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Article ; Online: Low Bone Mineral Density as a Risk Factor for Liver Cirrhosis: A Prospective Cohort Study.

Zhang, Xiaowen / Cheung, Ka-Shing / Mak, Lung-Yi / Tan, Kathryn C B / Kung, Annie W C / Wong, Ian Chi-Kei / Cheung, Ching-Lung

The Journal of clinical endocrinology and metabolism

2024

Abstract: Context: Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown.: Objective: This ... ...

Abstract	Context: Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown. Objective: This study aims to investigate the relationship between BMD and the risk of incident cirrhosis in the Hong Kong Osteoporosis Study (HKOS). Methods: BMD was measured at the lumbar spine, femoral neck, total hip, and trochanter of 7,752 participants by the dual-energy X-ray absorptiometer (DXA), and the incidence of cirrhosis and mortality were followed by linking to the territory-wide electronic health records database. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI. Results: With a median follow-up of 18.43 years, 42 incident cirrhosis were identified. Higher BMD T-scores at the femoral neck, total hip and trochanter were significantly associated with a reduced risk of cirrhosis (femoral neck: HR 0.56, 95% CI 0.39 to 0.82; total hip: HR 0.60, 95% CI 0.44 to 0.82; trochanter: HR 0.63, 95% CI 0.46 to 0.88). Similar associations were observed in participants without risk factors of cirrhosis at the baseline and further adjusting for the baseline level of alkaline phosphatase, albumin, and alanine transaminase. Consistent relationships in multiple sensitivity analyses suggest the robustness of the results. Conclusion: Low BMD could be a novel risk factor and early predictor for cirrhosis, with consistent associations observed in multiple sensitivity analyses.
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae223
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Article ; Online: Endocuff With or Without Artificial Intelligence-Assisted Colonoscopy in Detection of Colorectal Adenoma: A Randomized Colonoscopy Trial.

Lui, Thomas Ka-Luen / Lam, Carla Pui-Mei / To, Elvis Wai-Pan / Ko, Michael Kwan-Lung / Tsui, Vivien Wai Man / Liu, Kevin Sze-Hang / Hui, Cynthia Ka-Yin / Cheung, Michael Ka-Shing / Mak, Loey Lung-Yi / Hui, Rex Wan-Hin / Wong, Siu-Yin / Seto, Wai Kay / Leung, Wai K

The American journal of gastroenterology

2024

Abstract: Introduction: Both artificial intelligence (AI) and distal attachment devices have been shown to improve adenoma detection rate and reduce miss rate during colonoscopy. We studied the combined effect of Endocuff and AI on enhancing detection rates of ... ...

Abstract	Introduction: Both artificial intelligence (AI) and distal attachment devices have been shown to improve adenoma detection rate and reduce miss rate during colonoscopy. We studied the combined effect of Endocuff and AI on enhancing detection rates of various colonic lesions. Methods: This was a 3-arm prospective randomized colonoscopy study involving patients aged 40 years or older. Participants were randomly assigned in a 1:1:1 ratio to undergo Endocuff with AI, AI alone, or standard high-definition (HD) colonoscopy. The primary outcome was adenoma detection rate (ADR) between the Endocuff-AI and AI groups while secondary outcomes included detection rates of polyp (PDR), sessile serrated lesion (sessile detection rate [SDR]), and advanced adenoma (advanced adenoma detection rate) between the 2 groups. Results: A total of 682 patients were included (mean age 65.4 years, 52.3% male), with 53.7% undergoing diagnostic colonoscopy. The ADR for the Endocuff-AI, AI, and HD groups was 58.7%, 53.8%, and 46.3%, respectively, while the corresponding PDR was 77.0%, 74.0%, and 61.2%. A significant increase in ADR, PDR, and SDR was observed between the Endocuff-AI and AI groups (ADR difference: 4.9%, 95% CI: 1.4%-8.2%, P = 0.03; PDR difference: 3.0%, 95% CI: 0.4%-5.8%, P = 0.04; SDR difference: 6.4%, 95% CI: 3.4%-9.7%, P < 0.01). Both Endocuff-AI and AI groups had a higher ADR, PDR, SDR, and advanced adenoma detection rate than the HD group (all P < 0.01). Discussion: Endocuff in combination with AI further improves various colonic lesion detection rates when compared with AI alone.
Language	English
Publishing date	2024-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000002684
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Article: The Functions of BET Proteins in Gene Transcription of Biology and Diseases.

Cheung, Ka Lung / Kim, Claudia / Zhou, Ming-Ming

Frontiers in molecular biosciences

2021 Volume 8, Page(s) 728777

Abstract: The BET (bromodomain and extra-terminal domain) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT, are widely acknowledged as major transcriptional regulators in biology. They are characterized by two tandem bromodomains (BDs) ... ...

Abstract	The BET (bromodomain and extra-terminal domain) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT, are widely acknowledged as major transcriptional regulators in biology. They are characterized by two tandem bromodomains (BDs) that bind to lysine-acetylated histones and transcription factors, recruit transcription factors and coactivators to target gene sites, and activate RNA polymerase II machinery for transcriptional elongation. Pharmacological inhibition of BET proteins with BD inhibitors has been shown as a promising therapeutic strategy for the treatment of many human diseases including cancer and inflammatory disorders. The recent advances in bromodomain protein biology have further uncovered the complex and versatile functions of BET proteins in the regulation of gene expression in chromatin. In this review article, we highlight our current understanding of BET proteins' functions in mediating protein-protein interactions required for chromatin-templated gene transcription and splicing, chromatin remodeling, DNA replication, and DNA damage repair. We further discuss context-dependent activator
Language	English
Publishing date	2021-09-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2021.728777
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Article ; Online: EBV latent membrane protein 1 augments γδ T cell cytotoxicity against nasopharyngeal carcinoma by induction of butyrophilin molecules.

Liu, Yue / Lui, Ka Sin / Ye, Zuodong / Fung, Tsz Yan / Chen, Luo / Sit, Ping Yiu / Leung, Chin Yu / Mak, Nai Ki / Wong, Ka-Leung / Lung, Hong Lok / Tanaka, Yoshimasa / Cheung, Allen Ka Loon

Theranostics

2023 Volume 13, Issue 2, Page(s) 458–471

Abstract: Nasopharyngeal carcinoma (NPC) is a diverse cancer with no well-defined tumor antigen, associated with oncogenic Epstein-Barr Virus (EBV), and with usually late-stage diagnosis and survival <40%. Current radiotherapy and chemotherapy have low ... ...

Abstract	Nasopharyngeal carcinoma (NPC) is a diverse cancer with no well-defined tumor antigen, associated with oncogenic Epstein-Barr Virus (EBV), and with usually late-stage diagnosis and survival <40%. Current radiotherapy and chemotherapy have low effectiveness and cause adverse effects, which calls for the need of new therapy. In this regard, adoptive immunotherapy using γδ T cells has potential, but needs to be coupled with butyrophilin 2A1 and 3A1 protein expression to achieve tumoricidal effect.
MeSH term(s)	Animals ; Humans ; Mice ; Antigens, CD ; Butyrophilins ; Epstein-Barr Virus Infections/complications ; Herpesvirus 4, Human ; Intracellular Signaling Peptides and Proteins ; Nasopharyngeal Carcinoma/immunology ; Nasopharyngeal Carcinoma/therapy ; Nasopharyngeal Carcinoma/virology ; Nasopharyngeal Neoplasms/immunology ; Nasopharyngeal Neoplasms/therapy ; Nasopharyngeal Neoplasms/virology ; Immunotherapy ; T-Lymphocytes, Cytotoxic
Chemical Substances	Antigens, CD ; BTN3A1 protein, human ; Butyrophilins ; Intracellular Signaling Peptides and Proteins ; NLRC5 protein, human ; NLRC5 protein, mouse ; EBV-encoded nuclear antigen 1 (O5GA75RST7)
Language	English
Publishing date	2023-01-01
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.78395
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Article ; Online: The Functions of BET Proteins in Gene Transcription of Biology and Diseases

Ka Lung Cheung / Claudia Kim / Ming-Ming Zhou

Frontiers in Molecular Biosciences, Vol

2021 Volume 8

Abstract	The BET (bromodomain and extra-terminal domain) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT, are widely acknowledged as major transcriptional regulators in biology. They are characterized by two tandem bromodomains (BDs) that bind to lysine-acetylated histones and transcription factors, recruit transcription factors and coactivators to target gene sites, and activate RNA polymerase II machinery for transcriptional elongation. Pharmacological inhibition of BET proteins with BD inhibitors has been shown as a promising therapeutic strategy for the treatment of many human diseases including cancer and inflammatory disorders. The recent advances in bromodomain protein biology have further uncovered the complex and versatile functions of BET proteins in the regulation of gene expression in chromatin. In this review article, we highlight our current understanding of BET proteins’ functions in mediating protein–protein interactions required for chromatin-templated gene transcription and splicing, chromatin remodeling, DNA replication, and DNA damage repair. We further discuss context-dependent activator vs. repressor functions of individual BET proteins, isoforms, and bromodomains that may be harnessed for future development of BET bromodomain inhibitors as emerging epigenetic therapies for cancer and inflammatory disorders.
Keywords	bromodomain ; bromodomain and extra-terminal domain proteins ; gene transcription ; inhibitors ; cancer ; Biology (General) ; QH301-705.5
Subject code	572 ; 570
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Hepatocellular carcinoma: recent advances and emerging medical therapies.

Ko, Kwan-Lung / Mak, Lung-Yi / Cheung, Ka-Shing / Yuen, Man-Fung

F1000Research

2020 Volume 9

Abstract: Hepatocellular carcinoma remains a deadly disease with poor prognosis in patients with unresectable cancer. Trans-arterial chemoembolization is the primary locoregional therapy for intermediate-stage hepatocellular carcinoma, with an estimated median ... ...

Abstract	Hepatocellular carcinoma remains a deadly disease with poor prognosis in patients with unresectable cancer. Trans-arterial chemoembolization is the primary locoregional therapy for intermediate-stage hepatocellular carcinoma, with an estimated median overall survival of less than two years. For almost a decade, sorafenib has been the only standard systemic treatment for metastatic disease or tumors which progress or are considered unsuitable for locoregional therapy. Major breakthroughs have been made over the past few years in the management of hepatocellular carcinoma, especially in medical therapies for advanced disease. In this article, recent advances in intra-arterial therapy, multi-kinase inhibitors, and immunotherapy will be reviewed.
MeSH term(s)	Carcinoma, Hepatocellular/therapy ; Humans ; Immunotherapy ; Liver Neoplasms/therapy ; Sorafenib/therapeutic use
Chemical Substances	Sorafenib (9ZOQ3TZI87)
Language	English
Publishing date	2020-06-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.24543.1
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Article ; Online: Carvedilol Versus Other Nonselective Beta Blockers for Variceal Bleeding Prophylaxis and Death: A Network Meta-analysis.

Cheung, Ka-Shing / Mok, Chiu-Hang / Lam, Lok-Ka / Mao, Xian-Hua / Mak, Lung-Yi / Seto, Wai-Kay / Yuen, Man-Fung

Journal of clinical and translational hepatology

2023 Volume 11, Issue 5, Page(s) 1143–1149

Abstract: Background and aims: We aimed to perform a network meta-analysis (NWM) to examine comparative effectiveness of non-selective beta blockers (NSBBs) on prophylaxis of gastroesophageal variceal bleeding (GVB) and mortality benefit.: Methods: MEDLINE ( ... ...

Abstract	Background and aims: We aimed to perform a network meta-analysis (NWM) to examine comparative effectiveness of non-selective beta blockers (NSBBs) on prophylaxis of gastroesophageal variceal bleeding (GVB) and mortality benefit. Methods: MEDLINE (OVID) and EMBASE databases were searched for eligible randomized clinical trials (RCTs) from inception to July 3, 2021. Outcomes of interest included primary/secondary prophylaxis of GVB, failure to achieve hepatic venous pressure gradient (HVPG) decremental response, liver-related and all-cause mortality. A Bayesian NWM was performed to derive relative risk (RR) with 95% credible intervals (CrIs). The ranking probability of each NSBB was assessed by surface under cumulative ranking curve (SUCRA). Results: Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were included. Compared with placebo, nadolol ranked first for reducing variceal bleeding [RR:0.25, (95% CrI:0.11-0.51); SUCRA:0.898], followed by carvedilol [RR:0.33, (95% CrI: 0.11-0.88); SUCRA:0.692] and propranolol [RR:0.52, (95% CrI:0.37-0.75); SUCRA:0.405]. Carvedilol was more effective than propranolol in achieving HVPG decremental response [RR:0.43, (95% CrI: 0.26-0.69)]. Carvedilol ranked first for reducing all-cause mortality [RR: 0.32, (95% CrI:0.17-0.57); SUCRA:0.963), followed by nadolol [RR:0.48, (95% CI:0.29-0.77); SUCRA:0.688], and propranolol [RR:0.77, (95% CI:0.58-1.02); SUCRA: 0.337]. Similar findings were observed for liver-related mortality. Carvedilol ranked the safest. The RR of adverse events was 4.38, (95% CrI:0.33-161.4); SUCRA:0.530, followed by propranolol [RR: 7.54, (95% CrI:1.90-47.89); SUCRA:0.360], and nadolol [RR: 18.24, (95% CrI:91.51-390.90); SUCRA:0.158]. Conclusions: Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices.
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019822-7
ISSN	2310-8819 ; 2225-0719
ISSN (online)	2310-8819
ISSN	2225-0719
DOI	10.14218/JCTH.2022.00130S
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Article ; Online: Increased histological severity and chronicity of interface inflammation in anti-MDA5 dermatomyositis-A comparative dermatopathological analysis.

Chan, Agnes Wai Sze / Cheung, Christina Man-Tung / Wong, Priscilla Ching-Han / Choi, Paul Cheung Lung / Ng, Joanna Ka Man / Li, Joshua Jing Xi

International journal of rheumatic diseases

2023 Volume 26, Issue 10, Page(s) 2031–2036

Abstract: ... by serological detection of anti-MDA5 antibody and rapidly progressive interstitial lung disease. In this study ...

Abstract	Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis is characterized by serological detection of anti-MDA5 antibody and rapidly progressive interstitial lung disease. In this study, the largest cohort of skin biopsies to date of anti-MDA5 dermatomyositis was reviewed and compared with cases of dermatomyositis with negative serology. Findings contribute to the histological diagnosis and evaluation of the severity of cutaneous inflammation in anti-MDA5 dermatomyositis. Skin biopsies collected over a 7-year period from individuals with clinically and histologically confirmed dermatomyositis with anti-MDA5 serology were reviewed. A total of 46 cases with 17 anti-MDA5 positive cases were retrieved. Patients with positive antibody were younger (53.7 vs. 60.6 years, p = .013). No differences in epidermal changes (p > .05) were observed. Pertaining to interface changes, anti-MDA5 dermatomyositis showed a higher degree of pigmentary incontinence (p = .014), suggesting increased and sustained cutaneous inflammation. Periodic acid-Schiff (PAS) stain demonstrated a greater degree of basement membrane thickening (p = .045). Other parameters, including dermal inflammation, dermal mucin deposition and vasculitic/vasculopathic features did not show statistical difference between anti-MDA5 positive and negative dermatomyositis (p > .05). Findings suggest increased cutaneous inflammation for anti-MDA5 dermatomyositis. In skin biopsies, marked pigmentary incontinence or basement membrane thickening should raise suspicion of anti-MDA5 dermatomyositis.
Language	English
Publishing date	2023-08-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2426924-4
ISSN	1756-185X ; 1756-1841
ISSN (online)	1756-185X
ISSN	1756-1841
DOI	10.1111/1756-185X.14866
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Article ; Online: Effects of empagliflozin on liver fat in metabolic-dysfunction associated steatotic liver disease patients without diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

Cheung, Ka Shing / Ng, Ho Yu / Hui, Rex Wan Hin / Lam, Lok Ka / Mak, Lung Yi / Ho, Yuen Chi / Tan, Jing Tong / Chan, Esther W / Seto, Wai Kay / Yuen, Man Fung / Leung, Wai K

Hepatology (Baltimore, Md.)

2024

Abstract: Background and aims: We investigated whether empagliflozin reduces hepatic steatosis in metabolic-dysfunction associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM).: Approach and results: This was an investigator- ... ...

Abstract	Background and aims: We investigated whether empagliflozin reduces hepatic steatosis in metabolic-dysfunction associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM). Approach and results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without DM (fasting plasma glucose <7 mmol/L and HbA1c <6.5%) who had magnetic resonance imaging-proton density fat fraction [MRI-PDFF] ≥5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. Primary outcome was difference in change of MRI-PDFF between two groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF <5%), ALT drop≥17U/L, MRI-PDFF decline≥30%, combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age:55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. Empagliflozin group had greater reduction in median MRI-PDFF compared to placebo group (-2.49% vs -1.43%;p=0.025), with a non-significant trend of resolution of hepatic steatosis (44.9% vs 28.6%;p=0.094). There was no significant difference in ALT drop≥17U/L (16.3% vs 12.2%;p=0.564), MRI-PDFF drop≥30% (49.0% vs 40.8%;p=0.417), and composite outcome (8.2% vs 8.2%;p=1.000). Empagliflozin group had greater drop in body weight (-2.7 vs -0.2 kg), waist circumference (-2.0 vs 0 cm), fasting glucose (-0.3 vs 0 mmol/L) and ferritin (-126 vs -22 pmol/L) (all p<0.05). Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in non-diabetic MASLD subjects. (ClinicalTrials.gov Identifier: NCT04642261).
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1097/HEP.0000000000000855
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Article ; Online: A rare presentation of pemphigus vegetans as an isolated vegetative lesion-Review of histopathological clues and treatment effects in multiple biopsy specimens.

Ng, Joanna Ka Man / Cheung, Christina Man-Tung / Choi, Paul Cheung Lung / Ip, Edric Chi-Ching / Li, Joshua Jing Xi / Chan, Agnes Wai Sze

Journal of cutaneous pathology

2023 Volume 50, Issue 3, Page(s) 201–208

Abstract: Background: Pemphigus is a group of immunobullous dermatoses characterized by the presence of autoantibodies directed against adhesion molecules of keratinocytes, with pemphigus vegetans being the rarest form, accounting for 1%-2% of all cases of ... ...

Abstract	Background: Pemphigus is a group of immunobullous dermatoses characterized by the presence of autoantibodies directed against adhesion molecules of keratinocytes, with pemphigus vegetans being the rarest form, accounting for 1%-2% of all cases of pemphigus. Pemphigus vegetans is characterized by verrucous vegetative lesions in addition to vesiculobullous lesions. Methods: We report a rare case of pemphigus vegetans presenting as an isolated vegetative lesion in the groin 3 months prior to the development of blisters. Owing to the atypical presentation, multiple biopsies were performed before and after corticosteroid treatment. Results: Comparing the histopathology of pre-treatment and post-treatment biopsy specimens, the resolution of intraepidermal microabscesses, and reduction in intraepidermal and dermal inflammatory infiltrates, spongiosis and interface change, attributable to treatment, were noted. However, direct immunofluorescence showed persistent intracellular intraepidermal deposition of IgG and C3 2 weeks into treatment, despite near-complete resolution of blisters on clinical examination. Clinical regression of the vegetative lesion was noted only after 6 weeks into corticosteroid treatment, while histopathological evidence of treatment was apparent at the second week. Conclusion: The current case illustrates the importance of a liberal use of immunofluorescence studies in establishing the uncommon yet significant diagnosis of pemphigus vegetans, particularly for vegetative lesions that are persistent, in the intertriginous areas and/or in the setting of concurrent cutaneous or mucosal symptoms.
MeSH term(s)	Humans ; Pemphigus/pathology ; Blister/pathology ; Skin/pathology ; Adrenal Cortex Hormones/therapeutic use ; Biopsy
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Case Reports
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.14375
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