Reoperation for ipsilateral local recurrence following prior nephron-sparing surgery: innovative surgical insights from a high-volume urological center with cross-sectional study.

BACKGROUND: The main aim of this study was to examine the perioperative results of reoperations and suggest novel surgical approaches. Based on a substantial number of robotic and laparoscopic nephron-sparing surgery (NSS), we aim to propose novel surgical strategies that offer practical recommendations to surgeons. METHODS: Renal cell carcinoma patients with ipsilateral recurrent tumors, without evidence of metastasis, and who underwent primary NSS at our center between 2013 and 2023 were enrolled in this study, and all received the second time surgery. We conducted an analysis to evaluate perioperative outcomes and observed trends over a decade. Additionally, based on the findings from this study, we developed our surgical strategies. RESULTS: In the past decade, our center has successfully conducted a total of 2546 surgeries for renal cell carcinoma, out of which this study includes 15 patients who met the specified criteria. For reoperation, robotic-assisted surgery was applied in 5 cases (33.3%), laparoscopic surgery in 6 cases (40%), and open surgeries in 4 cases (26.7%). While 4 (26.7%) patients underwent NSS while radical nephrectomy was performed on 11 patients (73.3%). The median operative time was 215 minutes (IQR: 135-300), and the median estimated blood loss was 50 ml (IQR: 50-100). The median length of postoperative hospitalization was 6 days (IQR: 5-9). Furthermore, there has been a yearly increase in the application of robotic-assisted NSS at our institution. CONCLUSION: Reoperation following the pNSS is a secure and effective surgical approach. We introduce novel surgical strategies for primary surgery and reoperation, which offer valuable insights to surgeons in current study.

Nutrition-Related Knowledge Graph Neural Network for Food Recommendation.

Food recommendation systems are becoming increasingly vital in modern society, given the fast-paced lifestyle and diverse dietary habits. Existing research and implemented solutions often rely on user preferences and past behaviors for recommendations, which poses significant issues. Firstly, this approach inadequately considers the nutritional content of foods, potentially leading to recommendations that are overly homogeneous and lacking in diversity. Secondly, it may result in repetitive suggestions of the same types of foods, thereby encouraging users to develop unhealthy dietary habits that could adversely affect their overall health. To address this issue, we introduce a novel nutrition-related knowledge graph (NRKG) method based on graph convolutional networks (GCNs). This method not only enhances users' ability to select appropriate foods but also encourages the development of healthy eating habits, thereby contributing to overall public health. The NRKG method comprises two key components: user nutrition-related food preferences and recipe nutrition components. The first component gathers nutritional information from recipes that users show interest in and synthesizes these data for user reference. The second component connects recipes with similar nutritional profiles, forming a complex heterogeneous graph structure. By learning from this graph, the NRKG method integrates user preferences with nutritional data, resulting in more accurate and personalized food recommendations. We evaluated the NRKG method against six baseline methods using real-world food datasets. In the 100% dataset, the five metrics exceeded the performance of the best baseline method by 2.8%, 5.9%, 1.5%, 9.7%, and 6.0%, respectively. The results indicate that our NRKG method significantly outperforms the baseline methods, including FeaStNet, DeepGCN, GraphSAGE, GAT, UniMP, and GATv2, demonstrating its superiority and effectiveness in promoting healthier and more diverse eating habits. Unlike these baseline methods, which primarily focus on hierarchical information propagation, our NRKG method offers a more comprehensive approach by integrating the nutritional information of recipes with user preferences.

P2X7R Modulates NEK7-NLRP3 Interaction to Exacerbate Experimental Autoimmune Prostatitis via GSDMD-mediated Prostate Epithelial Cell Pyroptosis.

Chronic prostatitis is one of the most common urologic diseases that troubles young men, with unclear etiology and ineffective treatment approach. Pyroptosis is a novel model of cell death, and its roles in chronic prostatitis are unknown. In this study, P2X7R, NEK7, and GSDMD-NT expression levels were detected in prostate tissues from benign prostate hyperplasia (BPH) patients and experiment autoimmune prostatitis (EAP) mice. P2X7R agonist, antagonist, NLRP3 inhibitor, and disulfiram were used to explore the roles of the P2X7R-NEK7-NLRP3 axis in prostate epithelial cell pyroptosis and chronic prostatitis development. We found that P2X7R, NEK7, and GSDMD-NT were highly expressed in the prostate epithelial cells of BPH patients with prostatic inflammation and EAP mice. Activation of P2X7R exacerbated prostatic inflammation and increased NLRP3 inflammasome component expressions and T helper 17 (Th17) cell proportion. Moreover, P2X7R-mediated potassium efflux promoted NEK7-NLRP3 interaction, and NLRP3 assembly and activation, which caused GSDMD-NT-mediated prostate epithelial cell pyroptosis to exacerbate EAP development. Disulfiram could effectively improve EAP by inhibiting GSDMD-NT-mediated prostate epithelial cell pyroptosis. In conclusion, the P2X7R-NEK7-NLRP3 axis could promote GSDMD-NT-mediated prostate epithelial cell pyroptosis and chronic prostatitis development, and disulfiram may be an effective drug to treat chronic prostatitis.

Integrated analysis of histone modification features in clear cell renal cancer for risk stratification and therapeutic prediction.

Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy that is involved in tumor genesis and development. However, few studies have focused on the predictive role of the global histone modification status in ccRCC. A total of 621 patients with complete transcript information and corresponding clinical profiles were obtained from TCGA-KIRC, GSE22541, and EMTAB3267 cohorts. A total of 122 histone modification relevant pathways were derived from MSigDB, and their activation status was quantified using GSVA. Differentially expressed genes (DEGs) were identified and filtrated using univariate Cox regression analysis. The signature was built relied on the least absolute shrinkage and selection operator (LASSO) regression analysis, and evaluated from survival difference, chemotherapy response, and activated pathways. A novel nomogram was established to quantify the probability of death in different patients. Seven risky and fifty-eight protective genes were used in LASSO analysis, and six genes were used to build the histone modification gene (HiMG) signature, which showed significant independent prognostic potential in all three cohorts. The nomogram showed acceptable incremental predictions. CKS2 (p = 0.004) and PD1 (p = 0.002) expression were significantly higher in grade 3 ccRCC than in grades 1-2. CKS2 siRNA in renal cancer cells caused reductions in cellular proliferation, migration, and invasion. Patients with low HiMG may be potential responders to rapamycin, erlotinib and FH535, while AZD6482 and CHIR-99,021 may be more suitable for patients with high HiMG levels. ccRCC histone modification distribution and a clinical signature for prognosis prediction, clinical decision making, and molecular mechanism exploration, were established for risk stratification and personalized treatments.

Modifying carbon dots with L-phenylalanine for rapid discrimination of tryptophan enantiomers.

New chiral carbon dots (CDs), L-PCDs, for discriminating tryptophan (Trp) enantiomers were prepared in this work. Firstly, original CDs were synthesized through a hydrothermal method using pyridine-2,6-dicarboxylic acid and o-phenylenediamine as raw materials. Then, the surface of original CDs was modified with L-phenylalanine to create chiral fluorescent carbon L-PCDs. In the presence of D-Trp, the fluorescence intensity of L-PCDs decreased significantly while it remained unchanged in the presence of L-Trp. The chiral sensing system used in this study has a rapid response time of 3 minutes and can identify enantiomers with an enantioselectivity (ID/IL) of up to 3.3. For D-Trp, a good linear relationship can be obtained in the range of 0.3-4.2 mM with a limit of detection of 0.06 mM. This sensor allows for both quantitative detection of D-Trp and determination of enantiomeric percentage in the racemate. The chiral recognition mechanism is attributed to the different interaction between D-/L-Trp and L-PCDs.

Smart Biosensor for Breast Cancer Survival Prediction Based on Multi-View Multi-Way Graph Learning.

Biosensors play a crucial role in detecting cancer signals by orchestrating a series of intricate biological and physical transduction processes. Among various cancers, breast cancer stands out due to its genetic underpinnings, which trigger uncontrolled cell proliferation, predominantly impacting women, and resulting in significant mortality rates. The utilization of biosensors in predicting survival time becomes paramount in formulating an optimal treatment strategy. However, conventional biosensors employing traditional machine learning methods encounter challenges in preprocessing features for the learning task. Despite the potential of deep learning techniques to automatically extract useful features, they often struggle to effectively leverage the intricate relationships between features and instances. To address this challenge, our study proposes a novel smart biosensor architecture that integrates a multi-view multi-way graph learning (MVMWGL) approach for predicting breast cancer survival time. This innovative approach enables the assimilation of insights from gene interactions and biosensor similarities. By leveraging real-world data, we conducted comprehensive evaluations, and our experimental results unequivocally demonstrate the superiority of the MVMWGL approach over existing methods.

The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis.

Objective: Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors. Methods: We performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303). Results: A total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism. Conclusion: Risk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians. Systematic review registration: crd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).

Incidence, clinical features, and risk factors of hemocoagulase-induced hypofibrinogenemia: A retrospective real-world study.

The objective of this study was to explore the real-world incidence, severity, clinical features, and potential risk factors associated with hypofibrinogenemia induced by hemocoagulase. Based on Chinese Hospital Pharmacovigilance System, a retrospective case-control study was conducted, enrolling hospitalized patients who received hemocoagulase for the treatment or prevention of hemorrhage in Weifang People's Hospital in China from January 2021 to May 2022. Univariate and multivariate logistic regression was performed to analyze the potential risk factors. Out of 10,397 hospitalized patients who received hemocoagulase, 341 patients showed positive triggers, with 235 patients ultimately conformed as hemocoagulase-associated hypofibrinogenemia. The system positive alarm rate was 68.91%, and the overall incidence of hemocoagulase-induced hypofibrinogenemia was 2.26%, predominantly characterized by mild to moderate severity levels. The incidence varied among the 4 types of hemocoagulase, with the highest incidence observed in hemocoagulase Agkistrodon Halys Pallas at 4.59%. The incidence of hemocoagulase from Deinagkistrodon acutus, Bothrops Atrox and Adder were 0.97%, 0.44% and 0.12%, respectively. Multivariate logistic regression analysis revealed that age (odds ratios [OR] = 177.328, P < .001), source of snake venom (OR = 5.641, P < .05), albumin (OR = 2.487, P < .001), and cumulative dosage (OR = 1.106, P < .001) were independent risk factors. Increased risk of hemocoagulase-related hypofibrinogenemia may be associated with children, elderly patients, low albumin levels, high cumulative doses and hemocoagulase from Agkistrodon Halys Pallas. Early recognition and close drug monitoring for these high-risk patients are vital in clinical practice.

Effect of various different pretreatment methods on infrared combined hot air impingement drying behavior and physicochemical properties of strawberry slices.

In current work, the effect of freezing (F), ultrasound (U), and freeze- ultrasound (FU) pretreatment on infrared combined with hot air impingement drying kinetics, cell ultrastructure, enzyme activity, and physicochemical properties of strawberry slices were explored. Results showed that FU pretreatment enhanced cell membrane permeability via forming micropores, altered water status by transforming bound water into free water and thus promoted moisture diffusivity and decreased drying time by 50% compared to the control group. FU pretreatment also extensively decreased pectin methylesterase enzyme activity and maintained quality. The contents of total phenols, anthocyanins, vitamin C, antioxidant activity, and a* value of dried strawberries pretreated by FU were extensively increased compared to the control group. U and FU pretreatments were beneficial for retaining aromatic components and organic sulfides according to e-nose analyses. The findings indicate that FU is a promising pretreatment technique as it enhances drying process and quality of strawberry slices.

Dual deficiency of melatonin and dihydrotestosterone promotes stromal cell damage and mediates prostatitis via the cGAS-STING pathway in sleep-deprived mice.

PURPOSE: Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target. METHODS: Sleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated. RESULTS: SD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-ß. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse. CONCLUSIONS: The cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.

Time-Aware Dual LSTM Neural Network with Similarity Graph Learning for Remote Sensing Service Recommendation.

Technological progress has led to significant advancements in Earth observation and satellite systems. However, some services associated with remote sensing face issues related to timeliness and relevance, which affect the application of remote sensing resources in various fields and disciplines. The challenge now is to help end-users make precise decisions and recommendations for relevant resources that meet the demands of their specific domains from the vast array of remote sensing resources available. In this study, we propose a remote sensing resource service recommendation model that incorporates a time-aware dual LSTM neural network with similarity graph learning. We further use the stream push technology to enhance the model. We first construct interaction history behavior sequences based on users' resource search history. Then, we establish a category similarity relationship graph structure based on the cosine similarity matrix between remote sensing resource categories. Next, we use LSTM to represent historical sequences and Graph Convolutional Networks (GCN) to represent graph structures. We construct similarity relationship sequences by combining historical sequences to explore exact similarity relationships using LSTM. We embed user IDs to model users' unique characteristics. By implementing three modeling approaches, we can achieve precise recommendations for remote sensing services. Finally, we conduct experiments to evaluate our methods using three datasets, and the experimental results show that our method outperforms the state-of-the-art algorithms.

The CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in experimental autoimmune prostatitis through the PI3K/AKT pathway.

OBJECTIVE: To investigate the mechanism of the CXCL10/CXCR3 axis regulating Th1 cell differentiation and migration through the PI3K/AKT pathway in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Experimental autoimmune prostatitis (EAP) model, a well-described and validated animal model of CP/CPPS, was used in our study. After treatment with CXCL10, the severity of EAP and Th1 cell proportion were respectively measured by HE stains, immunohistochemistry, and flow cytometry. Then, the protein expression of the PI3K/AKT pathway in CXCL10/CXCR3-regulated Th1 cell differentiation and migration was evaluated by western blotting. Additionally, by the CXCR3 antagonist AMG487 and the PI3K inhibitor LY294002 applications, the effects of CXCL10/CXCR3 through PI3K/AKT pathway on the Th1 cell differentiation and migration were further assessed. RESULTS: The EAP model was successfully built. CXCL10 increased the proportion of Th1 cells in EAP mice, accompanied by upregulation of the PI3K/AKT pathway. Additionally, the PI3K/AKT pathway was found to be involved in CXCL10/CXCR3 axis-mediated Th1 cell differentiation and migration. CONCLUSIONS: Our investigations indicate that the CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in EAP through the PI3K/AKT pathway, which provides a new perspective on the immunological mechanisms of CP/CPPS.

GSDMD inhibitor protects chondrocyte from mechanical injury in human articular cartilage.

Traumatic arthritis is caused by mechanical injury and results in the degeneration of articular cartilage, but it is unclear whether it is related to the pyroptosis of chondrocyte (CHs). Thus, this study was designed to investigate the role of GSDMD, the executor of pyroptosis, in the human cartilage during mechanical injury. We collected the human hip joint and used a loading apparatus to produce compression on the cartilage disc. After one hour of 15 MPa or 25 MPa injury, the acute and chronic effects of the mechanical injury on the cartilage were tested. We stained the CHs in the cartilage with calcein and DAPI to calculate the live-cell rate. The chondrogenic phenotype was determined by analyzing the mRNA levels of type II collagen alpha 1 (Col2A1), type I collagen alpha 2 (Col2A1), and SOX9. Besides, the pyroptosis process was determined by the mRNA levels of caspase-1/5, GSDMD, IL-1ß, and IL-18. We also explored the preventive role and therapeutic role of GSDMD inhibitors in mechanical injury via culturing the cartilage before and after the compression, respectively. Mechanical compression injured the viability and function of CHs in cartilage partly based on the pyroptosis. The pretreatment of GSDMD inhibitor in cartilage before injury could maintain the live cells and Col2A1 expression and prevent pyroptosis after injury. Besides, supplying the cartilage with GSDMD inhibitor after injury also alleviated the cell death and dysfunction of CHs, and suppressed the pyroptosis. Using an inhibitor of GSDMD can play a preventive role and play a therapeutic role in the mechanical injury of cartilage.

The transcription factor masculinizer in sexual differentiation and achieved full functional sex reversal in prawn.

Some Zinc finger (ZnF) proteins are required for masculinization in silkworms. In the present study, a masculinizer gene (Mr-Masc) with multi-tissue expression is identified in the freshwater prawn Macrobrachium rosenbergii. The Mr-Masc is clustered into a separate branch with ZnF proteins from decapoda by phylogenetic tree analysis. Moreover, Mr-Masc silencing in male postlarvae prawn results in functional sex reversal females known as neo-females, which are applied to all-male monosex offspring breeding. This manipulation has been significant in sexually dimorphic cultured species. In addition, several significantly expressed transcripts are enriched and the effects of crucial signal pathways are focused through the comparative transcriptomic analysis in Mr-Masc gene knockdown. The significantly differentially expressed epidermal growth factor, upregulated low-density lipoprotein receptor, flotillin, and sex-lethal unigenes, downregulated heat shock proteins and forkhead box homologs are focused. The finding offers an innovative perspective on Masc proteins' evolution and physiological function.

Root exudates contribute to belowground ecosystem hotspots: A review.

Root exudates are an essential carrier for material cycling, energy exchange, and information transfer between the belowground parts of plants and the soil. We synthesize current properties and regulators of root exudates and their role in the belowground ecosystem as substances cycle and signal regulation. We discussed the composition and amount of root exudates and their production mechanism, indicating that plant species, growth stage, environmental factors, and microorganisms are primary influence factors. The specific mechanisms by which root secretions mobilize the soil nutrients were summarized. First, plants improve the nutrient status of the soil by releasing organic acids for acidification and chelation. Then, root exudates accelerated the SOC turnover due to their dual impacts, forming and destabilizing aggregates and MASOC. Eventually, root exudates mediate the plant-plant interaction and plant-microbe interaction. Additionally, a summary of the current collection methods of root exudates is presented.

Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression.

Objective: Our previous work found COX4I2 was associated with angiogenesis in pheochromocytoma. The purpose of this study was to explore the role of COX4I2 in regulating angiogenesis in pheochromocytoma. Methods: Distribution of COX4I2 was evaluated by scRNA-seq in one case of pheochromocytoma and the findings were verified by immunostaining. COX4I2 was further knocked down in target cells. Changes of angiogenesis-related genes were evaluated by qPCR in target cells. Results: The scRNA-seq revealed high mRNA expression of COX4I2 in fibroblasts rather than tumor cells. Immunostaining of COX4I2 confirmed its distribution in fibroblasts. Knocking down COX4I2 in NIH3T3 cell line led to significant reduction of angiogenesis-related genes, especially ANG1 and HGF. Conclusions: Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression, possibly by affecting ANG1 and HGF.

Identification and expression pattern of the sex determination gene fruitless-like in Cherax quadricarinatus.

The fruitless (fru) gene has an important function in the courtship behavior and sex determination pathway of Drosophila melanogaster; however, the fru gene has never been reported in shrimps. In this study, the fruitless-like gene was identified in Cherax quadricarinatus (Cqfru) and is reported here for the first time. A sequence analysis revealed a conserved BTB domain in Cqfru which is the same as fru in D. melanogaster. An analysis of the expression level of Cqfru showed that it was highly expressed in the gastrula stage during embryonic development. Furthermore, in situ hybridization and expression distribution in tissues showed that its sexually dimorphic expression may be focused on the hepatopancreas, brains, and gonads. The gonads, brains, and hepatopancreas of males had a higher expression level of Cqfru than those of females; however, the expression level of the abdominal ganglion was found to be higher in females than in males in this study. The results of an RNA interference treatment showed that a knockdown of Cqfru reduced the expression of the insulin-like androgenic gland hormone (IAG) and tumor necrosis factor (TNF). The characteristic fru gene in shrimps is reported here for the first time, with the results providing basic information for research into the sex-determination mechanism in C. quadricarinatus.

High TNFSF13B expression as a predictor of poor prognosis in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an extremely rare malignant tumor with poor prognosis. Existing treatment options have limited effects, and new therapeutic targets urgently need to be discovered. TNFSF13B has been reported to be associated with the prognosis of clear cell renal cell carcinoma, but it has not been studied in ACC. METHODS: TNFSF13B expression was analyzed and compared between ACC tumors and normal tissues by using public datasets from TCGA and GTEx. Kaplan-Meier analysis was employed to evaluate survival, and Cox regression was employed to evaluate clinicopathologic features. The upstream and downstream regulatory mechanisms of TNFSF13B were also analyzed. GSEA was performed to explore the mechanisms of TNFSF13B in ACC. Finally, 14 ACC clinical samples were used to verify the relationships between TNFSF13B expression and disease-free survival (DFS) and overall survival (OS). RESULTS: TNFSF13B expression was significantly higher in ACC tissues than in normal tissues. The prognosis of ACC patients with high TNFSF13B expression was worse than that of patients with low TNFSF13B expression. High TNFSF13B expression was strongly correlated with poor prognosis, and TNFSF13B was a prognostic factor. TNFSF13B expression is modified by upstream miRNAs, methylation and ubiquitination, and downstream, it interacts with other proteins. GSEA showed that regulation of cholesterol biosynthesis by SREBP and SREBF, downstream signaling events of the B cell receptor (BCR) and activation of gene expression by SREBF and SREBP were significantly enriched in the TNFSF13B high-expression phenotype. Clinical samples confirmed that TNFSF13B expression was significantly associated with DFS but not with OS. CONCLUSIONS: TNFSF13B may be a potential prognostic molecular marker of poor survival in ACC patients, offering a new therapeutic target.

COX4I2 is a novel biomarker of blood supply in adrenal tumors.

BACKGROUND: Previous study has been reported that COX4I2 expression level demonstrated a positive correlation with microvessel density in pheochromocytomas (PCC) samples, suggesting that the expression of COX4I2 maybe related to blood supply level in other adrenal tumors as well. The aim of this study is to clarify the correlation of COX4I2 expression and blood supply in adrenal tumors. METHODS: A total of 84 patients were recruited, among which 46 was diagnosed as adrenocortical adenoma (ACA) and 38 was diagnosed as PCC. Contrast-enhanced CT values were used to evaluate the blood supply levels in those patients. The expression of mRNA was examined by quantitative real-time polymerase chain reaction (qPCR) and protein was detected by immunohistochemistry (IHC). RESULTS: The COX4I2 expression level in PCC group is significantly higher than that in ACA group (P<0.01). The expression of angiogenesis-related genes EPAS1, VEGFA and KDR mRNA in PCC group is higher than that of ACA group (P<0.05). Correlation analysis shows COX4I2 expression level is correlated with CT values (P<0.001), intraoperative blood loss (P<0.05) and operation time (P<0.05), and the expression of COX4I2 mRNA is correlated with EPAS1, VEGFA and KDR mRNA (P<0.01). CONCLUSIONS: The results displayed a distinct expression level of COX4I2 between ACA and PCC, suggesting that COX4I2 is a novel biomarker of blood supply in adrenal tumors. This research also opens the possibility for further research on COX4I2 as a novel target for anti-tumor angiogenesis.