Contrastive representation learning on dynamic networks.

Representation learning for dynamic networks is designed to learn the low-dimensional embeddings of nodes that can well preserve the snapshot structure, properties and temporal evolution of dynamic networks. However, current dynamic network representation learning methods tend to focus on estimating or generating observed snapshot structures, paying excessive attention to network details, and disregarding distinctions between snapshots with larger time intervals, resulting in less robustness for sparse or noisy networks. To alleviate these challenges, this paper proposes a contrastive mechanism for temporal representation learning on dynamic networks, inspired by the success of contrastive learning in visual and static network representation learning. This paper proposes a novel Dynamic Network Contrastive representation Learning (DNCL) model. Specifically, contrast objective functions are constructed using intra-snapshot and inter-snapshot contrasts to capture the network topology, node feature information, and network evolution information, respectively. Rather than estimating or generating ground-truth network features, the proposed approach maximizes mutual information between nodes from different time steps and views generated. The experimental results of link prediction, node classification, and clustering on several real-world and synthetic networks demonstrate the superiority of DNCL over state-of-the-art methods, indicating the effectiveness of the proposed approach for dynamic network representation learning.

Study on core competencies of midwives in China.

The aim of this study is to investigate the core competencies of midwives in China. Combination of qualitative research and quantitative research. A total of 100 midwives in 3 tertiary (Grade 3) hospitals in Shijiazhuang were investigated by using the Midwife Core Competency Scale, and simultaneously followed by semi-structured interviews with 12 midwives. The questionnaire survey showed that the average score of core competencies of midwives was 4.17 ± 0.17. The scores of midwives' competency for labor and delivery care (4.31 ± 0.09), new-born care (4.29 ± 0.04), and postpartum care (4.25 ± 0.13) were relatively high, while the prepregnancy care had the lowest score (3.88 ± 0.07). The interview results showed that the self-perception of core midwifery competencies was not bad, the limitations of midwives' work scope affect the core competencies, and midwifery education needs to strengthen the humanistic care and the training of obstetric knowledge and technology.

The SMAD2/miR-4256/HDAC5/p16INK4a signaling axis contributes to gastric cancer progression.

The dysregulation of exosomal microRNAs (miRNAs) plays a crucial role in the development and progression of cancer. This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer (GC) and the underlying mechanisms. The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics. Next, the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues, and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments. Then, the effect of miR-4256 on its downstream target genes HDAC5/p16INK4a was studied in GC cells, and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation (ChIP). Additionally, the role of the miR-4256/HDAC5/p16INK4a axis in GC was studied using in vitro and in vivo experiments. Finally, the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments. miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues; in vitro and in vivo results showed that miR-4256 promoted GC growth and progression. Mechanistically, miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells, and then restrained the expression of p16INK4a through the epigenetic modulation of HDAC5 at the p16INK4a promoter. Furthermore, miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells. Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16INK4a axis, which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.

Efficacy and safety of vedolizumab in the treatment of patients with inflammatory bowel disease: A systematic review and meta­analysis of randomized controlled trials.

Few studies have thoroughly assessed the efficacy and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD). Therefore, this systematic review and meta-analysis was performed to further evaluate this association. PubMed, Embase, and the Cochrane databases were searched until April 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of VDZ in the treatment of IBD were included. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome using a random effects model. A total of 12 RCTs, including 4,865 patients, met the inclusion criteria. In the induction phase, VDZ was more effective than placebo for patients with ulcerative colitis and Crohn's disease (CD) in clinical remission (RR=2.09; 95% CI=1.66-2.62) and clinical response (RR=1.54; 95% CI=1.34-1.78). In the maintenance therapy group, VDZ reached higher clinical remission (RR=1.98; 95% CI=1.58-2.49) and clinical response (RR=1.78; 95% CI=1.40-2.26) rates compared with the placebo group. VDZ particularly improved clinical remission (RR=2.07; 95% CI=1.48-2.89) and clinical response (RR=1.84; 95% CI=1.54-2.21) in patients with TNF antagonist failure. In terms of corticosteroid-free remission, VDZ was also more effective than placebo in patients with IBD (RR=1.98; 95% CI=1.51-2.59). In Crohn's patients, VDZ was more effective than placebo in terms of mucosal healing (RR=1.78; 95% CI=1.27-2.51). With respect to adverse events, VDZ significantly reduced the risk of IBD exacerbation compared with the placebo (RR=0.60; 95% CI=0.39-0.93; P=0.023). However, when compared with the placebo, VDZ increased the risk of nasopharyngitis in patients with CD (RR=1.77; 95% CI=1.01-3.10; P=0.045). No significant differences in other adverse events were observed. Although there might be underlying risk, such as selection bias, in the present study it can be safely concluded that VDZ is a safe and effective biological agent for IBD, particularly for patients with TNF antagonist failure.

A Freshwater Fish-Based Diet Alleviates Liver Steatosis by Modulating Gut Microbiota and Metabolites: A Clinical Randomized Controlled Trial in Chinese Participants With Nonalcoholic Fatty Liver Disease.

INTRODUCTION: We aimed to assess the effects of 2 isoenergetic intervention diets (a freshwater fish-based diet [F group] or freshwater fish-based and red meat-based diets alternately [F/M group]) on liver steatosis and their relationship with intestinal flora in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: In this open-label, 84-day randomized controlled trial, 34 NAFLD patients with hepatic steatosis ≥10% were randomly assigned to the F group or F/M group in a 1:1 ratio using a computer-generated random number allocation by a researcher not involved in the study. Liver fat content and gut microbiota and its metabolites were measured. RESULTS: At the end of intervention, the absolute reduction of hepatic steatosis was significantly greater in the F group than in the F/M group (-4.89% vs -1.83%, P = 0.032). Of the 16 secondary clinical outcomes, the improvement in 7 in the F group was greater compared with the F/M group, including alanine aminotransferase and gamma-glutamyl transferase. Furthermore, dietary freshwater fish and red meat consumption alternately did not exacerbate NAFLD. Moreover, changes in the enrichment of Faecalibacterium, short-chain fatty acids, and unconjugated bile acids and the depletion of Prevotella 9 and conjugated bile acids in the F group were significantly greater compared with the F/M group. DISCUSSION: Higher intake of freshwater fish may be beneficial to NAFLD by regulating gut microbiota and its metabolites, whereas intake of a similar total of animal protein and fat from the alternating freshwater fish and red meat may not be harmful for NAFLD in the dietary management of patients with NAFLD.

Insulin-Like Growth Factor 1 Receptor Drives Hepatocellular Carcinoma Growth and Invasion by Activating Stat3-Midkine-Stat3 Loop.

BACKGROUND: Activation of the insulin-like growth factor 1 receptor (IGF-1R)-mediated Janus kinase (JAK)1/2-Stat3 pathway contributes to hepatocarcinogenesis. Specifically, a previous study showed that IGF-1R inhibition downregulated Midkine expression in hepatocellular carcinoma (HCC). AIMS: The present study investigated the role of IGF-1R-JAK1/2-Stat3 and Midkine signaling in HCC, in addition to the molecular link between the IGF-1R-Stat3 pathway and Midkine. METHODS: The expression levels of IGF-1R, Stat3, and Midkine were measured using reverse transcription-quantitative PCR, following which the association of IGF-1R with Stat3 and Midkine expression was evaluated in HCC. The molecular link between the IGF-1R-Stat3 pathway and Midkine was then investigated in vitro before the effect of IGF-1R-Stat3 and Midkine signaling on HCC growth and invasion was studied in vitro and in vivo. RESULTS: IGF-1R, Stat3, and Midkine mRNA overexpressions were all found in HCC, where the levels of Stat3 and Midkine mRNA correlated positively with those of IGF-1R. In addition, Midkine mRNA level also correlated positively with Stat3 mRNA expression in HCC tissues. IGF-1R promoted Stat3 activation, which in turn led to the upregulation of Midkine expression in Huh7 cells. Similarly, Midkine also promoted Stat3 activation through potentiating JAK1/2 phosphorylation. Persistent activation of this Stat3-Midkine-Stat3 positive feedback signal loop promoted HCC growth and invasion, the inhibition of which resulted in significant antitumor activities both in vitro and in vivo. CONCLUSIONS: Constitutive activation of the IGF-1R-mediated Stat3-Midkine-Stat3 positive feedback loop is present in HCC, the inhibition of which can serve as a potential therapeutic intervention strategy for HCC.

Quantification of Liver Fat Content after Radiofrequency Ablation for Liver Cancer: Correlation with Hepatic Perfusion Disorders.

PURPOSE: To quantitatively investigate the correlation between liver fat content and hepatic perfusion disorders (HPD) after radiofrequency ablation (RFA) for liver cancer using magnetic resonance imaging (MRI)-determined proton density fat fraction (PDFF). MATERIALS AND METHODS: A total of 150 liver cancer patients underwent liver MRI examination within one month after RFA and at four months after RFA. According to the liver fat content, they were divided into non-, mild, moderate, and severe fatty liver groups. The liver fat content and hepatic perfusion disorders were determined using PDFF images and dynamic contrast-enhanced MRI images. The relationship between the liver fat content and HPD was investigated. RESULTS: At the first postoperative MRI examination, the proportion of patients in the nonfatty liver group with hyperperfused foci (11.11%) was significantly lower than that in the mild (30.00%), moderate (42.86%), and severe fatty liver (56.67%) groups (p < 0.05), whereas the proportions of patients with hypoperfused foci (6.67%, 7.5%, 5.71%, and 6.67%, respectively) were not significantly different among the four groups (p > 0.05). In the nonfatty liver group, the liver fat content was not correlated with hyperperfusion abnormalities or hypoperfusion abnormalities. By contrast, in the three fatty liver groups, the liver fat content was correlated with hyperperfusion abnormalities but was not correlated with hypoperfusion abnormalities. At the second postoperative MRI examination, six patients in the nonfatty liver group were diagnosed with fatty liver, including two patients with newly developed hyperperfusion abnormalities and one patient whose hypoperfusion abnormality remained the same as it was in the first postoperative MRI examination. CONCLUSION: There was a high correlation between the liver fat content and hyperperfusion abnormalities after RFA for liver cancer. The higher the liver fat content was, the higher the was risk of hyperperfusion abnormalities. However, there was little correlation between liver fat content and hypoperfusion abnormalities, and the increase in postoperative liver fat content did not induce or alter the presence of hypoperfused foci.

Research on Higher English Internationalization Education Model and Evaluation Index System Based on Multi-Source Information Fusion.

With the continuous development of the global economy, the degree of internationalization and openness has gradually deepened. Higher English internationalization education also needs to keep pace with the times and keep pace with international development. At this time, it is necessary to build a multi-source information fusion algorithmic higher English international education model and evaluation index system to better adapt to the trend of higher English international education in the future. In the current higher English teaching process, it is necessary to change the traditional teaching concepts, change the previous teaching ideas, continuously expand the horizons, build an international and diversified English teaching training program, and actively absorb excellent education concepts from foreign excellent teaching models, which has better promoted the development of English teaching.

A cluster-randomized field trial to reduce cesarean section rates with a multifaceted intervention in Shanghai, China.

BACKGROUND: Cesarean section (CS) rate has risen dramatically and stayed at a very high level in China over the past two to three decades. Given the short- and long-term adverse effects of CS, effective strategies are needed to reduce unnecessary CS. We aimed to evaluate whether a multifaceted intervention would decrease the CS rate in China. METHODS: We carried out a cluster-randomized field trial with a multifaceted intervention in Shanghai, China, from 2015 to 2017. A total of 20 hospitals were randomly allocated into an intervention or a control group. The intervention consisted of more targeted health education to pregnant women, improved hospital CS policy, and training of midwives/doulas for 8 months. The study included a baseline survey, the intervention, and an evaluation survey. The primary outcome was the changes of overall CS rate from the pre-intervention to the post-intervention period. A subgroup analysis stratified by the Robson classification was also conducted to examine the CS change among women with various obstetric characteristics. RESULTS: A total of 10,752 deliveries were randomly selected from the pre-intervention period and 10,521 from the post-intervention period. The baseline CS rates were 42.5% and 41.5% in the intervention and control groups, respectively, while the post-intervention CS rates were 43.4% and 42.4%, respectively. Compared with the control group, the intervention did not significantly reduce the CS rate (adjusted OR = 0.92; 95% CI 0.73, 1.15). Similar results were obtained in subgroup analyses stratified by the risk level of pregnancy, maternal age, number of previous CS, or parity. Scarred uterus and maternal request remained the primary reasons for CS after the interventions in both groups. The intervention did not alter the perinatal outcomes (adjusted change of risk score = - 0.06; 95%CI - 0.43, 0.31). CONCLUSIONS: A multifaceted intervention including more targeted prenatal health education, improved hospital CS policy, and training of midwives/doulas, did not significantly reduce the CS rate in Shanghai, China. However, our experience in implementing a multifaceted intervention may provide useful information to other similar areas with high CS use. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (ChiCTR-IOR-16009041) on 17 August 2016.

Mean peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis: a diagnostic meta-analysis.

BACKGROUND: Thyrotoxicosis is often caused by destructive thyroiditis (DT) or Graves' disease (GD), and a prompt and accurate differential diagnosis for thyrotoxicosis is needed as management strategy differs. A meta-analysis of published literature was performed to evaluate the diagnostic accuracy for differentiating GD from DT patients by the measurement of mean peak systolic velocity of superior thyroid artery (STA-PSV) using ultrasonography. METHODS: The databases of Embase, Pubmed, Cochrane, Web of Science, Wanfang, and CNKI were retrieved without time limit to identify eligible studies. The statistical information and scientific quality were assessed and classified. The data were analyzed using Stata12.0 software. RESULTS: A total of 11 studies with 1052 cases only from Asia were included. Meta-analysis results showed the pooled sensitivity and pooled specificity of STA-PSV by ultrasonography were 0.86 (95% CI, 0.80-0.90) and 0.93 (95% CI, 0.86-0.97) in distinguishing GD from DT, respectively, with the AUC of 0.94 (95% CI, 0.92-0.96) . CONCLUSION: STA-PSV by ultrasonography is a useful diagnostic method in differentiating GD from DT. More studies from other countries are needed to further evaluate the accuracy of STA-PSV for the differential diagnosis of thyrotoxicosis.

MiR-483-5p promotes IGF-II transcription and is associated with poor prognosis of hepatocellular carcinoma.

The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5'-untranslated region (5'UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5'UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5'UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.

Novel Symbol Learning-Induced Stroop Effect: Evidence for a Strategy-Based, Utility Learning Model.

The automaticity level and attention priority/strategy are two major theories that have attempted to explain the mechanism underlying the Stroop effect. Training is an effective way to manipulate the experience with the two dimensions (ink color and color word) in the Stroop task. In order to distinguish the above two factors (the automaticity or attention/strategy), we revised the training paradigm of MacLeod's study (J Exp Psychol Learn Mem Cogn 14(1):126-135, 1988) by adding a control condition for the Stroop task on Chinese. We found that with training, the changing pattern for the Stroop effect was similar in Stroop tasks in novel symbols and in Chinese, showing markedly increasing interference and marginally decreasing facilitation. The current findings support the strategy-based learning account at early stages of novel learning of written symbols.

The impact of auditory working memory training on the fronto-parietal working memory network.

Working memory training has been widely used to investigate working memory processes. We have shown previously that visual working memory benefits only from intra-modal visual but not from across-modal auditory working memory training. In the present functional magnetic resonance imaging study we examined whether auditory working memory processes can also be trained specifically and which training-induced activation changes accompany theses effects. It was investigated whether working memory training with strongly distinct auditory materials transfers exclusively to an auditory (intra-modal) working memory task or whether it generalizes to a (across-modal) visual working memory task. We used adaptive n-back training with tonal sequences and a passive control condition. The memory training led to a reliable training gain. Transfer effects were found for the (intra-modal) auditory but not for the (across-modal) visual transfer task. Training-induced activation decreases in the auditory transfer task were found in two regions in the right inferior frontal gyrus. These effects confirm our previous findings in the visual modality and extents intra-modal effects in the prefrontal cortex to the auditory modality. As the right inferior frontal gyrus is frequently found in maintaining modality-specific auditory information, these results might reflect increased neural efficiency in auditory working memory processes. Furthermore, task-unspecific (amodal) activation decreases in the visual and auditory transfer task were found in the right inferior parietal lobule and the superior portion of the right middle frontal gyrus reflecting less demand on general attentional control processes. These data are in good agreement with amodal activation decreases within the same brain regions on a visual transfer task reported previously.

[A survey on the dioxin level in breast milk in coastal and inland region].

OBJECTIVE: To study the dioxin level of breast milk among Chinese mothers, and to assess the dioxin intake of new-born babies from mother's milk and compare with the Tolerable Daily Intake (TDI) of dioxin. METHODS: The CALUX bioassay was used to detect the dioxin concentration of the first time mother's milk among the inland samples (Shenyang region; 32 cases) and the coastal city samples (Dalian region; 47 cases). RESULTS: The median value of the dioxin Toxic Equivalence (TEQ) in breast milk in the Dalian region was 15.84 pg TEQs.g(-1) fat, which was significantly higher than that in the Shenyang region 7.21 pg TEQs.g(-1) fat (P < 0.01). CONCLUSION: The dioxin level in breast milk in Chinese is at the world's average level. The dioxin intake of the new-born babies during the period of lactation was higher than the lowest limit of the Tolerable Daily Intake (TDI) proposed by WHO. This situation should be noticed by the related authorities.