The genetic causal relationship between type 2 diabetes, glycemic traits and venous thromboembolism, deep vein thrombosis, pulmonary embolism: a two-sample Mendelian randomization study.

OBJECTIVE: To investigate the genetic underpinnings of the association between type 2 diabetes (T2D), glycemic indicators such as fasting glucose (FG), fasting insulin (FI), and glycated hemoglobin (GH), and venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), thereby contributing novel insights to the scholarly discourse within this domain. METHODS: Genome-wide association study (GWAS) summary data pertaining to exposures (T2D, FG, FI, GH) and outcomes (VTE, DVT, PE) were acquired from the IEU Open GWAS database, encompassing participants of European descent, including both male and female individuals. Two-sample Mendelian randomization (MR) analyses were conducted utilizing the TwoSampleMR and MRPRESSO packages within the R programming environment. The primary analytical approach employed was the random-effects inverse variance weighted (IVW) method. Heterogeneity was assessed via Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger. Horizontal pleiotropy was evaluated using the intercept test of MR Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, with the latter also employed for outlier detection. Additionally, a "Leave one out" analysis was conducted to ascertain the influence of individual single nucleotide polymorphisms (SNPs) on MR results. RESULTS: The random-effects IVW analysis revealed a negative genetic causal association between T2D) and VTE (P = 0.008, Odds Ratio [OR] 95% confidence interval [CI] = 0.896 [0.827-0.972]), as well as between FG and VTE (P = 0.002, OR 95% CI = 0.655 [0.503-0.853]), GH and VTE (P = 0.010, OR 95% CI = 0.604 [0.412-0.884]), and GH and DVT (P = 0.002, OR 95% CI = 0.413 [0.235-0.725]). Conversely, the random-effects IVW analysis did not detect a genetic causal relationship between FI and VTE (P > 0.05), nor between T2D, FG, or FI and DVT (P > 0.05), or between T2D, FG, FI, or GH and PE (P > 0.05). Both the Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger indicated no significant heterogeneity (P > 0.05). Moreover, the intercept tests of MR Egger and MR-PRESSO suggested the absence of horizontal pleiotropy (P > 0.05). MR-PRESSO analysis identified no outliers, while the "Leave one out" analysis underscored that the MR analysis was not influenced by any single SNP. CONCLUSION: Our investigation revealed that T2D, FG, and GH exhibit negative genetic causal relationships with VTE at the genetic level, while GH demonstrates a negative genetic causal relationship with DVT at the genetic level. These findings furnish genetic-level evidence warranting further examination of VTE, DVT, and PE, thereby making a contribution to the advancement of related research domains.

Blue-emitting tryptophan-protected gold nanoclusters acted as a sensitive nanosensor for fluorescence sensing and visual imaging detection of furaltadone.

Herein, blue-emitting gold nanoclusters (Au NCs) were carried out through tryptophan as the protecting and reducing agents. In aqueous solution of Au NCs@tryptophan, the addition of furaltadone guaranteed the interaction of furaltadone with tryptophan around Au NCs. The propinquity of furaltadone to Au NCs caused that the fluorescence of Au NCs was weakened by furaltadone based on the inner filter effect (IFE). Under the optimal measurement conditions, the logarithm of relative fluorescence intensity of Au NCs@tryptophan was linearly carried out with the furaltadone amount increasing from 0.5 to 100 µM, the corresponding detection limit was 0.087 µM. The fluorescence change of Au NCs@tryptophan displayed excellent selectivity and sensitivity for furaltadone than other possible substance in the human body. In view of Au NCs@tryptophan, the as-performed fluorescence nanosensor suggested outstanding ability for furaltadone sensing in real samples. Obviously, this nanoprobe of furaltadone could implement the naked-eye visual fluorescence determination of furaltadone.

Rheumatoid arthritis increases the risk of malignant neoplasm of bone and articular cartilage: a two-sample bidirectional mendelian randomization study.

OBJECTIVE: Prior research has revealed a heightened prevalence of neoplasms in individuals diagnosed with rheumatoid arthritis (RA). The primary objective of this study is to delve into the causal association between RA and two distinct types of neoplasms: benign neoplasm of bone and articular cartilage (BNBAC) and malignant neoplasm of bone and articular cartilage (MNBAC). METHODS: We employed summary data from genome-wide association analyses (GWAS) to investigate the causal relationship between RA and two neoplasms, BNBAC and MNBAC, using a two-sample bidirectional Mendelian randomization (MR) study design. The IEU OpenGWAS database provided the GWAS summary data for RA, while the Finnish consortium supplied the GWAS summary data for BNBAC and MNBAC. Our analysis involved the utilization of eight distinct MR methods, namely random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed effects IVW. Subsequently, we conducted assessments to evaluate heterogeneity, horizontal pleiotropy, outliers, the impact of a single-nucleotide polymorphism (SNP), and adherence to the assumption of normal distribution in the MR analysis. RESULTS: The results from the MR analysis revealed that there was no significant genetic association between RA and BNBAC (P = 0.427, odds ratio [OR] 95% confidence interval [CI] = 0.971 [0.904-1.044]). However, a positive genetic association was observed between RA and MNBAC (P = 0.001, OR 95% CI = 1.413 [1.144-1.745]). Conducting a reverse MR analysis, we found no evidence to support a genetic causality between BNBAC (P = 0.088, OR 95% CI = 1.041 [0.994-1.091]) or MNBAC (P = 0.168, OR 95% CI = 1.013 [0.995-1.031]) and RA. Our MR analysis demonstrated the absence of heterogeneity, horizontal pleiotropy, and outliers and confirmed that the effect was not driven by a single SNP. Additionally, the data exhibited a normal distribution. CONCLUSION: The findings of this study demonstrate that RA constitutes a significant risk factor for MNBAC. In the context of clinical application, it is advisable to conduct MNBAC screening in RA patients and remain vigilant regarding its potential manifestation. Importantly, the outcomes of this investigation introduce a fresh vantage point into the understanding of the tumorigenesis associated with RA.

Novel pyroptosis-related lncRNAs and ceRNAs predict osteosarcoma prognosis and indicate immune microenvironment signatures.

Objective: To study pyroptosis-related biomarkers that are associated with the prognosis and immune microenvironment characteristics of osteosarcoma (OS). The goal is to establish a foundation for the prognosis and treatment of OS. Methods: We retrieved transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database for 88 OS patients. Using this data, we constructed a prognostic model to identify pyroptosis-related genes (PRGs) associated with OS prognosis. To further explore the biological function of these PRGs, we performed enrichment analysis. To identify pyroptosis-related long non-coding RNAs (PRLncs) associated with the prognosis of OS, we performed co-expression analysis. Subsequently, a risk prognostic model was constructed using these PRLncs to generate a risk score, termed as PRLncs-score, thereby obtaining PRLncs associated with the prognosis of OS. The accuracy of the prognostic model was verified through survival analysis, risk curve, independent prognostic analysis, receiver operating characteristic (ROC) curve, difference analysis between high- and low-risk groups, and clinical correlation analysis. And to determine whether PRLncs-score is independent prognostic factor for OS. In addition, we further conducted external and internal validation for the risk prognosis model. Further analyses of immune cell infiltration and tumor microenvironment were performed. A pyroptosis-related competitive endogenous RNA (PRceRNA) network was constructed to obtain PRceRNAs associated with the prognosis of OS and performed gene set enrichment analysis (GSEA) on PRceRNA genes. Results: We obtained five PRGs (CHMP4C, BAK1, GSDMA, CASP1, and CASP6) that predicted OS prognosis and seven PRLncs (AC090559.1, AP003119.2, CARD8-AS1, AL390728.4, SATB2-AS1, AL133215.2, and AC009495.3) and one PRceRNA (CARD8-AS1-hsa-miR-21-5p-IL1B) that predicted OS prognosis and indicated characteristics of the OS immune microenvironment. The PRLncs-score, in combination with other clinical features, was established as an independent prognostic factor for OS patients. Subsequent scrutiny of the tumor microenvironment and immune infiltration indicated that patients with low-PRLncs-scores were associated with reduced metastatic risk, improved survival rates, heightened levels of immune cells and stroma, and increased immune activity compared to those with high-PRLncs-scores. Conclusion: The study's findings offer insight into the prognosis of OS and its immune microenvironment, and hold promise for improving early diagnosis and immunotherapy.

Common autoimmune diseases and urticaria: the causal relationship from a bidirectional two-sample mendelian randomization study.

Objective: The immune response assumes a pivotal role in the underlying mechanisms of urticaria pathogenesis. The present study delves into an investigation of the genetic causal connections between urticaria and prevalent autoimmune afflictions, notably rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn's disease (CD). Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationships involving four autoimmune diseases and urticaria. The genome-wide association study (GWAS) summary data of four autoimmune disease were sourced from the IEU OpenGWAS database. The GWAS summary data for urticaria were derived from the Finnish consortium dataset. The principal analytical approach employed in this study was the random-effects inverse variance weighted (IVW) method. Subsequently, a series of sensitivity analyses were performed, encompassing assessments of heterogeneity, horizontal pleiotropy, outliers, "Leave-one-out" analyses, and tests for adherence to the assumption of normal distribution. Results: The random-effects IVW analysis indicate a positive genetic causal association between RA and urticaria (P < 0.001, OR 95% CI = 1.091 [1.051-1.133]). Conversely, SLE, UC, and CD do not exhibit a significant genetic causal relationship with urticaria. The reverse MR analysis reveals a positive genetic causal linkage between urticaria and SLE (P = 0.026, OR 95% CI = 1.289 [1.031-1.612]). However, the analysis demonstrates no substantial genetic causal relationship between urticaria and RA, UC, or CD. Importantly, the genetic causal assessment absence of heterogeneity, horizontal pleiotropy, and outliers. Furthermore, it remains unaffected by any individual single nucleotide polymorphism (SNP), demonstrating adherence to a normal distribution. Conclusion: This investigation establishing RA as a predisposing factor for urticaria. Moreover, urticaria as a plausible risk determinant for SLE. Heightened vigilance is recommended among RA patients to monitor the manifestation of urticaria within clinical settings. Similarly, individuals afflicted by urticaria should duly acknowledge the prospective susceptibility to SLE.

Ferroptosis-related lncRNAs guiding osteosarcoma prognosis and immune microenvironment.

OBJECTIVE: To investigate the ferroptosis-related long non-coding RNAs (FRLncs) implicated in influencing the prognostic and immune microenvironment in osteosarcoma (OS), and to establish a foundational framework for informing clinical decision making pertaining to OS management. METHODS: Transcriptome data and clinical data pertaining to 86 cases of OS, the GSE19276, GSE16088 and GSE33382 datasets, and a list of ferroptosis-related genes (FRGs) were used to establish a risk prognostic model through comprehensive analysis. The identification of OS-related differentially expressed FRGs was achieved through an integrated analysis encompassing the aforementioned 86 OS transcriptome data and the GSE19276, GSE16088 and GSE33382 datasets. Concurrently, OS-related FRLncs were ascertained via co-expression analysis. To establish a risk prognostic model for OS, Univariate Cox regression analysis and Lasso Cox regression analysis were employed. Subsequently, a comprehensive evaluation was conducted, comprising risk curve analysis, survival analysis, receiver operating characteristic curve analysis and independent prognosis analysis. Model validation with distinct clinical subgroups was performed to assess the applicability of the risk prognostic model to diverse patient categories. Moreover, single sample gene set enrichment analysis (ssGSEA) was conducted to investigate variations in immune cell populations and immune functions within the context of the risk prognostic model. Furthermore, an analysis of immune checkpoint differentials yielded insights into immune checkpoint-related genes linked to OS prognosis. Finally, the risk prognosis model was verified by dividing the samples into train group and test group. RESULTS: We identified a set of seven FRLncs that exhibit potential as prognostic markers and influence factors of the immune microenvironment in the context of OS. This ensemble encompasses three high-risk FRLncs, denoted as APTR, AC105914.2 and AL139246.5, alongside four low-risk FRLncs, designated as DSCR8, LOH12CR2, AC027307.2 and AC025048.2. Furthermore, our analysis revealed notable down-regulation in the high-risk group across four distinct immune cell types, namely neutrophils, natural killer cells, plasmacytoid dendritic cells and tumor-infiltrating lymphocytes. This down-regulation was also reflected in four key immune functions, antigen-presenting cell (APC)-co-stimulation, checkpoint, cytolytic activity and T cell co-inhibition. Additionally, we identified seven immune checkpoint-associated genes with significant implications for OS prognosis, including CD200R1, HAVCR2, LGALS9, CD27, LAIR1, LAG3 and TNFSF4. CONCLUSION: The findings of this study have identified FRLncs capable of influencing OS prognosis and immune microenvironment, as well as immune checkpoint-related genes that are linked to OS prognosis. These discoveries establish a substantive foundation for further investigations into OS survival and offer valuable insights for informing clinical decision making in this context.

Iron, copper, zinc and magnesium on rheumatoid arthritis: a two-sample Mendelian randomization study.

This study aimed to elucidate the causal genetic relationships between iron, copper, zinc, magnesium, and rheumatoid arthritis (RA). A two-sample Mendelian randomization (MR) analysis was conducted using the "TwoSampleMR" and "MendelianRandomization" packages in R. The random-effects inverse variance-weighted (IVW) method was used as the primary approach. We performed sensitivity analyses to test the reliability of the results. The random-effects IVW analysis revealed that there was no genetic causal relationship between iron (P = 0.429, odds ratio [OR] 95% confidence interval [CI] = 0.919 [0.746-1.133]), copper (P = 0.313, OR 95% CI = 0.973 [0.921-1.027]), zinc (P = 0.633, OR 95% CI = 0.978 [0.891-1.073]), or magnesium (P = 0.218, OR 95% CI = 0.792 [0.546-1.148]) and RA. Sensitivity analysis verified the reliability of the results. Therefore, there is no evidence to support a causal relationship between iron, copper, zinc, and magnesium intake at the genetic level and the development of RA.

Identification of the potential regulatory interactions in rheumatoid arthritis through a comprehensive analysis of lncRNA-related ceRNA networks.

OBJECTIVE: This study aimed at constructing a network of competing endogenous RNA (ceRNA) in the synovial tissues of rheumatoid arthritis (RA). It seeks to discern potential biomarkers and explore the long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) axes that are intricately linked to the pathophysiological mechanisms underpinning RA, and providing a scientific basis for the pathogenesis and treatment of RA. METHODS: Microarray data pertaining to RA synovial tissue, GSE103578, GSE128813, and GSE83147, were acquired from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ). Conducted to discern both differentially expressed lncRNAs (DELncRNAs) and differentially expressed genes (DEGs). A ceRNA network was obtained through key lncRNAs, key miRNAs, and key genes. Further investigations involved co-expression analyses to uncover the lncRNA-miRNA-mRNA axes contributing to the pathogenesis of RA. To delineate the immune-relevant facets of this axis, we conducted an assessment of key genes, emphasizing those with the most substantial immunological correlations, employing the GeneCards database. Finally, gene set enrichment analysis (GSEA) was executed on the identified key lncRNAs to elucidate their functional implications in RA. RESULTS: The 2 key lncRNAs, 7 key miRNAs and 6 key genes related to the pathogenesis of RA were obtained, as well as 2 key lncRNA-miRNA-mRNA axes (KRTAP5-AS1-hsa-miR-30b-5p-PNN, XIST-hsa-miR-511-3p/hsa-miR-1277-5p-F2RL1). GSEA of two key lncRNAs obtained biological processes and signaling pathways related to RA synovial lesions. CONCLUSION: The findings of this investigation hold promise in furnishing a foundational framework and guiding future research endeavors aimed at comprehending the etiology and therapeutic interventions for RA.

Genetic causal relationship between age at menarche and benign oesophageal neoplasia identified by a Mendelian randomization study.

Objective: The occurrence and development of oesophageal neoplasia (ON) is closely related to hormone changes. The aim of this study was to investigate the causal relationships between age at menarche (AAMA) or age at menopause (AAMO) and benign oesophageal neoplasia (BON) or malignant oesophageal neoplasia (MON) from a genetic perspective. Methods: Genome-wide association study (GWAS) summary data of exposures (AAMA and AAMO) and outcomes (BON and MON) were obtained from the IEU OpenGWAS database. We performed a two-sample Mendelian randomization (MR) study between them. The inverse variance weighted (IVW) was used as the main analysis method, while the MR Egger, weighted median, simple mode, and weighted mode were supplementary methods. The maximum likelihood, penalized weighted median, and IVW (fixed effects) were validation methods. We used Cochran's Q statistic and Rucker's Q statistic to detect heterogeneity. The intercept test of the MR Egger and global test of MR pleiotropy residual sum and outlier (MR-PRESSO) were used to detect horizontal pleiotropy, and the distortion test of the MR-PRESSO analysis was used to detect outliers. The leave-one-out analysis was used to detect whether the MR analysis was affected by single nucleotide polymorphisms (SNPs). In addition, the MR robust adjusted profile score (MR-RAPS) method was used to assess the robustness of MR analysis. Results: The random-effects IVW results showed that AAMA had a negative genetic causal relationship with BON (odds ratio [OR] = 0.285 [95% confidence interval [CI]: 0.130-0.623], P = 0.002). The weighted median, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with random-effects IVW (P < 0.05). The MR Egger, simple mode and weighted mode results showed that AAMA had no genetic causal relationship with BON (P > 0.05). However, there were no causal genetic relationships between AAMA and MON (OR = 1.132 [95%CI: 0.621-2.063], P = 0.685), AAMO and BON (OR = 0.989 [95%CI: 0.755-1.296], P = 0.935), or AAMO and MON (OR = 1.129 [95%CI: 0.938-1.359], P = 0.200). The MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW (fixed effects) were consistent with a random-effects IVW (P > 0.05). MR analysis results showed no heterogeneity, the horizontal pleiotropy and outliers (P > 0.05). They were not driven by a single SNP, and were normally distributed (P > 0.05). Conclusion: Only AAMA has a negative genetic causal relationship with BON, and no genetic causal relationships exist between AAMA and MON, AAMO and BON, or AAMO and MON. However, it cannot be ruled out that they are related at other levels besides genetics.

Late age at first birth is a protective factor for oesophageal cancer and gastro-oesophageal reflux: the evidence from the genetic study.

Objective: The primary objective of this research endeavor was to examine the underlying genetic causality between the age at first birth (AFB) and four prevalent esophageal diseases, namely oesophageal obstruction (OO), oesophageal varices (OV), gastro-oesophageal reflux (GOR), and oesophageal cancer (OC). Methods: We conducted a two-sample Mendelian randomization (MR) analysis to examine the causal association between AFB and four prevalent esophageal disorders. We employed eight distinct MR analysis techniques to evaluate causal relationships, encompassing random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed-effects IVW. The random-effects IVW method served as the primary approach for our analysis. Furthermore, we executed several sensitivity analyses to assess the robustness of the genetic causal inferences. Results: The random-effects IVW analysis revealed a significant negative genetic causal association between AFB and both GOR (P < 0.001, Odds Ratio [OR] 95% Confidence Interval [CI] = 0.882 [0.828-0.940]) and OC (P < 0.001, OR 95% CI = 0.998 [0.998-0.999]). Conversely, there was insufficient evidence support to substantiate a genetic causal link between AFB and OO (P = 0.399, OR 95% CI = 0.873 [0.637-1.197]) or OV (P = 0.881, OR 95% CI = 0.978 [0.727-1.314]). The results of sensitivity analyses underscore the robustness and reliability of our MR analysis. Conclusion: The findings of this investigation substantiate the notion that elevated AFB confers a protective effect against GOR and OC. In addition, no causative association was discerned between AFB and OO or OV at the genetic level.

Bioinformatics Analysis Identified the Hub Genes, mRNA-miRNA-lncRNA Axis, and Signaling Pathways Involved in Rheumatoid Arthritis Pathogenesis.

Objective: Rheumatoid arthritis (RA) is a nonspecific, chronic, systemic autoimmune disease characterized by symmetric polyarticular synovitis. Bioinformatics analysis of potential biomarkers, mRNA-miRNA-lncRNA axes, and signaling pathways in the pathogenesis of RA provides potential targets and theoretical basis for further research on RA. Methods: The GSE1919 and GSE77298 datasets were downloaded from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo). Perl was used to perform data merging, and R was used to perform batch correction. The "limma" package of R was used to screen differentially expressed genes, and the "clusterProfiler" package was used to perform enrichment analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network, Cytoscape was used for module analysis, and R was used to screen for hub genes. GraphPad Prism was used to plot the receiver operating characteristic curve of the hub genes. Gene set enrichment analysis and competitive endogenous RNA network analysis were performed on hub genes with the greatest diagnostic values. The hub gene with the greatest diagnostic value was verified using immunohistochemical staining. Results: We obtained nine hub genes (ITGB2, VAMP8, HLA-A, PTAFR, SYK, FCER1G, HLA-DPB1, LCP2, and ACTR2) and four mRNA-miRNA-lncRNA axes (ITGB2-hsa-miR-486-3p-SNHG3, ITGB2-hsa-miR-338-5p-XIST, ITGB2-hsa-miR-5581-3p-XIST, and ITGB2-hsa-miR-1226-5p-XIST) related to the pathogenesis of RA. The nine hub genes were highly expressed, and ITGB2 had the highest diagnostic value for RA. We also identified signaling pathways related to the pathogenesis of RA: Fc epsilon Rl and chemokine signaling pathways. The immunohistochemical results showed that ITGB2 expression was significantly upregulated in RA. Conclusion: The hub genes, mRNA-miRNA-lncRNA axes, and signaling pathways related to RA pathogenesis identified in this study provide a new research direction for the mechanism, diagnosis, and treatment of RA.

LRPPRC contributes to the cisplatin resistance of lung cancer cells by regulating MDR1 expression.

The development of multidrug resistance is the major obstacle to successful lung cancer chemotherapy. Cancer cells gain resistance through increased levels of P­glycoprotein (P­gp), which is encoded by the multidrug resistance­associated protein 1 (MDR1) gene. Leucine­rich PPR motif­containing protein (LRPPRC), a member of the PPR family, has been verified to regulate the transcription of MDR1. This regulation is influenced by the methylation status of the GC ­100 box in the MDR1 promoter. The present study aimed to investigate the effect of LRPPRC on cisplatin (DDP) resistance in lung cancer cells and explore the underlying mechanism. DDP­resistant non­small cell lung cancer cell lines (A549/DDP, H1299/DDP) were generated. The expression levels of LRPPRC and P­gp/MDR1, investigated by qPCR and western blot analysis, were increased in the A549/DDP and H1299/DDP cells compared with that in the parental cells. LRPPRC silencing with shRNA increased DDP sensitivity in vitro and in vivo. LRPPRC silencing inhibited the level of LRPPRC binding with the MDR1 promoter, investigated by chromatin immunoprecipitation­qPCR, and the corresponding MDR1 expression. Demethylation treatment rescued the decrease in the level of LRPPRC binding with MDR1 and the corresponding expression of MDR1 and the increase in DDP sensitivity due to LRPPRC silencing. Our study suggests that LRPPRC contributes to DDP resistance in lung cancer cells by regulating MDR1 transcription. Thus, LRPPRC may serve as a potential molecular target for chemo­resistance reversal in lung cancer.

LINC00641/miR-582-5p mediate oxaliplatin resistance by activating autophagy in gastric adenocarcinoma.

The poor prognosis of gastric adenocarcinoma is partly due to chemotherapy failure, especially the oxaliplatin-based chemotherapy. However, the specific mechanism of oxaliplatin resistance is unclear. We aim to find the roles that LINC00641 and miR-582-5p play in regulating oxaliplatin resistance. Quantitative reverse transcriptase-PCR was used to evaluate the expression of LINC00641 and microRNA-582-5p (miR-582-5p) in gastric cancer both in vivo and in vitro. Transwell and CCK-8 assays were performed; and LC3 I/II and p62 were detected by western blot to evaluate the activation of autophagy. LINC00641 expression was associated with prognosis and oxaliplatin resistance in patients with gastric adenocarcinoma. The expression of LINC00641 was higher in gastric cancer tissues; whereas miR-582-5p was down-regulated in gastric cancer tissues. Moreover, LINC00641 was highly expressed in oxaliplatin-resistant cell lines and miR-582-5p was down-regulated. In addition, LINC00641 negatively regulated the expression of miR-582-5p. With regard to biological functions, down-regulation of LINC00641 suppressed cell migration and proliferation. Further experiments indicated that down-regulation of LINC00641 inhibited the autophagy process, making gastric cancer cells more sensitive to oxaliplatin. LINC00641 and miR-582-5p are biomarkers for predicting overall survival, as they were involved in regulating oxaliplatin resistance by altering autophagy in gastric adenocarcinoma.

Prediction for cardiovascular diseases based on laboratory data: An analysis of random forest model.

BACKGROUND: To establish a prediction model for cardiovascular diseases (CVD) in the general population based on random forests. METHODS: A retrospective study involving 498 subjects was conducted in Xi'an Medical University between 2011 and 2018. The random forest algorithm was used to screen out the variables that greatly affected the CVD prediction and to establish a prediction model. The important variables were included in the multifactorial logistic regression analysis. The area under the curve (AUC) was compared between logistic regression model and random forest model. RESULTS: The random forest model revealed the variables, including the age, body mass index (BMI), fasting blood glucose (FBG), diastolic blood pressure (DBP), triglyceride (TG), systolic blood pressure (SBP), total cholesterol (TC), waist circumference, and high-density lipoprotein-cholesterol (HDL-C), were more significant for CVD prediction; the AUC was 0.802 in CVD prediction. Multifactorial logistic regression analysis indicated that the risk factors for CVD included the age [odds ratio (OR): 1.14, 95% confidence intervals (CI): 1.10-1.17, P < .001], BMI (OR: 1.13, 95% CI: 1.06-1.20, P < .001), TG (OR: 1.11, 95% CI: 1.02-1.22, P = .023), and DBP (OR: 1.04, 95% CI: 1.02-1.06, P = .001); the AUC was 0.843 in CVD prediction. The established logistic regression prediction model was Logit P = Log[P/(1 - P)] = -11.47 + 0.13 × age + 0.12 × BMI + 0.11 × TG + 0.04 × DBP; P = 1/[1 + exp(-Logit P)]. People were prone to develop CVD at the time of P > .51. CONCLUSIONS: A prediction model for CVD is developed in the general population based on random forests, which provides a simple tool for the early prediction of CVD.

Inhibition of endometrial carcinoma by Kaempferol is interceded through apoptosis induction, G2/M phase cell cycle arrest, suppression of cell invasion and upregulation of m-TOR/PI3K signalling pathway.

PURPOSE: The main purpose of this study was to investigate the selective anticancer effects of Kaempferol against MFE-280 endometrial carcinoma cells along with evaluating its effects on apoptotic pathway, cell cycle phase distribution, cell invasion, cell migration and m-TOR/PI3K/Akt signalling pathway. METHODS: Cell viability of MFE-280 endometrial carcinoma cells was assessed by MTS [(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)] assay. Apoptosis was determined by acridine orange (AO)/ ethidium bromide (EB) double staining. Cell cycle analysis was determined by flow cytometry, while Boyden chamber assay was performed to study the effects of Kaempferol on cell migration and cell invasion, respectively. The effects of Kaempferol on the protein expression of m-TOR/PI3K/Akt signalling pathway were analysed by Western blot assay. RESULTS: Kaempferol exerted considerable and selective anticancer effects on MFE-280 endometrial carcinoma cells with IC50 of 10 µM. The anticancer effects were found to be due to activation of mitochondrial-mediated apoptotic pathway and G2/M phase cell cycle arrest. Furthermore, the results also revealed that Kaempferol significantly inhibited cell migration and cell invasion trend of these cancer cells. Our results also showed that, in comparison to the untreated cells, Kaempferol-treated cells exhibited a dose-dependent downregulation of p-mTOR, p-PI3K and p-AKT proteins. However, mTOR, PI3K and Akt expression levels remained more or less unaltered. CONCLUSIONS: In conclusion, the present study indicates that Kaempferol could exert anticancer effects in MFE-280 endometrial carcinoma cells selectively and that these effects were mediated via apoptosis induction, cell cycle arrest and inhibition of m-TOR/PI3K/Akt signalling pathway.

Psychotropic and Anticonvulsant Medication: Individuals With Intellectual and Developmental Disabilities Who Transitioned to the Community From an Institution.

Influenced by Georgia's settlement agreement with the United States Department of Justice relating to the enforcement of the Americans with Disabilities Act, an increasing number of individuals with intellectual and developmental disabilities (IDD) are transitioning from institutions to community living. In this study we evaluate the pattern of medication use among individuals who recently transitioned to the community (IRTC), comparing results to the IDD population already residing in the community (comparison group). Average use and prevalence rates were trended over time, between January 1, 2010, and December 31. 2012. Findings indicate a significant increase in medication use in the IRTC and comparison group, with a greater and faster increase in the IRTC population. We suggest the transition process should be examined and revised, ensuring adequate preparation time and training for each person and relevant staff, particularly on medications and challenging behaviors. Several demographic trends were also significant and are discussed.

Evaluating intense rehabilitative therapies with and without acupuncture for children with cerebral palsy: a randomized controlled trial.

OBJECTIVE: To compare the outcomes of conventional therapies (physical, occupational, and hydrotherapies) plus acupuncture with those without acupuncture when administered intensely in the management of children with spastic cerebral palsy (CP). DESIGN: Evaluation-blind, prospective randomized controlled trial. SETTING: Therapies and video-recorded assessments at a children's hospital in Beijing, China, and blind scoring and data analyses at a university in the United States. PARTICIPANTS: Children (N=75), 12 to 72 months of age, with spastic CP. INTERVENTIONS: Intensely administered (5 times per week for 12wk) physical therapy, occupational therapy, and hydrotherapy either with acupuncture (group 1) or without acupuncture (group 2). To satisfy standard of care, group 2 subsequently received acupuncture (weeks 16-28). MAIN OUTCOME MEASURES: The Gross Motor Function Measure (GMFM)-66 and the Pediatric Evaluation of Disability Inventory (PEDI) assessments at 0, 4, 8, 12, 16, and 28 weeks. RESULTS: At the end of 12 weeks, there was no statistically significant difference between the 2 groups, but when group 2 received acupuncture (16-28wk) there was a shift toward improvement in the GMFM-66 and the PEDI-Functional Skills Self-Care and Mobility domain. When groups were combined, statistically significant improvements after intense therapies occurred from baseline to 12 weeks for each outcome measure at each Gross Motor Function Classification System (GMFCS) level. After adjusting for expected normative maturational gains based on age, the GMFM gains for children with GMFCS II level was statistically significant (P<.05) with a mean gain of 6.5 versus a predicted gain of 3.4. CONCLUSIONS: Intense early administered rehabilitation improves function in children with spastic CP. The contribution from acupuncture was unclear. Children's response varied widely, suggesting the importance of defining clinical profiles that identify which children might benefit most. Further research should explore how this approach might apply in the U.S.

Randomized controlled trial of traditional Chinese medicine (acupuncture and tuina) in cerebral palsy: part 1--any increase in seizure in integrated acupuncture and rehabilitation group versus rehabilitation group?

OBJECTIVE: The objective of this study was to observe for any change in baseline seizure frequency with acupuncture in children with cerebral palsy. METHODS: A randomized controlled study was conducted: Group I consisted of integrated acupuncture, tuina, and rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks; and Group II consisted of rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks. After a washout period of 4 weeks, Group II then received acupuncture and tuina for 12 weeks. Each subject received 5 daily acupuncture sessions per week for 12 weeks (total = 60 sessions). All children were assessed for any change in seizure frequency during treatment. RESULTS: One hundred and sixteen (116) children were recruited and randomized into Group I (N = 58) and Group II (N = 58). Thirty-three (33) children withdrew (9 from Group I and 24 from Group II). Of the remaining 83 children, Group I consisted of 49 and Group II of 34 children. For baseline, 5 children (6%; 5/83) had seizures. During phase 1 (12 weeks) of integrative treatment and subsequent 4-week follow-up, 3 children in Group I had seizures. Among those 3 children with seizures, 1 child with prior history of recurrent febrile seizure had 3 more recurrent febrile seizures during acupuncture treatment and 2 children without any prior history of seizures had new-onset seizures (1 with 3 recurrent febrile seizures and 1 with afebrile seizure). For Group I, 2 children with epilepsy had no increase in seizure frequency during acupuncture treatment. For Group II during the phase 2 acupuncture period, none had increase in seizure frequency. In both groups, 4 of 5 children (80%; 2 in Group I and 2 in Group II) with seizures had no increase in seizure frequency during acupuncture treatment and follow-up. CONCLUSIONS: The risk of increasing seizure is not increased with acupuncture treatment for cerebral palsy.

Thorough skin self-examination in patients with melanoma.

PURPOSE/OBJECTIVES: To examine the feasibility of using Weinstock et al.'s thorough skin self-examination (TSSE) assessment in patients with melanoma, to describe TSSE characteristics of patients with melanoma, and to explore associations of personal and disease variables with TSSE. DESIGN: Cross-sectional, descriptive feasibility study; part of a larger study of melanoma in families. SETTING: Outpatient melanoma clinics in a National Cancer Institute-designated comprehensive cancer center. SAMPLE: Purposive sample of 70 predominantly white participants (47% women, 53% men), with a mean age of 65 years (SD = 11 years) and pathologically confirmed cutaneous melanoma (any stage). METHODS: Weinstock et al.'s TSSE assessment (self-report of the number of times patients examined the surface of seven specific body areas during the prior two months) and items regarding partnered TSSE and skin examination from healthcare providers. MAIN RESEARCH VARIABLES: Frequency of TSSE and healthcare provider skin examination, partnered TSSE, and reasons for not performing TSSE. FINDINGS: Forty-one (59%) participants reported performing TSSE; by Weinstock et al.'s criteria, only 23 (33%) practiced TSSE. Use of a partner was significantly associated with TSSE (p = 0.001); patients indicated high rates of skin examination by healthcare providers. CONCLUSIONS: Patients with melanoma are at high risk for recurrent disease. TSSE contributes to early detection of melanoma. Although Weinstock et al.'s TSSE assessment is feasible for use among patients with melanoma in a clinical setting, the focus should be on examination of specific body areas, rather than global skin examination. Overall, patients with melanoma had a low frequency of TSSE; however, data regarding previous knowledge or instruction of TSSE were not collected. Involving a partner enhances the frequency of TSSE. IMPLICATIONS FOR NURSING: Patients with melanoma should be informed of the importance of conducting systematic TSSE and using a partner during examination; however, some patients may prefer skin examination by healthcare providers. Measurement of TSSE self-report merits further study.