognosis of patients with primary signet ring cell carcinoma of the urinary bladder.

BACKGROUND: Signet ring cell carcinoma (SRCC) is a rare but highly malignant variant of bladder carcinoma. Nomograms have demonstrated good accuracy in predicting the prognosis and guiding the management of pure urothelial carcinoma (UC). However, no accurate and applicable nomogram has been formulated for primary SRCC cases. This study aimed to determine significant prognostic factors and to construct nomograms for predicting the survival outcomes of patients with primary SRCCs of the urinary bladder. METHODS: A total of 317 eligible patients diagnosed with SRCC were analyzed using the 2004-2016 data from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses were performed to explore the prognostic values. Nomograms were established to estimate the overall survival (OS) and cancer-specific survival (CSS) based on the Cox regression results. The performance of SRCC nomograms was evaluated using the concordance index and calibration curves. Survival curves were applied according to various surgical methods, lymph node status, and risk groups distinguished by nomograms. RESULTS: Two nomograms included common indicators that were significantly associated with OS and CSS, including T stage, M stage, tumor size, surgery, and the lymph node ratio (LNR). The nomograms indicated appreciable accuracy in predicting the OS and CSS, with concordance index of 0.723 [95% confidence interval (95% CI: 0.692-0.754] and 0.740 (95% CI: 0.701-0.779), respectively. The calibration curves revealed satisfactory consistency between the prediction of deviation correction and ideal reference line. CONCLUSIONS: The two nomograms developed in this study showed high accuracy and reliability in predicting the survival outcomes of patients with SRCC and could be used to comprehensively assess the risk of SRCC. Moreover, they could assist in the optimal treatment selection for such patients.

Prognostic autophagy model based on CASP4 and BIRC5 expression in patients with renal cancer: independent datasets-based study.

The purpose of this study was to identify key autophagy-related genes (ARGs) in patients with renal cancer (RC) by bioinformatics analysis, and to clarify their potential prognostic value. Thirty-eight differentially expressed ARGs were identified between RC and normal tissues based on The Cancer Genome Atlas database. Functional enrichment analysis suggested that autophagy may play a tumor-promoting role in the initiation of RC. We established a prognostic model with two ARGs (CASP4 and BIRC5) demonstrating significant correlations in expression levels with patient overall survival (OS). Multivariate Cox regression analysis showed that age and the autophagy genes prognostic model were independent prognostic factors for patients with RC. Considering the known prognostic significance of clinical stage in RC, we constructed a nomogram based on age, clinical stage, and the prognostic model. The prognostic model was verified in a separate validation set and external cohort of patients from Beijing Hospital. Patients of low and high risk were defined based on the median risk value calculated by the model and the high risk appeared associated with a significant shorter OS (P < 0.01). Overall, our findings reveal that ARGs have potential prognostic value in patients with RC, providing new directions for targeted therapy.

Influence of patient sex on the effectiveness of sacral neuromodulation: A cohort study from China.

BACKGROUND: Sacral neuromodulation (SNM) has been widely used to treat lower urinary tract dysfunction. Studies have shown a higher conversion rate among female patients than among male patients. However, the influence of gender on the clinical effectiveness of SNM remains unclear. We aimed to confirm whether patients of both genders show similar benefits after SNM treatment. MATERIALS AND METHODS: Clinical data of patients with lower urinary tract symptoms associated with pelvic floor dysfunction (overactive bladder, neurogenic bladder, interstitial cystitis/painful bladder syndrome, idiopathic urinary retention) treated with SNM in 10 medical centres in China between January 2012 and December 2016 were retrospectively collected. The patients were classified by gender. Variations in objective (voiding diary) and subjective scores in the baseline, testing, and last follow-up periods were compared. Data were analysed using statistical measures. RESULTS: The study included 203 patients (93 males, 110 females). There were no statistical differences in baseline information between the two groups, both groups showed improvement over time. Unsatisfactory improvement was observed in the quality of life and sexual life scores of both groups over the entire treatment period (all p＞0.05). Although there was a difference in the maximum voiding volume between the groups at baseline, no difference was observed at the last follow-up (p = 0.004, p = 0.044, p = 0.124), unlike in the average volume where a difference was noted at the last follow-up (p = 0.085, p = 0.964, p = 0.031). While there were no differences in quality of life, sexual life, or pelvic pain and urinary urgency frequency scores at baseline, a significant difference was observed at the last follow-up, and the degree of improvement was less among female patients (p = 0.836, p = 0.131, p = 0.015; p = 0.294, p = 0.265, p = 0.013; p = 0.299, p = 0.087, p = 0.015). CONCLUSION: SNM treatment elicited a similar effect on patients of both gender; however, a significant difference was observed regarding patient satisfaction with the treatment. Further preoperative patient education, especially, for female patients with interstitial cystitis/painful bladder syndrome may improve patient satisfaction.