Effects of implementing non-nutritive sucking on oral feeding progression and outcomes in preterm infants: A systematic review and meta-analysis.

BACKGROUND: Preterm infants have imperfect neurological development, uncoordinated sucking-swallowing-breathing, which makes it difficult to realize effective oral feeding after birth. How to help preterm infants achieve complete oral feeding as soon as possible has become an important issue in the management of preterm infants. Non-nutritive sucking (NNS), as a useful oral stimulation, can improve the effect of oral feeding in preterm infants. This review aimed to explore the effect of NNS on oral feeding progression through a meta-analysis. METHODS: We systematically searched PubMed, CINHAL, Web of Science, Embase, Cochrane databases, China's National Knowledge Infrastructure (CNKI), Wanfang and VIP database from inception to January 20, 2024. Search terms included 'non-nutritive sucking' 'oral feeding' and 'premature.' Eligibility criteria involved randomized controlled studies in English or Chinese. Studies were excluded if they were reviews, case reports, or observational studies from which valid data could not be extracted or outcome indicators were poorly defined. The meta-analysis will utilize Review Manager 5.3 software, employing either random-effects or fixed-effects models based on observed heterogeneity. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous data, and estimated pooled odds ratios (ORs) for dichotomous data. Sensitivity and publication bias analyses were conducted to ensure robust and reliable findings. We evaluated the methodological quality of randomized controlled trials (RCTs) utilizing the assessment tool provided by the Cochrane Collaboration. RESULTS: A total of 23 randomized controlled trials with 1461 preterm infants were included. The results of the meta-analysis showed that NNS significantly shortened time taken to achieve exclusive oral feeding (MD = -5.37,95%CI = -7.48 to-3.26, p<0.001), length of hospital stay(MD = -4.92, 95% CI = -6.76 to -3.09, p<0.001), time to start oral feeding(MD = -1.41, 95% CI = -2.36 to -0.45, p = 0.004), time to return to birth weight(MD = -1.72, 95% CI = -2.54 to -0.91, p<0.001). Compared to the NNS group, the control group had significant weight gain in preterm infants, including weight of discharge (MD = -61.10, 95% CI = -94.97 to -27.23, p = 0.0004), weight at full oral feeding (MD = -86.21, 95% CI = -134.37 to -38.05, p = 0.0005). In addition, NNS reduced the incidence of feeding intolerance (OR = 0.22, 95% CI = 0.14 to 0.35, p<0.001) in preterm infants. CONCLUSION: NNS improves oral feeding outcomes in preterm infants and reduces the time to reach full oral feeding and hospitalization length. However, this study was limited by the relatively small sample size of included studies and did not account for potential confounding factors. There was some heterogeneity and bias between studies. More studies are needed in the future to validate the effects on weight gain and growth in preterm infants. Nevertheless, our meta-analysis provides valuable insights, updating existing evidence on NNS for improving oral feeding in preterm infants and promoting evidence-based feeding practices in this population.

Effects of responsive breastfeeding intervention on breastfeeding and infant growth in China: A randomised controlled trial.

Responsive feeding serves as an important protective factor for infant growth and overall health development. This study based on self-determination theory (SDT) aimed to assess the effects of a responsive breastfeeding (RBF) intervention programme on maternal breastfeeding and infant growth and development. A total of 110 mother-infant pairs were recruited and randomly divided into an intervention group (n = 55) and a control group (n = 55). The primary outcomes were breastfeeding motivation score, breastfeeding self-efficacy (BSE) and exclusive breastfeeding rate; the secondary outcomes were infant physical development at 6 weeks and 3 months. A repeated measures ANOVA indicated that the intervention group had significantly higher Enjoyment scores compared to the control group at three time points: at discharge (MD: 5.28; 95% CI: 3.68 to 6.89; p < 0.001), 6 weeks post-partum (MD: 5.06; 95% CI: 3.80 to 6.31; p < 0.001) and 3 months post-partum (MD: 5.24; 95% CI: 4.12 to 6.35; p < 0.001). Similarly, the intervention group reported significantly higher connection and mother's self-perception scores at discharge (MD: 4.31; 95% CI: 3.07 to 5.56; p < 0.001), 6 weeks post-partum (MD: 4.69; 95% CI: 3.71 to 5.68; p < 0.001) and 3 months post-partum (MD: 4.93; 95% CI: 4.14 to 5.72; p < 0.001), compared to the control group. In contrast, the pressure from significant others scores were higher in the control group relative to the intervention group at discharge (MD: -2.09; 95% CI: -2.88 to -1.31; p < 0.001), 6 weeks post-partum (MD: -4.35; 95% CI: -5.20 to -3.49; p < 0.001) and 3 months (MD: -4.89; 95% CI: -5.70 to -4.08; p < 0.001). Finally, the intervention group also reported higher Instrumental Needs scores at all three time points: at discharge (MD: 1.96; 95% CI: 1.35 to 2.58; p < 0.001), 6 weeks post-partum (MD: 3.58; 95% CI: 3.05 to 4.11; p < 0.001) and 3 months post-partum (MD: 1.18; 95% CI: 0.68 to 1.69; p < 0.001). BSE scores were significantly higher in the intervention group compared to the control group at discharge (MD: 14.29; 95% CI: 10.38 to 18.21; p < 0.001), 6 weeks post-partum (MD: 14.04; 95% CI: 11.05 to 17.02; p < 0.001) and 3 months post-partum (MD: 6.80; 95% CI: 4.66 to 8.94; p < 0.001). The rates of exclusive breastfeeding were higher in the intervention group than in the control group at each stage of the intervention (p < 0.01). At 6 weeks post-partum, the intervention group's infants showed slower weight (t = -0.90, p = 0.371) and length (t = -0.69, p = 0.495) growth compared to the control group, though not significantly. By 3 months post-partum, there was a significant difference in both weight (t = -3.46, p = 0.001) and length (t = -2.95, p = 0.004) between the groups. The findings in this study suggest that the RBF intervention programme based on SDT may be effective in improving mothers' motivation to breastfeed, building breastfeeding self-confidence and increasing the rate of exclusive breastfeeding. The effects of the intervention on infant physical development will need to be verified with longer follow-up in future research.

Clinical efficacy of traditional Chinese medicine therapy for female stress urinary incontinence: a meta-analysis.

OBJECTIVES: To investigate the efficacy of traditional Chinese medicine (TCM) in the treatment of female stress urinary incontinence (SUI). METHOD: PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang, and VIP databases were searched for articles published up to September 2022. Variables were analyzed using weighted mean difference (WMD), standardized mean difference (SMD), odds ratios (OR), and 95% confidence interval (CI). RESULTS: Eight studies containing 744 patients were included in this study. The results demonstrate that TCM therapy had more advantages in improving the clinical outcome of SUI patients (OR = 2.90, 95%CI:1.92-4.37, P = 0.000), reducing the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) score (WMD = -2.41, 95%CI:-2.83- -1.98, P = 0.000), reducing 1-h urinary pad leakage urine volume (WMD = -1.86, 95%CI:-2.23- -1.49, P = 0.000) and increasing Maximum urethral closure pressure (MUCP) (SMD = 0.86, 95%CI: 0.61-1.11, P = 0.000). CONCLUSION: TCM therapy is effective in improving urinary incontinence symptoms, urodynamics, and quality of life in patients with SUI. This article provides a reference for the application of TCM therapy in women with urinary incontinence.

Factors influencing necrotizing enterocolitis in premature infants in China: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. However, studies with large samples on the factors of NEC in China have not been reported. This meta-analysis aims to systematically review the literature to explore the influencing factors of necrotizing enterocolitis in premature infants in China and provide a reference for the prevention of NEC. METHODS: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang and VIP databases were systematically searched from inception to February 2023. We used Stata14.0 software to perform the systematic review and meta-analysis. We used fixed or random effects models with combined odds ratios (ORs) and 95% confidence intervals (CIs), and quality was evaluated using the Newcastle‒Ottawa Scale (NOS). RESULTS: The total sample was 8616 cases, including 2456 cases in the intervention group and 6160 cases in the control group. It was found that 16 risk factors and 3 protective factors were related to necrotizing enterocolitis in premature infants. Septicemia (OR = 3.91), blood transfusion (OR = 2.41), neonatal asphyxia (OR = 2.46), pneumonia (OR = 6.17), infection (OR = 5.99), congenital heart disease (OR = 4.80), intrahepatic cholestasis of pregnancy (ICP) (OR = 2.71), mechanical ventilation (OR = 1.44), gestational diabetes mellitus (GDM) (OR = 3.08), respiratory distress syndrome (RDS) (OR = 3.28), hypoalbuminemia (OR = 2.80), patent ductus arteriosus (PDA) (OR = 3.10), respiratory failure (OR = 7.51), severe anemia (OR = 2.86), history of antibiotic use (OR = 2.12), and meconium-stained amniotic fluid (MSAF) (OR = 3.14) were risk factors for NEC in preterm infants in China. Breastfeeding (OR = 0.31), oral probiotics (OR = 0.36), and prenatal use of glucocorticoids (OR = 0.38) were protective factors for NEC in preterm infants. CONCLUSIONS: Septicemia, blood transfusion, neonatal asphyxia, pneumonia, infection, congenital heart disease, ICP, GDM, RDS, hypoproteinemia, PDA, respiratory failure, severe anemia, history of antibiotic use and MSAF will increase the risk of NEC in premature infants, whereas breastfeeding, oral probiotics and prenatal use of glucocorticoids reduce the risk. Due to the quantity and quality of the included literature, the above findings need to be further validated by more high-quality studies.

SS-GNN: A Simple-Structured Graph Neural Network for Affinity Prediction.

Efficient and effective drug-target binding affinity (DTBA) prediction is a challenging task due to the limited computational resources in practical applications and is a crucial basis for drug screening. Inspired by the good representation ability of graph neural networks (GNNs), we propose a simple-structured GNN model named SS-GNN to accurately predict DTBA. By constructing a single undirected graph based on a distance threshold to represent protein-ligand interactions, the scale of the graph data is greatly reduced. Moreover, ignoring covalent bonds in the protein further reduces the computational cost of the model. The graph neural network-multilayer perceptron (GNN-MLP) module takes the latent feature extraction of atoms and edges in the graph as two mutually independent processes. We also develop an edge-based atom-pair feature aggregation method to represent complex interactions and a graph pooling-based method to predict the binding affinity of the complex. We achieve state-of-the-art prediction performance using a simple model (with only 0.6 M parameters) without introducing complicated geometric feature descriptions. SS-GNN achieves Pearson's Rp = 0.853 on the PDBbind v2016 core set, outperforming state-of-the-art GNN-based methods by 5.2%. Moreover, the simplified model structure and concise data processing procedure improve the prediction efficiency of the model. For a typical protein-ligand complex, affinity prediction takes only 0.2 ms. All codes are freely accessible at https://github.com/xianyuco/SS-GNN.

Effect of prophylactic caffeine in the treatment of apnea in very low birth weight infants: a meta-analysis.

OBJECTIVE: The purpose of this meta-analysis is to investigate the effect of prophylactic caffeine use in the treatment of apnea and other clinical outcomes in very low birth weight infants. METHODS: We searched PubMed, Embase, Web of Science, Scopus, EBSCO, CNKI, and Cochrane databases for all relevant studies up to May 20, 2022. The meta-analysis was carried out using Stata16.0 and RevMan5.4 software. RESULTS: Eleven randomized controlled trials were evaluated, including a total of 4375 very low birth weight infants. The results demonstrated that prophylactic caffeine use was linked with a significantly lower probability of AOP (OR 0.31, 95% CI: 0.19-0.49, p < .001), duration of mechanical ventilation and oxygen therapy when compared to the control group. It also reduced the incidence of BPD (OR 0.62, 95% CI: 0.54-0.71, p < .001), PDA (OR 0.49, 95% CI: 0.30-0.80, p = .005) and ROP (OR 0.76, 95% CI: 0.65-0.90, p = .001), without raising the risk of NEC, IVH and death before hospital discharge (p > .05). CONCLUSION: This meta-analysis confirmed the beneficial effects of prophylactic caffeine in preventing apnea of prematurity and improving clinical outcomes.

Prevalence and risk factors of delayed onset lactogenesis II in China: a systematic review and meta-analysis.

BACKGROUND: In 2017, China proposed to achieve the goal that 50% of infants aged 0-6 months should be exclusively breastfed by 2025 proposed by the World Health Assembly in 2012. However, delayed onset lactogenesis II has adverse effects on breastfeeding and thus on neonatal health. There has been no meta-analysis of the prevalence and risk factors of delayed onset lactogenesis II among parturient women in China. To provide best practices, updated evidence-based evidence is needed to supplement reviews on this topic. OBJECTIVE: The purpose of this systematic review and meta-analysis was to quantitatively analyze the prevalence and risk factors of delayed onset lactogenesis II in China. METHODS: We identified relevant studies by searching literature published prior to October 2022 in PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases for all available observational studies. Stata 16.0 were used for performing the systematic review and meta-analysis. RESULTS: The researchers examined data from 14 observational studies involving 17610 females. The prevalence of delayed onset lactogenesis II from these studies was 31% (95% CI = 25.0%-38.0%, p < .001), and the prevalence showed a significant increasing trend in China over the past decade. The frequency of breastfeeding was >2 times per day at 24-48 h after delivery was one protective factor against delayed onset lactogenesis II (OR = 0.41). The significant risk factors for delayed onset lactogenesis II were breastfeeding initiation > 30min after birth (OR = 1.31), maternal age > 35 years (OR = 2.19), primiparous women (OR = 2.38), maternal overweight/obesity (OR = 2.22), cesarean section (OR = 1.33), anxiety (OR = 3.23), depression (OR = 3.21) and gestational hypertension (OR = 3.43). CONCLUSIONS: There is a high incidence of delayed onset lactogenesis II in Chinese parturient women. We identified eight risk factors and one protective factor for DOL II. These findings suggest health care professionals should pay attention to these risk parturients so as to better provide early preventive interventions to increase the breastfeeding rate.

Clinical efficacy of traditional Chinese medicine therapy for female stress urinary incontinence: a meta-analysis / Eficácia clínica da terapia da medicina tradicional chinesa para a incontinência urinária de esforço feminina: uma meta-análise / Eficacia clínica de la terapia de medicina tradicional china para la incontinencia urinaria de esfuerzo femenina: un metaanálisis

ABSTRACT Objectives: To investigate the efficacy of traditional Chinese medicine (TCM) in the treatment of female stress urinary incontinence (SUI). Method: PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang, and VIP databases were searched for articles published up to September 2022. Variables were analyzed using weighted mean difference (WMD), standardized mean difference (SMD), odds ratios (OR), and 95% confidence interval (CI). Results: Eight studies containing 744 patients were included in this study. The results demonstrate that TCM therapy had more advantages in improving the clinical outcome of SUI patients (OR = 2.90, 95%CI:1.92-4.37, P = 0.000), reducing the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) score (WMD = -2.41, 95%CI:-2.83- -1.98, P = 0.000), reducing 1-h urinary pad leakage urine volume (WMD = -1.86, 95%CI:-2.23- -1.49, P = 0.000) and increasing Maximum urethral closure pressure (MUCP) (SMD = 0.86, 95%CI: 0.61-1.11, P = 0.000). Conclusion: TCM therapy is effective in improving urinary incontinence symptoms, urodynamics, and quality of life in patients with SUI. This article provides a reference for the application of TCM therapy in women with urinary incontinence.

RESUMEN Objetivo: Investigar la eficacia de la medicina tradicional china (MTC) en el tratamiento de la incontinencia urinaria de esfuerzo (IUE) femenina. Método: Se llevaron a cabo búsquedas de artículos publicados hasta septiembre de 2022 en las bases de datos PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang y VIP. Las variables se analizaron mediante la diferencia de medias ponderada (DMP), la diferencia de medias estandarizada (DME), la razón de momios (RM) y el intervalo de confianza (IC) del 95%. Resultados: Este estudio incluyó ocho investigaciones con la participación de 744 pacientes. Los resultados indican que la terapia de medicina tradicional china (MTC) presentó mejoras significativas en los resultados clínicos de pacientes con incontinencia urinaria de esfuerzo (IUE) (RM = 2.90, IC del 95%: 1.92-4.37, P = 0.000), al reducir la puntuación del Cuestionario Internacional sobre la Incontinencia y su impacto en la calidad de vida (ICIQ-SF) (DMP = -2.41, IC del 95%: -2.83- -1.98, P = 0.000), así como la disminución del volumen de orina a la 1 hora de fuga de la almohadilla urinaria (DMP = -1.86, IC del 95%: -2.23- -1.49, P = 0.000) y el aumento de la presión de cierre uretral máxima (PCUM) (DME = 0.86, IC del 95%: 0.61-1.11, P = 0.000). Conclusión: La terapia de medicina tradicional china (MTC) resulta efectiva en la mejora de los síntomas de la incontinencia urinaria, la urodinámica y la calidad de vida en pacientes con incontinencia urinaria de esfuerzo (IUE). Este artículo ofrece una referencia para la aplicación de la terapia de MTC en mujeres con incontinencia urinaria.

RESUMO Objetivo: Investigar a eficácia da medicina tradicional chinesa (MTC) no tratamento da incontinência urinária de esforço (IUE) feminina. Método: Foram realizadas pesquisas de artigos publicados até setembro de 2022 nas bases de dados PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang e VIP. As variáveis foram analisadas por meio da diferença de média ponderada (DMP), da diferença média padronizada (DMP), da razão de chances (RC) e do intervalo de confiança (IC) de 95%. Resultados: Esta pesquisa envolveu oito estudos, contando com a participação de 744 pacientes. Os resultados indicam que a terapia da medicina tradicional chinesa (MTC) apresentou melhorias significativas nos resultados clínicos de pacientes com incontinência urinária de esforço (IUE) (RM = 2.90, IC de 95%: 1.92-4.37, P = 0.000), ao reduzir a pontuação do Questionário Internacional sobre a Incontinência Urinária - Versão Breve (ICIQ-SF) (Diferença de Média Ponderada = -2.41, IC de 95%: -2.83- -1.98, P = 0.000), assim como na diminuição do volume de urina na 1 hora de vazamento do absorvente urinário (Diferença de Média Ponderada = -1.86, IC de 95%: -2.23- -1.49, P = 0.000) e no aumento da pressão máxima de encerramento uretral (PMCU) (Diferença Média Padronizada = 0.86, IC de 95%: 0.61-1.11, P = 0.000). Conclusão: A terapia da medicina tradicional chinesa (MTC) é eficaz na melhoria dos sintomas da incontinência urinária, na urodinâmica e na qualidade de vida em pacientes com incontinência urinária de esforço (IUE). Este artigo fornece uma referência para a aplicação da terapia da MTC em mulheres com incontinência urinária.

Impact of Epstein-Barr virus infection in patients with inflammatory bowel disease.

A high prevalence of Epstein-Barr virus (EBV) infection in patients with inflammatory bowel disease (IBD) has been reported in many case reports and studies; thus, the association between EBV and IBD has gained increasing attention. Patients with IBD are at an increased risk of opportunistic EBV infection owing to the common use of immunomodulators. EBV infection in IBD patients can cause various complications, including superimposed viral colitis, which is associated with chronicity, exacerbation, and poor prognosis of refractory IBD, and can induce progression to lymphoproliferative disorders, such as EBV-positive mucocutaneous ulcer (EBVMCU), lymphomatoid granulomatosis (LYG), hemophagocytic lymphohistiocytosis (HLH) and diffuse large B-cell lymphoma (DLBCL). It has been suggested to screen for EBV before initiating immunosuppressive therapy and monitor the status of EBV infection in patients with IBD, especially those who are EBV-seronegative and have a risk of primary EBV infection. Clinicians should also be careful of misdiagnosing IBD and EBV-associated lymphoproliferative diseases due to similarities in both clinical symptoms and endoscopic manifestations. Withdrawal of immunosuppressants has been shown to be an effective strategy to achieve remission of disease at the time of EBV diagnosis, but antiviral therapy remains controversial. The present review aims to describe the characteristics of the complications caused by EBV infection and generalize the recent research progress on and challenges caused by EBV infection in IBD patients. The literature for writing this review was collected from 'PubMed' research engine. The keywords 'inflammatory bowel disease and Epstein-Barr virus' or 'ulcerative colitis and Epstein-Barr virus' or 'Crohn's disease and Epstein-Barr virus' were used to collect the literature and relevant papers were collected to help writing this review.

Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity: A systematic review and meta-analysis.

BACKGROUND: Methylxanthine, including caffeine citrate and aminophylline, is the most common pharmacologic treatment for apnea of prematurity. However, due to the lack of high-quality evidence, there are no clear recommendations or guidelines on how to choose between caffeine and aminophylline. OBJECTIVE: This meta-analysis aimed to assess the comparative efficacy and safety of caffeine and aminophylline for apnea of prematurity, and provide reliable evidence for clinical medication in the treatment for apnea of prematurity. METHODS: PubMed, Scopus, Embase, EBSCO, Web of Science, and Cochrane databases were systematically searched from May 1975 to June 2022. RESULTS: Ten studies including a total of 923 preterm infants were evaluated. Our results showed that there was no significant difference in the effective rate of 1-3days between caffeine and aminophylline (OR 1.05, 95%CI: 0.40-2.74, P = 0.914). However, for side effects such as tachycardia (OR 0.22, 95%CI: 0.13-0.37, P<0.001) and feeding intolerance (OR 0.40, 95%CI: 0.23-0.70, P = 0.001), the incidence rate was lower in the caffeine group compared with the aminophylline group. No significant difference was found in hyperglycemia (OR 0.45, 95%CI: 0.19-1.05, P = 0.064). CONCLUSION: This meta-analysis reveals that caffeine citrate and aminophylline have similar therapeutic effectiveness on respiratory function, but caffeine has fewer side effects and should be considered first for treatment.

The Emerging Portrait of Glial Cell Line-derived Neurotrophic Factor Family Receptor Alpha (GFRα) in Cancers.

Glial cell line-derived neurotrophic factor family receptor alpha (GFRα) members have been widely connected to the mechanisms contributing to cell growth, differentiation, cell migration and tissue maturation. Here we review GFRα biological functions and discussed the evidence indicating whether GFRα signaling complex present novel opportunities for oncogenic intervention and treatment resistance. Thus, our work systematically reviewed the emerging role of GFRα family members in cancers, and provided novel insights for further researches.

USP21 regulates Hippo signaling to promote radioresistance by deubiquitinating FOXM1 in cervical cancer.

The ectopic expression of ubiquitin-specific peptidase 21 (USP21) is common in different types of cancer. However, its relationship with radio-sensitivity in cervical cancer (CC) remains unclear. In this study, we aimed to uncover the effect of USP21 on CC radio-resistance and its underlying mechanism. Our results showed that the expression of USP21 was markedly increased in CC tissues of radio-resistant patients and CC cells treated with radiation. Besides, knockdown of USP21 restrained the survival fractions, and facilitated apoptosis of CC cells in the absence or presence of radiation. Additionally, USP21 in combination with FOXM1 regulated the stability and ubiquitination of FOXM1. However, FOXM1 reversed the effects of USP21 knockdown on the radio-resistance of CC cells. Furthermore, FOXM1 knockdown activated the Hippo pathway by inhibiting the nuclear translocation of Yes-associated protein 1 (YAP1), and FOXM1 knockdown attenuated the radio-resistance of CC cells via inhibiting the Hippo-YAP1 pathway. USP21 activated the Hippo pathway by mediating FOXM1. Knockdown of USP21 enhanced the radio-sensitivity of CC cells in vivo. In summary, USP21 contributed to the radio-resistance of CC cells via FOXM1/Hippo signaling, and may serve as a promising target for radio-sensitizers in the radiotherapy of CC.

A Multiscale Clustering Approach for Non-IID Nominal Data.

Multiscale brings great benefits for people to observe objects or problems from different perspectives. Multiscale clustering has been widely studied in various disciplines. However, most of the research studies are only for the numerical dataset, which is a lack of research on the clustering of nominal dataset, especially the data are nonindependent and identically distributed (Non-IID). Aiming at the current research situation, this paper proposes a multiscale clustering framework based on Non-IID nominal data. Firstly, the benchmark-scale dataset is clustered based on coupled metric similarity measure. Secondly, it is proposed to transform the clustering results from benchmark scale to target scale that the two algorithms are named upscaling based on single chain and downscaling based on Lanczos kernel, respectively. Finally, experiments are performed using five public datasets and one real dataset of the Hebei province of China. The results showed that the method can provide us not only competitive performance but also reduce computational cost.

The SUMO E3 ligase CBX4 is identified as a poor prognostic marker of gastric cancer through multipronged OMIC analyses.

Gastric cancer (GC) is one of the most common malignancies, with an ever-increasing incidence and high mortality rate. Chromobox4 (CBX4), also named hPC2, is a small ubiquitin-related modifier (SUMO) E3 ligase. Previous studies have found that high CBX4 expression is associated with tumor size, pathologic differentiation and decreased patient survival in hepatocellular carcinoma (HCC). However, the expression and prognostic value of CBX4 in GC have not been clarified. In our study, ONCOMINE, UALCAN, Kaplan-Meier Plotter, cBioPortal, DAVID 6.8 and TIMER were utilized. RT-PCR, immunohistochemistry (IHC), Western blot, CCK-8 assay, cell apoptosis assay, cell cycle assay were used to further verify in GC tissue samples or cell line. The transcriptional and protein level of CBX4 in GC tissues was found significantly elevated and a significant association between the expression of CBX4 and clinicopathological parameters was found in GC patients. Low expression of CBX4 in GC patients were correlated with a significantly improved prognosis. The functions of CBX4 are primarily related to the stem cell pluripotency signaling pathway, Hippo signaling pathway, HTLV-I infection, Notch signaling pathway, and N-glycan biosynthesis. Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for GC.

Genome-wide identification, evolution, and expression analysis of the NPR1-like gene family in pears.

The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) plays a master regulatory role in the salicylic acid (SA) signal transduction pathway and plant systemic acquired resistance (SAR). Members of the NPR1-like gene family have been reported to the associated with biotic/abiotic stress in many plants, however the genome-wide characterization of NPR1-like genes has not been carried out in Chinese pear (Pyrus bretschneideri Reld). In this study, a systematic analysis was conducted on the characteristics of the NPR1-like genes in P. bretschneideri Reld at the whole-genome level. A total nine NPR1-like genes were detected which eight genes were located on six chromosomes and one gene was mapped to scaffold. Based on the phylogenetic analysis, the nine PbrNPR1-like proteins were divided into three clades (Clades I-III) had similar gene structure, domain and conserved motifs. We sorted the cis-acting elements into three clades, including plant growth and development, stress responses, and hormone responses in the promoter regions of PbrNPR1-like genes. The result of qPCR analysis showed that expression diversity of PbrNPR1-like genes in various tissues. All the genes were up-regulated after SA treatment in leaves except for Pbrgene8896. PbrNPR1-like genes showed circadian rhythm and significantly different expression levels after inoculation with Alternaria alternata. These findings provide a solid insight for understanding the functions and evolution of PbrNPR1-like genes in Chinese pear.

Knockdown of lncRNA PCAT1 Enhances Radiosensitivity of Cervical Cancer by Regulating miR-128/GOLM1 Axis.

PURPOSE: Cervical cancer (CC) is the fourth most common cancer with high death rate in females. The study aims to detect the mechanism of long non-coding RNA (LncRNA) PCAT1 on radiosensitivity of CC. METHODS: The expression of PCAT1, miR-128 and GOLM1 in CC tissues and cells was measured by qRT-PCR. Different doses of X-ray were used for radiation treatment of CC cells and 6 Gy was chosen to perform the following experiments. The proliferation, migration and invasion of CC cells were measured by MTT assay, wound healing assay and transwell assay, respectively. The target relationships among PCAT1, miR-128 and GOLM1 were predicted by StarBase and TargetScan and verified by luciferase reporter assay. The protein level of GOLM1 was determined by Western blot. The xenograft tumor model was constructed in nude mice to verify the effect of PCAT1 on radiosensitivity of CC in vivo. RESULTS: The PCAT1 expression was upregulated in CC tissues and cells. PCAT1 silencing enhances radiosensitivity of CC cells on proliferation, migration and invasion. MiR-128 was the target of PCAT1 and was negatively regulated by PCAT1. Upregulation of miR-128 enhances radiosensitivity of CC cells on proliferation, migration and invasion. GOLM1 was a target of miR-128 and was negatively regulated by miR-128. Upregulation of GOLM1 and downregulation of miR-128 both reversed the enhanced effect of PCAT1 knockdown on radiosensitivity of CC cells, which partly promoted the proliferation, migration and invasion of CC cells. CONCLUSION: Silencing of PCAT1 enhanced radiosensitivity of CC via targeting miR-128/GOLM1, which provided a new idea for treating CC.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of Chromobox Family Members in Colorectal Cancer.

Objective: Colorectal cancer (CRC) is one of the common malignant tumors worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and are implicated in the development of multiple cancers by blocking differentiation and promoting proliferation. However, little is known about the function of distinct CBX proteins in colorectal cancer. Methods: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of CBXs in colorectal cancer patients. Results: The expression levels of CBX1/2/3/4/5 and CBX8 were significantly elevated in CRC tissues, whereas the expression levels of CBX6/7 were reduced. CBX3 was significantly associated with the clinical cancer stage and short disease-free survival (DFS) in CRC patients. High mRNA expression of CBX5/6 was associated with short overall survival (OS) in rectal cancer patients. CBX3/5/6 could be potential prognostic biomarkers for the survival of CRC patients. Moreover, the functions of the differentially expressed CBXs were primarily related to the SUMOylation of DNA methylation proteins and chromatin organization and may regulate the pluripotency of stem cells. The expression of CBXs were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells in colon cancers and rectal cancers. Conclusions: Our study may provide novel insights for the selection of prognostic biomarkers of CBX family in colorectal cancer.

Genome-wide identification of the PEBP genes in pears and the putative role of PbFT in flower bud differentiation.

Although Phosphatidylethanolamine-binding protein (PEBP) genes have been identified in several plants, little is known about PEBP genes in pears. In this study, a total of 24 PEBP genes were identified, in which 10, 5 and 9 were from Pyrus bretschneideri genome, Pyrus communis genome and Pyrus betuleafolia genome, respectively. Subsequently, gene structure, phylogenetic relationship, chromosomal localization, promoter regions, collinearity and expression were determined with these PEBP genes. It was found that only PbFT from PEBP genes of P. bretschneideri was relatively highly expressed in leaves during flower bud differentiation. Whereas, expression patterns of TFL1 homologues, gene23124 and gene16540, were different from PbFT in buds. The expression pattern and the treatment of reduction day-length indicated that the expression of PbFT in leaves were regulated by day-length and circadian clock. Additionally, the phenotype of transgenic Arabidopsis suggested that PbFT played a role in not only promoting flower bud differentiation, but also regulating the balance between vegetative and reproductive growth. These results may provide important information for further understanding of the evolution and function of PEBP genes in pears.

Radiomics signature extracted from diffusion-weighted magnetic resonance imaging predicts outcomes in osteosarcoma.

OBJECTIVE: Osteosarcoma often requires multidisciplinary treatment including surgery, chemotherapy and radiotherapy. However, tumor behavior can vary widely among patients and selection of appropriate therapies in any individual patient remains a critical challenge. Radiomics seeks to quantify complex aspects of tumor images under the assumption that this information is related to tumor biology. This study tested the hypothesis that a radiomic signature extracted from Diffusion-weighted magnetic resonance images (DWI-MRI) can improve prediction of overall survival (OS) compared with clinical factors alone in localised osteosarcoma. MATERIALS/METHODS: Pre-treatment DWI-MRI were collected from 112 patients (9-67 years of age) with histological-proven osteosarcoma that were treated with curative intent. The entire dataset was divided in two subsets: the training and validation cohorts containing 76 and 24% of the data respectively. Clinical data were extracted from our medical record. Two experienced radiotherapists evaluated DWI-MRIs for quality and segmented the tumor. A total of 103 radiomic features were calculated for each image. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features. Association between the radiomics signature and OS was explored. Further validation of the radiomics signature as an independent biomarker was performed by using multivariate Cox regression. The Cox proportional-hazard regression model was also used to analyze the correlation between the prognostic factor and the survival for the clinical (C) model after the univariate analysis. Radiomics (R) model identified radiomics signature, which is the best predictor from the radiomic variable classes based on LASSO regression. Harrell's C-index was used to demonstrate the incremental value of the radiomics signature to the traditional clinical risk factors for the individualized prediction performance. RESULTS: Cox proportional-hazard regression model shows that: Tumor size, alkaline phosphatase (ALP) status before treatment and number of courses of chemotherapy were proven as the dependent clinical prognostic factors of osteosarcoma's overall survival time. The radiomics signature was significantly associated with OS, independent of clinical risk factors (radiomics signature: HR: 5.11, 95% CI: 2.85, 9.18, P < 0.001). Incorporating the radiomics signature into the coalition (C+R) model resulted in better performance (P < .001) for the estimation of OS (C-index: 0.813; 95% CI: 0.75, 0.89) than with the clinical (C) model (C-index: 0.764; 95% CI: 0.69, 0.85), or the single radiomics (R) model (C-index: 0.712; 95% CI: 0.65, 0.78). CONCLUSION: This study shows that the radiomics signature extracted from pre-treatment DWI-MRI improve prediction of OS over clinical features alone. Combination of the radiomics signature and the traditional clinical risk factors performed better for individualized OS estimation in patients with osteosarcoma, which might enable a step forward precise medicine. This method may help better select patients most likely to benefit from intensified multimodality diagnosis and therapies. Future studies will focus on multi-center validation of an optimized model.

Innovation stages, knowledge spillover, and green economy development: moderating role of absorptive capacity and environmental regulation.

In the past 20 years, the green economy has increasingly attracted the attention of governments and policy makers. However, most studies have only focused on the relationship between the green economy and innovation, and little attention has been given to the relationship between the different innovation stages and the green economy. This study draws on eco-innovation and institutional theories and proposes a model to empirically investigate the effects between the different innovation stages and green economy. Furthermore, it explores how these effects are mediated by knowledge spillover and moderated by absorptive capacity and environment regulations. We use data from the last 5 years (2012-2016) obtained from different China regions to empirically test the model. Results show that knowledge innovation, research and development (R&D) innovation, and product innovation have the same significant positive impact on knowledge spillovers. R&D and product innovation have a significant positive impact on green economy, whereas knowledge innovation has no significant effect on the development of the green economy. Knowledge spillover partially mediates the relationship between the innovation stage and the green economy. Meanwhile, absorptive capacity positively moderates the relationship between knowledge spillover and the green economy. However, environmental regulation negatively moderates the relationship between knowledge spillover and the green economy. In addition, corresponding measures are proposed based on the conclusions.