The cytokine FAM3B/PANDER is an FGFR ligand that promotes posterior development in Xenopus.

Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior-posterior (A-P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in Xenopus embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals. However, the molecular mechanism of FAM3B action in these processes remains poorly understood, largely because its receptor is still unidentified. Here we uncover an unexpected role of FAM3B acting as a FGF receptor (FGFR) ligand in Xenopus embryos. fam3b messenger RNA (mRNA) is initially expressed maternally and uniformly in the early Xenopus embryo and then in the epidermis at neurula stages. Overexpression of Xenopus fam3b mRNA inhibited cephalic structures and induced ectopic tail-like structures. Recombinant human FAM3B protein was purified readily from transfected tissue culture cells and, when injected into the blastocoele cavity, also caused outgrowth of tail-like structures at the expense of anterior structures, indicating FGF-like activity. Depletion of fam3b by specific antisense morpholino oligonucleotides in Xenopus resulted in macrocephaly in tailbud tadpoles, rescuable by FAM3B protein. Mechanistically, FAM3B protein bound to FGFR and activated the downstream ERK signaling in an FGFR-dependent manner. In Xenopus embryos, FGFR activity was required epistatically downstream of Fam3b to mediate its promotion of posterior cell fates. Our findings define a FAM3B/FGFR/ERK-signaling pathway that is required for axial patterning in Xenopus embryos and may provide molecular insights into FAM3B-associated human diseases.

Enhancing antioxidant levels and mitochondrial function in porcine oocyte maturation and embryonic development through notoginsenoside R1 supplementation.

This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.

Segmental and global myocardial work in hypertensive patients with different left ventricular geometry.

BACKGROUND: Myocardial work acquired by echocardiography has emerged as a novel method to evaluate myocardial function. We investigated global and segmental myocardial work in hypertension (HT) among patients with different patterns of left ventricular (LV) geometry in order to analyze the contribution of segmental myocardial work to global myocardial work. METHODS AND RESULTS: One hundred twenty-five patients with HT were divided into 4 groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH) and eccentric hypertrophy (EH). Longitudinal strain (LS) and the following indices were obtained by echocardiography: myocardial work index (MWI), myocardial constructive work (MCW), myocardial wasted work (MWW), and myocardial work efficiency (MWE). The global longitudinal strain (GLS) decreased gradually among the groups: NG, CR, CH and EH (P < 0.001). Global MWI (GWI) and global MCW (GCW) did not change across the different LV remodeling groups. Global MWW (GWW) increased and global MWE (GWE) decreased in both CH and EH group (P < 0.001). The LS of basal and middle regions reduced gradually in all HT subgroups, while apical LS decreased only in the CH and EH groups (P < 0.001). Basal MWI and MCW decreased in the CH and EH groups (P = 0.025, 0.007, respectively). Apical MWI and MCW increased in the NG and CR groups (P = 0.015, 0.044, respectively), with a decreasing trend in the CH and EH groups. All segmental MWW elevated and MWE reduced significantly in the CH and EH groups (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated a significant association between left atrial volume index (LAVI), GLS, GWE and LV hypertrophy. At the receiver operating characteristic (ROC) analysis, optimal cutoff values of GLS, Apical LS, GWE and Apical MWE discriminating LV hypertrophy were 0.9072, 0.8049, 0.8325 and 0.7414, respectively. CONCLUSION: Apical myocardial work increases in the early stages of LV remodeling, likely as a compensatory mechanism to maintain normal global myocardial work. Segmental myocardial work analysis offers a reliable means to explore the distribution of myocardial impairment in hypertensive patients at different LV remodeling stages.

A392V and R945X mutations cause orofacial clefts via impairing PTCH1 function.

The Hedgehog (HH) signaling plays key roles in embryogenesis and organogenesis, and its dysfunction causes a variety of human birth defects. Orofacial cleft (OFC) is one of the most common congenital craniofacial defects, and its etiology is closely related to mutations in multiple components in the HH pathway, including the PTCH1 receptor. A quantity of PTCH1 variants have been associated with OFC, but the pathogenicity and underlying mechanism of these variants have not been functionally validated. In our previous studies, we identified two PTCH1 variants (A392V and R945X) in two families with hereditary OFC. Here we explore the functional consequences of these two variants. In zebrafish embryos, microinjection of wild type PTCH1 mRNA causes curved body axis and craniofacial anomalies. In contrast, microinjection of A392V and R945X PTCH1 mRNAs results in much milder phenotypes, suggesting these two variants are loss-of-function mutations. In mammalian cells, A392V and R945X mutations reverse the inhibitory effect of PTCH1 on HH signaling. Biochemically, the two mutants PTCH1 show lower expression levels and shortened half-life, indicting these mutations decrease the stability of PTCH1. A392V and R945X mutations also appear to cause PTCH1 to localize away from vesicles. Taken together, our findings indicate that A392V and R945X variants are loss-of-function mutations that disrupt the function of PTCH1 and thus cause dysregulation of HH signaling, leading to the pathogenesis of OFC.

Establishment of a novel classification system for alveolar morphology in infants with unilateral complete cleft lip and palate.

OBJECTIVES: Unilateral complete cleft lip and palate (UCCLP) is one of the most severe clinical subtypes among cleft lip and palate (CLP), making repair surgery and subsequent orthodontic treatment particularly challenging. Presurgical nasoalveolar molding (PNAM) has shown conflicting and heterogeneous results in the treatment of UCCLP patients, raising questions about whether the diversity in alveolar anatomical morphology among these patients plays a role in the effectiveness of PNAM treatment. MATERIALS AND METHODS: We collected 90 digital maxillary models of infants with UCCLP and performed mathematical clustering analysis, including principal component analysis (PCA), decision tree modeling, and area under the ROC Curve (AUC) analysis, to classify alveolar morphology and identify key measurements. We also conducted clinical evaluations to assess the association between the alveolar morphology and CLP treatment outcomes. RESULTS: Using mathematical clustering analysis, we classified the alveolar morphology into three distinct types: average form, horizontal form, and longitudinal form. The decision tree model, AUC analysis, and comparison analysis revealed that four measurements (Trans ACG-ACL, ML length, MG length and Inc length) were essential for clustering the alveolar morphology of infants with UCCLP. Furthermore, the blinded clinical evaluation indicated that UCCLP patients with alveolar segments of horizontal form had the lowest treatment outcomes. CONCLUSION: Overall, our findings establish a novel quantitative classification system for the morphology of alveolar bone in infants with UCCLP and suggest that this classification may be associated with the outcomes of CLP treatment. CLINICAL RELEVANCE: The multidisciplinary CLP team should thoroughly evaluate and classify the specific alveolar morphology when administering PNAM to infants with UCCLP.

Comparative Phosphoproteomic Profiling in the Prefrontal Cortex of Prenatally Stressed Male Offspring Rats.

Many investigations have indicated that prenatal stress (PS) causes depressive-like disturbances in offspring rats. However, the underlying pathogenic mechanisms have not yet been fully elucidated. The prefrontal cortex (PFC) has been shown to play a role in susceptibility to stress during fetal development; thus, we focused our attention on differential protein phosphorylation in this region of PS-S (susceptibility to PS) offspring rats. The sucrose preference test was used to screen for susceptibility to PS. The validity of the prenatally stressed model was verified by other common depression-like behaviors. We used MS-based TMT quantitative proteomics in combination with the phosphopeptide enrichment method to compare phosphoproteomic profiling in the PFC of PS-S and control male offspring rats. In total, 3,418 phosphoproteins, 8,404 phosphopeptides, and 12,175 phosphosites were identified in this analysis. According to the screening criteria, 902 phosphopeptides increased and 609 decreased in the PFC of the PS-S group compared to the control rats. Gene ontology enrichment analysis indicated that the main enriched terms in the cellular component category were "synapse part," "myelin sheath," "synapse," "neuron part," and "axon." The phosphoproteins enriched in the molecular function and biological process categories were mainly related to cytoskeleton- and projection morphogenesis-associated proteins. KEGG pathway enrichment analyses identified 30 significant KEGG pathways; the top five pathways included salivary secretion, endocrine and other factor-regulated calcium reabsorption, pancreatic secretion, and insulin secretion. Motifs such as ……_S_P…RR, ……S_PE……, ……_S_PV……, ……_S_P.H……, and …S…_S_PT…. were the top five motifs enriched in phosphorylated sites. PS may induce depressive-like behaviors in male offspring rats by regulating the phosphorylation of proteins mainly related to synapses, myelin sheaths, neurons, and the cytoskeleton. The phosphorylation of related proteins may act as key pathogenic hits. Data are available via ProteomeXchange with identifier PXD026563.

GmNAC181 promotes symbiotic nodulation and salt tolerance of nodulation by directly regulating GmNINa expression in soybean.

Soybean (Glycine max) is one of the most important crops world-wide. Under low nitrogen (N) condition, soybean can form a symbiotic relationship with rhizobia to acquire sufficient N for their growth and production. Nodulation signaling controls soybean symbiosis with rhizobia. The soybean Nodule Inception (GmNINa) gene is a central regulator of soybean nodulation. However, the transcriptional regulation of GmNINa remains largely unknown. Nodulation is sensitive to salt stress, but the underlying mechanisms are unclear. Here, we identified an NAC transcription factor designated GmNAC181 (also known as GmNAC11) as the interacting protein of GmNSP1a. GmNAC181 overexpression or knockdown in soybean resulted in increased or decreased numbers of nodules, respectively. Accordingly, the expression of GmNINa was greatly up- and downregulated, respectively. Furthermore, we showed that GmNAC181 can directly bind to the GmNINa promoter to activate its gene expression. Intriguingly, GmNAC181 was highly induced by salt stress during nodulation and promoted symbiotic nodulation under salt stress. We identified a new transcriptional activator of GmNINa in the nodulation pathway and revealed a mechanism by which GmNAC181 acts as a network node orchestrating the expression of GmNINa and symbiotic nodulation under salt stress conditions.

Genome-Wide Identification and Characterization of the Soybean DEAD-Box Gene Family and Expression Response to Rhizobia.

DEAD-box proteins are a large family of RNA helicases that play important roles in almost all cellular RNA processes in model plants. However, little is known about this family of proteins in crops such as soybean. Here, we identified 80 DEAD-box family genes in the Glycine max (soybean) genome. These DEAD-box genes were distributed on 19 chromosomes, and some genes were clustered together. The majority of DEAD-box family proteins were highly conserved in Arabidopsis and soybean, but Glyma.08G231300 and Glyma.14G115100 were specific to soybean. The promoters of these DEAD-box genes share cis-acting elements involved in plant responses to MeJA, salicylic acid (SA), low temperature and biotic as well as abiotic stresses; interestingly, half of the genes contain nodulation-related cis elements in their promoters. Microarray data analysis revealed that the DEAD-box genes were differentially expressed in the root and nodule. Notably, 31 genes were induced by rhizobia and/or were highly expressed in the nodule. Real-time quantitative PCR analysis validated the expression patterns of some DEAD-box genes, and among them, Glyma.08G231300 and Glyma.14G115100 were induced by rhizobia in root hair. Thus, we provide a comprehensive view of the DEAD-box family genes in soybean and highlight the crucial role of these genes in symbiotic nodulation.

Dissecting the association between psychiatric disorders and neurological proteins: a genetic correlation and two-sample bidirectional Mendelian randomization study.

OBJECTIVES: The role of neurological proteins in the development of bipolar disorder (BD) and schizophrenia (SCZ) remains elusive now. The current study aims to explore the potential genetic correlations of plasma neurological proteins with BD and SCZ. METHODS: By using the latest genome-wide association study (GWAS) summary data of BD and SCZ (including 41,917 BD cases, 11,260 SCZ cases, and 396,091 controls) derived from the Psychiatric GWAS Consortium website (PGC) and a recently released GWAS of neurological proteins (including 750 individuals), we performed a linkage disequilibrium score regression (LDSC) analysis to detect the potential genetic correlations between the two common psychiatric disorders and each of the 92 neurological proteins. Two-sample Mendelian randomisation (MR) analysis was then applied to assess the bidirectional causal relationship between the neurological proteins identified by LDSC, BD and SCZ. RESULTS: LDSC analysis identified one neurological protein, NEP, which shows suggestive genetic correlation signals for both BD (coefficient = -0.165, p value = 0.035) and SCZ (coefficient = -0.235, p value = 0.020). However, those association did not remain significant after strict Bonferroni correction. Two sample MR analysis found that there was an association between genetically predicted level of NEP protein, BD (odd ratio [OR] = 0.87, p value = 1.61 × 10-6) and SCZ (OR = 0.90, p value = 4.04 × 10-6). However, in the opposite direction, there is no genetically predicted association between BD, SCZ, and NEP protein level. CONCLUSION: This study provided novel clues for understanding the genetic effects of neurological proteins on BD and SCZ.

High-efficient and precise base editing of C•G to T•A in the allotetraploid cotton (Gossypium hirsutum) genome using a modified CRISPR/Cas9 system.

The base-editing technique using CRISPR/nCas9 (Cas9 nickase) or dCas9 (deactivated Cas9) fused with cytidine deaminase is a powerful tool to create point mutations. In this study, a novel G. hirsutum-Base Editor 3 (GhBE3) base-editing system has been developed to create single-base mutations in the allotetraploid genome of cotton (Gossypium hirsutum). A cytidine deaminase sequence (APOBEC) fused with nCas9 and uracil glycosylase inhibitor (UGI) was inserted into our CRISPR/Cas9 plasmid (pRGEB32-GhU6.7). Three target sites were chosen for two target genes, GhCLA and GhPEBP, to test the efficiency and accuracy of GhBE3. The editing efficiency ranged from 26.67 to 57.78% at the three target sites. Targeted deep sequencing revealed that the C→T substitution efficiency within an 'editing window', approximately six-nucleotide windows of -17 to -12 bp from the PAM sequence, was up to 18.63% of the total sequences. The 27 most likely off-target sites predicted by CRISPR-P and Cas-OFFinder tools were analysed by targeted deep sequencing, and it was found that rare C→T substitutions (average < 0.1%) were detected in the editing windows of these sites. Furthermore, whole-genome sequencing analyses on two GhCLA-edited and one wild-type plants with about 100× depth showed that no bona fide off-target mutations were detectable from 1500 predicted potential off-target sites across the genome. In addition, the edited bases were inherited to T1 progeny. These results demonstrate that GhBE3 has high specificity and accuracy for the generation of targeted point mutations in allotetraploid cotton.

Expression and Prognostic Significance of Cadherin 4 (CDH4) in Renal Cell Carcinoma.

BACKGROUND Aberrant expression of cadherin family members and their possible biological function have been widely studied in renal cell carcinoma (RCC). However, the expression of cadherin 4 (CDH4) and its value in RCC diagnosis and prognosis remains elusive. MATERIAL AND METHODS The TCGA database was used to analyze the expression of CDH4 and its clinical parameters and prognosis in 891 RCC patients. In addition, real-time PCR was used to verify the transcription of CDH4 in renal clear cell carcinoma tissue, and the distribution of protein was observed by immunohistochemical staining. RESULTS We found that the mRNA level of CDH4 was elevated in primary RCC in contrast with normal kidney samples using bioinformatics analysis based on the TCGA database. Among the 3 main subtypes of RCC, transcriptional CDH4 was significantly increased in KIRC and KIRP, while it was downregulated in KICH. Interestingly, CDH4 mRNA gradually decreased with the progression of KIRC and KIRP. The transcription of CDH4 in the primary tumor of KIRP patients at T3-T4 stages and KIRC patients with lymph node and distant metastasis were decreased significantly. Overall survival (OS) showed that KIRC and KICH patients with lower expression of CDH4 had worse outcomes. CONCLUSIONS The transcriptional level of CDH4 may serve as an effective diagnostic and prognostic biomarker for RCC patients.

Impact of Sevoflurane Versus Propofol Anesthesia on Post-Operative Cognitive Dysfunction in Elderly Cancer Patients: A Double-Blinded Randomized Controlled Trial.

BACKGROUND Research on the clinical outcomes of surgical patients anaesthetized with sevoflurane and the association of sevoflurane with post-operative cognitive dysfunction (POCD) is scarce. We evaluated whether sevoflurane-based anesthesia increased the incidence of POCD and worsened prognosis compared to propofol-based anesthesia in elderly cancer patients. MATERIAL AND METHODS This single-center, prospective, double-blind randomized controlled trial included 234 patients aged 65 to 86 years undergoing tumor resection who received sevoflurane-based (Group S) or propofol-based (Group P) anesthesia during surgery. A series of neuropsychological tests was performed to evaluate cognitive function before surgery and at 7 days and 3 months post-operation, and the results were compared to those of healthy controls. RESULTS At 7 days post-operation there were no significant differences in the incidence of POCD between patients who received sevoflurane-based or propofol-based anesthesia during surgery: Group S was at 29.1% (32 out of 110 patients) versus Group P at 27.3% (30 out of 110), P=0.764. At 3 months, Group S was at 11.3% (12 out of 106 patients) versus Group P at 9.2% (10 out of 109), P=0.604. During the first 2 days post-operation, the QoR-40 global score was significantly lower in Group S compared to Group P [POD 1: P=0.004; POD 2: P=0.001]. There were no significant differences in in-hospital post-operative complications, post-operative length of hospital stay, all-cause mortality at 30 days, and 3 months post-operation, or post-operative quality of life at 3 months between patients in Group S and Group P. CONCLUSIONS Sevoflurane-based anesthesia did not increase the incidence of POCD compared to propofol-based anesthesia at 7 days or 3 months post-operation or impact short-term post-operative prognosis.

Prevalence and risk factors of nocturnal enuresis among children ages 5-12 years in Xi'an, China: a cross-sectional study.

BACKGROUND: Nocturnal enuresis (NE) has a negative impact on children's health and imposes a long-term burden on families. With economic development and cultural improvements, parents and medical professionals pay more attention to NE. The aim of this study was to investigate the prevalence and risk factors of NE among children ages 5-12 years in Xi'an, China. METHODS: A stratified cluster sampling method was used to conduct a cross-sectional study of NE in 10 kindergartens and 20 primary schools in Xi'an. We used univariate analysis to compare the prevalences of characteristics such as gender, duration of disposable diaper (DD) use, toilet training onset time, daily living habits, academic performance, and family history of NE. Logistic regression analysis was used to calculate odds ratio and to determine risk factors of NE. RESULTS: The study included 6568 children ages 5-12 years, of which 262 (3.99%) had NE. The prevalence rates of NE decreased with age, with the highest prevalence at age 5 (9.09% for boys; 6.03% for girls). However, the prevalence increased with duration of DD use. Children experienced more NE if they never accepted toilet training (7.83%) or if they drank sugary beverages during the day (5.36%). Sleep disorders, sweets intake, drinking low amounts of plain water during the day, and family history of NE, were statistically associated with NE. CONCLUSION: NE was closely associated with a family history of NE, being male, long-term use of DD, delayed toilet training, drinking sugary beverages and/or consuming little plain water, and sleep disorders. A supportive parental attitude towards NE and timely medical treatment can improve the quality of life of enuretic children.

Cancer-Related Anemia Is a Risk Factor for Medium-Term Postoperative Cognitive Dysfunction in Laparoscopic Surgery Patients: An Observational Prospective Study.

Anemia in the elderly may impair cognitive function. Our primary objective was to determine whether cancer-related anemia was associated with postoperative cognitive dysfunction (POCD) in nonelderly patients. We conducted an observational prospective study of 177 patients scheduled for laparoscopic surgery. Patients aged 18-64 were divided into two groups according to whether they were anemic due to cancer or not. The cognitive function was assessed by the Mini-Mental State Examination (MMSE) 1 day before and 1 week after operation. The cognitive function of the patients was evaluated by using the Telephone Interview for Cognitive Status-Modified (TICS-M) 3 months after operation. The quality of life of patients was evaluated after operation. The hemoglobin level and other clinical data were recorded before operation. Of the 170 patients, 100 without anemia and 70 anemia patients had been evaluated 1 week after operation. POCD was detected in 43 cases (25.3% of 170 cases) at 1 week and 30 cases (19% of 158 cases) at 3 months postoperatively. Anemia was an independent risk factor for 3-month POCD occurrence (P = 0.034). The education level of the patients who had POCD at 1 week and 3 months after operation was lower (P < 0.001, P = 0.011, respectively). Age was independently associated with the incidence of POCD at 3 months (P = 0.011). In general, these findings suggested that anemia may increase the incidence of medium-term POCD in cancer patients undergoing laparoscopic surgery.

Down-regulation of microRNA-144-3p and its clinical value in non-small cell lung cancer: a comprehensive analysis based on microarray, miRNA-sequencing, and quantitative real-time PCR data.

BACKGROUND: Previous studies have shown that miR-144-3p might be a potential biomarker in non-small cell lung cancer (NSCLC). Nevertheless, the comprehensive mechanism behind the effects of miR-144-3p on the origin, differentiation, and apoptosis of NSCLC, as well as the relationship between miR-144-3p and clinical parameters, has been rarely reported. METHODS: We investigated the correlations between miR-144-3p expression and clinical characteristics through data collected from Gene Expression Omnibus (GEO) microarrays, the relevant literature, The Cancer Genome Atlas (TCGA), and real-time quantitative real-time PCR (RT-qPCR) analyses to determine the clinical role of miR-144-3p in NSCLC. Furthermore, we investigated the biological function of miR-144-3p by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Protein-protein interaction (PPI) network was created to identify the hub genes. RESULTS: From the comprehensive meta-analysis, the combined SMD of miR-144-3p was - 0.95 with 95% CI of (- 1.37, - 0.52), indicating that less miR-144-3p was expressed in the NSCLC tissue than in the normal tissue. MiR-144-3p expression was significantly correlated with stage, lymph node metastasis and vascular invasion (all P <  0.05). As for the bioinformatics analyses, a total of 37 genes were chosen as the potential targets of miR-144-3p in NSCLC. These promising target genes were highly enriched in various key pathways such as the protein digestion and absorption and the thyroid hormone signaling pathways. Additionally, PPI revealed five genes-C12orf5, CEP55, E2F8, STIL, and TOP2A-as hub genes with the threshold value of 6. CONCLUSIONS: The current study validated that miR-144-3p was lowly expressed in NSCLC. More importantly, miR-144-3p might function as a latent tumor biomarker in the prognosis prediction for NSCLC. The results of bioinformatics analyses may present a new method for investigating the pathogenesis of NSCLC.

Integrative analysis of transcriptome-wide association study data and mRNA expression profiles identified candidate genes and pathways associated with atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia characterized by extensive structural, contractile and electrophysiological remodeling. The genetic basis of AF remained elusive until now. Transcriptome-wide association study (TWAS) was conducted by FUSION tool using gene expression weights of 7 tissues combined with a large-scale genome-wide association study (GWAS) dataset of AF, totally involving 8180 AF cases and 28,612 controls. Significant genes identified by TWAS were then subjected to gene ontology (GO) and pathway enrichment analysis. The genome-wide mRNA gene expression profiling of AF was compared with the results of TWAS to detect common genes shared by TWAS and mRNA expression profiling of AF. TWAS detected a group of candidate genes with PTWAS values < 0.05 across the seven tissues for AF, such as CMAH (PTWAS = 3.15 × 10-25 for whole blood), INCENP (PTWAS = 1.77 × 10-22 for artery aorta), CMAHP (PTWAS = 4.57 × 10-20 for artery aorta). Pathway enrichment analysis identified multiple candidate pathways, such as protein K48-linked ubiquitination (P value = 0.0124), positive regulation of leukocyte chemotaxis (P value = 0.0046) and fatty acid degradation (P value = 0.0295). Further comparing the GO results of TWAS and mRNA expression profiling, 2 common GO terms were identified, including actin binding (PTWAS = 0.0446, PmRNA = 7.00 × 10-4) and extracellular matrix (PTWAS = 0.0037, PmRNA = 3.00 × 10-6). We detected multiple novel candidate genes, GO terms and pathways for AF, providing novel clues for understanding the genetic mechanism of AF.

Value of Ferritin Heavy Chain (FTH1) Expression in Diagnosis and Prognosis of Renal Cell Carcinoma.

BACKGROUND Serum ferritin is a useful tumor marker for renal cell carcinoma (RCC). However, the expression of ferritin heavy chain (FTH1), the main subunit of ferritin, is unclear in primary RCC tissues. In this study, we investigated FTH1 mRNA expression and its diagnostic and prognostic value in RCC. MATERIAL AND METHODS The mRNA expression of FTH1 was analyzed using including Oncomine, Gene Expression Omnibus, and Cancer Genome Atlas datasets, while the protein level of FTH1 was analyzed using the Human Protein Atlas database. The associations between FTH1 and clinicopathologic characteristics and survival time and Cox multivariate survival analysis were analyzed using SPSS 22.0 software. A meta-analysis was performed to assess consistency of FTH1 expression. GO, KEGG, and PPI analyses were used to predict biological functions. RESULTS According to TCGA data, overexpression of FTH1 was detected in 890 RCC tissues (15.2904±0.63157) compared to 129 normal kidney tissues (14.4502±0.51523, p<0.001). Among the clinicopathological characteristics evaluated, patients with increased pathologic T staging, lymph node metastasis, and distant metastasis were significantly associated with higher expression of FTH1. Elevated FTH1 mRNA levels were correlated with worse prognosis of RCC patients. Cox multivariate survival analysis indicated that age, stage, and M stage were predictors of poor prognosis in patients with RCC. CONCLUSIONS Our data suggest that FTH1 expression is an effective prognostic and diagnosis biomarker for RCC.

[Project to Increase the Percentage of Nursing Staffs Passing Clinical Ladder-3 Certification in the Intensive Care Unit].

BACKGROUND & PROBLEMS: Clinical ladder (CL)-3 nurses should have both an ability to integrate the clinical information of critically ill patients and to carry out the administrative work of the intensive care unit. However, in our unit, only 15.3% of nurses hold CL-3 certification, which is much lower than the hospital average of 23.1%. Thus, we initiated a project to raise this percentage in our unit. An analysis in January 2016 showed that the main obstacles to obtaining CL-3 certification in our unit were inability to write case reports, inadequate in-service education, and a lack of certified educators. PURPOSE: The purpose of this project was to increase the number of CL-3-certified nurses in our intensive care unit. RESOLUTION: The resolution included holding courses on case report writing, briefings, and oral presentation techniques; assigning a preceptor to make nursing staff assignments; encouraging nurses to participate in the clinical nursing preceptor education training camp; and conducting practice tests using a multiple assessment tool. RESULTS: After implementation of this project, the percentage of unit nurses who had passed CL-3 increased to 39.0%. CONCLUSIONS: This project not only allowed our fellow nurses to share in the joy of clinical ladder advancement but also improved the atmosphere in the unit by encouraging self-development. This project helped stimulate professional growth among our staff and improved the quality of clinical care.

[Clinical Simulation Teaching Program to Promote the Effectiveness of Nurses in Coping With Workplace Violence].

BACKGROUND: Workplace violence is a phenomenon that is prevalent around the world. Nursing personnel are one of the most frequent victims of workplace attacks. Beyond the harm done to physical health, mental health, and workplace morale, workplace violence also leads to the loss of personnel and causes severe injury to institutions and nursing professionals. PURPOSE: The aim of this study is to improve the awareness, attitudes, and self-confidence of nurses with regard to workplace violence using clinical simulation teaching and training courses. METHODS: A total of 400 clinical nurses at a tertiary hospital in Taipei City were enrolled and randomly assigned into either the experimental group, which received the education intervention, or the control group, which received no intervention. A total of 392 enrolled participants completed the study, including 200 in the experimental group and 192 in the control group. Before and after the intervention, a structured questionnaire was used to collect data, which were analyzed using a GEE model with SPSS V.23. RESULTS: After the clinical simulation teaching course, awareness of workplace violence as well as related attitudes and self-confidence were higher in the experimental group than the control group. Moreover, the posttest scores and pretest-posttest differences in scores were significantly higher in the experimental group than in the control group (p < .001). Advanced analysis of the data showed that cognition scores, being older in age, and having a registered nurse grade of N3 were all associated with earning a higher score. In addition, in terms of attitude, registered nurse grade was found to correlate positively with score. Further, male participants earned higher self-confidence scores than their female colleagues and participants who worked in either the emergency or psychiatric departments earned higher scores. CONCLUSIONS: The "Workplace Violence Clinical Simulation Teaching and Training Course" was shown to improve the awareness, attitudes, and self-confidence of clinical nurses with regard to workplace violence and may thus help reduce the risk and harm of violence in this category. In the future, contextual teaching courses on workplace violence prevention should be developed for different nursing levels, divisions, and units based on their specific characteristics and needs.

Investigation on left ventricular multi-directional deformation in patients of hypertension with different LVEF.

BACKGROUND: This study is aimed at investigating myocardial multi-directional systolic deformation in hypertensive with different left ventricular ejection fraction (LVEF), and exploring its contribution to LVEF. METHODS: One hundred and twenty-three patients with primary hypertension (HT) were divided into group A (LVEF ≥ 55%), group B (45% ≤ LVEF < 50%, or 50% ≤ LVEF < 55% + LVEDVI ≥ 97 ml/m2), and group C (LVEF < 45%). Two-dimensional strain echocardiography (2DSE) including LV longitudinal strain (SL), radial strain (SR) and circumferential strain (SC) were measured. RESULTS: SL decreased gradually from group A, B to C (all p < 0.05) while SR and SC were reduced only in group B and C (all p < 0.05). All strain measurements correlated to LVEF, with the strongest correlation in SC (r = -0.82, p < 0.01) and the second in SL (r = -0.76). The diastolic E/e increased from group A, B to C. CONCLUSIONS: Left ventricular multi-directional deformation correlated well to LVEF in hypertension and particularly SC, indicating that it was SC, not SL or SR, that makes the prominent contribution to left ventricular pump function.