The identification of novel schizophrenia-related metabolites using untargeted lipidomics.

Human lipidome still remains largely unexplored among Chinese schizophrenia patients. We aimed to identify novel lipid molecules associated with schizophrenia and cognition among schizophrenia patients. The current study included 96 male schizophrenia patients and 96 gender-matched healthy controls. Untargeted lipidomics profiling was conducted among all participants. Logistic regression models were used to assess metabolite associations with schizophrenia. We further assessed the incremental predictive value of identified metabolites beyond conventional risk factors on schizophrenia status. In addition, identified metabolites were tested for association with cognitive function among schizophrenia patients using linear regression models. A total of 34 metabolites were associated with schizophrenia. Addition of these identified metabolites to age, body mass index, smoking, and education significantly increased the risk reclassification of schizophrenia. Among the schizophrenia-related metabolites, 10 were further associated with cognition in schizophrenia patients, including four metabolites associated with immediate memory, two metabolites associated with delayed memory, three metabolites associated with visuospatial, four metabolites associated with language, one metabolite associated with attention, and two metabolites associated with the total score. Our findings provide novel insights into the biological mechanisms of schizophrenia, suggesting that lipid metabolites may serve as potential diagnostic or therapeutic targets of schizophrenia.

Variations to plasma H2O2 levels and TAC in chronical medicated and treatment-resistant male schizophrenia patients: Correlations with psychopathology.

Accumulating evidence suggests that imbalanced oxidative stress (OS) may contribute to the mechanism of schizophrenia. The aim of the present study was to evaluate the associations of OS parameters with psychopathological symptoms in male chronically medicated schizophrenia (CMS) and treatment-resistant schizophrenia (TRS) patients. Levels of hydrogen peroxide (H2O2), hydroxyl radical (·OH), peroxidase (POD), α-tocopherol (α-toc), total antioxidant capacity (TAC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assayed in males with CMS and TRS, and matched healthy controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The results demonstrated significant differences in the variables H2O2 (F = 5.068, p = 0.008), ·OH (F = 31.856, p < 0.001), POD (F = 14.043, p < 0.001), α-toc (F = 3.711, p = 0.027), TAC (F = 24.098, p < 0.001), and MMP-9 (F = 3.219, p = 0.043) between TRS and CMS patients and healthy controls. For TRS patients, H2O2 levels were correlated to the PANSS positive subscale (r = 0.386, p = 0.032) and smoking (r = -0,412, p = 0.021), while TAC was significantly negatively correlated to the PANSS total score (r = -0.578, p = 0.001) and POD and TAC levels were positively correlated to body mass index (r = 0.412 and 0.357, p = 0.021 and 0.049, respectively). For patients with CMS, ·OH levels and TAC were positively correlated to the PANSS general subscale (r = 0.308, p = 0.031) and negatively correlated to the PANSS total score (r = -0.543, p < 0.001). Furthermore, H2O2, α-toc, and ·OH may be protective factors against TRS, and POD was a risk factor. Patients with CMS and TRS exhibit an imbalance in OS, thus warranting future investigations.

Clinical characteristics and removal approaches of tracheal and bronchial foreign bodies in elders.

The symptoms of tracheobronchial foreign body in the elderly are not typical, so they are often missed or misdiagnosed. This study aims to depict the clinical characteristics of tracheobronchial foreign body inhalation in the elderly. We retrospectively analysed the clinical data of elder patients (age ≥ 65 years) diagnosed with tracheal and bronchial foreign bodies. The data included age, sex, clinical symptoms, type and location of foreign bodies, prehospital duration, Chest CT, bronchoscopic findings, and frequencies and tools for removing these elderly patients' tracheal and bronchial foreign bodies. All patients were followed up for a half year. Fifty-nine cases were included, of which only 32.2% had a definite aspiration history. Disease duration > 30 days accounted for 27.1% of the patients. 27.1% of the patients had a history of stroke, and 23.8% had Alzheimer's Disease. Regarding clinical symptoms, patients mainly experience cough and expectoration. The most common CT findings were abnormal density shadow (37.3%) and pulmonary infiltration (22.0%). Under bronchoscopy, purulent secretions were observed in 52.5% of patients, and granulation tissue hyperplasia was observed in 45.8%. Food (55.9%) was the most common foreign object, including seafood shells (5.1%), bones (20.3%), dentures (18.6%), and tablets (20.3%). The success rate of foreign body removal under a bronchoscope was 96.7%, 28.8% of the foreign bodies were on the left and 69.5% on the right. 5.1% of the elderly patients required rigid bronchoscopy, and 6.8% required two bronchoscopies. In elderly cohorts, tracheal foreign bodies are obscured by nonspecific clinical presentations and a paucity of aspiration history, challenging timely diagnosis. Predominantly constituted by food particles, with a notable predilection for the left bronchial tree, these cases demand skilled bronchoscopic management, occasionally requiring sophisticated approaches for successful extraction.

LINC00540 promotes sorafenib resistance and functions as a ceRNA for miR-4677-3p to regulate AKR1C2 in hepatocellular carcinoma.

Sorafenib resistance is one of the main causes of poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) function as suppressors or oncogenic factors during tumor progression and drug resistance. Here, to identify therapeutic targets for HCC, the biological mechanisms of abnormally expressed lncRNAs were examined in sorafenib-resistant HCC cells. Specifically, we established sorafenib-resistant HCC cell lines (Huh7-S and SMMC7721-S), which displayed an epithelial-mesenchymal transition (EMT) phenotype. Transcriptome sequencing (RNA-Seq) was performed to established differential lncRNA expression profiles for sorafenib-resistant cells. Through this analysis, we identified LINC00540 as significantly up-regulated in sorafenib-resistant cells and a candidate lncRNA for further mechanistic investigation. Functionally, LINC00540 knockdown promoted sorafenib sensitivity and suppressed migration, invasion, EMT and the activation of PI3K/AKT signaling pathway in sorafenib-resistant HCC cells, whereas overexpression of LINC00540 resulted in the opposite effects in parental cells. LINC00540 functions as a competing endogenous RNA (ceRNA) by competitively binding to miR-4677-3p , thereby promoting AKR1C2 expression. This is the first study that demonstrates a role for LINC00540 in enhancing sorafenib resistance, migration and invasion of HCC cells through the LINC00540/miR-4677-3p/AKR1C2 axis, suggesting that LINC00540 may represent a potential therapeutic target and prognosis biomarker for HCC.

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia.

BACKGROUND: Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. METHODS: The study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function. RESULTS: Serum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P < 0.05). MMP-2 levels were positively correlated with TNF-α levels (P < 0.05), but not with cognitive function (P > 0.05). CONCLUSION: The results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

Sodium tanshinone IIA sulfonate inhibits tumor growth via miR-138 upregulation in intermittent hypoxia-induced xenograft mice.

PURPOSE: We studied the functions of sodium tanshinone IIA sulfonate (TSA) in inducing tumor growth in obstructive sleep apnea (OSA)-mimicking intermittent hypoxia (IH) xenograft mice and the underlying potential molecular mechanism. METHODS: RNA sequencing was conducted to screen the differentially expressed microRNAs in cell lines exposed to IH with or without TSA treatment. As part of the 5-week in vivo study, we treated xenograft mice with 8-h IH once daily. TSA and miR-138 inhibitors or mimics were administrated appropriately. In addition, we performed real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), microvessel density (MVD), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. RESULTS: RNA sequencing and RT-PCR results demonstrated that TSA increased the levels of miR-138 under IH conditions in vitro. TSA reduced the IH-stimulated high levels of hypoxia-induced factor-1α and vascular endothelial growth factor. Furthermore, IH contributed to high tumor migration, invasion, MVD, and low apoptosis. TSA attenuated IH-mediated tumor proliferation, migration, invasion, MVD, and increased apoptosis, whereas miR-138 inhibitor interrupted the effect of TSA on treating IH-induced tumor behaviors. CONCLUSIONS: OSA mimicking IH facilitates tumor growth and reduces miR-138 levels. TSA inhibits IH-induced tumor growth by upregulating the expression of miR-138.

Identifying causal associations between women's reproductive traits and risk of schizophrenia: a multivariate validated two-sample Mendelian randomization analysis.

BACKGROUND: A significant association between women's reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings. METHODS: From extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses. RESULTS: The UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512-0.777; P < 0.01) and decreased SCZ risk. Pleiotropy analysis of the AFS-SCZ association confirmed the robustness of the MR results (P > 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407-0.862; P < 0.01) on the risk of SCZ were demonstrated after adjusting for body mass index, years of schooling, and smoking initiation using MVMR. CONCLUSIONS: Our findings provide convincing evidence that early AFS is a risk factor for SCZ. SCZ risk may be decreased by raising awareness of reproductive healthcare for women.

Identification of key genes in chronic intermittent hypoxia-induced lung cancer progression based on transcriptome sequencing.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of lung cancer mortality. Nevertheless, little is known about the underlying molecular mechanisms. This research aimed to investigate differentially expressed genes (DEGs) and explore their function in Lewis lung carcinoma (LLC)-bearing mice exposed to chronic intermittent hypoxia (CIH) by transcriptome sequencing. METHODS: Lung cancer tissues in LLC-bearing mice exposed to CIH or normoxia were subjected for transcriptome sequencing to examine DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to explore the function of DEGs. To evaluate the prognostic value of DEGs, the Kaplan-Meier survival analysis in combination with Cox proportional hazard model were applied based on The Cancer Genome Atlas. RESULTS: A total of 388 genes with 207 up-regulated and 181 down-regulated genes were differentially expressed between the CIH and normoxia control groups. Bioinformatics analysis revealed that the DEGs were related to various signaling pathways such as chemokine signaling pathway, IL-17 signaling pathway, TGF-ß signaling pathway, transcriptional misregulation in cancer, natural killer cell mediated cytotoxicity, PPAR signaling pathway. In addition, the DEGs including APOL1, ETFB, KLK8, PPP1R3G, PRL, SPTA1, PLA2G3, PCP4L1, NINJ2, MIR186, and KLRG1 were proven to be significantly correlated with poorer overall survival in lung adenocarcinoma. CONCLUSIONS: CIH caused a significant change of gene expression profiling in LLC-bearing mice. The DEGs were found to be involved in various physiological and pathological processes and correlated with poorer prognosis in lung cancer.

Cancer-associated fibroblast-associated gene IGFBP2 promotes glioma progression through induction of M2 macrophage polarization.

We elucidated the molecular mechanism of cancer-associated fibroblast (CAF)-associated gene insulin-like growth factor binding protein-2 (IGFBP2)-induced M2 macrophage polarization in the tumor microenvironment involved in glioma progression. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) provided bulk RNA-sequencing datasets, ESTIMATE scores for glioma stromal cells, and overall survival-clinicopathological correlation analyses. TIMER provided CAF abundance in the TCGA glioma-related dataset, differential gene analysis was performed for high- and low-CAF groups, and weighted gene coexpression network analysis identified CAF-related genes. Univariate and multifactorial cyclooxygenase (COX) regression analyses created the CAF risk models single sample gene set enrichment analysis, CIBERSORT, and GSE84465. Mice were implanted with gliomas, and Western blot and RT-quantitative PCR showed IGFBP2 in tumor tissues. Adeno-associated virus (AAV) decreased IGFBP2, flow cytometry measured M1 and M2 macrophage ratios, and immunohistochemistry detected markers. TCGA and CGGA transcriptome data showed malignant gliomas had higher stromal cell scores and worse prognoses. Low- and high-CAF TCGA gliomas were detected, and differential expression, WGCNA, and multifactorial COX identified 132 CAF-related genes and seven high-risk genes (CPQ, EFEMP2, IGFBP2, RAB42, TNFRSF12A, and VASN). Neither CAF risk score, grade, nor 1p/19q affected glioma prognosis. CAF only enriched EFEMP2 and IGFBP2. Gene Expression Profiling Interactive Analysis compared EFEMP2 and IGFBP2 expression in normal brain tissue and gliomas. Low-grade glioma and malignant glioblastoma highly expressed IGFBP2 and EFEMP2. GSEA raised IGFBP2. CIBERSORT linked M2 macrophage infiltration to TCGA glioma immune cell subpopulation IGFBP2 expression. IGFBP2 knockdown stopped mouse glioma and M2 macrophage polarization. CAF plays a procarcinogenic role in glioma, and the CAF-related gene IGFBP2 could promote glioma progression by inducing M2 macrophage polarization.NEW & NOTEWORTHY The cancer-associated fibroblast (CAF)-related gene insulin-like growth factor binding protein-2 (IGFBP2) is highly expressed in gliomas and is associated with poor prognosis. CAF-related gene IGFBP2 promotes glioma progression by inducing polarization of M2 macrophages. This study provides a new basis for an in-depth investigation of the functional mechanisms of the glioma tumor microenvironment and the search for key genes involved in immune regulation in CAF.

Potential Causal Association between Depression and Oral Diseases: A Mendelian Randomization Study.

BACKGROUND: Globally, oral diseases are common, pose an economic burden, and significantly decline the quality of life of affected individuals. Recently, researchers have substantially highlighted the effect of depression on oral disease incidence and development. In this study, we elucidated the correlation between depression and oral diseases. METHODS: Using two-sample Mendelian randomization (MR), the association between depression and the risk of 17 oral diseases was evaluated. Three methods were used to perform MR analysis: the inverse variance-weighted, weighted median, and MR-Egger methods. Furthermore, Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, and leave-one-out analysis were performed to analyze sensitivity. RESULTS: After implementing multiple test corrections, we observed that genetic susceptibility to depression was associated with an increased risk of mouth ulcers, toothache, loose teeth, bleeding gums, painful gums, chronic periodontitis, chronic tonsil and adenoid diseases, peritonsillar abscess, and excessive tooth attrition. However, a causal relationship between depression and other oral diseases was not observed. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: We confirmed the causal relationship between depression and several oral diseases, thereby providing a novel viewpoint on the prevention and treatment of oral diseases. Our findings suggest the integration of depression control into routine clinical care to enhance the effectiveness of oral disease treatment.

Machine-learning predictions for acute kidney injuries after coronary artery bypass grafting: a real-life muticenter retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) surgery is associated with poor outcomes. The objective of this study was to apply a new machine learning (ML) method to establish prediction models of AKI after CABG. METHODS: A total of 2,780 patients from two medical centers in East China who underwent primary isolated CABG were enrolled. The dataset was randomly divided for model training (80%) and model testing (20%). Four ML models based on LightGBM, Support vector machine (SVM), Softmax and random forest (RF) algorithms respectively were established in Python. A total of 2,051 patients from two other medical centers were assigned to an external validation group to verify the performances of the ML prediction models. The models were evaluated using the area under the receiver operating characteristics curve (AUC), Hosmer-Lemeshow goodness-of-fit statistic, Bland-Altman plots, and decision curve analysis. The outcome of the LightGBM model was interpreted using SHapley Additive exPlanations (SHAP). RESULTS: The incidence of postoperative AKI in the modeling group was 13.4%. Similarly, the incidence of postoperative AKI of the two medical centers in the external validation group was 8.2% and 13.6% respectively. LightGBM performed the best in predicting, with an AUC of 0.8027 in internal validation group and 0.8798 and 0.7801 in the external validation group. The SHAP revealed the top 20 predictors of postoperative AKI ranked according to the importance, and the top three features on prediction were the serum creatinine in the first 24 h after operation, the last preoperative Scr level, and body surface area. CONCLUSION: This study provides a LightGBM predictive model that can make accurate predictions for AKI after CABG surgery. The LightGBM model shows good predictive ability in both internal and external validation. It can help cardiac surgeons identify high-risk patients who may experience AKI after CABG surgery.

[Differential diagnosis of autism spectrum disorder and global developmental delay based on machine learning and Children Neuropsychological and Behavioral Scale]. / åŸºäºŽæœºå™¨å­¦ä¹ å’Œå„¿ç«¥ç¥žç»å¿ƒç†è¡Œä¸ºæ£€æŸ¥é‡è¡¨é‰´åˆ«å­¤ç‹¬ç—‡è°±ç³»éšœç¢å’Œå ¨é¢å‘è‚²è¿Ÿç¼“å„¿ç«¥çš„ç ”ç©¶.

OBJECTIVES: To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD). METHODS: A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier. RESULTS: DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%. CONCLUSIONS: Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.

USP10 promotes the progression of triple-negative breast cancer by enhancing the stability of TCF4 protein.

Investigating the role of ubiquitin-specific peptidase 10 (USP10) in triple-negative breast cancer (TNBC). Analyzed USP10 expression levels in tumors using public databases. Detected USP10 mRNA and protein levels in cell lines. Examined USP10 expression in tumor tissues from breast cancer patients. Conducted USP10 knockdown experiments and analyzed changes in cell proliferation and metastasis. Confirmed protein-protein interactions with USP10 through mass spectrometry, Co-IP, and fluorescence experiments. Assessed impact of USP10 on transcription factor 4 (TCF4) ubiquitination and validated TCF4's influence on TNBC cells. We initially identified a pronounced overexpression of USP10 across multiple tumor types, including TNBC. Subsequently, we observed a conspicuous upregulation of USP10 expression levels in breast cancer cell lines compared to normal breast epithelial cells. However, upon subsequent depletion of USP10 within cellular contexts, we noted a substantial attenuation of malignant proliferation and metastatic potential in TNBC cells. In subsequent experimental analyses, we elucidated the physical interaction between USP10 and the transcription factor TCF4, whereby USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC. Collectively, this study demonstrates that USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC.

MiR-210-3p enhances intermittent hypoxia-induced tumor progression via inhibition of E2F3.

PURPOSE: Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. Although micro-ribonucleic acid-210-3p (miR-210-3p) is correlated with hypoxia-induced tumor development, its role in the relationship between IH and tumor function remains poorly understood. The present work focused on elucidating the molecular mechanism through which miR-210-3p drives tumor progression under IH. METHODS: MiR-210-3p levels were quantified within tumor samples from patients with lung adenocarcinoma who had or did not have OSA. Correlations between miR-210-3p and polysomnographic variables were analyzed. For in vitro experiments, miR-210-3p was inhibited or overexpressed via transfection under IH conditions. Cell viability, growth, invasion and migration assays were carried out. For in vivo modeling of IH using mouse xenografts, a miR-210-3p antagomir was intratumorally injected, tumor biological behaviors were evaluated, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry and western blot were carried out for detecting miR-210-3p and E2F transcription factor 3 (E2F3) expression. RESULTS: For patients with lung adenocarcinoma and OSA, high miR-210-3p levels showed positive relation to polysomnographic variables, such as oxygen desaturation index, apnea-hypopnea index, and proportion of total sleep time with oxygen saturation in arterial blood < 90%. IH enhanced tumor viability, proliferation, migration, and invasion, downregulated E2F3 expression, and increased miR-210-3-p levels. miR-210-3p overexpression induced similar changes. These changes were reversed by miR-210-3p inhibition in vitro or miR-210-3p antagomir through intratumoral injection in vivo. CONCLUSIONS: IH-induced tumor development is driven through miR-210-3p by E2F3 suppression. MiR-210-3p represents a potential therapeutic target among patients with concomitant cancer and OSA.

Identification of novel lncRNA prognostic biomarkers and their associated ceRNAs in bladder urothelial carcinoma.

Bladder urothelial carcinoma (BUCA) is a common malignant tumor with a high rate of metastasis and recurrence. The lack of specific and sensitive biomarkers for the prognostic assessment makes it important to seek alternatives. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) function as competitive endogenous RNAs (ceRNAs) and play an important role in BUCA prognosis. Therefore, this study aimed to establish a prognosis-related lncRNAs-microRNAs (miRNAs)-messenger RNA (mRNA) (pceRNA) network and identify novel prognostic biomarkers. Integrated weighted coexpression analysis, functional clustering, and ceRNA network were used for the prognostic assessment of BUCA. The transcriptome sequencing datasets of lncRNA, miRNA, and mRNA from The Cancer Genome Atlas database were used for the identification of key lncRNAs and construction of the lncRNAs expression signature for prognostic prediction of BUCA patients. Then, 14 differentially expressed lncRNAs (DE-lncRNAs) were identified as candidate prognostic RNAs based on the ceRNAs network and functional clustering. In the Cox regression analysis, two (AC008676.1 and ADAMTS9-AS1) of all DE-lncRNAs were significantly associated with overall survival (OS) of BUCA patients. This two DE-lncRNA signature was significantly correlated with OS and was an independent prognostic factor, which was confirmed in an independent dataset of GSE216037. Moreover, we constructed the pceRNA network that includes 2 DE-lncRNAs, 9 DE-miRNAs, and 10 DE-mRNAs. Pathway enrichment analysis showed that AC008676.1 and ADAMTS9-AS1 are involved in several cancer-related pathways such as proteoglycans in cancer and TGF-beta signaling pathway. The novel-identified DE-lncRNA prognostic signature and the pceRNA network in this study will be valuable risk predictors and diagnostic markers for BUCA.

Log odds of positive lymph nodes show better predictive performance on the prognosis of early-onset colorectal cancer.

BACKGROUND: As the incidence of colorectal cancer tends to be younger, early-onset colorectal cancer (EOCRC) has attracted more attention in recent years. We aimed to assess the optimal lymph node staging system among EOCRC patients, and then, establish informative assessment models for prognosis prediction. METHODS: Data of EOCRC were retrieved from the Surveillance, Epidemiology, and End Results database. Survival prediction ability of three lymph node staging systems including N stage of the tumor node metastasis (TNM) staging system, lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) was assessed and compared using Akaike information criterion (AIC), Harrell's concordance index (C-index), and likelihood ratio (LR) test. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic predictors for overall survival (OS) and cancer-specific survival (CSS). Effectiveness of the model was demonstrated by receiver operative curve and decision curve analysis. RESULTS: A total of 17,535 cases were finally included in this study. All three lymph node staging systems showed significant performance in survival prediction (p < 0.001). Comparatively, LODDS presented a better ability of prognosis prediction with lower AIC (OS: 70,510.99; CSS: 60,925.34), higher C-index (OS: 0.6617; CSS: 0.6799), and higher LR test score (OS: 998.65; CSS: 1103.09). Based on independent factors identified from Cox regression analysis, OS and CSS nomograms for EOCRC were established and validated. CONCLUSIONS: LODDS shows better predictive performance than N stage or LNR among patients with EOCRC. Novel validated nomograms based on LODDS could effectively provide more prognostic information than the TNM staging system.

Percent Recovery Index Predicts Poor Asthma Control and Exacerbation in Adults.

Background: Previous studies indicate that the percent recovery index (PRI: the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation), one of the indexes of methacholine bronchial provocation, may predict acute asthma exacerbations in childhood and elderly asthmatics. It is known that childhood (<12) and elder (>60) asthmatics may be different to adult patients in many aspect including prognosis. However, in adults, a research for predicting value of PRI to exacerbation is still absence. Besides exacerbation, predicting value of PRI to poor asthma control is also unknown. We try to detect whether PRI can predict poor asthma control and exacerbation in adults in this research. Meanwhile, we try to detect whether treatment can influence PRI. Methods: In 61 adults with asthma, baseline PRI was measured during enrollment. And then baseline PRI was evaluated as a predictor of exacerbation or poor asthma control at an upcoming 3-month follow-up. The covariates included age, sex, BMI, previous exacerbation, smoking status and baseline lung function. After treatment for 3 months, PRI was measured again and compared with baseline PRI. Results: After the 3-month follow-up, we found that baseline PRI was significantly related to asthma exacerbation (P = 0.023), poor asthma control (ACT at 3 months, P = 0.014), decreased quality of life (decrease of MiniAQLQ, P = 0.010) and cumulative number of EDHO at 3 months (P = 0.039). Meanwhile, no significant correlation was observed between baseline PRI and inflammation factors (FENO, CaNO, and EOS). Finally, PRI was dramatically reduced after standard treatment for 3 months. Conclusion: PRI is efficient in the prediction of poor asthma control and exacerbation in adults. The predictive value of PRI may rely on the inherent property of asthmatic airway smooth muscle (ASM) independent of inflammation factors. Effective treatment can alleviate PRI dramatically and that indicate PRI may also be valuable in evaluation of curative effect.

A neuromarker for deficit syndrome in schizophrenia from a combination of structural and functional magnetic resonance imaging.

AIM: Deficit schizophrenia (DS), defined by primary and enduring negative symptoms, has been proposed as a promising homogeneous subtype of schizophrenia. It has been demonstrated that unimodal neuroimaging characteristics of DS were different from non-deficit schizophrenia (NDS), however, whether multimodal-based neuroimaging features could identify deficit syndrome remains to be determined. METHODS: Functional and structural multimodal magnetic resonance imaging of DS, NDS and healthy controls were scanned. Voxel-based features of gray matter volume, fractional amplitude of low-frequency fluctuations, and regional homogeneity were extracted. The support vector machine classification models were constructed using these features separately and jointly. The most discriminative features were defined as the first 10% of features with the greatest weights. Moreover, relevance vector regression was applied to explore the predictive values of these top-weighted features in predicting negative symptoms. RESULTS: The multimodal classifier achieved a higher accuracy (75.48%) compared with the single modal model in distinguishing DS from NDS. The most predictive brain regions were mainly located in the default mode and visual networks, exhibiting differences between functional and structural features. Further, the identified discriminative features significantly predicted scores of diminished expressivity factor in DS but not NDS. CONCLUSIONS: The present study demonstrated that local properties of brain regions extracted from multimodal imaging data could distinguish DS from NDS with a machine learning-based approach and confirmed the relationship between distinctive features and the negative symptoms subdomain. These findings may improve the identification of potential neuroimaging signatures and improve the clinical assessment of the deficit syndrome.

Tumor-suppressive function and mechanism of miR-873-5p in glioblastoma: evidence based on bioinformatics analysis and experimental validation.

This study aims to clarify the mechanistic actions of microRNA-873-5p (miR-873-5p) on glioblastoma (GBM) progression. The most differentially expressed miRNAs were retrieved from the GEO database. It was established that miR-873-5p was downregulated in GBM tissues and cells. Based on in silico prediction and experimental data, HMOX1 was demonstrated to be a target gene of miR-873-5p. Further, miR-873-5p was then ectopically expressed in GBM cells to examine its effect on the malignant behaviors of GBM cells. Overexpression of miR-873-5p inhibited GBM cell proliferation and invasion by targeting HMOX1. HMOX1 promoted SPOP expression by increasing HIF1α expression, thus stimulating GBM cell malignant phenotypes. miR-873-5p suppressed the malignant phenotypes of GBM cells and tumorigenesis in vitro and in vivo by inhibiting the HMOX1/HIF1α/SPOP signaling axis. This study uncovers a novel miR-873-5p/HMOX1/HIF1α/SPOP axis in GBM, providing new insights into GBM progression and therapeutic targets for GBM treatment.

Enhancing effects of 60Co irradiation on the extraction and activities of phenolic components in edible Citri Sarcodactylis Fructus.

In this study, the impact of 60Co-γ ray irradiation treatment on the content of active chemicals and their functions in Citri Sarcodactylis Fructus (CSF) was assessed. Scanning electron microscopy, Fourier transform infrared spectroscopy, and γ-ray diffraction revealed physical structure changes in CSF powder. According to the findings, the content of total flavonoids in the ethanol extract of CSF increased by 9.5%-21.62%, 7-hydroxycoumarin, hesperidin, 5,7-dimethoxycoumarin, and 5-methoxypsoralen increased by 5.31%-51.8%, 10.07%-99.81%, 6.6%-62.29%, and 3.03%-300%, respectively, when the irradiation dosage was raised, and the antibacterial, anti-inflammatory, antioxidant, and anticancer properties were all raised considerably. These results imply that the principal components and activity changes are proportional to the irradiation dosage. At present, the findings of this study serve as a reference for the use of irradiation technology in assisting extraction and enhancing the effects of functional foods.