Mental health status and coping strategies of Chinese university students during the COVID-19 pandemic: A rapid review.

Since the coronavirus (COVID-19) outbreak in December 2019, students have been under unparalleled psychological stress worldwide. As part of its prevention and control strategies, the Chinese Ministry of Education proposed online teaching activities for universities. For the first time, teaching and learning shifted completely online, significantly impacting university students used to classroom learning. This research addresses the knowledge gap about the mental health and coping strategies employed by Chinese university students during the COVID-19 pandemic. Electronic databases (PsycINFO, Scopus, Medline, Cochranes and CNKI) were searched systematically from 2019 to 2023, as part of this literature review. From the 349 articles found, 25 met the inclusion criteria for analysis. Thematic analysis was used to identify six sub-themes, organized under two main themes: Mental health issues of Chinese university students and their coping mechanisms. Heightened stress, anxiety, and depression appeared in Chinese university students during the pandemic, which may have been compounded by their isolation and the disruptions to their studies. Although the impact of COVID-19 on Chinese university students is waning, this study emphasizes the potential long-lasting impact on their mental health, which requires further investigation, particularly regarding gender differences. Moreover, positive and negative coping strategies were found in this review. Strategies for seeking social and family support and participating in sports activities had significant alleviating effects, while negative coping strategies such as alcohol-use and smoking did not. This rapid review informs the development of policies and interventions to enhance the mental health of university students during crisis events. The findings serve to inform health policymakers, university psychologists, and educators in improving the well-being of this student population.

Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a devastating condition common in patients with Alzheimer's disease but also observed in the general population. Vascular oxidative stress and neurovascular dysfunction have been implicated in CAA but the cellular source of reactive oxygen species (ROS) and related signaling mechanisms remain unclear. We tested the hypothesis that brain border-associated macrophages (BAM), yolk sac-derived myeloid cells closely apposed to parenchymal and leptomeningeal blood vessels, are the source of radicals through the Aß-binding innate immunity receptor CD36, leading to neurovascular dysfunction, CAA, and cognitive impairment. METHODS: Tg2576 mice and WT littermates were transplanted with CD36-/- or CD36+/+ bone marrow at 12-month of age and tested at 15 months. This approach enables the repopulation of perivascular and leptomeningeal compartments with CD36-/- BAM. Neurovascular function was tested in anesthetized mice equipped with a cranial window in which cerebral blood flow was monitored by laser-Doppler flowmetry. Amyloid pathology and cognitive function were also examined. RESULTS: The increase in blood flow evoked by whisker stimulation (functional hyperemia) or by endothelial and smooth muscle vasoactivity was markedly attenuated in WT → Tg2576 chimeras but was fully restored in CD36-/- → Tg2576 chimeras, in which BAM ROS production was suppressed. CAA-associated Aß1-40, but not Aß1-42, was reduced in CD36-/- → Tg2576 chimeras. Similarly, CAA, but not parenchymal plaques, was reduced in CD36-/- → Tg2576 chimeras. These beneficial vascular effects were associated with cognitive improvement. Finally, CD36-/- mice were able to more efficiently clear exogenous Aß1-40 injected into the neocortex or the striatum. CONCLUSIONS: CD36 deletion in BAM suppresses ROS production and rescues the neurovascular dysfunction and damage induced by Aß. CD36 deletion in BAM also reduced brain Aß1-40 and ameliorated CAA without affecting parenchyma plaques. Lack of CD36 enhanced the vascular clearance of exogenous Aß. Restoration of neurovascular function and attenuation of CAA resulted in a near complete rescue of cognitive function. Collectively, these data implicate brain BAM in the pathogenesis of CAA and raise the possibility that targeting BAM CD36 is beneficial in CAA and other conditions associated with vascular Aß deposition and damage.

The predictive values of monocyte-lymphocyte ratio in postoperative acute kidney injury and prognosis of patients with Stanford type A aortic dissection.

Objectives: Postoperative acute kidney injury (pAKI) is a serious complication of Stanford type A aortic dissection (TAAD) surgery, which is significantly associated with the inflammatory response. This study aimed to explore the relationship between blood count-derived inflammatory markers (BCDIMs) and pAKI and to construct a predictive model for pAKI. Methods: Patients who underwent TAAD surgery were obtained from our center and the Medical Information Mart for Intensive Care (MIMIC)-IV database. The differences in preoperative BCDIMs and clinical outcomes of patients with and without pAKI were analyzed. Logistic regression was used to construct predictive models based on preoperative BCDIMs or white cell counts (WCCs). The performance of the BCDIMs and WCCs models was evaluated and compared using the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), Hosmer-Lemeshow test, calibration plot, net reclassification index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA). The Kaplan-Meier curves were applied to compare the survival rate between different groups. Results: The overall incidence of pAKI in patients who underwent TAAD surgery from our center was 48.63% (124/255). The presence of pAKI was associated with longer ventilation time, higher incidence of cerebral complications and postoperative hepatic dysfunction, and higher in-hospital mortality. The results of the logistic regression indicated that the monocyte-lymphocyte ratio (MLR) was an independent risk factor for pAKI. The BCDIMs model had good discriminating ability, predictive ability, and clinical utility. In addition, the performance of the BCDIMs model was significantly better than that of the WCCs model. Analysis of data from the MIMIC-IV database validated that MLR was an independent risk factor for pAKI and had predictive value for pAKI. Finally, data from the MIMIC-IV database demonstrated that patients with a high MLR had a significantly poor 28-day survival rate when compared to patients with a low MLR. Conclusion: Our study suggested that the MLR is an independent risk factor for pAKI. A predictive model based on BCDIMs had good discriminating ability, predictive ability, and clinical utility. Moreover, the performance of the BCDIMs model was significantly better than that of the WCCs model. Finally, a high MLR was significantly associated with poor short-term survival of patients who underwent TAAD surgery.

BMSC cells alleviate liver injury induced by ulcerative colitis via repairing the intestinal-liver barrier and activating hepatocyte growth factor.

Ulcerative colitis (UC), which belongs to inflammatory bowel diseases (IBD), frequently induces liver inflammation and injury. Previous studies have proved that bone marrow-derived mesenchymal stem cells (BMSCs) can suppress inflammation and improve intestinal mucosal injury in colitis, however, the effects of BMSCs on colitis-induced liver injury and the underlying molecular mechanisms remain unclear. Here, we investigated the effects and mechanisms of BMSCs in acute ulcerative colitis BALB/c mice, which were induced by 4 % dextran sodium sulphate (DSS). In this study, BMSCs derived from BALB/c mice were administrated by single intravenous injection with a dose of 5*10^7 cells/kg. And then, the effects and underlying molecular mechanisms were investigated. Firstly, the degree of liver injury in colitis mice was evaluated by hepatic ALT, AST, ALP and TBIL levels, which were measured by specific determination kits, the levels of TNF-α, IL-6, IFNγ and LPS were examined by ELISA. Secondly, as the indicator of intestinal-liver barrier disorder, tight junction proteins were analyzed by western blot. Thirdly, the pathological changes in the colon and liver were detected by H&E staining. At last, homing of BMSCs to lesion tissues was investigated by Immunofluorescence. The results indicated that histopathological changes in model mice had been greatly alleviated, BMSCs infusion remarkably decreased the serum ALT, AST, ALP and TBIL levels, and meanwhile reduced pro-inflammatory cytokines in liver tissues. Furthermore, homing of BMSCs was observed in the colon and liver, and the disorder of the intestinal-liver barrier declined significantly. In conclusion, BMSCs alleviate liver injury induced by ulcerative colitis via repairing the intestinal-liver barrier and activating hepatocyte growth factor, it has potential application prospects in the treatment of liver injury induced by ulcerative colitis.

Gold nanoclusters Cys-Au NCs as selective fluorescent probes for "on-off-on" detection of Fe3+ and ascorbic acid.

Gold nanoclusters exhibit attractive properties owing to their excellent biocompatibility and strong photostability in the biomedical domain. In this research, cysteine-protected fluorescent gold nanoclusters (Cys-Au NCs) were synthesized via decomposing Au(i)-thiolate complexes for the detection of Fe3+ and ascorbic acid in a bidirectional "on-off-on" mode. Meanwhile, the detailed characterization confirmed that the mean particle size of the prepared fluorescent probe was 2.43 nm and showed a fluorescence quantum yield of 3.31%. In addition, our results indicate that the fluorescence probe for ferric ions exhibited a broad detection scope ranging from 0.1 to 2000 µM and excellent selectivity. The as-prepared Cys-Au NCs/Fe3+ was demonstrated to be an ultrasensitive and selective nanoprobe for the detection of ascorbic acid. This study indicated that the "on-off-on" fluorescent probes Cys-Au NCs held a promising application for the bidirectional detection of Fe3+ and ascorbic acid. Furthermore, our novel "on-off-on" fluorescent probes provided insight into the rational design of thiolate-protected gold nanoclusters for biochemical analysis of high selectivity and sensitivity.

Healing Wounds Efficiently with Biomimetic Soft Matter: Injectable Self-Healing Neutral Glycol Chitosan/Dibenzaldehyde-Terminated Poly(ethylene glycol) Hydrogel with Inherent Antibacterial Properties.

The high prevalence of acquiring skin wounds, along with the emergence of antibiotic-resistant strains that lead to infections, impose a threat to the physical, mental, and socioeconomic health of society. Among the wide array of wound dressings developed, hydrogels are regarded as a biomimetic soft matter of choice owing to their ability to provide a moist environment ideal for healing. Herein, neutral glycol chitosan (GC) was cross-linked via imine bonds with varying concentrations of dibenzaldehyde-terminated polyethylene glycol (DP) to give glycol chitosan/dibenzaldehyde-terminated polyethylene glycol hydrogels (GC/DP). These dynamic Schiff base linkages (absorption peak at 1638 cm-1) within the hydrogel structure endowed their ability to recover from damage as characterized by high-low strain exposure in continuous step strain rheology. Along with their good injectability and biodegradability, the hydrogels exhibited remarkable inhibition against E. coli, P. aeruginosa, and S. aureus. GC/DP hydrogels demonstrated high LC50 values in vivo using zebrafish embryos as a model system due to their relative biocompatibility and a remarkable 93.4 ± 0.88% wound contraction at 30-dpw against 49.1 ± 3.40% of the control. To the best of our knowledge, this is the first study that developed injectable glycol chitosan/dibenzaldehyde-terminated polyethylene glycol self-healing hydrogels for application in wound healing with intrinsic bacteriostatic properties against the three bacteria.

Upregulation of KIF18B facilitates malignant phenotype of esophageal squamous cell carcinoma by activating CDCA8/mTORC1 pathway.

BACKGROUND: Kinesin family member 18B (KIF18B) has been regarded as an oncogene that is abnormally overexpressed in some cancers, but its mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear, which is thereby investigated in this study. METHODS: Bioinformatics analysis was performed to analyze the expression of KIF18B in esophageal carcinoma (ESCA). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect KIF18B expression in ESCC cells. After KIF18B overexpression or cell division cycle associated 8 (CDCA8) deficiency, ESCC cells were subjected to determination of qRT-PCR, Western blot, cell counting kit-8 assay, flow cytometry, wound healing, and Transwell assay. The mechanism of KIF18B in the mechanistic target of rapamycin complex 1 (mTORC1) pathway was detected by Western blot. RESULTS: KIF18B was overexpressed in ESCA samples and ESCC cells. Upregulation of KIF18B enhanced the viability, accelerated cell cycle by elevating CDK4 and Cyclin D3 levels as well as promoted the migration and invasion by decreasing E-cadherin level and increasing Vimentin and N-cadherin levels in ESCC cells, which was counteracted by CDCA8 silencing. The expression of CDCA8 in ESCC cells was upregulated by KIF18B overexpression. KIF18B overexpression activated the mTORC1 pathway by upregulating phosphorylated (p)-/p70S6K and p-/mTOR levels in the ESCC cells, which was reversed by CDCA8 silencing. CONCLUSION: KIF18B overexpression promotes the proliferation, migration, and invasion of ESCC cells via CDCA8-mediated mTORC1 signaling pathway in vitro.

ACSL4 Expression Is Associated With CD8+ T Cell Infiltration and Immune Response in Bladder Cancer.

OBJECTIVE: This study aimed to explore the role of ACSL4 in CD8+ T cell tumor infiltration and outcomes of bladder cancer (BLCA) patients after immunotherapy. METHODS: The correlation between ACSL4 expression and tumor infiltration of immune cells was analyzed using the Tumor Immune Estimation Resource database. The prognostic significance of ACSL4 in BLCA was analyzed using Kaplan-Meier curves. Immunohistochemistry was used to detect CD8+ T cell infiltration in tumors with high and low ACSL4 expression obtained from patients at the Fudan University Shanghai Cancer Center. The relationships between immune checkpoint genes and immune response were analyzed using The Cancer Genome Atlas and IMvigor 210 cohorts. The molecular functions, cellular components, and biological processes involving ACSL4 were explored using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathway analyses. RESULTS: The expression level of ACSL4 was significantly correlated with the infiltration of CD8+ T cells in BLCA tumors (r = 0.192, P = 2.22e-04). Elevated ACSL4 was associated with suppressed tumor progression and better outcomes for BLCA patients. The higher expression level of ACSL4 predicted better immunotherapeutic responses and was associated with higher expression levels of core immune checkpoint genes, including CD274, CTLA4, PDCD1, and LAG3, compared with the low ACSL4 expression group. CONCLUSION: This study demonstrated for the first time that elevated ACSL4 correlated significantly with CD8+ T cell infiltration and contributed to better immunotherapeutic responses in BLCA patients. Furthermore, ACSL4 serves as a novel biomarker for predicting patient outcomes after immunotherapeutic treatments, which may improve the development of individualized immunotherapy for BLCA.

AD-linked R47H-TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation.

The hemizygous R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific gene in the brain, increases risk for late-onset Alzheimer's disease (AD). Using transcriptomic analysis of single nuclei from brain tissues of patients with AD carrying the R47H mutation or the common variant (CV)­TREM2, we found that R47H-associated microglial subpopulations had enhanced inflammatory signatures reminiscent of previously identified disease-associated microglia (DAM) and hyperactivation of AKT, one of the signaling pathways downstream of TREM2. We established a tauopathy mouse model with heterozygous knock-in of the human TREM2 with the R47H mutation or CV and found that R47H induced and exacerbated TAU-mediated spatial memory deficits in female mice. Single-cell transcriptomic analysis of microglia from these mice also revealed transcriptomic changes induced by R47H that had substantial overlaps with R47H microglia in human AD brains, including robust increases in proinflammatory cytokines, activation of AKT signaling, and elevation of a subset of DAM signatures. Pharmacological AKT inhibition with MK-2206 largely reversed the enhanced inflammatory signatures in primary R47H microglia treated with TAU fibrils. In R47H heterozygous tauopathy mice, MK-2206 treatment abolished a tauopathy-dependent microglial subcluster and rescued tauopathy-induced synapse loss. By uncovering disease-enhancing mechanisms of the R47H mutation conserved in human and mouse, our study supports inhibitors of AKT signaling as a microglial modulating strategy to treat AD.

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer.

Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 "sponges" miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.

Primary tumor surgery improves survival in non-metastatic primary urethral carcinoma patients: a large population-based investigation.

BACKGROUND: Primary urethral carcinoma (PUC) is a rare genitourinary malignancy with a relatively poor prognosis. The aim of this study was to examine the impact of surgery on survival of patients diagnosed with PUC. METHODS: A total of 1544 PUC patients diagnosed between 2004 and 2016 were identified based on the SEER database. The Kaplan-Meier estimate and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). The multivariate Cox regression model and competing risks regression model were used to identify independent risk factors of OS and cancer-specific survival (CSS). RESULTS: The 5-yr OS was significantly better in patients who received either local therapy (39.8%) or radical surgery (44.7%) compared to patients receiving no surgery of the primary site (21.5%) (p < 0.001). Both local therapy and radical surgery were each independently associated with decreased CSM, with predicted 5-yr cumulative incidence of 45.4 and 43.3%, respectively, compared to 64.7% for patients receiving no surgery of the primary site (p < 0.001). Multivariate analyses demonstrated that primary site surgery was independently associated with better OS (local therapy, p = 0.037; radical surgery, p < 0.001) and decreased CSM (p = 0.003). Similar results were noted regardless of age, sex, T stage, N stage, and AJCC prognostic groups based on subgroup analysis. However, patients with M1 disease who underwent primary site surgery did not exhibit any survival benefit. CONCLUSION: Surgery for the primary tumor conferred a survival advantage in non-metastatic PUC patients.

ALPK2 acts as tumor promotor in development of bladder cancer through targeting DEPDC1A.

Bladder cancer is one of the most common malignant tumors in the urinary system. The development and improvement of treatment efficiency require the deepening of the understanding of its molecular mechanism. This study investigated the role of ALPK2, which is rarely studied in malignant tumors, in the development of bladder cancer. Our results showed the upregulation of ALPK2 in bladder cancer, and data mining of TCGA database showed the association between ALPK2 and pathological parameters of patients with bladder cancer. In vitro and in vivo experiments demonstrated that knockdown of ALPK2 could inhibit bladder cancer development through regulating cell proliferation, cell apoptosis, and cell migration. Additionally, DEPDC1A is identified as a potential downstream of ALPK2 with direct interaction, whose overexpression/downregulation can inhibit/promote the malignant behavioral of bladder cancer cells. Moreover, the overexpression of DEPDC1A can rescue the inhibitory effects of ALPK2 knockdown on bladder cancer. In conclusion, ALPK2 exerts a cancer-promoting role in the development of bladder cancer by regulating DEPDC1A, which may become a promising target to improve the treatment strategy of bladder cancer.

Prognostic Value of an Immunohistochemical Signature in Patients With Bladder Cancer Undergoing Radical Cystectomy.

BACKGROUND: This study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy. METHODS: IHC was performed on tumor specimens from 366 patients with transitional cell bladder cancer. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with bladder cancer. The Kaplan-Meier estimate was performed to assess DFS, and unadjusted and adjusted Cox regression models were used to identify independent risk factors to predict DFS of patients with bladder cancer. RESULTS: Based on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (71%) compared with high-risk patients (18%) (p < 0.001); in the validation cohort, the 10-year DFS was 86% for the low-risk group and 20% for the high-risk group (p < 0.001). Multivariable Cox regression analyses showed that the high-risk group based on the classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the classifier and clinicopathological factors was developed for clinical application. CONCLUSION: The nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of bladder cancer.

Construction of an immune-related LncRNA signature with prognostic significance for bladder cancer.

Bladder cancer (BLCA) is one of the most common urological cancer with increasing cases and deaths every year. In the present study, we aim to construct an immune-related prognostic lncRNA signature (IRPLS) in bladder cancer (BLCA) patients and explore its immunogenomic implications in pan-cancers. First, the immune-related differentially expressed lncRNAs (IRDELs) were identified by 'limma' R package and the score of IRPLS in every patient were evaluated by Cox regression. The dysregulation of IRDELs expression between cancer and para-cancer normal tissues was validated through RT-qPCR. Then, we further explore the biological functions of a novel lncRNA from IRPLS, RP11-89 in BLCA using CCK8 assay, Transwell assay and Apoptosis analysis, which indicated that RP11-89 was able to promote cell proliferation and invasive capacity while inhibits cell apoptosis in BLCA. In addition, we performed bioinformatic methods and RIP to investigate and validate the RP11-89/miR-27a-3p/PPARγ pathway in order to explore the mechanism. Next, CIBERSORT and ESTIMATE algorithm were used to evaluate abundance of tumour-infiltrating immune cells and scores of tumour environment elements in BLCA with different level of IRPLS risk scores. Finally, multiple bioinformatic methods were performed to show us the immune landscape of these four lncRNAs for pan-cancers. In conclusion, this study first constructed an immune-related prognostic lncRNA signature, which consists of RP11-89, PSORS1C3, LINC02672 and MIR100HG and might shed lights on novel targets for individualized immunotherapy for BLCA patients.

Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes.

Background: Of patients with upper urinary tract urothelial carcinoma (UTUC), 22-47% developed bladder recurrence after radical nephroureterectomy. Furthermore, the effect of surgery for UTUC-bladder cancer (BC) has not been well validated. The aim of this study was to assess the impact of standard primary BC surgical strategy on survival of patients diagnosed with UTUC-BC. Patients and Methods: A total of 676 UTUC-BC patients and 197,753 primary BC patients diagnosed from 2004 to 2016, were identified based on the SEER database. The Kaplan-Meier method and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). Multivariate Cox regression model and competing risks regression model were used to identify independent risk factors. Propensity score matching (PSM) was also performed to adjust potential confounding factors. Results: The baseline characteristics and survival outcomes of the two BC patient cohorts are quite different. For UTUC-BC patients, no significant difference in OS (NMIBC: p = 0.88; MIBC: p = 0.98) or cumulative incidence of CSM (NMIBC: p = 0.12; MIBC: p = 0.96) were noted for various surgical procedures. Local tumor treatment and partial cystectomy for UTUC-NMIBC patients produced lower 1-year (6.1%) and 3-year CSM (16.2%). Radical cystectomy for UTUC-MIBC patients produced lower 1-year (11.8%) but higher 3-year CSM (62.7%). After PSM for covariates, UTUC-BC patients still had a worse prognosis after surgery compared with primary BC patients. Based on regression models, older age, advanced T stage, N positive disease, M positive disease, and shorter interval between UTUC and BC were identified as independent risk factors for UTUC-BC patients. Conclusion: Standard primary BC surgical strategy did not provide significant survival benefit for UTUC-BC patients. Compared with primary BC patients, UTUC-BC patients had a worse prognosis after surgery, suggesting that current primary BC surgical guidelines are not entirely appropriate for UTUC-BC patients. Our findings underscore the continued importance and need for better prognosis and improved guidelines for management of UTUC-BC patients.

Construction of a robust prognostic model for adult adrenocortical carcinoma: Results from bioinformatics and real-world data.

This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large-scale multiomics analysis and real-world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis-related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI's GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P < .001), TFRC (P < .001), TSC1 (P < .001) expression indicated significantly worse overall survival for adult ACC patients. Risk assessment suggested significantly a strong predictive capacity of IPRPs model for poor overall survival (P < .05). IPRPs model showed a little stronger ability for predicting prognosis than Ki-67 protein in FUSCC cohort (P = .003, HR = 3.947; P = .005, HR = 3.787). In external validation of IPRPs model using gene expression data, IPRPs model showed strong ability for predicting prognosis in TCGA cohort (P = .005, HR = 3.061) and it exhibited best ability for predicting prognosis in GSE10927 cohort (P = .0898, HR = 2.318). This research constructed IPRPs model for predicting adult ACC patients' prognosis using proteomic data, gene expression data and real-world data and this prognostic model showed stronger predictive value than other biomarkers (Ki-67, Beta-catenin, etc) in multi-cohorts.

High Expression of CD39 is Associated with Poor Prognosis and Immune Infiltrates in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: The cell-surface ectonucleotidase CD39 is a key molecule of the immunosuppressive adenosine pathway within the tumor microenvironment. However, the relationship between CD39 and clear cell renal cell carcinoma (ccRCC) is rarely reported and still remains unclear. METHODS: CD39 expression was first analyzed using the Oncomine and the Tumor IMmune Estimation Resource (TIMER) databases, and then examined in ccRCC patients (n=367) who had undergone radical nephrectomy using immunohistochemistry (IHC) and real-time quantitative PCR analysis (qPCR). The prognosis value of CD39 in ccRCC was evaluated by Cox proportional hazards analysis. Functional and gene set enrichment analysis (GSEA) was performed using transcriptomic data of ccRCC from TCGA. Correlation analysis between CD39 and tumor-infiltrating lymphocytes (TILs) was performed using the TISIDB database. The impact of CD39 on immune checkpoint therapy (ICT) was evaluated by two public cohorts. RESULTS: CD39 mRNA and protein expression was upregulated in tumor tissues from ccRCC patients and aberrant expression of CD39 was associated with advanced tumor stage and poor prognosis in ccRCC patients. EMT, IL-2/STAT5, inflammatory response, interferon gamma and KRAS hallmark gene sets were identified as CD39-related signaling pathway. The expression level of CD39 was significantly and positively correlated with high abundance of the regulatory TILs including NK cells, macrophages, Th cells and Treg cells. CD39 was correlated with expression of several immune checkpoints and higher CD39 expression was associated with better OS of ccRCC patients who received ICT. CONCLUSION: CD39 is a powerful prognostic marker of ccRCC patients. Increased tumor expression of CD39 mRNA is significantly correlated with infiltrating levels of TILs, and better efficacy of ICT to ccRCC. CD39 could be a novel therapeutic target for ccRCC.

Diagnostic Performance of Confocal Laser Endomicroscopy for the Detection of Bladder Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the diagnostic efficacy of confocal laser endomicroscopy (CLE) in detection of bladder cancer. METHODS: A systematic literature search on CLE in diagnosing bladder cancer in PubMed, Embase, and the Cochrane Library databases was performed. A bivariate meta-regression model was used for meta-analysis to evaluate the pooled diagnostic value of CLE. RESULTS: A total of 5 eligible studies involving 302 lesions were available for this meta-analysis. In a per-lesion analysis, pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver-operating curve (SROC) area under the curve (AUC) of CLE for malignant lesions were 0.90 (95% confidence interval [CI]: 0.85-0.94), 0.72 (95% CI: 0.59-0.82), 3.20 (95% CI: 2.14-4.79), 0.14 (95% CI: 0.09-0.21), 23.27 (95% CI: 11.71-46.25), and 0.91 (95% CI: 0.89-0.94), respectively. For low-grade urothelial carcinomas, pooled sensitivity, specificity, PLR, NLR, DOR, and AUC for CLE were 0.72 (95% CI: 0.57-0.84), 0.87 (95% CI: 0.77-0.93), 5.48 (95% CI: 3.12-9.62), 0.32 (95% CI: 0.20-0.50), 17.19 (95% CI: 8.01-36.89), and 0.85 (95% CI: 0.82-0.88), respectively. For high-grade urothelial carcinomas, pooled sensitivity, specificity, PLR, NLR, DOR, and AUC for CLE were 0.82 (95% CI: 0.62-0.92), 0.84 (95% CI: 0.73-0.91), 4.96 (95% CI: 2.58-9.54), 0.22 (95% CI: 0.09-0.52), 22.49 (95% CI: 5.33-94.85), and 0.89 (95% CI: 0.86-0.91), respectively. CONCLUSION: CLE is a promising endoscopy technique for real-time tumor grading of bladder cancer.

MicroRNA-4317 predicts the prognosis of breast cancer and inhibits tumor cell proliferation, migration, and invasion.

Previous researches have indicated that miR-4317 was aberrantly expressed in several tumors. However, the potential role of miR-4317 in breast cancer is still unclear. The aim of this study was to investigate the potential role of miR-4317 in breast cancer. The relative expression levels of miR-4317 were detected in breast cancer tissues and cell lines using qRT-PCR analysis. The Kaplan-Meier survival curve and multivariate Cox regression analyses were used to investigate the prognostic significance of miR-4317 in breast cancer. CCK-8 and Transwell assays were performed to evaluate the effects of miR-4317 on cell proliferation, migration, and invasion. The results showed that miR-4317 expression was decreased in breast cancer tissues and cell lines. Downregulation of miR-4317 was significantly associated with lymph node metastasis, TNM stage, and poor prognosis. Overexpression of miR-4317 inhibited proliferation, migration, and invasion of breast cancer cells, while downregulation of miR-4317 exhibited the opposite effects. MYD88 may be a direct target of miR-4317. The results suggest miR-4317 may play a tumor suppressor role in breast cancer and inhibit proliferation, migration, and invasion of breast cancer cells by targeting MYD88. The findings provide novel evidence of miR-4317 as a potential prognostic biomarker and therapeutic target for breast cancer.