Dynamic nanomechanical characterization of cells in exosome therapy.

Exosomes derived from mesenchymal stem cells (MSCs) have been confirmed to enhance cell proliferation and improve tissue repair. Exosomes release their contents into the cytoplasmic solution of the recipient cell to mediate cell expression, which is the main pathway through which exosomes exert therapeutic effects. The corresponding process of exosome internalization mainly occurs in the early stage of treatment. However, the therapeutic effect of exosomes in the early stage remains to be further studied. We report that the three-dimensional cell traction force can intuitively reflect the ability of exosomes to enhance the cytoskeleton and cell contractility of recipient cells, serving as an effective method to characterize the therapeutic effect of exosomes. Compared with traditional biochemical methods, we can visualize the early therapeutic effect of exosomes in real time without damage by quantifying the cell traction force. Through quantitative analysis of traction forces, we found that endometrial stromal cells exhibit short-term cell roundness accompanied by greater traction force during the early stage of exosome therapy. Further experiments revealed that exosomes enhance the traction force and cytoskeleton by regulating the Rac1/RhoA signaling pathway, thereby promoting cell proliferation. This work provides an effective method for rapidly quantifying the therapeutic effects of exosomes and studying the underlying mechanisms involved.

Recombination and amino acid point mutations in VP3 exhibit a synergistic effect on increased virulence of rMDPV.

Recombinant Muscovy duck parvovirus (rMDPV) is a product of genetic recombination between classical Muscovy duck parvovirus (MDPV) and goose parvovirus (GPV). The recombination event took place within a 1.1-kb DNA segment located in the middle of the VP3 gene, and a 187-bp sequence extending from the P9 promoter to the 5' initiation region of the Rep1 ORF. This resulted in the alteration of five amino acids within VP3. Despite these genetic changes, the precise influence of recombination and amino acid mutations on the pathogenicity of rMDPV remains ambiguous. In this study, based on the rMDPV strain ZW and the classical MDPV strain YY, three chimeric viruses (rZW-mP9, rZW-mPR187, and rYY-rVP3) and the five amino acid mutations-introduced mutants (rZW-g5aa and rYY-5aa(ZW)) were generated using reverse genetic technology. When compared to the parental virus rZW, rZW-g5aa exhibited a prolonged mean death time (MDT) and a decreased median lethal dose (ELD50) in embryonated duck eggs. In contrast, rYY-5aa(ZW) did not display significant differences in MDT and ELD50 compared to rYY. In 2-day-old Muscovy ducklings, infection with rZW-g5aa and rYY-5aa(ZW) resulted in mortality rates of only 20% and 10%, respectively, while infections with the three chimeric viruses (rZW-mP9, rZW-mPR187, rYY-rVP3) and rZW still led to 100% mortality. Notably, rYY-rVP3, containing the VP3 region from strain ZW, exhibited 50% mortality in 6-day-old Muscovy ducklings and demonstrated significant horizontal transmission. Collectively, our findings indicate that recombination and consequent amino acid changes in VP3 have a synergistic impact on the heightened virulence of rMDPV in Muscovy ducklings.

Analysis of risk factors affecting wound healing and wound infection after meningioma resection.

To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent spinal meningioma resection at our hospital from January 2021 to January 2024 was analysed. The data collected included physical examination findings, haematological and biochemical measurements, and various scales assessed upon admission and after surgery. These data were then analysed. The surgical wound healing, infection and postoperative complications were statistically analysed. Multiple logistic regression analysis method was used to conduct risk factor analysis on corresponding indicators; the odds ratio and p value of 95% confidence interval were calculated. Factors such as age and smoking history were significantly negatively correlated with wound healing after meningioma resection (odds ratio < 1.000, p < 0.05), while preoperative albumin and platelet count were significantly positively correlated with wound healing (odds ratio > 1.000, p < 0.05). Age, WHO Meningioma Grading, preoperative albumin and preoperative platelet were significantly negatively correlated with wound infection after meningioma resection (odds ratio < 1.000, p < 0.05). The history of virus infection and history of neurological disorders were significantly positively correlated with wound infection (odds ratio > 1.000, p < 0.05). The influence of each factor is different. Age, smoking history, WHO Meningioma Grading, preoperative albumin, preoperative platelets, history of virus infection and history of neurological disorders had the greatest influence on wound healing and infection after meningioma resection.

Transplantation of human umbilical cord blood mononuclear cells promotes functional endometrium reconstruction via downregulating EMT in damaged endometrium.

Introduction: Cell transplantation is an emerging and effective therapeutic approach for enhancing uterine adhesions caused by endometrial damage. Currently, human umbilical cord blood mononuclear cells (HUCBMCs) have been extensively for tissue and organ regeneration. However, their application in endometrial repair remains unexplored. Our investigation focuses on the utilization of HUCBMCs for treating endometrial injury. Methods: The HUCBMCs were isolated from health umbilical cord blood, and co-cultured with the injured endometrial stromal cells and injured endometrial organoids. The cell proliferation and apoptosis were measured by cck8 assays and flow cytometry. Western blotting was used to detect the expression of PTEN, AKT and p-AKT. Immunofluorescence assay revealed expression levels of epithelial-mesenchymal transition (EMT) -related markers such as E-cadherin, N-cadherin, and TGF-ß1. The endometrial thickness, fibrosis level, and glandular number were examined after the intravenous injection of HUCBMCs in mouse endometrial models. Immunohistochemistry was employed to assess changes in growth factors vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) as well as fibrosis markers α-SMA and COL1A1. Additionally, expressions of EMT-related proteins E-cadherin and N-cadherin were evaluated. Results: HUCBMCs significantly improved the proliferation and reduced the apoptosis of damaged endometrial stromal cells (ESCs), accompanied by up-regulation of phospho-AKT expression. HUCBMCs increased endometrial thickness and glandular count while decreasing fibrosis and EMT-related markers in mouse endometrial models. Furthermore, EMT-related markers of ESCs and endometrial organoids were significantly decreased. Conclusions: Our findings suggest that HUCBMCs plays a pivotal role in mitigating endometrial injury through the attenuation of fibrosis. HUCBMCs may exert a reverse effect on the EMT process during the endometrium reconstruction.

TFRC, associated with hypoxia and immune, is a prognostic factor and potential therapeutic target for bladder cancer.

BACKGROUND: Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported. PURPOSE: Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients. METHODS: First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan-Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments. RESULTS: A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells. CONCLUSION: A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.

NRP1 downregulation correlates with enhanced ILC2 responses during IL-33 challenge.

Group 2 innate lymphoid cells (ILC2s) play critical roles in driving the pathogenesis of allergic airway inflammation. The mechanisms underlying the regulation of ILC2s remain to be fully understood. Here, we identified neuropilin-1 (NRP1) as a surface marker of ILC2s in response to IL-33 stimulation. NRP1 was abundantly expressed in ILC2s from lung under steady state, which was significantly reduced upon IL-33 stimulation. ILC2s with high expression of NRP1 (NRP1high) displayed lower response to IL-33, as compared with NRP1low ILC2s. Transcriptional profiling and flow cytometric analysis showed that downregulation of AKT-mTOR signalling participated in the diminished functionality of NRP1high ILC2s. These observations revealed a potential role of NRP1 in ILC2s responses under allergic inflammatory condition.

Deciphering the significance of anoikis in bladder cancer and systematic analysis of S100A7 as a potential therapeutic target.

BACKGROUND: Bladder cancer is an epidemic and life-threating urologic carcinoma. Anoikis is a unusual type of programmed cell death which plays a vital role in tumor survival, invasion and metastasis. Nevertheless, the relationship between anoikis and bladder cancer has not been understood thoroughly. METHODS: We downloaded the transcriptome and clinical information of BLCA patients from TCGA and GEO databases. Then, we analyzed different expression of anoikis-related genes and established a prognostic model based on TCGA database by univariate Cox regression, lasso regression, and multivariate Cox regression. Then the Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were performed. GEO database was used for external validation. BLCA patients in TCGA database were divided into two subgroups by non-negative matrix factorization (NMF) classification. Survival analysis, different gene expression, immune cell infiltration and drug sensitivity were calculated. Finally, we verified the function of S100A7 in two BLCA cell lines. RESULTS: We developed a prognostic risk model based on three anoikis-related genes including TPM1, RAC3 and S100A7. The overall survival of BLCA patients in low-risk groups was significantly better than high-risk groups in training sets, test sets and external validation sets. Subsequently, the checkpoint and immune cell infiltration had significant difference between two groups. Then we identified two subtypes (CA and CB) through NMF analysis and found CA had better OS and PFS than CB. Besides, the accuracy of risk model was verified by ROC analysis. Finally, we identified that knocking down S100A7 gene expression restrained the proliferation and invasion of bladder cancer cells. CONCLUSION: We established and validated a bladder cancer prognostic model consisting of three genes, which can effectively evaluate the prognosis of bladder cancer patients. Additionally, through cellular experiments, we demonstrated the significant role of S100A7 in the metastasis and invasion of bladder cancer, suggesting its potential as a novel target for future treatments.

Analysis of the Therapeutic Efficacy of Percutaneous Balloon Double Compression for the Treatment of Recurrent Trigeminal Neuralgia.

BACKGROUND: A more secure and efficacious therapy than has been developed so far is imperative for patients suffering from recurrent trigeminal neuralgia (TN). Despite numerous reports on the use of enhanced percutaneous balloon compression (PBC) techniques, such as altering compression duration and balloon pressure, none have yielded satisfactory outcomes. With these issues in mind, we have employed the PBC double-compression technique for the first time. This technique involves initially inflating a balloon to expand the adhesive tissue in Meckel's lumen, followed by emptying of the contrast medium and subsequent slight catheter adjustment for further compression. The total duration of compression remains unchanged and may even be shortened. OBJECTIVES: The objective of this study was to assess the clinical effectiveness of the PBC double-compression technique in patients with recurrent TN and to analyze the technique's efficacy, subsequent duration of patients' facial numbness, and other complications. STUDY DESIGN: Retrospective study. SETTING: A single-center study. METHODS: Retrospective analysis was conducted on clinical data from 125 patients with postoperative recurrent TN who underwent double compression of the PBC and 65 patients who underwent single compression of the PBC between August 2017 and April 2022. The Barrow Neurological Institute Pain Intensity (BNI-P) score was utilized to quantify the severity of pain, while the Barrow Neurological Institute Facial Numbness (BNI-N) score was employed to separately evaluate the extent of postoperative pain relief and facial numbness. RESULTS: The BNI-P and BNI-N scores before and after PBC treatment are presented herein. At T0, there was no significant difference in the BNI-P scores between the single-compression group and the double-compression group; however, at T1-T4, the BNI-P scores of the double-compression group were lower than those of the single-compression group (P < 0.05). There was no significant difference in BNI-P scores between the 2 groups at T5. At T1-T4, the BNI-N score of the double-compression group was significantly lower than that of the single-compression group (P < 0.05). However, there was no significant difference in BNI-N score between the double and single compression groups at T5. In the single-compression group, one patient (1.5%) experienced insignificant pain relief on postoperative day one, while 2 patients (3.1%) suffered from pain recurrence during the 1-4-year follow-up period. Similarly, in the double-compression group, one patient (0.8%) had inadequate pain relief on postoperative day one, and 3 patients (2.4%) experienced pain recurrence during the same follow-up period. The remaining patients did not require further surgical intervention but continued to rely on regular oral analgesia. In the single-compression group, masticatory muscle weakness was observed in 50 cases (76.9%), while in the double-compression group, it was observed in 92 cases (73.6%). Perioral herpes affected 4 patients (7.1%) and 6 patients (4.8%) in the single- and double-compression groups, respectively. Facial hematoma occurred in 7 cases (10.8%) and 13 cases (10.4%) of the single- and double-compression groups, respectively; each group included one patient suffered who from diplopia. Notably, none of the patients in this study reported any instances of corneal anesthesia, anesthesia pain, aseptic meningitis, cerebrospinal fluid leakage, subarachnoid hemorrhage, carotid-cavernous fistula, or mortality. LIMITATIONS: This was a single-center retrospective study with a small sample size and relatively short follow-up time. Therefore, further evaluation of the long-term efficacy of PBC for postoperative recurrent TN is needed from multiple centers with larger sample sizes and longer follow-up periods. CONCLUSIONS: The double PBC method boasts a high cure rate, a low recurrence rate, and minimal complications, rendering the option appropriate for patients with recurrent TN and thus deserving of clinical promotion.

A visualization analysis of hotspots and global trends on pelvic floor dysfunction in cervical cancer.

BACKGROUND/OBJECTIVE: Cervical cancer is the major cause of cancer-related mortalities in women globally. It constitutes one of the life-threatening conditions for women in developing countries. The popularization of cervical cancer screening and the improvement of treatment levels has caused the mortality rate of cervical cancer to decrease gradually, but pelvic floor dysfunction before and after cervical cancer treatment has become prominent and attracted more and more attention. Bibliometric analysis has been carried out in this research. The main goal of this research is to provide a comprehensive insight into the knowledge structure and global research hotspots about pelvic floor dysfunction in cervical cancer. METHODS: Literature related to cervical cancer and pelvic floor dysfunction as of May 2023 was searched on the Web of Science Core Collection (WOSCC). The visualization and bibliometric analyses of the number and contents of publications were performed to analyze the temporal trends, spatial distribution, collaborative networks, influential references, keyword co-occurrence, and clustering. RESULTS: There were 870 publications from 74 countries or regions, with the U.S. publications in a leading position. Since 2020, the number of publications has rapidly increased with the emphasis on the quality of life of cervical cancer patients. Although pelvic floor dysfunction in cervical cancer mainly occurs in developing countries, developed countries have made great contributions to this disease. However, in developing countries such as China and India, the quality of publications needs to be improved. In this field, the studies focused on the sexual dysfunction or urinary incontinence of cervical cancer patients, and the most cited papers discussed the effect of cervical cancer treatment on the sexual activities of females. The frontier keywords were represented by pelvic radiotherapy and risk factors. CONCLUSION: This study provides an objective and comprehensive analysis of the literature available on pelvic floor dysfunction in cervical cancer and identifies future trends and current hotspots. It can provide a valuable reference for researchers in this field.

Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLSs) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLSs in relapse and remission of RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease-modifying antirheumatic drugs. METHODS: Combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three patients with relapse RA and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using quantitative real-time PCR (qPCR) and multiplex immunohistochemistry (mIHC). We further targeted the critical signals in vitro and in vivo using the collagen-induced arthritis (CIA) model in rats. RESULTS: Lining and sublining FLS subsets were identified using scRNA-seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLSs from patients with relapse RA for which mIHC confirmed the increased expression of FGF10. Although the type I interferon pathway was also activated in the lining FLSs, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by small interfering RNA in FLSs significantly reduced the expression of receptor activator of NF-κB ligand. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human-derived pannus cell culture, whereas the FGF receptor (FGFR) 1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model. CONCLUSION: The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue-specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.

Progress in the Management of Pregnancy with Paroxysmal Nocturnal Hemoglobinuria: A Review.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired complement-mediated hemolytic disease characterized by intravascular hemolysis, thrombosis, smooth muscle dystonia, and so on. Thrombosis is the principal cause of death in PNH patients. During the perinatal period, pregnant PNH patients have increased morbidity and mortality with a heightened risk of complications, including significant preterm birth. The management of pregnancy complicated by PNH is difficult. Therefore, early diagnosis, standardized treatment protocols, and improving perinatal outcomes are crucial. However, there is a lack of consensus on treating patients with PNH during pregnancy. This article reviews 32 studies of pregnancy affected by PNH, focusing on the clinical presentation, diagnosis, and treatment strategies of PNH, to provide guidance for obstetricians on how to handle pregnant patients with PNH, and to offer academic support for the management of PNH patients. We found that Eculizumab has become the primary choice for treating PNH, effectively controlling intravascular hemolysis and reducing the frequency of blood transfusions necessary to stabilize the condition, with no severe threat to the safety of the mother and fetus.

Cuproptosis-related long noncoding RNAs predicts overall survival and reveal immune microenvironment of bladder cancer.

Background: Recently, a newly programmed cell death has been discovered, namely cuproptosis. It is considered a novel copper-dependent cell death model. Long non-coding RNA (lncRNA) influence the prognosis of bladder cancer. In this study, we established a scoring system based on 7 cuproptosis-related lncRNA to predict the prognosis and immune landscape of bladder cancer (BCa). Method: Gene expression and clinical data of 431 tissues were downloaded from The Cancer Genome Atlas (TCGA), including 19 normal samples and 419 cancer samples. All samples were randomly categorized into train and test cohorts. Cuproptosis-related lncRNA were distinguished. Then we conduct univariate COX and multivariate COX regression, paralleled with LASSO regression to cultivate a cuproptosis-related lncRNA risk model. Kaplan-Meier curves, scatter diagram, C-index, ROC curves, nomogram, PCA analysis and univariate and multivariate Cox regression were used to test the accuracy of risk model and to predict patient survival. Additional, gene mutation status between high- and low-risk groups was calculated.GO and KEGG were used to access the DEGs (different expression genes)-related pathway.The ssGSEA and ESTIMATE algorithms were used to assess the immune function in different tumor samples. Besides, patient's response to immunotherapy and drug susceptibility were also been estimated. Results: 7 cuproptosis-related lncRNA (LINC01184, LINC00513, LINC02443, SMARCA5-AS1, BDNF-AS, SOD2-OT1, HYI-AS1) were selected to construct the risk model in the train cohort. This model can well predict the overall survival (OS) in test group and entire cohort with different stage. Despite no significant different is observed in gene mutation between high- and low-risk group, different immune infiltration, different survival and sensitivity to drugs are discovered. Conclusion: We established a novel cuproptosis-related lncRNA risk model which can predict the outcome and immunotherapy response with satisfactory predictive effects. This risk model can provide a new insight into prognostic evaluation and may have potential to guide comprehensive treatment in bladder cancer.

Which institutional investors can improve the level of corporate ESG information disclosure?

The inconsistency of existing findings on the relationship between institutional investors' shareholdings and the level of corporate Environmental, Social and Governance (ESG) disclosure may lie in the insufficient consideration of the heterogeneity of institutional investors and investee firms. In this paper, from the perspective of institutional investor heterogeneity, we use a two-way fixed effects model to examine the impact of institutional investors on corporate ESG disclosure and the possible mechanism of this impact using a sample of Chinese A-share-listed firms from 2012 to 2020. We show that institutional investor shareholding can improve the level of corporate ESG information disclosure by enhancing auditor supervision and analyst attention to these external supervision. In terms of institutional investor heterogeneity, it is found that independent institutional investors and stable institutional investors play a stronger role in promoting the level of ESG information disclosure. Moreover, the positive net effect of the institutional investors on improving the level of ESG information disclosure is more pronounced in non-heavily polluting industries and state-owned enterprises. This paper enriches the impact of institutional investors' shareholding on corporate ESG disclosure from a heterogeneity perspective.

Immunomodulatory roles of metalloproteinases in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, autoimmune pathology characterized by persistent synovial inflammation and gradually advancing bone destruction. Matrix metalloproteinases (MMPs), as a family of zinc-containing enzymes, have been found to play an important role in degradation and remodeling of extracellular matrix (ECM). MMPs participate in processes of cell proliferation, migration, inflammation, and cell metabolism. A growing number of persons have paid attention to their function in inflammatory and immune diseases. In this review, the details of regulation of MMPs expression and its expression in RA are summarized. The role of MMPs in ECM remodeling, angiogenesis, oxidative and nitrosative stress, cell migration and invasion, cytokine and chemokine production, PANoptosis and bone destruction in RA disease are discussed. Additionally, the review summarizes clinical trials targeting MMPs in inflammatory disease and discusses the potential of MMP inhibition in the therapeutic context of RA. MMPs may serve as biomarkers for drug response, pathology stratification, and precision medicine to improve clinical management of rheumatoid arthritis.

Development and validation of a nomogram based on geriatric nutritional risk index for predicting prognosis and postoperative complications in surgical patients with upper urinary tract urothelial carcinoma.

BACKGROUND: This study aimed to evaluate the potential role of the Geriatric Nutritional Risk Index (GNRI) in predicting oncological outcomes and postoperative complications in UTUC patients undergoing radical nephroureterectomy (RNU) and to develop a nomogram incorporating GNRI to predict outcomes. METHODS: A retrospective analysis was performed on 458 consecutive patients who underwent RNU in our center. According to nutritional scores, patients were divided into the following groups: low GNRI (GNRI ≤ 98) and high GNRI (GNRI > 98). Univariable and multivariable logistic regression were performed to investigate the role of GNRI in predicting the perioperative complications. The survival was compared with Kaplan - Meier curve, and test by log-rank tests. Risk factors associated with cancer-specific survival (CSS) and overall survival (OS) were evaluated using Cox proportional hazards regression model and were integrated into a nomogram for individualized risk prediction. The calibration and discrimination ability of the model were evaluated by concordance index (C-index) and risk group stratification. RESULTS: When compared with high GNRI, low GNRI had significantly lower survival (CSS, p < 0.001; OS, p < 0.001). Across all patients, multivariable analyses revealed that low GNRI was an independent prognostic factor (CSS, p = 0.007; OS, p = 0.005). Nomograms for 1-, 3-, and 5 years of CSS and OS had good performance. Patients can be stratified into different groups based on the nomogram, with significant differences in OS and CSS. Further, GNRI was also found to be an independent risk factor for postoperative complications. The complication - prediction nomogram based on GNRI was also internally validated and showed good performance. CONCLUSIONS: The GNRI score is an independent predictor for the prognosis and postoperative complications of UTUC following RNU. This study presented a nomogram incorporating preoperative GNRI that might be used as a convenient tool to facilitate the preoperative individualized prediction of short- and long-term outcomes for patients with UTUC.

Systematic oxidative stress indices predicts prognosis in patients with urothelial carcinoma of the upper urinary tract after radical nephroureterectomy.

BACKGROUND: Oxidative stress plays an important role in the occurrence and development of malignancy. However, the relationship between oxidative stress and upper urinary tract urothelial carcinoma (UTUC) prognosis remains elusive. This study aimed to evaluate the prognostic value of systematic oxidative stress indices as a predictor of patient outcomes in UTUC after radical nephroureterectomy. METHODS: Clinical data for 483 patients with UTUC who underwent radical nephroureterectomy were analyzed. Patients were categorized according to an optimal value of systematic oxidative stress indices (SOSIs), including fibrinogen (Fib), gamma-glutamyl transpeptidase (γ-GGT), creatinine (CRE), lactate dehydrogenase (LDH) and albumin (ALB). Kaplan-Meier analyses were used to investigate associations of SOSIs with overall survival (OS) and progression-free survival (PFS). Moreover, associations between SOSIs and OS and PFS were assessed with univariate and multivariate analyses. RESULTS: High values of Fib, γ-GGT, CRE, and LDH, and low values of ALB were associated with reduced OS. SOSIs status correlated with age, tumor site, surgical approach, hydronephrosis, tumor size, T stage, and lymph node status. The Kaplan-Meier survival analysis showed a significant discriminatory ability for death and progression risks in the two groups based on SOSIs. Multivariate Cox proportional hazards models showed that SOSIs were an independent prognostic indicator for OS (p = 0.007) and PFS (p = 0.021). SOSIs and clinical variables were selected to establish a nomogram for OS. The 1-, 3-, and 5-year AUC values were 0.77, 0.78, and 0.81, respectively. Calibration curves of the nomogram showed high consistencies between the predicted and observed survival probability. Decision curve analysis curves showed that the nomogram could well predict the 1-year, 3-year, and 5-year OS. CONCLUSIONS: SOSIs are an independent unfavorable predictor of OS and PFS in patients diagnosed with UTUC undergoing RNU. Therefore, incorporating SOSIs into currently available clinical parameters may improve clinical decision-making.

A simplified frailty index and nomogram to predict the postoperative complications and survival in older patients with upper urinary tract urothelial carcinoma.

Purpose: This study was designed to investigate the clinical value of a simplified five-item frailty index (sFI) for predicting short- and long-term outcomes in older patients with upper urinary tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). Method: This retrospective study included 333 patients (aged ≥65 years) with UTUC. Patients were classified into five groups: 0, 1, 2, 3, and 3+, according to sFI score. The variable importance and minimum depth methods were used to screen for significant variables, and univariable and multivariable logistic regression models applied to investigated the relationships between significant variables and postoperative complications. Survival differences between groups were analyzed using Kaplan-Meier plots and log-rank tests. Cox proportional hazards regression was used to evaluate risk factors associated with overall survival (OS) and cancer-specific survival (CSS). Further, we developed a nomogram based on clinicopathological features and the sFI. The area under the curve (AUC), Harrel's concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. Result: Of 333 cases identified, 31.2% experienced a Clavien-Dindo grade of 2 or greater complication. Random forest-logistic regression modeling showed that sFI significantly influenced the incidence of postoperative complications in older patients (AUC= 0.756). Compared with patients with low sFI score, those with high sFI scores had significantly lower OS and CSS (p < 0.001). Across all patients, the random survival forest-Cox regression model revealed that sFI score was an independent prognostic factor for OS and CSS, with AUC values of 0.815 and 0.823 for predicting 3-year OS and CSS, respectively. The nomogram developed was clinically valuable and had good ability to discriminate abilities for high-risk patients. Further, we developed a survival risk classification system that divided all patients into high-, moderate-, and low-risk groups based on total nomogram points for each patient. Conclusion: A simple five-item frailty index may be considered a prognostic factor for the prognosis and postoperative complications of UTUC following RNU. By using this predictive model, clinicians may increase their accuracy in predicting complications and prognosis and improve preoperative decision-making.