P C Ng

The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Publications (193)686.51 Total impact

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    ABSTRACT: The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and non-inflammatory surgical conditions (Surg-CTL), and (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation. Our results showed that expressions of arginine synthesizing enzymes ALDH18A1, ASL, ASS1, CPS1, GLS, OAT and PRODH were significantly decreased in NEC compared with Surg-CTL or SIP tissues. Catabolic enzyme ARG1 was increased (>100 fold) in NEC tissues and histologically demonstrated to be expressed by infiltrating neutrophils. No change in arginine metabolic enzymes was observed between SIP and Surg-CTL tissues. In CaCO2 cells, arginine metabolic enzymes were differentially dysregulated by lipopolysaccharide or lipoteichoic acid. Depletion of arginine reduced cell proliferation and this phenomenon could be partially rescued by NO. Overexpression of ARG1 also reduced enterocyte proliferation. We provided the first expressional profile of arginine metabolic enzymes at the tissue level of NEC. Our findings suggested that arginine homeostasis was severely disturbed and could be triggered by inflammatory responses of enterocytes and infiltrating neutrophils as well as bacterial components. Such reactions could reduce arginine and NO, resulting in mucosal damage. The benefit of arginine supplementation for NEC prophylaxis merits further clinical evaluation.
    No preview · Article · Nov 2015
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    ABSTRACT: Background: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology. Methods: We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples. Results: We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction. Conclusions: The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology.
    Full-text · Article · Aug 2015 · PLoS ONE
  • Maggie Lo-Yee Yau · Eva Lai-Wah Fung · Pak Cheung Ng
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    ABSTRACT: To review the clinical response to levetiracetam (LEV) in neonatal seizure management in intensive care unit. Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via PubMed and EMBASE with keywords - "neonates", "seizures", "epilepsy" and "LEV" up to Sep 2014 and retrieved the publications. The response rate to LEV was compared. Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven (58%) and nine (75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures. LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy.
    No preview · Article · Aug 2015
  • Pak Cheung Ng · Terence Ping Yuen Ma · Hugh Simon Lam
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    ABSTRACT: Biomarkers have been used to differentiate systemic neonatal infection and necrotising enterocolitis (NEC) from other non-infective neonatal conditions that share similar clinical features. With increasing understanding in biochemical characteristics of different categories of biomarkers, a specific mediator or a panel of mediators have been used in different aspects of clinical management in neonatal sepsis/NEC. This review focuses on how these biomarkers can be used in real-life clinical settings for daily surveillance, bedside point-of-care testing, early diagnosis and predicting the severity and prognosis of neonatal sepsis/NEC. In addition, with recent development of 'multi-omic' approaches and rapid advancement in knowledge of bioinformatics, more novel biomarkers and unique signatures of mediators would be discovered for diagnosis of specific diseases and organ injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Article · Jan 2015 · Archives of Disease in Childhood - Fetal and Neonatal Edition

  • No preview · Article · Dec 2014 · Blood
  • HS Lam · HM Cheung · CLS Chau · PC Ng
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    ABSTRACT: Background and aim Decisions whether or not to perform high-risk surgery in preterm infants depend on prognosis and preferences/values of society as well as parents and healthcare workers. We aimed to assess differences in preferences between these groups to life-saving surgery in critically ill infants. Methods Paediatric doctors and nurses, parents of preterm infants (PPs) and term infants (PTs) were recruited. A scenario with a critically ill preterm infant with necrotising enterocolitis requiring surgery was presented. Surgery would result in gastrointestinal complications and one of five possible disability health-states (HS1 mild cognitive, severe physical; HS2 moderate respiratory; HS3 severe cognitive and mild physical; HS4 otherwise uncomplicated; HS5 moderate cognitive and mild respiratory complications). Without surgery, the infant would die. Subjects (i) ranked death and the health-states according to perceived severity and (ii) decided for each health-state whether or not to proceed with surgery “at all costs”. Results 55 doctors, 102 nurses, 178 PPs and 201 PTs were recruited. (i) Nurses more likely ranked states with predominant cognitive disability (HS3 and HS5) as worse than death compared with other groups. (ii) In less adverse health-states (HS1 and HS4) there were no differences between groups. Again, nurses were least likely to decide to save-at-all-costs in HS3 and HS5 and PPs were more likely to decide to save-at-all-costs than healthcare workers in a poor outcome (HS5). Conclusions Nurses were least tolerant to adverse health-states. We show that health state preferences vary between doctors, nurses and parents. Parental counselling should account for these differences.
    No preview · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Makorin-2 (MKRN2) is a highly conserved protein and yet its functions are largely unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and malignant hematopoietic cells, and leukemia cell lines. We also attempted to delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus transduction and shRNA nucleofection, respectively. Our results provided the first evidence on the ubiquitous expression of MKRN2 in normal hematopoietic cells, embryonic stem cell lines, primary leukemia and leukemic cell lines of myeloid, lymphoid, erythroid and megakaryocytic lineages. The expression levels of MKRN2 were generally higher in primary leukemia samples compared with those in age-matched normal BM cells. In all leukemia subtypes, there was no significant correlation between expression levels of MKRN2 and RAF1. sh-MKRN2-silenced CD34+ cells had a significantly lower proliferation capacity and decreased levels of the early stem/progenitor subpopulation (CFU-GEMM) compared with control cultures. Over-expression of MKRN2 in K562 cells increased cell proliferation. Our results indicated possible roles of MKRN2 in normal and malignant hematopoiesis.
    Full-text · Article · Mar 2014 · PLoS ONE

  • No preview · Article · Jan 2014
  • H. S. Lam · P. C. Ng

    No preview · Article · Jan 2014 · Neonatology
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    ABSTRACT: To provide a comprehensive database of gene regulation and compare differentially regulated molecular networks in human tissues of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP). Both NEC and SIP are devastating surgical emergencies associated with high morbidity and mortality in preterm infants. Their pathophysiology and molecular mechanisms remain unclear. Differential whole genome microarray analysis was performed on intestinal tissues collected from NEC (n = 15) and SIP (n = 12) infants and compared with tissues collected from surgical-control patients with noninflammatory intestinal conditions (n = 14). Validation of 52 target gene expressions was performed by quantitative polymerase chain reaction. Regulatory networks of significantly affected genes were constructed according to functional pathways. Extensive and significant changes of gene expression were observed in NEC tissues, which comprised multiple pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia and oxidative stress, inflammation, and muscle contraction. These dysregulated genes could be networked downstream of key receptors, TLR2, TLR4, and TREM1, and mediated via NF-κB, AP-1, and HIF1A transcription factor pathways, indicating predominant microbial and inflammatory involvement. In contrast, SIP tissues exhibited much milder and less diversified expressional changes, with target genes significantly associated with G-protein-mediated muscle contraction and extracellular matrix remodeling. The molecular evidence suggests that NEC and SIP are likely 2 different diseases caused by distinct etiology and pathophysiology. This first comprehensive database on differential gene expression profiles of human NEC and SIP tissues could lead to development of disease-specific diagnostic and prognostic biomarkers and new therapeutic strategies for improving outcomes.
    No preview · Article · Dec 2013 · Annals of surgery
  • T F Leung · A M Li · G Wk Wong · S Ps Wong · C Wk Lam · P C Ng
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    ABSTRACT: 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.
    No preview · Article · Dec 2013 · Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine

  • No preview · Article · Dec 2013 · Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine

  • No preview · Article · Dec 2013 · Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine
  • Pak Cheung Ng
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    ABSTRACT: Different categories of biomarkers of necrotising enterocolitis (NEC), including (i) non-specific mediators of the inflammatory cascade, e.g. acute phase reactants, chemokines, cytokines, and cell surface antigens, (ii) enhanced non-specific biomarkers, and (iii) specific gut-associated proteins, have distinctive biochemical characteristics and properties. The appropriateness of using these mediators in specific clinical situations, and the pros and cons of their applications as indicators or predictors of intestinal injury and NEC are highlighted. Many potentially new biomarkers such as micro-RNA, volatile organic compounds and gut microbiomes are currently under investigation. A stringent protocol for biomarker discovery is revealed so that investigators can consider this methodology as a reference for future discovery of organ-specific and/or disease-specific biomarkers for preterm infants.
    No preview · Article · Sep 2013 · Seminars in Fetal and Neonatal Medicine
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    ABSTRACT: Background: Early detection and treatment of infected preterm infants could decrease morbidity and mortality. Neutrophil CD64 has been shown to be an excellent early diagnostic biomarker of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). We aimed to study whether using CD64 as a daily surveillance biomarker could predict LOS/NEC before clinical manifestation. Methods: We collected 0.1 mL whole blood from very low birth weight (VLBW) infants from day 7 postnatal age until routine daily blood tests were no longer required. Four categories of responses were defined: proven sepsis, clinical sepsis, nonsepsis/non-NEC, and asymptomatic CD64 activation. Results: A total of 146 infants were consecutively recruited and 155 episodes of sepsis evaluation were performed. The biomarker screening utility, sensitivity, specificity, positive predictive value, and negative predictive value for surveillance of LOS/NEC using a cutoff of 5655 antibody-PE (phycoerythrin) molecules bound/cell were 89%, 98%, 41%, and 99.8%, respectively. LOS/NEC was detected a mean of 1.5 days before clinical presentation. However, 63 episodes of CD64 activation occurred in asymptomatic infants who would not otherwise have required sepsis evaluations. Conclusions: As a surveillance biomarker, neutrophil CD64 detected LOS/NEC 1.5 days before clinical presentation, but at the expense of performing 41% additional sepsis evaluations. This was mainly attributed to an unexpected group of asymptomatic infants with CD64 activation, who recovered spontaneously and did not require antimicrobial treatment. The latter group has not been previously recognized in VLBW infants and could represent subclinical infection secondary to transient bacterial translocation or mild viral infection.
    Preview · Article · Sep 2013 · Clinical Chemistry
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    ABSTRACT: In newborn infants, the innate cellular system plays a crucial role in the first line of defense against pathogens. Neutrophils are the most abundant leukocytes, and their response to the commonly encountered nosocomial bacterial (Gram positive) infection in newborns remains largely unclear. In this study, a genome-wide expression array analysis was performed on CB neutrophils after challenge by PGN in vitro and compared with neutrophils in CTL cultures without PGN. We investigated responses of neutrophils to PGN and LPS, with respect to cytokine synthesis, chemotaxis, ROS production, cell death, and pathways of HSP response. Our results provide the first comprehensive expressional profile of neonatal neutrophils stimulated by PGN. mRNA levels of 16 up-regulated genes and 6 down-regulated genes were validated by qPCR. Their regulatory networks were identified downstream of TLR-2 and NOD-2, which work in concert toward signals of death, cytoprotection, inflammation, and stress responses. Members of the HSP family were significantly up-regulated in PGN-stimulated neutrophils, compared with those in LPS-stimulated cells. We confirmed protein co-precipitation of HSPA1A and OLR1 in stimulated neutrophils, and their transcription, induced by NF-κB but not by MAPK signals. We found increased CD11b, chemotaxis, TNF-α, and IL-8 in neutrophils stimulated by PGN or LPS. PGN, but not LPS, increased ROS production. We conclude that neonatal neutrophils are capable of vigorous molecular and functional responses to PGN and suggest that HSP plays a critical role in the host defense mechanism, possibly involving proinflammatory OLR1 and CD11b-facilitated chemotaxis.
    Preview · Article · Aug 2013 · Journal of leukocyte biology
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    Full-text · Dataset · Jul 2013
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    Full-text · Dataset · Jul 2013
  • T F Leung · P K S Chan · G W K Wong · T F Fok · P C Ng
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    ABSTRACT: 1. Respiratory viruses and atypical bacteria were detected in 51.0% of Hong Kong children with asthma exacerbations, which was significantly higher than the detection rate of 27.3% in children with chronic stable asthma. 2. Co-infections of two or more respiratory pathogens were more commonly found in children with asthma exacerbations (10.7%) than in patients with stable asthma (2.6%). 3. Human rhinovirus infection was a significant risk factor for asthma exacerbations. 4. There was no significant association between the severity of asthma exacerbations and respiratory viral or atypical bacterial infections. 5. Routine use of macrolide antibiotics in the treatment of childhood asthma exacerbations should be discouraged.
    No preview · Article · Jun 2013 · Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine
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    ABSTRACT: BACKGROUND: International studies suggest that low dose prenatal methylmercury exposure (>29nmol/L) has long-term adverse neurocognitive effects. There is evidence that the majority of children in Hong Kong exceed this level as a result of high fish consumption of mothers during pregnancy. OBJECTIVE: To study whether there are any associations between low-dose prenatal methylmercury exposure and neurocognitive outcomes in Hong Kong children. MATERIALS AND METHODS: All 1057 children from the original birth cohort were eligible for entry into the study, except children with conditions that would affect neurocognitive development, but were unrelated to methylmercury exposure. Subjects were assessed by a wide panel of tests covering a broad range of neurocognitive functions: Hong Kong Wechsler Intelligence Scale for Children (HK-WISC), Hong Kong List Learning Test (HKLLT), Tests of Everyday Attention for Children (TEACH), Boston Naming Test, and Grooved Pegboard Test. RESULTS: 608 subjects were recruited (median age 8.2years, IQR 7.3, 8.8; 53.9% boys). After correction by confounders including child age and sex, multivariate analysis showed that cord blood mercury concentration was significantly associated with three subtests: Picture Arrangement of HK-WISC (coefficient -0.944, P=0.049) and Short and Long Delay Recall Difference of the HKLLT (coefficient -1.087, P=0.007 and coefficient -1.161, P=0.005, respectively), i.e., performance worsened with increasing prenatal methylmercury exposure in these subtests. CONCLUSIONS: Small, but statistically significant adverse associations between prenatal methylmercury exposure and long-term neurocognitive effects (a visual sequencing task and retention ability of verbal memory) were found in our study. These effects are compatible with findings of studies with higher prenatal methylmercury exposure levels and suggest that safe strategies to further reduce exposure levels in Hong Kong are desirable.
    Full-text · Article · Feb 2013 · Environment international

Publication Stats

4k Citations
686.51 Total Impact Points

Institutions

  • 1994-2015
    • The Chinese University of Hong Kong
      • • Department of Paediatrics
      • • Department of Mathematics
      Hong Kong, Hong Kong
  • 1994-2013
    • Prince of Wales Hospital, Hong Kong
      Chiu-lung, Kowloon City, Hong Kong
  • 2004
    • Queen Elizabeth Hospital
      Hong Kong, Hong Kong