The clinical value of high mobility group box-1 and CRP/Alb ratio in the diagnosis and evaluation of sepsis in children.

OBJECTIVE: To explore the clinical value of high mobility group box-1 (HMGB-1), C-reactive protein (CRP), procalcitonin (PCT), and CRP to albumin (Alb) ratio in the diagnosis and evaluation of the severity of sepsis in children. PATIENTS AND METHODS: A total of 90 children, 50 with sepsis and 40 with general infection, whose symptoms did not meet the criteria for diagnosis of sepsis, were admitted to the Pediatrics Department of Jingzhou Central Hospital in Hubei Province between November 2021 and December 2022, were enrolled and selected as experimental and control group, respectively. The serum of two groups was collected within 24 hours after admission, the levels of HMGB-1 were detected by enzyme-linked immunosorbent assay (ELISA), and CRP, PCT, Alb, and hospitalization days were recorded. The differences in indicators between the two groups were compared, and correlation analysis was performed between hospitalization days and various indicators. The receiver operating characteristic (ROC) curve was drawn to evaluate the independent or combined value of CRP, PCT, HMGB-1, and CRP/Alb ratio in the early diagnosis of sepsis in children. RESULTS: These four indicators of children with sepsis were significantly higher than those in the general infection group (all p=0.000). The levels of CRP, PCT and CRP/Alb ratio were significantly positively correlated with the hospitalization days (r=0.329, 0.333, 0.329; p=0.02, 0.01, 0.002). The area under curve (AUC) of CRP, PCT, HMGB-1, and CRP/Alb ratio for the diagnosis of sepsis in children was 0.798, 0.817, 0.838, 0.809, respectively, and that of the combination of four indicators was 0.952. CONCLUSIONS: CRP, PCT, HMGB-1, and CRP/Alb ratio resulted as effective indicators for early diagnosis and evaluation of childhood sepsis, having a higher value in combined diagnosis.

Prognostic factors affecting overall survival in patients with spinal metastasis due to lung cancer: a systematic review and meta-analysis.

OBJECTIVE: Metastatic lung cancer often spreads to the musculoskeletal structures and spinal column. Patients suffering from spinal metastasis due to lung cancer present poorer prognostic outcomes in terms of overall survival compared to spinal metastases from other origins. To date, no meta-analysis has attempted to evaluate the prognostic impact of various predictive factors that may influence the overall survival of patients with spinal metastasis due to metastatic lung cancer. The aim of the study was to evaluate the prognostic impact of different predictive factors that might influence the overall survival of patients with spinal metastasis due to metastatic lung cancer. MATERIALS AND METHODS:  Five electronic databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE) were screened for eligible studies according to PRISMA guidelines. We conducted a random-effects meta-analysis to evaluate the prognostic impact of aging, pre-ambulatory status, radiotherapy, adenocarcinoma, performance status, visceral metastasis, and number of affected vertebrae on the overall survival of patients with spinal metastasis due to lung cancer. RESULTS:  From 963 studies, we found 13 eligible studies with data on 1144 patients. Our meta-analysis revealed that pre-treatment ambulatory status (2.08), Eastern cooperative oncology group score (1.78), and aging (1.68) had significant impacts on overall survival. CONCLUSIONS:  We provide preliminary evidence highlighting three factors potentially predictive of overall survival for patients suffering from spinal metastasis due to metastatic lung cancer. These findings may help clinicians stratify and manage patients more effectively.

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.

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.

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.

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.

Spirometric reference standards for preschool children in Hong Kong.

1. Prediction equations and normograms are established using incentive spirometry in a community cohort of 770 Hong Kong Chinese children aged 2 to 6 years. 2. All spirometric parameters depend mainly on standing height. Boys have higher values than girls. 3. Forced expiratory volumes depend on birth weight, place of birth, history of wheezing, and environmental tobacco smoke (ETS) exposure. 4. High urinary cotinine level as a biomarker of ETS exposure is noted in about one tenth of the children. 5. Urinary cotinine level is inversely associated with all spirometric parameters. This supports implementation of the smoking cessation programme.

Natural history and predictors for progression of mild childhood obstructive sleep apnoea.

AIMS: The natural history of mild childhood obstructive sleep apnoea (OSA) was examined and factors associated with disease progression were identified. METHODS: Subjects were recruited from an epidemiological study which examined the prevalence of OSA in Chinese children aged 6-13 years. The first 56 consecutive children identified with mild OSA (apnoea-hypopnoea index 1-5) were invited for a repeat assessment 2 years after the diagnosis. RESULTS: 45 children participated in the follow-up study, in 13 of whom (29%) the OSA was found to have worsened. Compared with those in whom OSA had not worsened, the worsened OSA group had a greater increase in waist circumference, a higher prevalence of large tonsils (occupying > or =50% of the airway) at both baseline and follow-up, and a higher prevalence of habitual snoring at both baseline and follow-up. The presence of large tonsils had a positive predictive value of 53% and a negative predictive value of 83% for worsening OSA over a 2-year period. Multivariate linear regression analysis showed that the change in obstructive apnoea-hypopnoea index was associated with age at baseline (beta (SE) = -0.92 (0.34), p = 0.009), gender (male = 1; female = 0) (beta (SE) = 4.69 (1.29), p<0.001), presence of large tonsils at baseline (beta (SE) = 4.36 (1.24), p = 0.001), change in waist circumference (beta (SE) = 0.30 (0.09), p = 0.002) and persistently large tonsils (beta (SE) = 5.69 (1.36), p<0.001) over the 2-year period. CONCLUSIONS: Mild OSA in the majority of children does not resolve spontaneously. Subjects with tonsillar hypertrophy, especially boys, should be closely monitored to allow early detection of worsening OSA. Weight control should be stressed in the management of childhood OSA.

Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is suggested to be associated with cardiac structural abnormalities and dysfunction but existing evidence is limited and the treatment effect on echocardiographic outcome remains controversial. OBJECTIVE: To examine the presence of subclinical cardiac abnormalities in childhood OSA and the effects of treatment on cardiac changes. METHODS: Polysomnography (PSG) and echocardiographic examinations were performed in 101 children aged between 6 and 13 years who were invited from a community based questionnaire survey. They were classified into a reference group (apnoea-hypopnoea index (AHI) <1, n = 35), mild OSA group (AHI 1-5, n = 39) and moderate to severe group (AHI >5, n = 27) based on the PSG results. Treatments, including adenotonsillectomy or nasal steroids, were offered to the mild and moderate to severe OSA groups. RESULTS: The moderate to severe OSA group had greater right ventricular (RV) systolic volume index (RVSVI), lower RV ejection fraction (RVEF) and higher RV myocardial performance index (RVMPI) than the reference group. They also had more significant left ventricular (LV) diastolic dysfunction and remodelling with larger interventricular septal thickness index (IVSI) and relative wall thickness than those with lower AHI values. The moderate to severe OSA group had an increased risk of abnormal LV geometry compared with the reference group (odds ratio 4.21 (95% CI 1.35 to 13.12)). Log transformed AHI was associated with RVSVI (p = 0.0002), RVEF (p = 0.0001) and RVMPI (p<0.0001), independent of the effect of obesity. Improvement in RVMPI, IVSI and E/e' were observed in those with a significant reduction in AHI (>50%) comparing 6 month with baseline data. CONCLUSIONS: OSA is an independent risk factor for subclinical RV and LV dysfunction, and improvement in AHI is associated with reversibility of these abnormalities.

Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays.

Acute respiratory tract infection is a leading cause of hospital admission of children. This study used a broad capture, rapid and sensitive method (multiplex PCR assay) to detect 20 different respiratory pathogens including influenza A subtypes H1, H3, and H5; influenza B; parainfluenza types 1, 2, 3, and 4; respiratory syncytial virus (RSV) groups A and B; adenoviruses; human rhinoviruses; enteroviruses; human metapneumoviruses; human coronaviruses OC43, 229E, and SARS-CoV; Chlamydophila pneumoniae; Legionella pneumophila; and Mycoplasma pneumoniae; from respiratory specimens of 475 children hospitalized over a 12-month period for acute respiratory tract infections. The overall positive rate (47%) was about twice higher than previous reports based on conventional methods. Influenza A, parainfluenza and RSV accounted for 51%, and non-cultivable viruses accounted for 30% of positive cases. Influenza A peaked at March and June. Influenza B was detected in January, February, and April. Parainfluenza was prevalent throughout the year except from April to June. Most RSV infections were found between February and September. Adenovirus had multiple peaks, whereas rhinovirus and coronavirus OC43 were detected mainly in winter and early spring. RSV infection was associated with bronchiolitis, and parainfluenza was associated with croup; otherwise the clinical manifestations were largely nonspecific. In general, children infected with influenza A, adenovirus and mixed viruses had higher temperatures. In view of the increasing concern about unexpected outbreaks of severe viral infections, a rapid multiplex PCR assay is a valuable tool to enhance the management of hospitalized patients, and for the surveillance for viral infections circulating in the community.

Induced sputum in childhood asthma.

Asthma is characterised by variable degrees of airway obstruction, airway hyper-responsiveness, and chronic airway inflammation. Current guidelines emphasise that inhaled corticosteroid treatment is the mainstay of asthma therapy because it targets the underlying airway inflammation. It is prudent to use the lowest possible dose of inhaled corticosteroid compatible with good asthma control. In clinical practice, the use of or the reduction of inhaled corticosteroid dosage is based on symptoms and lung function, both of which have been shown to have a poor correlation with airway inflammation. The use of induced sputum as a marker of airway inflammation improves asthma monitoring and optimises treatment in adults. This review discusses the technique of sputum induction, its clinical application, and our experience of its use in asthmatic children.

Non-CF bronchiectasis: does knowing the aetiology lead to changes in management?

The aim of the current study was to review the aetiology of non-cystic fibrosis (CF) bronchiectasis from two tertiary paediatric respiratory units in order to determine how often making a specific aetiological diagnosis leads to a change in management, and to assess the contribution of computed tomography (CT) in determining the underlying diagnosis. The case records of all patients who were diagnosed as having bronchiectasis by CT, currently being seen at the Royal Brompton Hospital and Great Ormond Street Hospital for Children (London, UK), were reviewed. All patients had undergone extensive investigations, and the underlying aetiology and the area of pulmonary involvement (as seen on CT) were recorded. A total of 136 patients were identified; there were 65 young males and the group median (range) age was 12.1 yrs (3.1-18.1). Immunodeficiency, aspiration and primary ciliary dyskinesia accounted for 67% of the cases. In 77 (56%) children, the identification of a cause led to a specific change in management. There was no association between aetiology and the distribution of CT abnormalities. In conclusion, immunodeficiency and other intrinsic abnormalities account for the majority of cases of non-cystic fibrosis bronchiectasis seen in the current authors' units. Computed tomography scans do not contribute towards identifying the aetiology and, most importantly, a specific aetiological diagnosis frequently leads to a change in management.

Risk factors for childhood overweight in 6- to 7-y-old Hong Kong children.

OBJECTIVE: To identify risk factors for overweight in Hong Kong children aged 6-7 y. DESIGN: Case-control study. SETTING: Student Health Service Centres, Hong Kong. SUBJECTS: A total of 343 Hong Kong Chinese children aged 6-7 y old categorised into three groups, an overweight group (> or =92 nd centile for BMI), a normal middle-weight group (45th-55th centile for BMI) and a normal low-weight group (< or =8th centile for BMI). MEASUREMENTS: Subjects and their parents/caregivers were interviewed at home. Data on lifestyle habits, dietary habits, family structure and demographic background were collected by questionnaire. A 3-day dietary record was administrated by the parents/caregivers to assess dietary intake of the children. RESULTS: Logistic regression analyses (overweight group compared with middle-weight plus low-weight groups) showed that childhood overweight was significantly associated with parental obesity (BMI > or =25 kg/m(2), Asian reference) (paternal: OR=2.66, 95% CI=1.51-4.70; maternal: 5.07, 2.62-9.79) but not parental overweight (BMI=23-25 kg/m(2)). After adjustment for parental obesity, the odds ratio for childhood overweight was increased by birth weight (<3.0 kg as reference, 3.0-3.5 kg: 2.13, 1.18-3.84; > or =3.5 kg: 4.89, 2.49-9.60) and decreased by sleeping duration (<9 h/day as reference, 9-11 h/day: 0.54, 0.30-0.97; > or =11 h/day: 0.31, 0.11-0.87). Childhood overweight was also significantly associated with higher energy consumption (2.62, 1.20-5.74) and having a father who was a current smoker (2.08, 1.25-3.46). CONCLUSIONS: Although healthy diet and regular exercise will remain the cornerstones of obesity management in children, our data support the view that education about maintaining a healthy weight could be introduced much earlier in those families with high-risk children, as indicated by high parental BMI or high birth weight. The utility and practicality of such an approach should be carefully evaluated before becoming part of any public health policy. Further study of the role of short sleeping duration and parental smoking on childhood obesity development is warranted.

Respiratory function in patients with thalassaemia major: relation with iron overload.

AIMS: (1) To determine the pattern of respiratory impairment in children with thalassaemia major (TM); (2) to assess the relation between the degree of respiratory impairment and total body iron content. METHODS: Twenty nine TM patients were recruited. All underwent physical examination, standardised pulmonary function tests (spirometry, lung volume, and single breath diffusion capacity for carbon monoxide), and magnetic resonance imaging measurements of the liver. Serum ferritin was measured. The signal intensity ratio of liver to that of paraspinal muscle (T1 weighted sequence) and serum ferritin were used as surrogate index of body iron content. RESULTS: Sixteen boys and 13 girls (median age 14.2 years) were studied. None had clinical evidence of congestive heart failure. Sixteen had normal lung function. Impairment of diffusion capacity (median DL(co) 83.5% predicted) was the most common abnormality, being observed in 34% of patients. Pure restrictive and obstructive ventilatory impairment was found in one and two patients respectively. Five patients had a combination of ventilation and diffusion defects. There was no correlation between the degree of impairment of each respiratory abnormality and body iron content. CONCLUSION: Diffusion impairment was the commonest abnormality found in our cohort of paediatric TM patients. Our data did not support the notion that respiratory function impairment was correlated with body iron content.