Oxidative stress-induced EGR1 upregulation promotes NR4A3-mediated nucleus pulposus cells apoptosis in intervertebral disc degeneration.

This study aimed to reveal the specific role of early growth response protein 1 (EGR1) and nuclear receptor 4A3 (NR4A3) in nucleus pulposus cells (NPCs) and the related molecular mechanism and to identify a new strategy for treating intervertebral disc degeneration (IVDD). Bioinformatics analysis was used to explore and predict IVDD-related differentially expressed genes, and chromatin immunoprecipitation sequencing (ChIP-seq) revealed NR4A3 as the EGR1 target gene. An in vitro NPC model induced by tributyl hydrogen peroxide (TBHP) and a rat model induced by fibrous ring acupuncture were established. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical staining, immunofluorescence staining, and flow cytometry were used to detect the effects of EGR1 and NR4A3 knockdown and overexpression on NPC apoptosis and the expression of extracellular matrix (ECM) anabolism-related proteins. Interactions between EGR1 and NR4A3 were analyzed via ChIP-qPCR and dual luciferase assays. EGR1 and NR4A3 expression levels were significantly higher in severely degenerated discs (SDD) than in mildly degenerated discs (MDD), indicating that these genes are important risk factors in IVDD progression. ChIP-seq and RNA-seq revealed NR4A3 as a direct downstream target of EGR1, and this finding was verified by ChIP-qPCR and dual luciferase reporter experiments. Remarkably, the rescue experiments showed that EGR1 promotes TBHP-induced NPC apoptosis and impairs ECM anabolism, dependent on elevated NR4A3 expression. In summary, the EGR1-NR4A3 axis mediates the progression of NPC apoptosis and ECM impairment and is a potential therapeutic target in IVDD.

Chestnut-Inspired Hollow Hydroxyapatite 3D Printing Scaffolds Accelerate Bone Regeneration by Recruiting Calcium Ions and Regulating Inflammation.

This study aims to overcome the drawbacks associated with hydroxyapatite (HAP) dense structures after sintering, which often result in undesirable features such as large grain size, reduced porosity, high crystallinity, and low specific surface area. These characteristics hinder osseointegration and limit the clinical applicability of the material. To address these issues, a new method involving the preparation of hollow hydroxyapatite (hHAP) microspheres has been proposed. These microspheres exhibit distinctive traits including weak crystallization, high specific surface area, and increased porosity. The weak crystallization aligns more closely with early mineralization products found in the human body and animals. Moreover, the microspheres' high specific surface area and porosity offer advantages for protein loading and facilitating osteoblast attachment. This innovative approach not only mitigates the limitations of conventional HAP structures but also holds the potential for improving the effectiveness of hydroxyapatite in biomedical applications, particularly in enhancing osseointegration. Three-dimensional printed hHAP/chitosan (CS) scaffolds with different hHAP concentration gradients were manufactured, and the physical and biological properties of each group were systematically evaluated. In vitro and in vivo experiments show that the hHAP/CS scaffold has excellent performance in bone remodeling. Furthermore, in-scaffold components, hHAP and CS were cocultured with bone marrow mesenchymal stem cells to explore the regulatory role of hHAP and CS in the process of bone healing and to reveal the cell-level specific regulatory network activated by hHAP. Enrichment analysis showed that hHAP can promote bone regeneration and reconstruction by recruiting calcium ions and regulating inflammatory reactions.

Finite element study on three osteotomy methods for treating thoracolumbar osteoporotic fracture vertebral collapse complicated with neurological dysfunction.

BACKGROUND: Surgical methods for patients with osteoporotic fracture vertebral collapse complicated with neurological dysfunction are still a topic of debate. We designed an improved osteotomy for the treatment of osteoporotic compression fracture patients with neurological dysfunction. Compared with traditional osteotomy methods such as pedicle subtraction osteotomy (PSO) and bone-disc-bone osteotomy (BDBO), the osteotomy range is reduced. Therefore, we use a finite element method to analyze the biomechanical conditions of these three osteotomy methods and provide a mechanical theoretical basis for the surgical treatment of these three osteotomy methods. METHODS: Based on the CT scan of a patient with L1 osteoporotic fracture vertebral collapse and neurological dysfunction, the finite element model was constructed by importing Mimics software, and three different osteotomy models were established. The forces and displacements of internal fixation device, T1-L5 whole segment, T10 vertebral body, and T10/11 intervertebral disc were recorded under different working conditions. RESULTS: The displacement levels of internal fixation device, T1-L5 spine, T10 vertebral body, and T10/11 intervertebral disc in the modified osteotomy group were between BDBO group and PSO group. The stress in BDBO group was concentrated in titanium mesh and its maximum stress was much higher than that in PSO group and modified osteotomy group. The mechanical distribution of T10/11 intervertebral disc showed that the maximum stress distribution of the three osteotomy methods was similar. CONCLUSION: The relatively simple modified osteotomy has certain advantages in stress and displacement. In contrast, the stability of BDBO group was poor, especially in the lumbar intervertebral disc and lumbar body. For this type of osteotomy patients, it is recommended to avoid postoperative flexion so as not to increase the load.

pH-Responsive nanoplatform synergistic gas/photothermal therapy to eliminate biofilms in poly(L-lactic acid) scaffolds.

To date, implant-associated infection is still a significant clinical challenge, which cannot be effectively eliminated by single therapies due to the formation of microbial biofilms. Herein, a pH-responsive nanoplatform was constructed via the in situ growth of zinc sulfide (ZnS) nanoparticles on the surface of Ti3C2 MXene nanosheets, which was subsequently introduced in poly(L-lactic acid) (PLLA) to prepare a composite bone scaffold via selective laser sintering technology. In the acidic biofilm microenvironment, the degradation of ZnS released hydrogen sulfide (H2S) gas to eliminate the biofilm extracellular DNA (eDNA), thus destroying the compactness of the biofilm. Then, the bacterial biofilm became sensitive to hyperthermia, which could be further destroyed under near-infrared light irradiation due to the excellent photothermal property of MXene, finally achieving gas/photothermal synergistic antibiofilm and efficient sterilization. The results showed that the synergistic gas/photothermal therapy for the composite scaffold not only evidently inhibited the formation of biofilms, but also effectively eradicated the eDNA of the already-formed biofilms and killed 90.4% of E. coli and 84.2% of S. aureus under near infrared light irradiation compared with single gas or photothermal therapy. In addition, the composite scaffold promoted the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Thus, the designed scaffold with excellent biofilm elimination and osteogenesis ability has great potential as an alternative treatment for implant-associated bone infections.

DLP fabrication of HA scaffold with customized porous structures to regulate immune microenvironment and macrophage polarization for enhancing bone regeneration.

The immune microenvironment plays a pivotal role in osteoanagenesis. Biomaterials can modulate osteogenic efficacy by inducing specific local immune reactions. As 3D-printing technology advances, digital light projection printing has emerged as a promising method for creating large scale, high-precision biomaterial scaffolds. By adjusting the solid content and the sintering conditions during printing, the pore size of biomaterials can be meticulously controlled. Yet, the systematic influence of pore size on the immune microenvironment remains uncharted. We fabricated 3D-printed hydroxyapatite bioceramic scaffolds with three distinct pore sizes: 400 µm, 600 µm, and 800 µm. Our study revealed that scaffolds with a pore size of 600 µm promote macrophage M2 polarization, which is achieved by upregulating interferon-beta and HIF-1α production. When these materials were implanted subcutaneously in rats and within rabbit skulls, we observed that the 600 µm scaffolds notably improved the long-term inflammatory response, fostered vascular proliferation, and augmented new bone growth. This research paves the way for innovative therapeutic strategies for treating large segmental bone defects in clinical settings.

The association between basal metabolic rate and osteoarthritis: a Mendelian randomization study.

BACKGROUND: The role of the basal metabolic rate (BMR) in osteoarthritis (OA) remains unclear, as previous retrospective studies have produced inconsistent results. Therefore, we performed a Mendelian randomization (MR) study to systematically investigate the causal relationship between the BMR and OA. METHODS: Single-nucleotide polymorphism (SNP) data related to BMR and OA were collected in a genome-wide association study. Using OA as the outcome variable and BMR as the exposure factor, SNPs with strong correlation with the BMR as the tool variable were screened. The correlation between the BMR and OA risk was evaluated using the inverse-variance weighted method, and heterogeneity and pleiotropy were evaluated using a sensitivity analysis. RESULTS: There was a potential causal relationship between the BMR and OA risk (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.008-1.020; P = 2.29e - 6). A causal relationship was also revealed between the BMR and knee OA (OR, 1.876; 95% CI, 1.677-2.098; P = 2.98e - 28) and hip OA (OR, 1.475; 95% CI, 1.290-1.686; P = 1.26e - 8). Sensitivity analysis confirmed the robustness of these results. CONCLUSION: Here, we identified a latent causal relationship between the BMR and the risk of OA. These results suggest that the risk of OA in the hip or knee joint may be reduced by controlling the BMR.

Molecular mechanism of different flower color formation of Cymbidium ensifolium.

Cymbidium ensifolium is one of the national orchids in China, which has high ornamental value with changeable flower colors. To understand the formation mechanism of different flower colors of C. ensifolium, this research conducted transcriptome and metabolome analyses on four different colored sepals of C. ensifolium. Metabolome analysis detected 204 flavonoid metabolites, including 17 polyphenols, 27 anthocyanins, 75 flavones, 34 flavonols, 25 flavonoids, 18 flavanones, and 8 isoflavones. Among them, purple-red and red sepals contain a lot of anthocyanins, including cyanidin, pelargonin, and paeoniflorin, while yellow-green and white sepals have less anthocyanins detected, and their metabolites are mainly flavonols, flavanones and flavonoids. Transcriptome sequencing analysis showed that the expression levels of the anthocyanin biosynthetic enzyme genes in red and purple-red sepals were significantly higher than those in white and yellow-green sepals of C. ensifolium. The experimental results showed that CeF3'H2, CeDFR, CeANS, CeF3H and CeUFGT1 may be the key genes involved in anthocyanin production in C. ensifolium sepals, and CeMYB104 has been proved to play an important role in the flower color formation of C. ensifolium. The results of transformation showed that the CeMYB104 is involved in the synthesis of anthocyanins and can form a purple-red color in the white perianth of Phalaenopsis. These findings provide a theoretical reference to understand the formation mechanism of flower color in C. ensifolium.

Modified posterior osteotomy for osteoporotic vertebral collapse with neurological dysfunction in thoracolumbar spine: a preliminary study.

OBJECTIVE: The risk of osteoporotic vertebral collapse (OVC) associated with delayed neurological dysfunction (DND) is substantial, and performing surgery for this condition in elderly patients presents challenges. The focus of the current research is on simplifying surgical procedures while maintaining their effectiveness. This study was designed to contribute clinical data supporting the use of modified posterior osteotomy for treating thoracolumbar OVC with DND. The study compares perioperative clinical parameters, imaging data characteristics, and changes in efficacy outcome indicators to provide evidence for the advancement of this technique. METHODS: A total of 12 patients diagnosed with osteoporotic vertebral collapse and neurological dysfunction were included in the study. All patients underwent modified posterior osteotomy. Data regarding perioperative and radiological parameters as well as complications such as surgery duration, blood loss, ASIA grade, VAS, ODI, regional kyphosis angle (RKA), anterior vertebral height ratio (AVHr), and spinal canal clearance ratio (SCCr), were collected retrospectively. These parameters were then analysed to evaluate the clinical efficacy and safety of the modified posterior osteotomy technique. RESULTS: A total of 12 patients were included in the study, with a mean age of 65.5 ± 9.7 years. The average follow-up period was 29.4 ± 5.0 months. The mean operative blood loss was 483.3 ± 142.0 ml, and the average operative time was 3.7 ± 0.7 h. The visual analogue scale (VAS) score decreased from a preoperative value of 5.8 ± 0.7 to a final follow-up value of 1.3 ± 0.8 (P < 0.05), indicating a significant improvement in pain. The ODI decreased from 65.2 ± 6.0 before surgery to 20.5 ± 7.0, indicating a decrease in disability, and the postoperative neurological function showed a significant improvement. Correction of the RKA was observed, with the angle changing from 35.8 ± 10.8° before surgery to 20.0 ± 3.5° after surgery and to 22.5 ± 3.1° at the final follow-up. Similarly, correction of the AVHr was observed, with the height changing from 39.3 ± 18.0 to 63.0 ± 14.3 after surgery and to 53.9 ± 8.9 at the final follow-up. Correction of the SCCr was also observed, with the ratio changing from 54.9 ± 5.4 to 68.1 ± 5.3 after surgery and to 68.68 ± 6.76 at the final follow-up. CONCLUSIONS: Posterior modified osteotomy is an effective treatment for thoracolumbar osteoporotic fractures with OVC combined with DND. It can significantly preserve vertebral height, increase vertebral canal volume, correct kyphotic angle, and improve postoperative neurological function. The simplified osteotomy also offers advantages in terms of operating time, blood loss, postoperative VAS score, and improvement in lumbar function.

Hollow Hydroxyapatite Microspheres Loaded with rhCXCL13 to Recruit BMSC for Osteogenesis and Synergetic Angiogenesis to Promote Bone Regeneration in Bone Defects.

Introduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing. Methods: Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model. Results: SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery. Conclusion: The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.

Study on the influence of scaffold morphology and structure on osteogenic performance.

The number of patients with bone defects caused by various bone diseases is increasing yearly in the aging population, and people are paying increasing attention to bone tissue engineering research. Currently, the application of bone tissue engineering mainly focuses on promoting fracture healing by carrying cytokines. However, cytokines implanted into the body easily cause an immune response, and the cost is high; therefore, the clinical treatment effect is not outstanding. In recent years, some scholars have proposed the concept of tissue-induced biomaterials that can induce bone regeneration through a scaffold structure without adding cytokines. By optimizing the scaffold structure, the performance of tissue-engineered bone scaffolds is improved and the osteogenesis effect is promoted, which provides ideas for the design and improvement of tissue-engineered bones in the future. In this study, the current understanding of the bone tissue structure is summarized through the discussion of current bone tissue engineering, and the current research on micro-nano bionic structure scaffolds and their osteogenesis mechanism is analyzed and discussed.

Effect of basal metabolic rate on osteoporosis: A Mendelian randomization study.

Purpose: Basal metabolic rate may play a key role in the pathogenesis and progression of osteoporosis. We performed Mendelian random analysis to evaluate the causal relationship between basal metabolic rate and osteoporosis. Methods: Instrumental variables for the basal metabolic rate were selected. We used the inverse variance weighting approach as the main Mendelian random analysis method to estimate causal effects based on the summary-level data for osteoporosis from genome-wide association studies. Results: A potential causal association was observed between basal metabolic rate and risks of osteoporosis (odds ratio = 0.9923, 95% confidence interval: 0.9898-0.9949; P = 4.005e - 09). The secondary MR also revealed that BMR was causally associated with osteoporosis (odds ratio = 0.9939, 95% confidence interval: 0.9911-0.9966; P = 1.038e - 05). The accuracy and robustness of the findings were confirmed using sensitivity tests. Conclusion: Basal metabolic rate may play a causal role in the development of osteoporosis, although the underlying mechanisms require further investigation.

A dataset of dynamical social map in ancient China: 618-1644.

The data set of this article is related to the paper "Dynamical structure of social map in ancient China" (2022)[1]. This article demonstrates the data of social relations between cities in ancient China, ranging from 618 AD to 1644 AD. The raw data of social associations between elites used to build social maps are extracted from the China Biographical Database. The raw data contain 14,610 elites and 29,673 social associations, which cover 366 cities. The dataset of this article is relevant both for social and natural scientists interested in the social and economic history of ancient China. The data can be used for further insights/analyses on the evolutionary pattern of geo-social architecture, and the geo-history from the viewpoint of social network.

Preparation and Experimental Investigations of Low-Shrinkage Commercial Concrete for Tunnel Annular Secondary Lining Engineering.

Secondary lining concrete is frequently used in underground tunnels. Due to the internal restriction of the annular concrete segment, micro-cracks may be caused by temperature stress and volume deformation, thus affecting the safe transportation of the tunnel. The purpose of this study is to provide a concrete experimental basis with low hydration heat and low shrinkage for tunnel engineering with different construction requirements. Different amounts of expansion agent (EA), shrinkage-reducing agent (SRA), and superabsorbent polymer (SAP) were considered in commercial concrete. It was found that EA elevated the degree of hydration and the hydration exothermic rate, while SRA and SAP showed the opposite regularity. SRA has the optimum shrinkage reduction performance with a 79% reduction in shrinkage, but the strength decreases significantly compared to EA and SAP groups. The effect of the combination of different shrinkage reducing components in commercial concrete is instructive for the hydration rate and shrinkage compensation in secondary lining engineering.

Surgical timing for primary encapsulating peritoneal sclerosis: A case report and review of literature.

BACKGROUND: Primary encapsulating peritoneal sclerosis (EPS) is a rare but devastating disease that causes fibrocollagenous cocoon-like encapsulation of the bowel, resulting in bowel obstruction. The pathogenesis, prevention, and treatment strategies of EPS remain unclear so far. Since most patients are diagnosed during exploratory laparotomy, for the non-surgically diagnosed patients with primary EPS, the surgical timing is also uncertain. CASE SUMMARY: A 44-year-old female patient was referred to our center on September 6, 2021, with complaints of abdominal distention and bilious vomiting for 2 d. Physical examination revealed that the vital signs were stable, and the abdomen was slightly distended. Computerized tomography scan showed a conglomerate of multiple intestinal loops encapsulated in a thick sac-like membrane, which was surrounded by abdominal ascites. The patient was diagnosed with idiopathic EPS. Recovery was observed after abdominal paracentesis, and the patient was discharged on September 13 after the resumption of a normal diet. This case raised a question: When should an exploratory laparotomy be performed on patients who are non-surgically diagnosed with EPS. As a result, we conducted a review of the literature on the clinical manifestations, intraoperative findings, surgical methods, and therapeutic effects of EPS. CONCLUSION: Recurrent intestinal obstructions and abdominal mass combined with the imaging of encapsulated bowel are helpful in diagnosing idiopathic EPS. Small intestinal resection should be avoided.

Empirical study and model simulation of global stock market dynamics during COVID-19.

At the beginning of 2020, COVID-19 swept the world and changed various aspects of human society, such as economy and finance, life and health, migration and population. We first empirically study how the dynamic behaviors of stock markets are affected by COVID-19, and focus on the large volatility dynamics, variation-fluctuation correlation function and epidemic-fluctuation correlation function. Then we generalize the Heston model to simulate the global stock market dynamics, and an epidemic index computed from empirical data is directly taken as the external force in the modelling.

A combination of deep eutectic solvent and ethanol pretreatment for synergistic delignification and enhanced enzymatic hydrolysis for biorefinary process.

A novel pretreatment system containing deep eutectic solvents and ethanol (DES-E) for synergistic carbohydrate conversion and delignification was reported in this study. The DES-E pretreatment resulted in an enhanced glucose yield compared to individual DES and ethanol pretreatment for the three tested biomass, including Broussonetia papyrifera, corn stover and pine. To further explore the delignification mechanism, the solubilized lignin and residual lignin from Broussonetia papyrifera was recovered and extracted, then thoroughly characterized. The highest total OH content was found in the DES-E solubilized lignin, which could be used as antioxidant. The presence of ethanol in pretreatment liquor could protect the ß-O-4 substructure from breakage and reduce lignin condensation, which favors the subsequent enzymatic hydrolysis. Comparable glucose yield and delignification performance was achieved by recycled DES. DES-E pretreatment offers a promising method for lignin isolation and cellulose digestibility improvement simultaneously.

Single-cell transcriptomics reveals a low CD8+ T cell infiltrating state mediated by fibroblasts in recurrent renal cell carcinoma.

PURPOSE: Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments. RESULTS: reRCC had reduced CD8+ T cells but increased cancer-associated fibroblasts (CAFs) infiltration compared with pRCC. Reduced CD8+ T cells and increased CAFs infiltration were significantly associated with a worse response from immunotherapy. Remarkably, CAFs showed substantial expression of LGALS1 (Gal1). In vitro, CAFs could induce CD8+ T cells apoptosis via Gal1. In vivo, knockdown of Gal1 in CAFs suppressed tumor growth, increased CD8+ T cells infiltration, reduced the proportion of apoptotic CD8+ T cells and enhanced the efficacy of immunotherapy. CONCLUSIONS: We delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8+ T cells via Gal1. Targeting Gal1 combined with anti-PD1 showed promising efficacy in treating RCC.

Ureteral stents cannot decrease the incidence of ureteroileal anastomotic stricture and leakage: A systematic review and meta-analysis.

BACKGROUND: The ileal conduit and ileal orthotopic neobladder were the most popular methods for urinary diversion following radical cystectomy. Stenting the anastomosis of ileo-ureter or ureter-neobladder was a common practice. However, it is still controversial if ureteral stents could prevent complications such as ureteroileal anastomosis stricture (UIAS) and ureteroileal anastomosis leakage (UIAL) after ureteral anastomosis. OBJECTIVES: This study aims to investigate the role of the ureteral stent in preventing UIAS and UIAL. DATA SOURCES: We systematically searched the related studies in PubMed, Embase, and Cochrane Library up to June 2020. STUDY ELIGIBILITY CRITERIA: Cohort studies that identified the use of stent and the incidence of UIAS or UIAL were recorded. DATA SYNTHESIS: Comparative meta-analysis was conducted on four cohort studies for comparison of UIAS and UIAL between the stented and nonstented groups. Besides, eleven studies which reported the events of UIAS and UIAL were used for meta-analysis of single proportion. RESULTS: A total of 11 studies were qualified for analysis. Comparative meta-analysis identified that the incidence of UIAS was higher in the stented group than that in the nonstented group, but this did not reach a significant difference (odds ratio [OR]: 1.64; 95% confidence interval [CI]: 0.88-3.05; P = 0.12). Besides, there was no difference in the incidences of UIAL between the stented and the nonstented groups. On meta-analysis of single proportion, the incidence of UIAS was 7% (95% CI: 3%-10%) in the stented group and 3% (95% CI: 1%-6%) in the nonstented group. The UIAL rate was 1% (95% CI, 0%-4%) in stented patients and 2% (95% CI, 1%-4%) in nonstented patients. CONCLUSION: Stenting the ureteroileal anastomosis resulted in a higher incidence of UIAS. There is no evidence to support ureteral stents could prevent the occurrence of UIAL after urinary diversion.

Prognostic significance of tumor-infiltrating immune cells in muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a lethal disease with poor treatment response and a high death rate. Immune cells infiltrating the tumor tissues have been shown to play a vital role in tumorigenesis and tumor progression, but their prognostic significance in MIBC remains unclear. OBJECTIVES: To explore the landscape and prognostic significance of tumor-infiltrating immune cells (TIICs) in MIBC, and to develop a model to improve the prognostic predictions of MIBC. METHODS AND MATERIALS: The gene expression profile and clinical data of MIBC patients were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas portal. The fractions of 22 TIIC subtypes were calculated using the Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. A TIICs-based model was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in a training cohort and validated in the validation cohort. RESULTS: Ten types of TIICs demonstrated different infiltration abundance between MIBC and normal tissue. We also found 11 types of TIICs that were significantly associated with overall survival (OS). A TIICs-based model was established, consisting of 15 types of immune cells, and an immunoscore was calculated. Significant differences in OS were found between the high and low immunoscore groups, in both training (n = 343) and validation (n = 146) cohorts. The model could identify patients who would have worse OS despite having similar clinical characteristics. Furthermore, multivariate analysis identified the immunoscore as an independent risk factor (hazard ratio, 3.23; 95% confidence interval; 2.22-4.70) for OS in MIBC patients. CONCLUSION: The landscape of immune infiltration is different between MIBC and normal tissue. The TIICs-based model could provide promising predictive value to complement the existing staging system for predicting the OS of MIBC patients.