[Regulatory mechanisms and clinical significance of circadian disruption in intensive care unit patients].

Organisms adapt to the circadian changes in the external environment by regulating various life activity processes and establishing regular circadian cycles. A growing number of studies indicate that there is an extensive association between circadian disruption and critical illness, and circadian disruption is a pathological syndrome influencing the clinical outcome of critically ill patients. As a result of the disease itself, the ICU environment and medical interventions, critically ill patients often experience severe circadian disruption, which leads to aberrations in a wide range of physiological and behavioral functions of the organism, and finally exacerbates disease progression. In this paper, we reviewed the regulatory mechanisms of biological circadian rhythms, the causes and consequences of circadian disruption in critically ill patients, the assessment of circadian disruption, and strategies to restore circadian homeostasis to assist in the comprehensive treatment of critically ill patients.

LncRNA SNHG4 promotes neuroblastoma proliferation, migration, and invasion by sponging miR-377-3p.

Long non-coding RNAs (lncRNAs) have been demonstrated to act as essential regulators in the growth and progression of neuroblastoma. In the present research, the high expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) in neuroblastoma was tested via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and then the function of SNHG4 was explored and verified by CCK-8 assay, EdU assay, cell cycle assay, cell apoptosis test, wound healing test and invasion test in neuroblastoma cell lines. It was discovered that lncRNA SNHG4 exhibited high expression in neuroblastoma tissues and cell lines, and the expression of SNHG4 was associated with the survival of neuroblastoma patients. Additionally, SNHG4 decrement markedly repressed neuroblastoma cells to proliferate and stimulate their apoptosis in vivo and in vitro. Moreover, SNHG4 decrement impeded the abilities of SH-SY5Y and IMR-32 cells to migrate and invade as well as epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG4 acted as a competing endogenous RNA to sponge miR-377-3p, which was downregulated in neuroblastomas and inhibited cell proliferation and invasion. The findings manifested that SNHG4 was inversely associated with miR-377-3p expression in neuroblastoma cases. Collectively, we revealed the functions of SNHG4 and miR-377-3p in neuroblastoma.

Correction to: In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

In the original version of this article, the Publisher incorrectly listed the affiliation of the author, G.M. Leung. The correct affiliation for this author should be: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Correction to: Effects of growth hormone on pregnancy rates of patients with thin endometrium.

Unfortunately, there are errors that occurred in the name and manufacture of the growth hormone (GH) received by the patients in the GH group on page two, Table 1 and figure 1 on page three.

Effects of growth hormone on pregnancy rates of patients with thin endometrium.

PURPOSE: To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments. MATERIALS AND METHODS: Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM). RESULTS: Patients treated with GH had a significantly (P < 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (P < 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells. CONCLUSION: GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.

In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

BACKGROUND/OBJECTIVES: Short-term breastfeeding from mothers with gestational diabetes (GDM) may programme metabolism and increase offspring diabetes risk. We examined the association of in utero GDM exposure with adiposity from infancy to adolescence, and whether any association was modified by breastfeeding during early infancy. METHODS: In the prospective Chinese birth cohort "Children of 1997" (n = 7342, 88% follow-up rate), generalised estimate equations with multiple imputation were used to assess associations of in utero GDM exposure with age- and sex-specific body mass index (BMI) z-score during infancy (3 and 9 months), childhood (2- < 8 years) and adolescence (8-16 years), adjusted for sex, parity, maternal age, birth place, preeclampisa, smoking, and family socio-economic position. We also tested whether the associations differed by mode of infant feeding (always formula-fed, mixed, always breastfed) during the first three months of life. RESULTS: In utero GDM exposure (7.5%) was associated with a lower BMI z-score during infancy (-0.13, 95% confidence interval (CI) -0.22, -0.05) but higher BMI z-scores during childhood (0.14, 95% CI 0.03, 0.25) and adolescence (0.25 95% CI 0.11, 0.38). Breastfeeding for the first three months did not modify the association of in utero GDM status with subsequent BMI (all p values for interaction >0.4). CONCLUSIONS: In utero GDM exposure was associated with greater adiposity during childhood and adolescence. Breastfeeding in early infancy from mothers with GDM was not associated with greater adiposity in children and thus should still be encouraged.

Dietitian-led lifestyle modification programme for obese Chinese adolescents with non-alcoholic fatty liver disease: a randomized controlled study.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in children is increasing. This study evaluated the efficacy of a dietitian-led lifestyle modification programme (D-LMP) to reduce NAFLD in obese adolescents. METHODS: Subjects with intra-hepatic triglyceride content (IHTC) equal to or greater than 5% diagnosed by proton-magnetic resonance spectroscopy (1H-MRS) were enroled and randomly assigned to either the D-LMP intervention or conventional paediatrician-led consultation (P-CON) group. Subjects in the P-CON group received usual care consisting of a consultation by a paediatrician with the child and parents every 16 weeks. Intention-to-treat analysis was used for data analysis. RESULTS: Fifty-two subjects were recruited, with 26 in each group. After the initiation phase (at week-16), there was a greater difference in the change in the IHTC and BMI z-score in the D-LMP group (P = 0.029 and <0.001, respectively) and there was a decrease in dietary intake of fat content (P = 0.019). After 52 weeks of the maintenance phase, both groups had reductions of IHTC to 2-3% and there was no intergroup difference in the rate of reduction. During the maintenance phase, parents' involvement was minimal in the D-LMP group, with only three parents accompanying their children to attend the dietitian sessions. In contrast, over 90% of the parents in the P-CON group regularly accompanied their children to attend the consultations suggesting the possibility that regular parental and paediatrician involvement may contribute to increasing awareness on fatty liver complications. Multivariate analysis showed that only reduction in body fat remained as an independent factor associated with remission of NAFLD at the end of both study phases. CONCLUSIONS: A dietitian-led lifestyle modification intervention reduced IHTC, BMI z-score and body fat in obese Chinese adolescents with NAFLD. To sustain the effect of this intervention, regular parental and paediatrician involvement may be important.

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.

BACKGROUND: MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated. METHODS: In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice. RESULTS: MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial-mesenchymal transition (EMT)-associated proteins. TGF-ß1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF-ß1-induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo, it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1. CONCLUSIONS: miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.

Waist-to-height ratio as a measure of abdominal obesity in southern Chinese and European children and adolescents.

BACKGROUND: Waist-to-height ratio (WHtR), with a 0.5 threshold (WHtR0.5), is regarded as a simple age- and gender-independent criterion of abdominal obesity (AO) and a better predictor than the 90th percentile of waist circumference (WCP90). OBJECTIVE: An analysis of gender and ethnic differences of WHtR and other AO indices between children and adolescents from southern China (HK: Hong-Kong, China) and Europe (LD: Lódz, Poland). SUBJECTS: Two large cross-sectional surveys of children and adolescents aged 7-19 years, one from LD (13 172) and one from HK (14 566). METHODS: The percentile and standardized values of WHtR and other parameters (WC, body mass index (BMI)) were assessed using the LMS method. The WHtR values corresponding to WCP90 and to the BMI definition of global obesity (BMIP95) were evaluated with the polynomial regression model. The compliance of the AO prevalence data, obtained with two criteria (WCP90 vs WHtR0.5) was analyzed using Cohen's kappa index (κC). RESULTS: The WHtR data of Polish subjects were generally higher than those of their HK peers, and the ethic differences increased with age. The WHtR values of HK boys showed a stronger relationship with BMI z-score. WHtR corresponding to WCP90 assumed values <0.5. An application of Cohen's kappa coefficient (κC) to Polish subjects showed either 'substantial' (κC>0.6) or 'almost perfect' (κC>0.8) agreement in the AO prevalence for both criteria (WCP90 and WHtR0.5). For these criteria, either 'fair' (κC <0.4) or 'moderate' (κC<0.6) AO consistency ratings were observed among HK girls. In HK boys, a significant difference in the prevalence of AO was observed, independent of the criterion used. CONCLUSIONS: Our results provide further evidence of the need for developing ethnic-specific WC charts and for recommending that a WHtR cutoff of 0.5 may not be appropriate to predict cardiometabolic risk in children of different ethnic groups.

Effect of tumor necrosis factor-induced protein 8 on T-cell-mediated immunity in mice after thermal injury.

Tumor necrosis factor-induced protein 8(TNFAIP8), the first identified member of the TNFAIP8 family, shares considerable sequence homology with members of this family. It is expressed in a wide variety of human normal tissues, with relatively higher levels in lymphoid tissues and placenta. The present study was designed to examine the effect of TNFAIP8 on T-cell-mediated immunity secondary to burn injury. Sixty male mice were randomly divided into four groups as follows: sham burn group, burn group, burn with TNFAIP8-siRNA transfection group, and burn with negative control transfection group, and they were sacrificed at designated time points. CD4+ T cells were isolated using MACS microbeads. T-Cell proliferation was analyzed with MTT assay, and IL-2, soluble IL-2R, IL-4, interferon-γ (IFN-γ) were determined with enzyme-linked immunosorbent assay kits. It was found that CD4+ T lymphocyte proliferative activity was significantly down-regulated when TNFAIP8 gene was silenced by siRNA in mice at 24 h post burn. Down-regulation of TNFAIP8 can significantly decrease expression levels of IL-2 and soluble IL-2R at 24 h after thermal injury. These results demonstrated that TNFAIP8 appeared to be involved in the immune regulation of CD4+ T lymphocytes, and the decreased expression of TNFAIP8 could affect T lymphocyte functions after thermal injury.

Detection of Piwi-interacting RNAs based on sequence features.

Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs. Distinguishing piRNAs from other non-coding RNAs is important because of their important role in the physiological regulation of spermatogenesis, genome protection from transposons, and regulation of mRNAs and long non-coding RNAs. Few computational studies have addressed piRNAs detection, and both effectiveness and efficiency of piRNA detection tools require improvement. In this study, a piRNA detection method based on sequence features and a support vector machine was developed. Four types of features are proposed: weighted k-mer, weighted k-mer with wildcards, position-specific base, and piRNA length. The piRNA sequences from human, mouse, rat, and drosophila were respectively used in this experiment. Compared to existing algorithms, the proposed method provides a better balance between precision and sensitivity (both are approximately 90%), and although these values were slightly slower than those obtained using the piRNA annotation approach, the proposed method was four-fold faster than piRPred and 229-fold faster than piRNA predictor.

Mode of delivery and childhood hospitalizations for asthma and other wheezing disorders.

BACKGROUND: Observationally, delivery by Caesarean section is associated with higher risk of childhood asthma and wheeze in developed Western settings, but associations are less consistent in other settings. OBJECTIVE: To examine the association of mode of delivery with hospitalizations for asthma and other wheezing disorders in a developed non-Western setting with high rates of Caesarean section. METHODS: Using Cox regression, we examined the adjusted association of mode of delivery with public hospital admissions for asthma, bronchitis, and bronchiolitis (International Classification of Diseases, Ninth Version Clinical Modification 466, 490 and 493) from 9 days to 12 years of age in a population-representative prospective birth cohort of 8327 Chinese children in Hong Kong. Confounders included sex, birth and parental characteristics, and socio-economic position (SEP). RESULTS: Delivery by Caesarean section accounted for 27% of all births and was not clearly associated with hospitalizations for asthma and other wheezing disorders to 12 years [hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.91 to 1.36] compared to vaginal delivery. Similarly, there were no clear associations to 2 years (HR 1.07, 95% CI 0.83 to 1.38) or 6 years (HR 1.12, 95% CI 0.91 to 1.37), although we cannot rule out residual confounding by SEP. CONCLUSIONS AND CLINICAL RELEVANCE: We cannot rule out an association, but our findings suggest that the observed associations of delivery by Caesarean section with childhood wheezing disorders may vary with setting and may not be biologically mediated. Further studies with different designs are needed to clarify the role of the microbiome and mode of delivery in the aetiology of asthma and other childhood wheezing disorders.

Oridonin inhibits tumor growth in glioma by inducing cell cycle arrest and apoptosis.

Glioma is the most common malignant intracranial tumors. Despite newly developed therapies, these treatments mainly target oncogenic signals, and unfortunately, fail to provide enough survival benefit in both human patients and mouse xenograft models, especially the first-generation therapies. Oridonin is purified from the Chinese herb Rabdosia rubescens and considered to exert extensive anti-cancer effects on human tumorigenesis. In this study, we systemically investigated the role of Oridonin in tumor growth and the underlying mechanisms in human glioma. We found that Oridonin inhibited cell proliferations in a dose- and time-dependent manner in both glioma U87 and U251 cells. Moreover, these anti-cancer effects were also confirmed in a mouse model bearing glioma. Furthermore, cell cycle arrest in S phase was observed in Oridonin-mediated growth inhibition by flow cytometry. Cell cycle arrest in S phase led to eventual cell apoptosis, as revealed by Hoechst 33342 staining and annexin V/PI double-staining. The cell apoptosis might be accomplished through a mitochondrial manner. In all, we were the first to our knowledge to report that Oridonin could exert anti-cancer effects on tumor growth in human glioma by inducing cell cycle arrest and eventual cell apoptosis. The identification of Oridonin as a critical mediator of glioma growth may potentiate Oridonin as a novel therapeutic strategies in glioma treatments.