Ubiquitin ligase MDM2 mediates endothelial inflammation in Kawasaki disease vasculitis development.

Background: Kawasaki disease (KD) often complicates coronary artery lesions (CALs). Despite the established significance of STAT3 signaling during the acute phase of KD and signal transducer and activator of transcription 3 (STAT3) signaling being closely related to CALs, it remains unknown whether and how STAT3 was regulated by ubiquitination during KD pathogenesis. Methods: Bioinformatics and immunoprecipitation assays were conducted, and an E3 ligase, murine double minute 2 (MDM2) was identified as the ubiquitin ligase of STAT3. The blood samples from KD patients before and after intravenous immunoglobulin (IVIG) treatment were utilized to analyze the expression level of MDM2. Human coronary artery endothelial cells (HCAECs) and a mouse model were used to study the mechanisms of MDM2-STAT3 signaling during KD pathogenesis. Results: The MDM2 expression level decreased while the STAT3 level and vascular endothelial growth factor A (VEGFA) level increased in KD patients with CALs and the KD mouse model. Mechanistically, MDM2 colocalized with STAT3 in HCAECs and the coronary vessels of the KD mouse model. Knocking down MDM2 caused an increased level of STAT3 protein in HCAECs, whereas MDM2 overexpression upregulated the ubiquitination level of STAT3 protein, hence leading to significantly decreased turnover of STAT3 and VEGFA. Conclusions: MDM2 functions as a negative regulator of STAT3 signaling by promoting its ubiquitination during KD pathogenesis, thus providing a potential intervention target for KD therapy.

Discovery of BMP10 as a new gene underpinning congenital heart defects.

OBJECTIVE: Aggregating evidence convincingly establishes the predominant genetic basis underlying congenital heart defects (CHD), though the heritable determinants contributing to CHD in the majority of cases remain elusive. In the current investigation, BMP10 was selected as a prime candidate gene for human CHD mainly due to cardiovascular developmental abnormalities in Bmp10-knockout animals. The objective of this retrospective study was to identify a new BMP10 mutation responsible for CHD and characterize the functional effect of the identified CHD-causing BMP10 mutation. METHODS: Sequencing assay of BMP10 was fulfilled in a cohort of 276 probands with various CHD and a total of 288 non-CHD volunteers. The available family members from the proband harboring an identified BMP10 mutation were also BMP10-genotyped. The effect of the identified CHD-causative BMP10 mutation on the transactivation of TBX20 and NKX2.5 by BMP10 was quantitatively analyzed in maintained HeLa cells utilizing a dual-luciferase reporter assay system. RESULTS: A novel heterozygous BMP10 mutation, NM_014482.3:c.247G>T;p.(Glu83*), was identified in one proband with patent ductus arteriosus (PDA), which was confirmed to co-segregate with the PDA phenotype in the mutation carrier's family. The nonsense mutation was not observed in 288 non-CHD volunteers. Functional analysis unveiled that Glu83*-mutant BMP10 had no transactivation on its two representative target genes TBX20 and NKX2.5, which were both reported to cause CHD. CONCLUSION: These findings provide strong evidence indicating that genetically compromised BMP10 predisposes human beings to CHD, which sheds light on the new molecular mechanism that underlies CHD and allows for antenatal genetic counseling and individualized precise management of CHD.

Insufficiency of Mrpl40 disrupts testicular structure and semen parameters in a murine model.

Approximately 31% of patients with 22q11.2 deletion syndrome (22q11.2DS) have genitourinary system disorders and 6% of them have undescended testes. Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS. In this study, we used mice with single-allele deletion in mitochondrial ribosomal protein L40 (Mrpl40 +/- ) as models to investigate the function of Mrpl40 in testes and spermatozoa development. The penetrance of cryptorchidism in Mrpl40 +/- mice was found to be higher than that in wild-type (WT) counterparts. Although the weight of testes was not significantly different between the WT and Mrpl40 +/- mice, the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40 +/- mice. Moreover, the concentration and motility of spermatozoa were significantly decreased in the Mrpl40 +/- mice. In addition, data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40 +/- testes. Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count. These findings suggest that Mrpl40 is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.

Post-traumatic growth in caregivers of children hospitalized in the PICU due to traffic accident: a qualitative study.

BACKGROUND: Globally, tens of millions of children are hospitalized every year for non-fatal traffic accident injuries, being confronted with an injured child can be extremely stressful for parents. Understandably, a significant level of psychological distress may ensue. Traumatic losses may lead parents to find new insights in life and develop a greater sense of spirituality and strength. METHOD: Semi-structured interviews were conducted with caregivers of children who were hospitalized in the pediatric intensive care unit (PICU) with traffic accident injuries at children's hospitals in China between January and June 2022. Caregivers were selected using a purposive sampling method until no new data were generated (n = 24). RESULTS: We identified eleven sub-themes and four higher-order themes based on these sub-themes: (1) changes in their life philosophy, (2) personal strength enhancement, (3) relationship improvements, and (4) effective responses. The findings of our research contribute to a better understanding of the psychological status of the caregivers of children injured by traffic accidents. CONCLUSION: Professionals should guide caregivers from a positive perspective, stimulate their strengths and potential, increase personnel support and communication, promote positive coping, formulate targeted management countermeasures to improve the PTG level of caregivers, and develop strategies to maintain stable mental health and well-being.

Effects of kangaroo care on pain relief in premature infants during painful procedures: A meta-analysis.

AIM: This study aimed to evaluate effects of kangaroo care on pain relief in premature infants during painful procedures. DESIGN: A meta-analysis. METHODS: Eight databases (Cochrane Library, PubMed, Embase, Web of Science, China Biology Medicine [CBM], China Science and Technology Journal Database [CSTJ], China National Knowledge Infrastructure [CNKI], and WanFang Data) were systematically reviewed from inception to November 2021 for randomized controlled and crossover trials. RESULTS: Thirteen studies, including 2311 infants (kangaroo care: 1153, control: 1158) were analyzed. Kangaroo care had a moderate effect on pain relief during painful procedures in premature infants at a gestational age of 32-36 + 6 weeks but no effect at 28-31 + 6 weeks. Furthermore, 15 or 30 min of kangaroo care had a moderate effect and could markedly relieve pain at the instant of and 30/60 s after, had a small effect at 90 s after, and no effect at 120 s after the procedure. PRACTICE IMPLICATIONS: Kangaroo care may be an effective nonpharmacologic alternative therapy to relieve procedural pain in premature infants born at a gestational age of 32-36 + 6 weeks.

AST-to-ALT ratio and coronary artery lesions among patients with Kawasaki disease.

BACKGROUND: The aim of this study was to explore the associations between the aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT) and coronary artery lesions (CALs) among patients with Kawasaki disease (KD). METHODS: Medical records of KD patients presenting to a single center between January 2019 and December 2020 were retrospectively collected and analyzed. Univariate, multivariable-adjusted analyses, subgroup analyses, restricted cubic spline test, and fitted curves were used to evaluate the associations between AST/ALT and CALs. RESULTS: A total of 831 patients were enrolled, of which 201 (24.2%) had CALs on admission and 21 (2.5%) developed CALs de novo after intravenous immunoglobulin (IVIG). Multivariable-adjusted analyses models revealed that a lower AST/ALT was associated with an increased risk of CALs on admission when AST/ALT was a continuous variable (P = 0.007) and when it was a categorical variable (P for trend = 0.004). Each unit increase in AST/ALT was associated with a 22% lower risk of CALs on admission (odds ratio = 0.78, 95% confidence interval 0.65-0.94). A negative linear relationship was noted between AST/ALT and the risk of CALs on admission in both observed and fitted models. However, such associations were not observed in AST/ALT and CALs de novo after IVIG. None of the variables significantly modified the association between AST/ALT and CALs on admission and CALs de novo after IVIG (P > 0.05). CONCLUSION: Our findings suggested that AST/ALT was a risk factor of CALs, but was not associated with progressive CALs.

Ultrasonography to detect cardiovascular damage in children with essential hypertension.

BACKGROUND: Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography. METHODS: All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid-femoral pulse wave velocity (cfPWV), intimal-medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography. RESULTS: The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E' among three groups. CONCLUSION: Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

Clinical characteristics of Kawasaki disease and concurrent pathogens during isolation in COVID-19 pandemic.

BACKGROUND: The aim of this study is to explore the characteristics of Kawasaki disease (KD) and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019 (COVID-19) epidemic. METHODS: All patients with KD admitted between February and April in 2015-2020, were classified into before (group 1, in 2015-2019) and after (group 2, in 2020) isolation groups. A total of 4742 patients [with KD (n = 98) and non-KD (n = 4644)] referred to Mycoplasma pneumoniae (MP) and virus detection were analyzed in 2020. Clinical characteristics, laboratory data, and 13 pathogens were analyzed retrospectively. RESULTS: Group 2 had a significantly increased incidence of KD (0.11%) with 107 patients compared to that of group 1 (0.03%) with 493 patients. The comparisons of oral mucosal change, strawberry tongue, desquamation of the fingertips, cervical lymphadenopathy and neutrophil percentage decreased in group 2 compared to group 1. The infection rate of MP increased significantly in group 2 (34.7%) compared to group 1 (19.3%), while the positive rate of viruses decreased significantly in group 2 (5.3%) compared to group 1 (14.3%). In 2020, the positive rate of MP infection increased significantly in patients with KD compared to the increase in patients with non-KD. The infection rate of MP for younger children aged less than 3 years old was higher in group 2 than in group 1. CONCLUSION: Compared with the characteristics of KD from 2015 to 2019 years, the incidence of KD was increased in 2020 and was accompanied by a high incidence of MP infection, especially in younger children (less than 3 years old) during the isolation due to COVID-19 pandemic.

The effect of gemcitabine combined with AMD3100 applying to cholangiocarcinoma RBE cell lines to CXCR4/CXCL12 axis.

PURPOSE: To evaluate the effect of AMD3100 treatment to cholangiocarcinoma by analyzing the relationship between them, and provide experimental evidence for whether AMD3100 can become a clinical treatment drug for cholangiocarcinoma. MATERIALS AND METHODS: Cholangiocarcinoma RBE cell lines were used in this study. MTT cell proliferation test was used for evaluating the effect of gemcitabine and AMD3100 to cell. CXCR4, N-cadherin, VEGF-C and MMP-9 were detect by RT-PCR and western. Transwell was used for evaluating the invasion effect. RESULTS: We demonstrated that as the concentration of gemcitabine increasing from 0.33, 3.33 to 33.33 uM, the cell survival rate was 76.65%, 71.40%, 52.25%, respectively. RT-PCR and Western blot that gemcitabine could affect the expression of CXCR4 protein and the level of mRNA transcription in a dose-dependent manner. N-cadherin VEGF-C, MMP-9 mRNA transcription level showed a significant upward trend in gemcitabine group. In Transwell test, the number of cells in the gemcitabine group was significantly higher than that in the no-medication group (p < .05), the AMD3100 group and the combination group of gemcitabine and AMD3100, the difference between the no-medication group and the AMD3100 monotherapy group was not significant, and the combination group was between them. CONCLUSIONS: This study showed that gemcitabine significantly inhibited the growth of cholangiocarcinoma RBE cells in a dose-dependent manner, and gemcitabine can affect the expression of CXCR4, N-cadherin, VEGF-C, MMP-9 protein and mRNA. Cell invasion and metastasis-related factors decreased after AMD3100 combined with gemcitabine.

Transitional care experiences of caregivers of preterm infants hospitalized in a neonatal intensive care unit: A qualitative descriptive study.

AIM: To describe the transitional care experiences and nursing needs of caregivers of preterm infants hospitalized in neonatal intensive care units (NICUs). DESIGN: A qualitative descriptive study. METHODS: We conducted semi-structured interviews with the 24 caregivers of preterm infants admitted to Children's Hospital, Soochow University. All data were collected by a trained and experienced interviewer. The caregivers' experiences were described using qualitative content analysis. RESULTS: Six Five themes emerged from the analysis: (a) uncertainty about the disease; (b) anxiety due to restricted visitation; (c) exhaustion from overwork; (d) emotional depression; (e) low care ability; (f) a variety of channels for help and a positive response. This study provides a basis for understanding the needs of their caregivers so that effective coping strategies can be implemented. Nurses' education and practice should focus on understanding the real experiences of the parents of preterm infants during transitional nursing.

Clinical outcome of open surgery versus laparoscopic surgery for cirrhotic hepatocellular carcinoma patients: a meta-analysis.

BACKGROUND AND AIM: Open surgery remains the major approach to treat hepatocellular carcinoma, and laparoscopy-assisted liver resection has been recommended as a superior treatment. However, the efficacy of laparoscopic surgery versus open surgery for cirrhotic patients is under debate. Therefore, the aim of this meta-analysis was to compare the clinical outcomes of laparoscopic and open resection of hepatocellular carcinoma in patients with cirrhosis. METHODS: Electronic databases were searched for eligible literature updated on November 2018. After rigorous review of quality, the data were extracted from eligible trials. All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated. RESULTS: Fourteen trials met the inclusion criteria. According to the pooled result of surgery duration, laparoscopic surgery was associated with significantly shorter hospital stay [STD mean difference (SMD) = -0.61, 95% confidence interval -0.89 to -0.32; P < 0.0001], lower intraoperative blood loss (SMD = -0.56, 95% confidence interval -0.99 to -0.12; P = 0.01), fewer complications (odds ratio = 0.38, 95% confidence interval 0.28 to 0.52; P < 0.00001) and lower transfusion rate (odds ratio = 0.58, 95% confidence interval 0.36-0.93; P = 0.02). Nevertheless, there was no remarkable difference in operative time (SMD = 0.17, 95% confidence interval -0.25 to -0.59; P = 0.42) between the two groups. The pooled analysis of overall survival showed that laparoscopic surgery did not achieve benefit compared with open surgery (P = 0.02). Moreover, the pooled results of three subgroups indicated that laparoscopic surgery was associated with significantly better disease-free survival (P < 0.05). CONCLUSION: The current analysis indicates that laparoscopic liver resection for hepatocellular carcinoma improved intraoperative and disease-free survival, with similar overall survival compared to the open procedure. Laparoscopic surgery may serve as a safe and feasible alternative for selected hepatocellular carcinoma patients with cirrhosis.

Corrigendum: MiR-223-3p Alleviates Vascular Endothelial Injury by Targeting IL6ST in Kawasaki Disease.

[This corrects the article DOI: 10.3389/fped.2019.00288.].

MiR-223-3p Alleviates Vascular Endothelial Injury by Targeting IL6ST in Kawasaki Disease.

Background: Kawasaki disease (KD) is a self-limiting illness with acute systematic vascular inflammation. It causes pathological changes in mostly medium and small-sized arteries, especially the arteria coronaria, which adds the risk of developing coronary heart disease in adults. Materials and methods: We detected the miR-223-3p expression in 30 KD patients combined with 12 normal controls using miRNA microarrays and RT-PCR. A KD mouse model was constructed using Candida albicans water insoluble substance (CAWS). We also checked the miR-223-3p's expression using qRT-PCR. The Luciferase reporting system was implemented to validate the correlation between miR-223-3p and Interleukin-6 receptor subunit beta (IL-6ST). TNF-α was used to stimulate human coronary artery endothelial cells (HCAECs), and miR-223-3p activator or inhibitor and KD serum were used to treat HCAECs. A Western blotting automatic quantitative analysis protein imprinting system was used to test the expression of signal transducer and the activator of transcription 3 (STAT3), phosphorylated-signal transducer and the activator of transcription 3 (pSTAT3) and NF-κB p65. Results: Clinical trials found that miR-223-3p expressions were markedly different (more than 2-fold) between the acute KD group and the control group. E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) levels were also significantly higher (about 2-fold) in KD especially with coronary artery lesions. MiR-223-3p could alleviate vascular endothelial damage in KD mice, and IL-6 (Interleukin-6), E-selectin and ICAM-1 were simultaneously negative. The values of IL-6, E-selectin, and ICAM-1 mRNA expressions decreased, while the value of IL-6ST was increased between the agonist treated mice and KD mice. The RT-qPCR consequences displayed that miR-223-3p explored the highest expression on the third day in both the KD mice as well as the agonist group. MiR-223-3p can directly combine with IL-6ST 3' untranslatable regions (UTR) and held back the IL-6's expression. Overexpression of miR-223 down regulated IL6ST expression and decreased the expression of p-STAT3 and NF-κB p65, while the miR-223 inhibitor could reverse the above process. Conclusion: MiR-223-3p is an important regulatory factor of vascular endothelial damage in KD and could possibly become a potential target of KD treatment in the future.

MiR-222-3p in Platelets Serves as a Distinguishing Marker for Early Recognition of Kawasaki Disease.

Kawasaki disease (KD) is an acute vasculitis, which leads to 20% of sufferers developing coronary artery aneurysm in children if not appropriately treated. Therefore, the early diagnosis of KD is essential for alleviating the risk of developing heart disease. MicroRNAs (miRNAs) are a large class of small non-coding RNAs which post-transcriptionally regulate gene expression and have been shown to play critical roles in numerous biological processes and diseases. In this study, we used high-throughput miRNA sequencing and found dozens of miRNAs are highly expressed in platelets. By comparing the miRNA expression profile of platelets of acute KD patients and other febrile patients, miR-222-3p is validated to be significantly upregulated in platelets of acute KD patients. Furthermore, KEGG pathway analysis shows that targets of miR-222-3p are enriched in immune-related signaling pathways. Our study uncovers the potential of miR-222-3p in platelets as biomarker for early diagnosis of Kawasaki disease.

Home care experience and nursing needs of caregivers of children undergoing congenital heart disease operations: A qualitative descriptive study.

AIMS AND OBJECTIVES: To explore the home care experiences of caregivers taking care of CHD children before and after cardiac surgery. BACKGROUND: Despite the prevalence of congenital heart disease (CHD) in childhood, little is known about the experiences and impacts on the children and their caregivers after CHD diagnosis and surgery. Such knowledge is needed for meaningful support. DESIGN: A qualitative descriptive study. METHODS: Twenty-two caregivers of CHD children undergoing cardiac surgery participated in semi-structured interviews at a University Children's Hospital in China. Data were collected by an experienced and trained interviewer. Qualitative content analysis was chosen to describe the experiences of the caregivers. RESULTS: Caregivers of CHD children experienced significant demands. After the children underwent their CHD operations, the caregivers experienced complex psychological feelings and excessive stress impacting upon theirlives. In addition, caregivers constantly adapted their roles with self-fulfillment in caring activities. CONCLUSIONS: CHD surgery has a major impact on the emotions and daily lives of children and their caregivers. This study offers a framework for understanding the importance of actively listening to caregivers so coping strategies can be implemented. RELEVANCE TO CLINICAL PRACTICE: Theexperiencesdescribed in this study contribute to a better understanding of the needs of caregivers whose children underwent CHD operations. They also provide valuable information to professional medical care staff that developfuture nursing assessments.

Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway.

BACKGROUND: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). METHODS: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. RESULTS: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. CONCLUSION: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.

Identification of differentially expressed microRNAs in acute Kawasaki disease.

The present study used microarray analysis to screen the plasma expression of microRNAs (miRNAs) in patients with acute Kawasaki disease (KD) and aimed to explore the pathogenesis of KD. Plasma was collected from children with acute KD (n=6) and from healthy control children (n=6). Total RNA was extracted and differential miRNA expression between the two groups was determined. Differentially expressed miRNAs were validated using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) in an independent cohort (n=8). Target genes of the differentially expressed miRNAs were predicted and analyzed for gene ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes pathways. miRNA microarray analysis revealed that seven miRNAs (miRs) were significantly upregulated (hsa­let­7b­5p, hsa­miR­223­3p, hsa­miR­4485, hsa­miR­4644, hsa­miR­4800­5p, hsa­miR­6510­5p and hsa­miR­765) and three were significantly downregulated (hsa­miR­33b­3p, hsa­miR­4443 and hsa­miR­4515) in acute KD compared with the healthy controls. hsa­miR­223­3p expression levels detected by RT­qPCR were consistent with the microarray results. A total of 62 target genes of hsa­miR­223­3p were predicted. In total, 10 differentially expressed miRNAs were identified in acute KD, of which hsa­miR­223­3p was verified by RT­qPCR.

Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721.

The present study explored the effect of long non-coding RNA-human ovarian cancer-specific transcript 2 (LncRNA-HOST2) on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma (HCC) cell line SMMC-7721. HCC tissues and adjacent normal tissues from 162 HCC patients were collected. The HCC cell lines were assigned into the control group (regular culture), negative control (NC) group (transfected with siRNA) and experimental group (transfected with Lnc-HOST2 siRNA). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of LncRNA-HOST2. Cell proliferation was detected by CCK-8 and colony-forming assays, cell apoptosis by flow cytometry and cell migration by Scratch test. Transwell assay was used to evaluate cell migration and invasion abilities. LncRNA-HOST2 expression in the HCC tissues increased 2-10 times than that in the adjacent normal tissues. Compared with the HL-7702 cell line, LncRNA-HOST2 expression in HepG2, SMMC-7721 and Huh7 cell lines was all up-regulated, but the SMMC-7721 cell had the highest Lnc-HOST2 expression. The LncRNA-HOST2 expression in the experimental group was down-regulated as compared with the control and NC groups. In comparison with the control and NC groups, cloned cells reduced, cell apoptosis increased, clone-forming ability weakened and inhibitory rate of colony formation increased in the experimental group. The cells migrating and penetrating into the transwell chamber were fewer in the experimental group than those in the control and NC groups. The experimental group exhibited slow wound healing and decreased cell migration area after 48 h. These findings indicate that LncRNA-HOST2 can promote cell proliferation, migration and invasion and inhibit cell apoptosis in human HCC cell line SMMC-7721.

Diagnostic accuracy of coronary angiography using 64-slice computed tomography in coronary artery disease.

OBJECTIVES: To conduct a meta-analysis and investigate the diagnostic value of 64-slice computed tomography (CT) angiography for diagnosing coronary artery disease (CAD) in patients. METHODS: A comprehensive literature search from March 2005 to August 2014 was performed on the following databases: Cochrane Library; Medline; EmBase; PubMed; and BioMed Central database. As a reference standard, studies that assessed 64-slice CT angiography in detecting coronary artery stenosis (CAS) with invasive coronary angiography were included. Coronary artery stenosis was defined as ≥50% diameter stenosis. Diagnostic value was determined by pooling sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) values at segment-level analysis. Diagnostic accuracy was undertaken using area under the curve (AUC) value and summary receiver operating characteristic (SROC) curves. Publication bias was examined by Deek's funnel plot asymmetry test. RESULTS: Eight studies were included in the analysis, enrolling a total of 579 patients (7,407 segment coronary vessels). At segment-level, pooled sensitivity value was 90% (95% confidence interval [CI]: 83-95%), specificity was 91% (95% CI: 61-98%), PLR value was 9.7 (95% CI: 1.8-53.3), and NLR value was 0.11 (95% CI: 0.05-0.22) for CAS. Optimal cut-off point of sensitivity was 90%, and specificity under the SROC curve was 91%. The AUC value was 0.94. CONCLUSION: The 64-slice CT angiography is a reliable tool for detection of CAD when using a cut-off of more than or equal to 50% diameter stenosis in elderly population.

Berberine protects endothelial progenitor cell from damage of TNF-α via the PI3K/AKT/eNOS signaling pathway.

Endothelial progenitor cells (EPCs) dysfunction is closely correlated with the coronary artery injury induced by Kawasaki disease (KD). The level of tumor necrosis factor-α (TNF-α) elevated significantly in acute phase of KD which can damage the functions of EPCs. The aim of this study was to investigate whether berberine (BBR) can protect EPCs from the inhibition caused by TNF-α via the PI3K (Phosphatidyl Inositol 3-kinase) /AKT (Serine/threonine protein kinase B) /eNOS (endothelial Nitric Oxide synthase) signaling pathway. The cell proliferative ability of EPCs was determined by MTT (methyl thiazolyl tetrazolium) assays. Nitric oxide (NO) level was determined in supernatants. The mRNA level of eNOS, PI3K and AKT were measured by Real Time-Polymerase Chain Reaction (RT-PCR), and the protein levels of eNOS, phospho-eNOS (p-eNOS), Akt, phospho-Akt (p-Akt) and PI3K were analyzed using Western-blot. The results demonstrated that TNF-α inhibits the proliferative ability of EPCs. However, BBR improves the proliferative activity of EPCs inhibited by TNF-α. Blockade of PI3K by 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (Ly294002) and blockade of eNOS by l-NAME (NG-Nitroarginine Methyl Ester) attenuates the effect of BBR. BBR can increase the level of PI3K/Akt/eNOS mRNA and the protein level of PI3K, p-Akt, eNOS and p-eNOS, which can be blocked by PI3K inhibitor (LY294002) and eNOS inhibitor (l-NAME). Therefore, we concluded that impaired EPCs proliferation could be reversed by BBR via the PI3K/AKT/eNOS signaling pathway.