1.Life’s Essential 8 and risk of non-communicable chronic diseases: Outcome-wide analyses
Yuetian YU ; Ying SUN ; Yuefeng YU ; Yuying WANG ; Chi CHEN ; Xiao TAN ; Yingli LU ; Ningjian WANG
Chinese Medical Journal 2024;137(13):1553-1562
		                        		
		                        			
		                        			Background::Life’s Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life’s Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life’s Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs.Methods::In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life’s Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined.Results::During the median follow-up of 10.85 years, 58, 889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however, the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%).Conclusions::Improving CVH score based on Life’s Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, avoiding overweight/obesity may be especially important to prevent new cases of metabolic diseases, NCDs in digestive system, mental and behavioral disorders, and cancer.
		                        		
		                        		
		                        		
		                        	
2.Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma
Chun-Ting HO ; Elise Chia-Hui TAN ; Pei-Chang LEE ; Chi-Jen CHU ; Yi-Hsiang HUANG ; Teh-Ia HUO ; Yu-Hui SU ; Ming-Chih HOU ; Jaw-Ching WU ; Chien-Wei SU
Clinical and Molecular Hepatology 2024;30(3):406-420
		                        		
		                        			 Background/Aims:
		                        			The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. 
		                        		
		                        			Methods:
		                        			The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. 
		                        		
		                        			Results:
		                        			In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. 
		                        		
		                        			Conclusions
		                        			Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance. 
		                        		
		                        		
		                        		
		                        	
3.A Prospective 1-Year Follow-Up of Glycemic Status and C-Peptide Levels of COVID-19 Survivors with Dysglycemia in Acute COVID-19 Infection
David Tak Wai LUI ; Chi Ho LEE ; Ying WONG ; Carol Ho Yi FONG ; Kimberly Hang TSOI ; Yu Cho WOO ; Kathryn Choon Beng TAN
Diabetes & Metabolism Journal 2024;48(4):763-770
		                        		
		                        			 Background:
		                        			We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. 
		                        		
		                        			Methods:
		                        			COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. 
		                        		
		                        			Results:
		                        			Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. 
		                        		
		                        			Conclusion
		                        			Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity. 
		                        		
		                        		
		                        		
		                        	
4.Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus
Chi-Ho LEE ; Mei-Zhen WU ; David Tak-Wai LUI ; Darren Shing-Hei CHAN ; Carol Ho-Yi FONG ; Sammy Wing-Ming SHIU ; Ying WONG ; Alan Chun-Hong LEE ; Joanne King-Yan LAM ; Yu-Cho WOO ; Karen Siu-Ling LAM ; Kelvin Kai-Hang YIU ; Kathryn Choon-Beng TAN
Diabetes & Metabolism Journal 2022;46(6):843-854
		                        		
		                        			 Background:
		                        			Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients. 
		                        		
		                        			Methods:
		                        			This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography. 
		                        		
		                        			Results:
		                        			Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037). 
		                        		
		                        			Conclusion
		                        			Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits. 
		                        		
		                        		
		                        		
		                        	
5.Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors
David Tak Wai LUI ; Chi Ho LEE ; Wing Sun CHOW ; Alan Chun Hong LEE ; Anthony Raymond TAM ; Carol Ho Yi FONG ; Chun Yiu LAW ; Eunice Ka Hong LEUNG ; Kelvin Kai Wang TO ; Kathryn Choon Beng TAN ; Yu Cho WOO ; Ching Wan LAM ; Ivan Fan Ngai HUNG ; Karen Siu Ling LAM
Endocrinology and Metabolism 2021;36(3):582-589
		                        		
		                        			Background:
		                        			The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. 
		                        		
		                        			Methods:
		                        			We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. 
		                        		
		                        			Results:
		                        			In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. 
		                        		
		                        			Conclusion
		                        			Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.
		                        		
		                        		
		                        		
		                        	
6.Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors
David Tak Wai LUI ; Chi Ho LEE ; Wing Sun CHOW ; Alan Chun Hong LEE ; Anthony Raymond TAM ; Carol Ho Yi FONG ; Chun Yiu LAW ; Eunice Ka Hong LEUNG ; Kelvin Kai Wang TO ; Kathryn Choon Beng TAN ; Yu Cho WOO ; Ching Wan LAM ; Ivan Fan Ngai HUNG ; Karen Siu Ling LAM
Endocrinology and Metabolism 2021;36(3):582-589
		                        		
		                        			Background:
		                        			The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. 
		                        		
		                        			Methods:
		                        			We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. 
		                        		
		                        			Results:
		                        			In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. 
		                        		
		                        			Conclusion
		                        			Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.
		                        		
		                        		
		                        		
		                        	
7.The therapeutic dilemma of idiopathic granulomatous mastitis.
Ee Ling Serene TANG ; Chi Shern Bernard HO ; Patrick Mun Yew CHAN ; Juliana Jia Chuan CHEN ; Mui Heng GOH ; Ern Yu TAN
Annals of the Academy of Medicine, Singapore 2021;50(8):598-605
		                        		
		                        			INTRODUCTION:
		                        			Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic breast condition that can cause repeated abscesses or mass formation in bilateral breasts. The condition can severely impact the quality of life of affected women. This study aims to evaluate effective treatment modalities, as well as understand the demographics and clinical presentation of patients with IGM.
		                        		
		                        			METHODS:
		                        			An 11-year retrospective review was performed of patients diagnosed with IGM from 1 January 2008 to 31 December 2018 at a tertiary breast unit.
		                        		
		                        			RESULTS:
		                        			A total of 77 patients were included in the study. The median age at presentation was 36 years old. IGM presented most commonly as a breast lump (98.1%). The median number of flares was 2 (1-12). Of the 77 patients, 68.8% (53) were treated with antibiotics, 50.6% (39) with steroids, and 44.2% (34) underwent surgery, in the course of their IGM treatment. Forty-five (59.2%) of the 76 patients with IGM required a multimodal treatment approach to achieve remission. There was no significant difference in the number of flares no matter the initial treatment (
		                        		
		                        			CONCLUSION
		                        			IGM is a clinical diagnosis. It is a rare, relapsing breast inflammatory condition that affects young females with no superior treatment modality. Smoking is associated with higher number of flares of IGM and should be discouraged in IGM patients.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Anti-Bacterial Agents/therapeutic use*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Granulomatous Mastitis/therapy*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
8.Mechanistic action of the acute toxicity of Bajitian (Morinda officinalis) in zebrafish embryos
Tan LIRONG ; Cheng MIN ; Gigi Chi Ting Auyeung ; Oscar Yu Suen Chan ; Chen XUEPING
Journal of Traditional Chinese Medical Sciences 2020;7(3):308-315
		                        		
		                        			
		                        			Objectives: To investigate acute toxicity of Bajitian (Morinda officinalis) in zebrafish embryos. Methods: Zebrafish embryos at 48-h post fertilization (hpf) were exposed to Bajitian ethanol extract for 72 h. The causative action of a delay in yolk sac absorption by Bajitian was investigated by RT-PCR analysis of lipid metabolism-related microsomal triglyceride transfer protein (MTP), apolipoprotein C-Ⅱ(ApoC2) and lipogenesis-related liver x receptor (LXR) genes. The effect of Bajitian eliciting an in-flammatory response was studied by exposing 72 hpf myeloperoxidase (MPO):GFP transgenic zebrafish embryos to Bajitian extract for 4 h. Assessment was done by TUNEL, caspase-3/7, and RT-PCR analysis of the apoptosis related pathway B-cell lymphoma 2 associated X protein (Bax), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) genes, neutrophil development-related stem cell leukaemia (SCL) and transcription factor PU.1 genes, to reveal the causative action of Bajitian reducing neutrophils. Results: RT-PCR analysis found that Bajitian extract had no effect on the expression of MTP or ApoC2 genes, but upregulated LXR gene, which might explain the delay in yolk sac absorption. Analysis of the inflammatory response showed that compared with negative controls, Bajitian extract significantly (P < .05) reduced the number of neutrophils in MPO: GFP embryos. TUNEL, caspase-3/7, and RT-PCR analysis of Bax and NF-kB genes found that Bajitian extract did not trigger the cell apoptosis. Further RT-PCR analysis found that Bajitian extract did not affect SCL expression, but did lead to down-regulation of PU.1. The inhibition of neutrophil development/differentiation may explain the decline in the total number of neutrophils following Bajitian treatment, which could be attributed to the anti-inflammatory effects found clinically for this drug. Conclusions: This study demonstrated that Bajitian caused a delay in yolk sac absorption and a decrease neutrophil in zebrafish embryos, which may be related to the inhibition of neutrophil development.
		                        		
		                        		
		                        		
		                        	
9.Bioassay method for Compound Danshen Tablets based on a platelet aggregation inhibition test
Yu-dong GUO ; Yu-chi HU ; Cun-ran CAO ; Zhi-bin WANG ; Ze-ping ZUO ; Yang GAO ; Tan-yu LOU ; Bei-bei MA
Acta Pharmaceutica Sinica 2019;54(12):2184-2188
		                        		
		                        			
		                        			 A bioassay method for inhibiting platelet aggregation 
		                        		
		                        	
10.Expression and significance of secreted frizzled-related protein 1 and β-catenin in gingival tissue of patients with chronic periodontitis.
Yu-Tan CHI ; Chun-Jiao XU ; Xiao-Juan SUN ; Dong-Mei LI ; Hong-Feng WANG ; Miao-Miao WANG ; Xiu-Fang HE
West China Journal of Stomatology 2018;36(3):257-261
OBJECTIVEThis study aimed to investigate the expression and correlation of secreted frizzled-related protein 1 (SFRP1) and β-catenin in gingival tissues of patients with chronic periodontitis (CP). The role of the classical Wnt/β-catenin signaling pathway in the development of periodontitis was also explored.
METHODSTwenty-eight patients with CP (CP group) were enrolled in this study. Among them, 16 cases were moderate CP, and 12 demonstrated severe CP. Twelve healthy cases comprised the controls (normal group). Gingival tissue was collected, and the probing depth, bleeding index, and clinical attachment loss were recorded. The expression levels of SFRP1 and β-catenin were detected by immunohistochemistry, and staining intensity was evaluated by double scoring method. SPSS 19.0 was used for statistical analysis.
RESULTSThe staining strength scores of SFRP1 and β-catenin were 2.16±0.65 and 1.12±0.51 in the normal group, 3.57±0.45 and 2.36±0.49 in the CP group, 3.61±0.40 and 2.30±0.44 in the moderate CP group, and 3.52±0.52 and 2.45±0.55 in the severe CP group, respectively. The expression of SFRP1 and β-catenin in the CP group was higher than that in the normal group (P<0.01). A significant difference was noted between the normal group and the moderate and severe CP groups (P<0.01) but none between the moderate and severe CP groups (P>0.05). A positive correlation was found between the expression of SFRP1 and β-catenin (r=0.657, P<0.01). The expression levels of β-catenin and SFRP1 were related to periodontal indexes. The correlation between the expression of SFRP1 and probing depth was most significant (r=0.723, P<0.01), as well as that between β-catenin and bleeding index (r=0.697, P<0.01).
CONCLUSIONSPatients with CP exhibit elevated expression of SFRP1 and β-catenin in gingival tissues, and this event is related to the degree of periodontal destruction. Abnormal expression of SFRP1 and β-catenin may promote the development of periodontitis.
            
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