ORCID Profile
0000-0002-1556-2538
Current Organisations
The University of Hong Kong
,
University of Bristol
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Publisher: The Endocrine Society
Date: 03-11-2020
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2–related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers. Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from July 21 to August 21, 2020, were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3), and antithyroid antibodies were measured on admission. Among 191 patients with COVID-19 (mean age 53.5 ± 17.2 years 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. Abnormal thyroid function was seen in 13.1%. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in 2 of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing nonthyroidal illness syndrome. Lower SARS-Cov-2 polymerase chain reaction cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (P = .030) and low fT3 (P = .007), respectively. A decreasing trend of fT3 with increasing COVID-19 severity (P = .032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes. Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance.
Publisher: Elsevier BV
Date: 2015
Publisher: Wiley
Date: 15-06-2011
DOI: 10.1002/MC.20807
Abstract: The role of X chromosome-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) in mediating apoptosis has been reported but the underlying mechanism remains unclear. The present study was designed to examine the putative interaction between XAF1 and p53 and the functional importance of this interaction in regulation of apoptosis in human gastric and colon cancer cells. We first identified XAF1 as a novel target gene of p53 by the chromatin immunoprecipitation (CHIP) assay and demonstrated that wild-type p53, but not mutant p53, down-regulated XAF1 at both mRNA and protein levels, which acted mostly under the condition of high expression of XAF1 and was associated with the physical interaction between p53 and the XAF1 promoter. We also found that the over-expression of XAF1 led to activation of wild-type p53 via post-translational modification in cells with or without DNA damage, which resulting in p53 nuclear accumulation and its increased transcriptional activity and enhancing p53-dependent apoptosis. These findings suggest that a potential novel feedback loop exists between XAF1 and wild-type p53.
Publisher: Oxford University Press (OUP)
Date: 11-2010
DOI: 10.1086/656587
Abstract: Despite World Health Organization recommendations, the rate of 23-valent pneumococcal (PPV) and influenza (TIV) vaccination among elderly persons in Hong Kong, China, is exceptionally low because of doubts about effectiveness of vaccination. The efficacy of dual vaccination remains unknown. From 3 December 2007 to 30 June 2008, we conducted a prospective cohort study by recruiting outpatients aged ≥65 years with chronic illness to participate in a PPV and TIV vaccination program. All were observed until 31 March 2009. The outcome of subjects, including the rates of death, hospitalization, pneumonia, ischemic stroke, acute myocardial infarction, and coronary and intensive care admissions, were determined. Of the 36,636 subjects recruited, 7292 received both PPV and TIV, 2076 received TIV vaccine alone, 1875 received PPV alone, and 25,393 were unvaccinated, with a duration of follow-up of 45,834 person-years. Baseline characteristics were well matched between the groups, except that there were fewer male patients in the PPV and TIV group and fewer cases of comorbid chronic obstructive pulmonary disease among unvaccinated persons. At week 64 from commencement of the study, dual-vaccinees experienced fewer deaths (hazard ratio [HR], 0.65 95% confidence interval [CI], 0.55-0.77] P<.001) and fewer cases of pneumonia (HR, 0.57 95% CI, 0.51-0.64 P<.001), ischemic stroke (HR, 0.67 95% CI, 0.54-0.83 P<.001), and acute myocardial infarction (HR, 0.52 95% CI, 0.38-0.71 P<.001), compared with unvaccinated subjects. Dual vaccination resulted in fewer coronary (HR, 0.59 95% CI, 0.44-0.79 P<.001) and intensive care admissions (HR, 0.45 95% CI, 0.22-0.94 P=.03), compared with among unvaccinated subjects. Dual vaccination with PPV and TIV is effective in protecting elderly persons with chronic illness from developing complications from respiratory, cardiovascular, and cerebrovascular diseases, thereby reducing hospitalization, coronary or intensive care admissions, and death.
Publisher: Oxford University Press (OUP)
Date: 23-07-2009
Abstract: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) was first recognized as an antagonist of X-linked inhibitor of apoptosis in suppressing caspase 3 activity. It has lower expression in cancer cells than normal tissue. Overexpression of XAF1 can inhibit cancer cell growth and sensitize tumor necrosis factor-related apoptosis-inducing ligand- or etoposide-induced apoptosis. The aim of this study is to elucidate the mechanism of XAF1 in regulating cell growth. Stable transfectants of gastrointestinal (GI) cancer cell lines AGS and SW1116 expressing XAF1 and vector control were generated. Cell growth, apoptosis, mitotic status and cell cycle distribution were assessed. The interaction between XAF1 and G(2)/M checkpoint proteins was evaluated by immunoblotting, kinase assay and co-immunoprecipitation assay. Mitotic catastrophe was identified by occurrence of aberrant nuclei and centrosomal lification. Our results showed that overexpression of XAF1 suppressed serum-dependent cancer cell growth, induced mitotic catastrophe and G(2)/M cell cycle arrest. Interestingly, XAF1 was predominantly expressed in G(2)/M phase after cell cycle synchronization. XAF1 interacted with and activated checkpoint kinase 1 (Chk1), inactivated Cdc25C and lead to inactivation of Cdc2-cyclin B complex. Suppression of Chk1 abrogated XAF1-induced G(2)/M arrest. Our findings implicate XAF1 as a novel cell cycle modulator that is recruited in G(2)/M phase and thus unravel a novel function pathway of XAF1, suggesting the potential role of XAF1 as the target for the management of GI cancers.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2023
DOI: 10.1161/HYPERTENSIONAHA.122.20752
Abstract: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension. We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women mean age, 54±6 years). The hypertensive group was associated with GM alterations however, significant differences in β- ersity and GM composition in hypertensive versus normotensive groups were only observed in women and not in men under various statistical models adjusting for the following covariates: age, sex, body mass index, sodium intake estimated by spot urine analysis, blood glucose, triglycerides, low- and high-density lipoprotein cholesterol, smoking, menopause, and fatty liver status. Specifically, Ruminococcus gnavus , Clostridium bolteae , and Bacteroides ovatus were significantly more abundant in the hypertensive women, whereas Dorea formicigenerans was more abundant in the normotensive women. No bacterial species were found to be significantly associated with hypertension in men. Furthermore, total plasma short-chain fatty acids and propionic acid were independent predictors of systolic and diastolic blood pressure in women but not men. GM dysregulation was strongly associated with 24-hour ambulatory blood pressure in women but not men, which may be mediated through propionic acid. Our work suggests that sex differences may be an important consideration while assessing the role of GM in the development and treatment of hypertension.
Publisher: Oxford University Press (OUP)
Date: 09-07-2010
Abstract: The expression of pancreatic-duodenal homeobox 1 (PDX1) in gastric cancer is aberrantly reduced. The aim of this study was to elucidate the regulation of DNA methylation and histone acetylation at the promoter for PDX1 silencing in gastric cancer. PDX1 expression in response to demethylation and acetylation was detected in human gastric cancer cell lines by reverse transcription-polymerase chain reaction (PCR) and western blot. Four CpG islands within the 5'-flanking region of PDX1 gene were analyzed with their transcription activities being detected by dual luciferase assay. Promoter hypermethylation was identified in gastric cancer cell lines and cancer tissues by methylation-specific PCR or bisulfite DNA sequencing PCR analysis. Histone acetylation was determined by chromatin immunoprecipitation (ChIP) assay. Demethylation by 5'-aza-2'-deoxycytidine (5'-aza-dC) and/or acetylation by trichostatin A (TSA) restored PDX1 expression in gastric cancer cells. Hypermethylation was found in four CpG islands in six of seven cancer cell lines. However, only the distal CpG island located in the promoter fragment of PDX1, F383 (c.-2063 to -1681 nt upstream of the ATG start codon) displayed significant transcriptional activity that could be suppressed by SssI methylase and increased by 5'-aza-dC and TSA. More than 70% of the single CpG sites in F383 were methylated with hypermethylation of F383 fragment more common in gastric cancerous tissues compared with the paired normal tissues (P < 0.05). ChIP assay showed F383 was also associated with low hypoacetylation level of the histones. Promoter hypermethylation and histone hypoacetylation contribute to PDX1 silencing in gastric cancer.
Publisher: The Endocrine Society
Date: 09-06-2022
Abstract: There are concerns for COVID-19 vaccination in triggering thyroid autoimmunity and causing thyroid dysfunction. Also, data on the effect of preexisting thyroid autoimmunity on the efficacy of COVID-19 vaccination are limited. We evaluated the effect of COVID-19 vaccination on thyroid function and antibodies, and the influence of preexisting thyroid autoimmunity on neutralizing antibody (NAb) responses. Adults without a history of COVID-19/thyroid disorders who received the COVID-19 vaccination during June to August 2021 were recruited. All received 2 doses of vaccines. Thyrotropin (TSH), free thyroxine (fT4), free 3,5,3′-triiodothyronine (fT3), antithyroid peroxidase (anti-TPO), and antithyroglobulin (anti-Tg) antibodies were measured at baseline and 8 weeks post vaccination. NAb against SARS-CoV-2 receptor-binding domain was measured. A total of 215 in iduals were included (129 [60%] BNT162b2 86 [40%] CoronaVac recipients): mean age 49.6 years, 37.2% men, and 12.1% anti-TPO/Tg positive at baseline. After vaccination, TSH did not change (P = .225), but fT4 slightly increased (from 12.0 ± 1.1 to 12.2 ± 1.2 pmol/L [from 0.93 ± 0.09 to 0.95 ± 0.09 ng/dL], P & .001) and fT3 slightly decreased (from 4.1 ± 0.4 to 4.0 ± 0.4 pmol/L [from 2.67 ± 0.26 to 2.60 ± 0.26 pg/mL], P & .001). Only 3 patients (1.4%) had abnormal thyroid function post vaccination, none clinically overt. Anti-TPO and anti-Tg titers increased modestly after vaccination (P & .001), without statistically significant changes in anti-TPO/Tg positivity. Changes in thyroid function and antithyroid antibodies were consistent between BNT162b2 and CoronaVac recipients, except for greater anti-TPO titer increase post BNT162b2 (P & .001). NAb responses were similar between in iduals with and without preexisting thyroid autoimmunity (P = .855). COVID-19 vaccination was associated with a modest increase in antithyroid antibody titers. Anti-TPO increase was greater among BNT162b2 recipients. However, there was no clinically significant thyroid dysfunction post vaccination. NAb responses were not influenced by preexisting thyroid autoimmunity. Our results provide important reassurance for people to receive the COVID-19 vaccination.
Publisher: Oxford University Press (OUP)
Date: 11-05-2010
Abstract: Cancer invasion and metastasis may associate with the phenotype transition called epithelial-mesenchymal transition (EMT). We aim to evaluate the impact of four-and-a-half LIM protein 2 (FHL2) on EMT and invasion of colon cancer. The functional role of FHL2 in EMT was determined by overexpression or small interfering RNA-mediated depletion of FHL2. Mechanisms of FHL2 on expression or activity of E-cadherin and beta-catenin were assessed. FHL2 was highly expressed in primary and metastatic colon cancer but not in normal tissues. FHL2 was critical for cancer cell adhesion to extracellular matrix, migration and invasion. FHL2 expression was stimulated by transforming growth factor (TGF)-beta1. Moreover, FHL2 acted as a potent EMT inducer by stimulating vimentin and matrix metalloproteinase-9 expressions and causing a loss of E-cadherin, whereas those alterations of EMT markers were not affected by silencing of Smad molecules (typical TGF-beta signal mediators) in FHL2 stable transfectant cells. Therefore, FHL2 induced EMT in a TGF-beta-dependent and Smad-independent manner. FHL2 downregulated E-cadherin expression and inhibited the formation of membrane-associated E-cadherin-beta-catenin complex. FHL2 also stabilized nuclear beta-catenin, resulting in enforcement of beta-catenin transactivation activity. FHL2 is a potent EMT inducer and might be an important mediator for invasion and/or metastasis of colon cancer.
Publisher: Springer Science and Business Media LLC
Date: 12-2004
Publisher: Wiley
Date: 29-10-2022
DOI: 10.1111/EPI.17436
Abstract: The risk of seizure following BNT162b2 and CoronaVac vaccinations has been sparsely investigated. This study aimed to evaluate this association. Patients who had their first seizure‐related hospitalization between February 23, 2021 and January 31, 2022, were identified in Hong Kong. All seizure episodes happening on the day of vaccination (day 0) were excluded, since clinicians validated that most of the cases on day 0 were syncopal episodes. Within‐in idual comparison using a modified self‐controlled case series analysis was applied to estimate the incidence rate ratio (IRR) with 95% confidence intervals (CIs) of seizure using conditional Poisson regression. We identified 1656 in iduals who had their first seizure‐related hospitalization (BNT162b2: 426 CoronaVac: 263 unvaccinated: 967) within the observation period. The incidence of seizure was 1.04 (95% CI .80–1.33) and 1.11 (95% CI .80–1.50) per 100 000 doses of BNT162b2 and CoronaVac administered, respectively. Sixteen and 17 in iduals, respectively, received a second dose after having a first seizure within 28 days after the first dose of BNT162b2 and CoronaVac vaccinations. None had recurrent seizures after the second dose. There was no increased risk during day 1–6 after the first (BNT162b2: IRR = 1.39, 95% CI = .75–2.58 CoronaVac: IRR = 1.19, 95% CI = .50–2.83) and second doses (BNT162b2: IRR = 1.36, 95% CI = .72–2.57 CoronaVac: IRR = .71, 95% CI = .22–2.30) of vaccinations. During 7–13, 14–20, and 21–27 days post‐vaccination, no association was observed for either vaccine. The findings demonstrated no increased risk of seizure following BNT162b2 and CoronaVac vaccinations. Future studies will be warranted to evaluate the risk of seizure following COVID‐19 vaccinations in different populations, with subsequent doses to ensure the generalizability .
Publisher: Springer Science and Business Media LLC
Date: 09-2021
Publisher: MDPI AG
Date: 14-11-2022
DOI: 10.3390/V14112519
Abstract: Hong Kong SAR has adopted universal masking, social distancing, testing of all symptomatic and high-risk groups for isolation of confirmed cases in healthcare facilities, and quarantine of contacts as epidemiological control measures without city lockdown or border closure. These measures successfully suppressed the community transmission of pre-Omicron SARS-CoV-2 variants or lineages during the first to the fourth wave. No nosocomial SARS-CoV-2 infection was documented among healthcare workers in the first 300 days. The strategy of COVID-19 containment was adopted to provide additional time to achieve population immunity by vaccination. The near-zero COVID-19 situation for about 8 months in 2021 did not enable adequate immunization of the eligible population. A combination of factors was identified, especially population complacency associated with the low local COVID-19 activity, together with vaccine hesitancy. The importation of the highly transmissible Omicron variant kickstarted the fifth wave of COVID-19, which could no longer be controlled by our initial measures. The explosive fifth wave, which was partially contributed by vertical airborne transmission in high-rise residential buildings, resulted in over one million cases of infection. In this review, we summarize the epidemiology of COVID-19 and the infection control and public health measures against the importation and dissemination of SARS-CoV-2 until day 1000.
Publisher: Informa UK Limited
Date: 12-12-2022
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ivan Fan Ngai Hung.