Publications by authors named "Changyi Wang"

54 Publications

Hypermethylation of dihydrofolate reductase promoter increases the risk of hypertension in Chinese.

J Res Med Sci 2020 30;25:117. Epub 2020 Dec 30.

Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, PR China.

Background: DNA methylation was considered to play an important role in hypertension. However, the direct association between dihydrofolate reductase () promoter methylation and hypertension remains unclear. We thus aimed to investigate the relationship between DNA methylation of promoter and hypertension.

Materials And Methods: A total of 371 hypertensive patients (diastolic blood pressure ≥90 mmHg and/or systolic blood pressure ≥140 mmHg or a history of antihypertensive treatment) and 320 age- and sex-matched healthy controls from the Hypertension Management Information System in Nanshan Community Health Service Centers were included in this case-control study. Quantitative methylation-specific polymerase chain reaction was used to measure the level of promoter methylation, which was presented as the percentage of methylated reference (PMR). A multivariate logistic regression model was used to explore the risk of promoter methylation.

Results: Our results indicated that the level of promoter methylation was higher in hypertensive patients (median PMR, 34.32%; interquartile range, 11.34-119.60) than in healthy controls (median PMR, 18.45%; interquartile range, 8.16-35.40) ( < 0.001). Multivariable analysis showed that the risk of promoter hypermethylation was significantly higher in hypertensive patients than in healthy controls (odds ratio = 3.94, 95% confidence interval = 2.56-6.02, < 0.001). Furthermore, hypermethylation was positively associated with sex, high blood homocysteine levels, and alcohol drinking. In particular, the area under the receiver operating characteristic curve was 0.688 (0.585-0.668) for the male hypertensive patients, suggesting the potential diagnostic value of promoter methylation in male hypertension.

Conclusion: Our results demonstrated that promoter hypermethylation is positively associated with the risk of hypertension in Chinese.
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http://dx.doi.org/10.4103/jrms.JRMS_895_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067893PMC
December 2020

A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.

J Clin Lab Anal 2021 Mar 31;35(3):e23689. Epub 2020 Dec 31.

Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Background: Ischemic stroke (IS) is a serious global health burden. In order to improve our understanding of the risk factors associated with IS, we investigated the combined effect of the methylation of five genes related to the metabolism of homocysteine on developing IS.

Methods: Quantitative methylation-specific PCR was used to measure the levels of promoter methylation in hypertensive and stroke patients. The cutoff value calculated by the maximum Youden index was used to classify the levels of gene methylation as hypomethylation and hypermethylation. Logistic regression was used to explore the relationship between gene methylation and IS.

Results: The methylation levels of the genes encoding methylenetetrahydrofolate dehydrogenase 1 [MTHFD1], cystathionine β-synthase [CBS], and dihydrofolate reductase [DHFR] in hypertensive patients were higher than those in stroke patients (all p < 0.01). MTHFD1 hypermethylation, CBS hypermethylation, and DHFR hypermethylation were protective factors for stroke after adjustment for confounding factors. Compared with individuals carrying none of the biomarkers, the ORs [95% CIs] for stroke of those with 1 and 2 elevated biomarkers were 4.068 [1.670-9.913] and 15.345 [6.198-37.994] after adjustment for confounding factors. The participants with a larger number of biomarkers had an increased risk of stroke (p for trend <0.001). For the combination biomarkers, the area under the curve of the receiver operating characteristic was 0.716.

Conclusion: A significant linear relationship between the number of elevated biomarkers and the risk of stroke has been observed, suggesting that elevations of these biomarkers could be used for potentially predicting the disease.
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http://dx.doi.org/10.1002/jcla.23689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957978PMC
March 2021

Ideal Cardiovascular Health Metrics and Incidence of Ischemic Stroke Among Hypertensive Patients: A Prospective Cohort Study.

Front Cardiovasc Med 2020 23;7:590809. Epub 2020 Nov 23.

Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

This study aimed to assess the relationship between ideal cardiovascular health (CVH) metrics and incident ischemic stroke (IS) in hypertensive patients, especially those with hyperhomocysteinemia (HHcy). A prospective cohort study enrolled 5,488 hypertensive patients in Nanshan District of Shenzhen City in southern China from September 2011 to December 2017. CVH metrics were defined according to the American Heart Association. Cox proportional hazards models were used to examine the associations between the number of ideal CVH metrics and the incidence of IS by calculating multivariable-adjusted hazard ratios (HRs) and 95% CI. During an average follow-up of 5.7 years, 340 IS patients were identified. Compared with those having 0 ideal CVH metrics, the HRs (95% CIs) for IS among those with 1, 2, 3, 4, and 5-6 ideal CVH metrics were 0.62 (0.31-1.25), 0.37 (0.19-0.74), 0.37 (0.18-0.74), 0.34 (0.16-0.71), and 0.28 (0.12-0.63), respectively ( < 0.001). An ideal healthy diet score and ideal fasting blood glucose level were independently associated with IS among participants, with HRs (95% CIs) of 0.53 (0.33-0.86) and 0.32 (0.17-0.66), respectively. Additionally, compared with those with normal total homocysteine (tHcy) levels (<15 μmol/L), the HR (95% CI) for IS among participants with HHcy and who had 5-6 ideal CVH metrics was 0.50 (0.27-0.92). An increased number of ideal CVH metrics was inversely associated with the incidence of IS in hypertensive patients. The participants with HHcy who had 5-6 ideal CVH metrics exhibited a lower IS risk than those with normal tHcy levels.
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http://dx.doi.org/10.3389/fcvm.2020.590809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719670PMC
November 2020

Prognostic significance of uric acid change in acute ischemic stroke patients with reperfusion therapy.

Eur J Neurol 2021 Apr 1;28(4):1218-1224. Epub 2020 Dec 1.

Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Uric acid (UA) is an important endogenous free radical scavenger that has been found to have a neuroprotective effect. However, there is uncertainty about the relationship between UA change and outcome in acute ischemic stroke (AIS) patients with reperfusion therapy.

Methods: We consecutively enrolled AIS patients with reperfusion therapy. UA was measured upon admission and during hospitalization. The change in UA levels (ΔUA) was determined by calculating the difference between admission UA and the lowest UA among all follow-up measurements, with a positive ΔUA suggesting a decrease in UA levels. Functional outcome was assessed by modified Rankin Scale (mRS) at 3 months. Poor outcome was defined as mRS >2.

Results: A total of 361 patients were included (mean age 68.7 ± 13.9 years, 54.3% males). The mean UA on admission was 355 ± 96.1 μmol/L. The median ΔUA was 121 μmol/L (IQR 50-192 μmol/L) and 18 (5%) patients had increased UA levels. UA on admission was positively associated with good outcome (p for trend = 0.017). When patients were classified into quartiles by ΔUA, patients with the largest decrease in UA (Q4: 199-434 μmol/L) had a higher risk of poor outcome at 3 months compared to patients with the least decrease in UA (Q1: 0-57 μmol/L) (OR 2.55, 95% CI 1.09-5.98, p = 0.031). The risk of poor outcome increased with ΔUA (p for trend = 0.048).

Conclusions: In patients with reperfusion therapy, high UA on admission was associated with a good 3-month outcome, while a greater decrease in UA was associated with poor outcome.
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http://dx.doi.org/10.1111/ene.14643DOI Listing
April 2021

Association of TG/HDLC ratio trajectory and risk of type 2 diabetes: A retrospective cohort study in China.

J Diabetes 2020 Oct 19. Epub 2020 Oct 19.

Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Center, Shenzhen, People's Republic of China.

Background: The association of ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C ratio) change trajectory with risk of type 2 diabetes mellitus (T2DM) remains unknown. The aim of this study was to evaluate the association between risk of T2DM and TG/HDL-C ratio change trajectory.

Methods: A total of 18 444 participants aged 18-80 years old were included in this cohort study. Linear regression and quadratic regression models were used to determine the TG/HDL-C ratio change trajectory. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TG/HDL-C ratio change trajectory and probability of T2DM.

Results: T2DM developed in 714 participants during a median follow-up of 5.74 years (92 076.23 person-years of follow-up). After adjusting for baseline potential confounders, odds of T2DM were greater for participants with the increasing, U-shape, bell-shape, and other shape change vs decreasing change (adjusted OR [aOR] 2.01, 95% CI 1.42-2.81; 1.56, 1.15-2.13; 1.60, 1.17-2.20; and 1.49, 1.13-2.00, respectively). The results were robust in the sensitivity analyses on excluding baseline participants with T2DM. Moreover, the associations remained significant with male sex, age <60 years and body mass index <24 kg/m .

Conclusions: This retrospective study revealed increased probability of T2DM with increasing, U-shape, bell-shape, and other-shape TG/HDL-C ratio change trajectories, especially with male sex, age <60 years and body mass index <24 kg/m .
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http://dx.doi.org/10.1111/1753-0407.13123DOI Listing
October 2020

Effect of Anthocyanins Supplementation on Serum IGFBP-4 Fragments and Glycemic Control in Patients with Fasting Hyperglycemia: A Randomized Controlled Trial.

Diabetes Metab Syndr Obes 2020 28;13:3395-3404. Epub 2020 Sep 28.

Internal Medicine Department, BaiYun Hospital, GuangZhou, GuangDong Province, People's Republic of China.

Background: Insulin-like growth factor binding protein-4 (IGFBP-4) fragments have been shown to be associated with cardiometabolic diseases. Anthocyanins as a subgroup of natural polyphenols could have benefits on treating cardiometabolic diseases. The aim of this study was to examine the effects of purified anthocyanins on serum IGFBP-4 fragments and glycemic control in patients with fasting hyperglycemia.

Methods: A set of 121 participants with elevated fasting glucose (≥5.6 mmol/L), who were originally randomly assigned to anthocyanins (320 mg/day) or placebo groups, were included in this study. Serum IGFBP-4 fragments, fasting and postload glucose, insulin, and C-peptide after a three-hour oral glucose tolerance test (OGTT) were measured at baseline and at the end of 12 weeks.

Results: Compared with placebo, anthocyanins increased serum IGFBP-4 fragments (net change 8.33 ng/mL, 95% CI [1.2, 15.47], =0.023) and decreased fasting glucose (-0.4 mmol/L [-0.71, -0.1], =0.01), 2-hour C-peptide (-1.02 ng/mL [-1.99, -0.04], =0.041) and the 3-hour area under the curve (AUC) of C-peptide (-2.19 [-4.11, -0.27], =0.026). No other significant difference in parameters for glycemic control and insulin resistance was observed.

Conclusion: Anthocyanins supplementation for 12 weeks improved serum IGFBP-4 fragments and decreased fasting glucose and postload C-peptide in patients with fasting hyperglycemia. Further studies are needed to confirm our findings and clarify the potential mechanism.

Trial Registration: ClinicalTrials.gov, NCT02689765. Registered on 6 February 2016, https://clinicaltrials.gov/ct2/show/NCT02689765.
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http://dx.doi.org/10.2147/DMSO.S266751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532046PMC
September 2020

Dose-response association of the ZJU index and fatty liver disease risk: A large cohort in China.

J Gastroenterol Hepatol 2021 May 14;36(5):1326-1333. Epub 2020 Oct 14.

Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.

Aim: The aim of this study is to investigate the sex-specific association between the ZJU index and risk of fatty liver disease in a large Chinese cohort.

Methods: A total of 28 729 adults without fatty liver disease at baseline and who completed at least one follow-up of annual examinations between 2009 and 2016 were included in this study. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for fatty liver disease risk associated with the ZJU index.

Results: During a median follow-up of 3.01 years, 7373 developed fatty liver disease. There were significant associations between the ZJU index and fatty liver disease for women and men with increasing HRs as the quartiles increase across Q2-Q4, corresponding HRs (95% CIs) in M3 were 2.28 (1.98-2.64), 3.52 (3.07-4.04), and 4.87 (4.24-5.59) for women and 2.44 (2.17-2.75), 4.18 (3.73-4.68), and 6.23 (5.56-6.98) for men. The association between the ZJU index and fatty liver disease risk remained significant in all the subgroups except that of T2DM and abdominal obesity subgroups for men. However, the association became nonsignificant when comparing Q3 and Q2 of the ZJU index with reference in the subgroups of T2DM for men, and nonsignificant when comparing Q3 of the ZJU index with reference in the subgroups of participants with T2DM and abdominal obesity for women.

Conclusion: The ZJU index was significantly associated with the risk of fatty liver disease in Chinese population. It will be better to keep body mass index, alanine aminotransferase, aspartate aminotransferase, triglyceride, and fasting plasma glucose at a normal level for preventing fatty liver disease.
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http://dx.doi.org/10.1111/jgh.15286DOI Listing
May 2021

Anthocyanins increase serum adiponectin in newly diagnosed diabetes but not in prediabetes: a randomized controlled trial.

Nutr Metab (Lond) 2020 21;17:78. Epub 2020 Sep 21.

Center for Chronic Disease Control, NanShan, Shenzhen, People's Republic of China.

Background: Epidemiological studies have suggested that adiponectin is associated with the development of insulin resistance and type 2 diabetes. This study first examined the effect of purified anthocyanins, a group of dietary flavonoids, on serum adiponectin in patients with prediabetes and newly diagnosed diabetes.

Methods: A total of 160 patients with prediabetes (n = 90) or newly diagnosed diabetes (n = 70) were randomly assigned to either the anthocyanins group or the placebo group for 12 weeks of intervention. Serum adiponectin, a set of biomarkers related to glucolipid metabolism, anthropometric parameters, dietary intake and physical activity were measured before and after intervention.

Results: Anthocyanins increased serum adiponectin compared with placebo (net change 0.46 µg/mL, 95% CI [0.03, 0.90],  = 0.038) in the subjects with newly diagnosed diabetes. No significant difference in the change in adiponectin was observed between the two groups either in the overall subjects (0.02 µg/mL [- 0.32, 0.36],  = 0.906) or in prediabetes (- 0.35 µg/mL [- 0.85, 0.16],  = 0.174). Anthocyanins also decreased fasting glucose (- 0.5 mmol/L [- 1, - 0.04],  = 0.035) in the subjects with newly diagnosed diabetes, but no such change was observed in those with prediabetes.

Conclusions: Anthocyanins supplementation for 12 weeks improved serum adiponectin and fasting glucose in patients with newly diagnosed diabetes, but not in patients with prediabetes.

Trial Registration: ClinicalTrials.gov, NCT02689765. Registered on 6 February 2016, https://clinicaltrials.gov/ct2/show/NCT02689765.
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http://dx.doi.org/10.1186/s12986-020-00498-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507266PMC
September 2020

Anthocyanins regulate serum adipsin and visfatin in patients with prediabetes or newly diagnosed diabetes: a randomized controlled trial.

Eur J Nutr 2021 Jun 15;60(4):1935-1944. Epub 2020 Sep 15.

GuangDong Province, BaiYun Hospital, YueXiu District, GuangZhou, PR China.

Background: Epidemiological studies have suggested that adipsin and visfatin are associated with the development of type 2 diabetes. This is the first study to investigate the effects of supplementation with purified anthocyanins on serum adipsin and visfatin in patients with prediabetes or newly diagnosed diabetes.

Methods: A total of 160 participants with prediabetes or newly diagnosed diabetes (40-75 years old) were given 320 mg anthocyanins or placebo daily for 12 weeks in a randomized trial. Serum adipsin, serum visfatin, lipids and glycated hemoglobin A1c (HbA1c) were measured. The areas under the curve (AUCs) for glucose, insulin and C-peptide were determined before-and after-treatment by a standard 3-h 75 g oral glucose tolerance test (OGTT).

Results: Relatively significant increases in serum adipsin (net change 0.15 µg/mL [0.03, 0.27], p = 0.018) and decreases in visfatin (-3.5 ng/mL [-6.69, -0.31], p = 0.032) were observed between the anthocyanins and placebo groups. We also observed significant improvements in HbA1c (-0.11% [-0.22, -0.11], p = 0.033), apolipoprotein A-1 (apo A-1) (0.12 g/L [0.03, 0.21], p = 0.012) and apolipoprotein B (apo B) (-0.07 g/L [-0.14, -0.01], p = 0.033) in response to the anthocyanins intervention.

Conclusion: Purified anthocyanins supplementation for 12 weeks increased serum adipsin and decreased serum visfatin in patients with prediabetes or newly diagnosed diabetes. Trial registration ClinicalTrials.gov, identifier: NCT02689765.
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http://dx.doi.org/10.1007/s00394-020-02379-xDOI Listing
June 2021

Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio and Carotid Intima-Media Thickness: A Cohort Study in China.

Lipids 2021 01 28;56(1):59-68. Epub 2020 Aug 28.

Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, No.1066 Xueyuan Avenue, Nanshan District, Shenzhen, Guangdong, 518060, People's Republic of China.

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio may carry additional information and has been suggested as a better predictor for atherosclerosis progression and cardiovascular disease (CVD) than LDL-C and HDL-C alone. Therefore, we aim to explore the association between LDL-C/HDL-C ratio and high carotid intima-media thickness (CIMT) risk in a large Cohort in Beijing, China. This cohort study included 13,612 adults without high CIMT at first entry and who attended the baseline examination and at least one follow-up annual examination between 2009 and 2016. We used multivariable Cox regression to estimate hazard ratios (HR) with their 95% confidence intervals (CI) for the association between LDL-C/HDL-C ratio and risk of high CIMT. During 37,912 person-years of follow-up, 1996 (1268 men and 728 women) developed high CIMT. Compared with the first quartile of LDL-C/HDL-C ratio, the risk of high CIMT was significantly increased for the fourth quartile of LDL-C/HDL-C ratio (HR = 1.51, 95% CI: 1.29-1.78). We observed a significant association between LDL-C/HDL-C ratio and high CIMT risk comparing LDL-C/HDL-C ratio >2.78 with LDL-C/HDL-C ratio ≤2.78 and significant dose-response relationship between LDL-C/HDL-C ratio and risk of high CIMT. The restricted cubic spline showed a significant nonlinear association between LDL-C/HDL-C ratio and the risk of high CIMT (p = 0.009). We identify a significant association between LDL-C/HDL-C ratio and the risk of high CIMT in the Chinese Cohort study. Future studies are needed to evaluate the effectiveness of reducing LDL-C/HDL-C ratio treatment on the development of high CIMT.
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http://dx.doi.org/10.1002/lipd.12274DOI Listing
January 2021

The contribution of plasma uric acid to the risk of stroke in hypertensive populations.

Cardiovasc J Afr 2020 Nov-Dec;31(6):298-303. Epub 2020 Aug 12.

Department of Physiology, School of Basic Medicine, Harbin Medical University, Harbin, PR China.

Background: There is limited available evidence of a relationship between uric acid (UA) level and stroke in hypertensive populations worldwide. We aimed to estimate the relationship between UA level and stroke in Chinese hypertensive populations.

Methods: A total of 4 710 essentially hypertensive Chinese patients, including 307 with stroke, were recruited consecutively by cluster sampling from 60 communities in Shenzhen from April 2010 to September 2011. Demographic characteristics, UA level and stroke diagnosis were collected from every participant. Logistic regression analysis was used to estimate the association between UA level and stroke.

Results: The study population comprised 2 361 females and 2 349 males, with a mean age of 58 ± 11.75 years. There were significant associations between UA level and stroke and ischaemic stroke (IS) risk for females in the crude model (M0), model 1 (M1) and model 2 (M2), with increasing odds ratios (OR) as the quartiles (Q) increased. The odds of stroke risk was highest in Q4 in M2 (UA > 396 µmol/l, OR: 3.05, 95% CI: 1.74-5.36 and OR: 3.19, 95% CI: 1.74-5.85), but not for males in M0, M1 and M2. A significant dose-response relationship existed between UA level and stroke, and between UA level and IS for females but not for males. Hyperuricaemia (HU) was also significantly associated with stroke and IS for females but not for males. Taking negative uric acid, homocysteine, triglycerides, total cholesterol and low-density lipoprotein cholesterol (UA-Hcy-TG-TC-LDL-C-) as the reference, the combinations of UA+Hcy+TG-TC-LDL-, UA+Hcy+TG+TC+LDL-C- and UA+Hcy+TG+TC+LDL-C+ were significantly associated with the risk of stroke for females (OR = 2.48, 7.85 and 3.04).

Conclusions: High UA level could significantly increase stroke risk in female hypertensive patients. Female hypertensive patients may benefit from managing UA at normal levels for stroke prevention.
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http://dx.doi.org/10.5830/CVJA-2020-023DOI Listing
July 2021

Sex-Specific Association of Serum Uric Acid Level and Change in Hyperuricemia Status with Risk of Type 2 Diabetes Mellitus: A Large Cohort Study in China.

J Diabetes Res 2020 23;2020:9637365. Epub 2020 Jul 23.

Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, China.

Background: Conflicting findings have been reported regarding the sex-specific association between serum uric acid (SUA) level and type 2 diabetes mellitus (T2DM) risk, and no study has explored the association between the change in hyperuricemia status and T2DM risk. The study was aimed at exploring the sex-specific association of baseline SUA and changes in hyperuricemia status with T2DM risk.

Methods: We included 37,296 eligible adults without T2DM at the first examination who attended the baseline examination and at least one follow-up annual examination. Cox and logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) for T2DM risk associated with baseline SUA and the change in hyperuricemia status, respectively.

Results: During a median follow-up of 3.09 years, of 37,296 eligible adults, 2,263 developed T2DM. Compared with the first SUA quartile, higher quartiles were associated with an increased risk of T2DM in women (HR 1.78, 95% CI 1.17-2.71 for Q3 and 1.93, 1.27-2.93 for Q4; < 0.001) but not in men. Compared with women with a persistent normal SUA level at baseline and the last follow-up, T2DM risk increased significantly among those whose SUA status changed from normal at baseline to hyperuricemia at the last follow-up (OR 1.71, 95% CI 1.12-2.55) and those with persistent hyperuricemia at baseline and the last follow-up (OR 2.37, 95% CI 1.60-3.46). However, for men, a nonsignificant association was found between the change in hyperuricemia status and T2DM risk.

Conclusions: Baseline SUA and the change in hyperuricemia status were associated with T2DM risk only among women. The findings suggest the importance of monitoring SUA levels and maintaining them within a normal range for preventing or reducing incident T2DM in Chinese women.
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http://dx.doi.org/10.1155/2020/9637365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396085PMC
July 2021

Plaque Distribution Correlates With Morphology of Lenticulostriate Arteries in Single Subcortical Infarctions.

Stroke 2020 09 6;51(9):2801-2809. Epub 2020 Aug 6.

Departments of Neurology (S.J., Y.Y., T.Y., Q.Z., C.W., X.B., Z.H., S.Z., B.W.), West China Hospital, Sichuan University, Chengdu, China.

Background And Purpose: We aimed to use novel whole-brain vessel-wall magnetic resonance imaging (WB-VWI) to investigate the association between plaque distribution of middle cerebral artery (MCA) and morphological changes of the lenticulostriate arteries (LSAs) in single subcortical infarctions.

Methods: Forty single subcortical infarction patients with no relevant MCA disease on magnetic resonance angiography were prospectively enrolled. Plaque location in the MCA was dichotomized as proximal (located adjacent to the LSA origin) or distal (located distal to the LSA origin) on whole-brain vessel-wall magnetic resonance imaging. The MCAs with proximal plaques were divided into the symptomatic and asymptomatic side, and asymptomatic side MCAs without proximal plaques were the control group. The morphological characteristics of the LSAs and features of proximal plaques were analyzed.

Results: A total of 71 MCAs in 40 patients were analyzed (31 on the symptomatic side, 22 on the asymptomatic side, and 18 in the control group). Superior-wall plaques of MCAs were observed more frequently on the symptomatic side than the asymptomatic side (45.2% versus 9.1%, =0.005). The wall area index, plaque burden, and remodeling index did not differ significantly between the symptomatic and asymptomatic side. The number of LSA branches was smaller (=0.011) in the symptomatic side (5.48±1.88) compared with the control group (6.83±1.92). The symptomatic side exhibited shorter average length of the LSAs (23.23±3.44 versus 25.75±3.76 mm, =0.025) and shorter average distance of the LSAs (16.47±3.11 versus 21.53±4.76 mm, <0.001) compared with the asymptomatic side.

Conclusions: Superiorly distributed MCA plaques at the LSA origin are closely associated with morphological changes of the LSA in symptomatic MCAs, suggesting that the distribution, rather than the inherent features of plaques, determines the occurrence of single subcortical infarctions. Our findings provide insight into the etiologic mechanism of branch atheromatous disease in single subcortical infarctions.
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http://dx.doi.org/10.1161/STROKEAHA.120.030215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447184PMC
September 2020

Balanced Genome Triplication in Wheat Causes Premature Growth Arrest and an Upheaval of Genome-Wide Gene Regulation.

Front Genet 2020 8;11:687. Epub 2020 Jul 8.

Key Laboratory of Molecular Epigenetics, Northeast Normal University, Changchun, China.

Polyploidy, or whole genome duplication (WGD), is a driving evolutionary force across the tree of life and has played a pervasive role in the evolution of the plant kingdom. It is generally believed that a major genetic attribute contributing to the success of polyploidy is increased gene and genome dosage. The evolution of polyploid wheat has lent support to this scenario. Wheat has evolved at three ploidal levels: diploidy, tetraploidy, and hexaploidy. Ample evidence testifies that the evolutionary success, be it with respect to evolvability, natural adaptability, or domestication has dramatically increased with each elevation of the ploidal levels. A long-standing question is what would be the outcome if a further elevation of ploidy is superimposed on hexaploid wheat? Here, we characterized a spontaneously occurring nonaploid wheat individual in selfed progenies of synthetic hexaploid wheat and compared it with its isogenic hexaploid siblings at the phenotypic, cytological, and genome-wide gene-expression levels. The nonaploid manifested severe defects in growth and development, albeit with a balanced triplication of the three wheat subgenomes. Transcriptomic profiling of the second leaf of nonaploid, taken at a stage when phenotypic abnormality was not yet discernible, already revealed significant dysregulation in global-scale gene expression with 25.2% of the 49,436 expressed genes being differentially expressed genes (DEGs) at a twofold change cutoff relative to the hexaploid counterpart. Both up- and downregulated DEGs were identified in the nonaploid vs. hexaploid, including 457 genes showing qualitative alteration, i.e., silencing or activation. Impaired functionality at both cellular and organismal levels was inferred from gene ontology analysis of the DEGs. Homoeologous expression analysis of 9,574 sets of syntenic triads indicated that, compared with hexaploid, the proportions showing various homeologous expression patterns were highly conserved in the nonaploid although gene identity showed moderate reshuffling among some of the patterns in the nonaploid. Together, our results suggest hexaploidy is likely the upper limit of ploidy level in wheat; crossing this threshold incurs severe ploidy syndrome that is preceded by disruptive dysregulation of global gene expression.
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http://dx.doi.org/10.3389/fgene.2020.00687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360807PMC
July 2020

LDL-cholesterol to HDL-cholesterol ratio discordance with lipid parameters and carotid intima-media thickness: a cohort study in China.

Lipids Health Dis 2020 Jun 18;19(1):141. Epub 2020 Jun 18.

Department of Health Management, Beijing Xiao Tang Shan Hospital, Beijing, People's Republic of China.

Background: The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China.

Methods: In total, 13,612 adults who didn't have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk.

Results: During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P < 0.001). A low LDL-C/HDL-C ratio with discordantly normal HDL-C and high LDL-C (13.2% of individuals) had a 32% (HR = 1.32, 95% CI 1.11, 1.57) higher risk of elevated CIMT than concordantly low LDL-C and normal HDL-C. Sensitivity analysis by excluding CIMT developed in the first 2 years follow-up further confirmed the above results.

Conclusions: A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with TC, TGs, LDL-C and HDL-C Even a low LDL-C/HDL-C ratio with discordantly high LDL-C and normal HDL-C could also significantly increase CIMT risk. Individuals should maintain both the LDL-C/HDL-C ratio and LDL-C at normal levels to prevent elevated CIMT.
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http://dx.doi.org/10.1186/s12944-020-01324-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302368PMC
June 2020

Association Between Neutrophil to Lymphocyte Ratio and Malignant Brain Edema in Patients With Large Hemispheric Infarction.

Curr Neurovasc Res 2020 ;17(4):429-436

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Introduction: Malignant brain edema (MBE) is a life-threatening complication for patients with large hemispheric infarction (LHI). Stroke-related inflammatory responses may cause secondary brain injury and lead to brain edema. The neutrophil to lymphocyte ratio (NLR) is a well-known systemic inflammatory biomarker. The aim of this study was to evaluate if NLR is associated with MBE in patients with LHI.

Methods: A retrospective analysis was performed of LHI patients within 24 h from stroke onset admitted to the Department of Neurology, West China Hospital from January 1, 2017 to December 31, 2018. Blood samples were collected upon admission. MBE was diagnosed by any neurological deterioration accompanied by brain edema in follow-up images. Patients were categorized according to NLR tertiles. Univariate analyses were performed to identify potential confounding variables and a multivariate logistic regression analysis was conducted to determine the correlation between NLR and MBE.

Results: A total of 257 patients with a mean age of 68.6 ± 14.0 years were identified. Among them, 83 (32.3%) patients developed MBE with a median time of one day (interquartile range [IQR] 0-2 days) from hospital admission. An elevated NLR was related to an increased risk of MBE when the lowest and highest tertiles were compared (odds ratio 2.27, 95% confidence interval 1.11-4.62, p = 0.024). The risk of MBE increased with the increase of NLR in a dosedependent manner (p for trend = 0.029). No interaction between potential modifiers and NLR on MBE was observed.

Conclusions: Higher NLR was associated with an increased risk of MBE in patients with LHI.
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http://dx.doi.org/10.2174/1567202617666200517110509DOI Listing
January 2020

High MTHFR promoter methylation levels in men confer protection against ischemic stroke.

Bosn J Basic Med Sci 2020 Nov 2;20(4):477-486. Epub 2020 Nov 2.

Nanshan Center for Chronic Disease Control, Shenzhen, China.

The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) - a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age-matched and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect MTHFR promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, MTHFR promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic curve to determine whether MTHFR promoter methylation levels can predict IS. The mean MTHFR methylation levels in the case group (8.10 ± 6.14) were significantly lower than those in the control group (17.44 ± 3.16; p < 0.05). MTHFR promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels <15 μmol/L (16.74 ± 4.26, p < 0.001). Finally, we found that MTHFR hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02-0.16; p < 0.001). Further, sex and MTHFR promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that MTHFR promoter methylation status might have diagnostic value in IS.
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http://dx.doi.org/10.17305/bjbms.2020.4636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664794PMC
November 2020

Dynamic Change of Neutrophil to Lymphocyte Ratios and Infection in Patients with Acute Ischemic Stroke.

Curr Neurovasc Res 2020 ;17(3):294-303

Department of Neurology, Sichuan University, West China Hospital, Sichuan, China.

Background: Neutrophil to lymphocyte ratio (NLR) on admission was reported to be a predictor of pneumonia after stroke. The aim of this study was to investigate the association between the temporal change of NLR and post-stroke infection and whether infection modified the effect of NLR on the outcome.

Methods: We enrolled patients with acute ischemic stroke within 24 h after onset. The blood was collected on admission, day 1, 3, 7 after admission to detect white blood cells (WBC), neutrophils, and lymphocytes. Primary outcomes included pneumonia, urinary tract infection (UTI), other infection, and the secondary outcome was 3-month death.

Results: Of 798 stroke patients, 299 (37.66%) developed infection with 240 (30.23%) pneumonia, 78 (9.82%) UTI, and 9 (1.13%) other infection. The median time of infection occurrence was 48 h (interquartile range 27-74 h) after onset. NLR reached to the peak at 36 h. For all outcomes, NLR at 36 h after stroke had the highest predictive value than WBC, neutrophil, lymphocyte. NLR was independently associated with the presence of any infection (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.17), pneumonia (OR 1.12, 95%CI 1.05-1.19), but not UTI (OR 0.95, 95%CI 0.89-1.01). Adding infection or the interaction term did not substantially change the OR of NLR predicting 3-month death (OR 1.09, 95%CI 1.01, 1.17).

Conclusion: Increased NLR around 36 h after stroke was a predictor of infection in patients with acute ischemic stroke. The increased NLR value was associated with a higher risk of 3-month death, which was independent of poststroke infection.
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http://dx.doi.org/10.2174/1567202617666200408091131DOI Listing
January 2020

Dose-response associations between serum creatinine and type 2 diabetes mellitus risk: A Chinese cohort study and meta-analysis of cohort studies.

J Diabetes 2020 Aug 2;12(8):594-604. Epub 2020 Apr 2.

Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Center, Shenzhen, People's Republic of China.

Background: This study aims to investigate the association between serum creatinine and risk of type 2 diabetes mellitus (T2DM) based on a cohort analysis and meta-analysis of cohort studies.

Methods: We enrolled 41 439 participants aged ≥18 years without T2DM at baseline, who had ≥2 health examinations based on an ongoing prospective cohort in Beijing. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs. For the meta-analysis, cohort studies reporting risk estimates for the serum creatinine-T2DM association were included. A random-effects model was used to calculate summary relative risks (RRs) and restricted cubic splines to model the dose-response association.

Results: During a mean follow-up of 3.54 years, 1867 developed T2DM. Low serum creatinine was associated with increased risk of T2DM; adjusted HRs (95% CIs) across sex-specific quartiles were 1.45 (1.24, 1.71), 1.19 (1.02, 1.39), 1.07 (0.92, 1.24), and 1.00 (reference). The association was significant for both sexes and individuals with overweight or obesity. In the meta-analysis of six cohort studies (including the current study) involving 115 767 participants and 5370 T2DM events, the pooled RR was 1.61 (95% CI 1.35, 1.92), comparing the lowest with the highest category of serum creatinine. We found a linear association between serum creatinine and T2DM risk (P = .082) and an increased risk of T2DM with each 0.1-mg/dL decrease in serum creatinine (RR = 1.07; 95% CI 1.04, 1.09).

Conclusions: The cohort study and meta-analysis provide further evidence supporting the negative association between serum creatinine and T2DM risk in a linear dose-response pattern.
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http://dx.doi.org/10.1111/1753-0407.13038DOI Listing
August 2020

Red blood cell distribution width is associated with mortality after acute ischemic stroke: a cohort study and systematic review.

Ann Transl Med 2020 Feb;8(4):81

Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China.

Background: Whether red blood cell distribution width (RDW) is associated with the prognosis of acute ischemic stroke is inconclusive according to recent studies. We performed a cohort study and meta-analysis to explore the association between RDW and functional outcome.

Methods: Patients with ischemic stroke admitted to the Department of Neurology within 24 hours of stroke onset between January 1, 2015 to December 31, 2018 were enrolled. Blood was sampled within 24 hours after admission. We searched PubMed, Embase, Web of Science databases up to Nov 2019 to identify studies investigating the association between RDW values and prognosis following stroke. Outcomes included 3-month death and poor functional outcome [defined by modified Rankin Scale (mRS) score ≥3].

Results: We included 1,558 patients in cohort study. RDW was independently associated with 3-month death [odds ratio (OR), 1.19; 95% confidence interval (CI), 1.03, 1.37], but not associated with 3-month poor outcome (OR 1.05, 95% CI, 0.95, 1.16), after adjustment for confounders. A dose-dependent relationship between RDW levels and 3-month death was revealed in the restricted cubic spline plot. Seven observational studies with 4,407 patients were identified for systematic review. When combining our study and previous studies, the association was significant for RDW predicting death (5 studies with 3,366 patients, OR 1.25, 95% CI, 1.15, 1.35), as well as for poor outcome (4 studies with 3,483 patients, OR 1.23, 95% CI, 1.05, 1.44).

Conclusions: RDW was an independent predictor of 3-month functional outcome, and a trend of dose-dependent relationship between RDW and 3-month death was detected.
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http://dx.doi.org/10.21037/atm.2019.12.142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049007PMC
February 2020

Mirror movements induced by hemiballism due to putamen infarction: a case report and literature review.

Ann Transl Med 2020 Jan;8(1):19

Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China.

Mirror movements (MMs), which are involuntary movements of one limb that synchronously mirror voluntary movements of the contralateral limb, are a relatively uncommon complication of strokes. Here we report what appears to be the first case of putamen infarction manifesting as MMs in one side of the body induced by contralateral hemiballism. MMs and hemiballism were nearly entirely eliminated after one week of clonazepam and haloperidol therapy. During the subsequent one year of standard ischemic stroke prevention measures, no further episodes of involuntary movement occurred. Our case and literature review highlight that acute stroke can manifest as hemiballism and MMs, which should be recognized as soon as possible to ensure timely management.
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http://dx.doi.org/10.21037/atm.2019.10.86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995745PMC
January 2020

Baseline serum albumin and its dynamic change is associated with type 2 diabetes risk: A large cohort study in China.

Diabetes Metab Res Rev 2020 07 20;36(5):e3296. Epub 2020 Feb 20.

School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, P. R. China.

Background: The study aimed to investigate the associations of baseline serum albumin level and its dynamic change with type 2 diabetes mellitus (T2DM) risk in a large Chinese cohort study.

Methods: This cohort study included 30 442 adults without T2DM at first entry, who completed at least one follow-up of annual examinations between 2009 and 2016. Serum albumin level was measured at baseline and at every annual check-up. The dynamic change in serum albumin level (∆ALB) was calculated by subtracting serum albumin level at baseline from that at the last follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox regression models.

Results: During 7 years of follow-up, we identified 1634 T2DM events. From the lowest to the highest quartile of serum albumin level, adjusted HRs (95% CI) were 1.00 (reference), 0.96 (0.94, 1.01), 0.98 (0.95, 1.02) and 0.88 (0.85, 0.98), respectively. As compared with stable change in serum albumin (-0.2 ≤ ∆ALB <1.0 g/L), the risk of T2DM increased for ∆ALB < -2.0 g/L (HR 1.44, 95% CI 1.24-1.68) and decreased for ∆ALB ≥3.0 g/L (0.81, 0.68-0.97) after adjusting for potential confounding factors. Restricted cubic splines showed a linear dose-response association between baseline serum albumin level and T2DM risk (P 0.715) and a nonlinear dose-response association between ∆ALB and T2DM risk (P 0.011).

Conclusions: Baseline serum albumin level appears to be inversely associated with T2DM risk. Adults with reduced serum albumin level could be early identified for diabetes risk in clinical practice.
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http://dx.doi.org/10.1002/dmrr.3296DOI Listing
July 2020

Effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors in adults with central obesity: study protocol for a randomised controlled study.

Trials 2020 Jan 6;21(1):32. Epub 2020 Jan 6.

Shenzhen Nanshan Centre for Chronic Disease Control, Shenzhen, 518054, China.

Background: The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity.

Methods: This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses.

Discussion: Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.
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http://dx.doi.org/10.1186/s13063-019-3998-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945790PMC
January 2020

Association Between Mean Platelet Volume and Hemorrhagic Transformation in Acute Ischemic Stroke Patients.

Curr Neurovasc Res 2020 ;17(1):3-10

Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Hemorrhagic transformation (HT) is a frequent complication of acute ischemic stroke (AIS). Mean platelet volume (MPV) is a marker of platelet function. The relationship between MPV and HT remains unclear.

Methods: From January 1st, 2012 to December 31st 2016, we consecutively enrolled AIS patients admitted to the Department of Neurology of West China Hospital. MPV was measured on admission. HT was diagnosed by brain imaging and classified into hemorrhagic infarct (HI) and parenchymal hematoma (PH). Moreover, subjects were divided into tertiles according to MPV levels. Confounders were identified by univariate analysis and multivariate logistic regression was performed to explore the association between MPV and HT as well as HT subtypes. Also, a generalized additive model was used to investigate whether a non-linear association existed between MPV and HT.

Results: A total of 783 AIS patients were included. 63 patients (8.0%) developed HT: 34 (4.3%) HI and 29 (3.7%) PH. It was observed that MPV positively correlated with HT. After adjustment for confounders, patients in the highest MPV tertile had a significantly increased risk of HT compared to patients in the lowest tertile (odds ratio 2.3, 95% confidence interval 1.0-5.4, P=0.04). The risk of HT increased step-wise across MPV tertiles (P for trend=0.04). MPV tertiles significantly correlated with HI rather than PH. The generalized additive model demonstrated a nonlinear association between MPV and HT (P=0.02).

Conclusion: The risk of HT increased with increasing MPV level in a dose-dependent manner. Patients with elevated MPV levels were more likely to develop HI rather than PH.
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http://dx.doi.org/10.2174/1567202617666191226115518DOI Listing
July 2021

Association between Red Blood Cell Distribution Width and Hemorrhagic Transformation in Acute Ischemic Stroke Patients.

Cerebrovasc Dis 2019 29;48(3-6):193-199. Epub 2019 Nov 29.

Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, China,

Background: Hemorrhagic transformation (HT) is a frequent complication of acute ischemic stroke (AIS). Red blood cell distribution width (RDW) is a cost-effective parameter associated with incidence and prognosis of cerebrovascular diseases. The purpose of this study was to assess whether RDW is associated with HT in AIS patients.

Methods: AIS patients within 24 h from stroke onset between January 1, 2014, and December 31, 2018, were consecutively enrolled. Blood samples were collected. The primary outcome was HT, which was diagnosed by follow-up brain image and classified into hemorrhagic infarct (HI) and parenchymal hematoma (PH). Multivariate logistic regression analysis was performed to determine the relationship between RDW and HT as well as its subtypes. Potential effect modifier was identified by stratified logistic regression analysis.

Results: Among the included 1383 patients, 220 (15.9%) developed HT (HI in 103 and PH in 117). Elevated RDW levels were associated with an increased risk of HT when 2 extreme tertiles were compared (OR 1.60, 95% CI 1.04-2.44, p = 0.031). The risk of HT increased stepwise across RDW tertiles (p for trend = 0.042). RDW significantly correlated with HI rather than PH. The association between RDW and HT could be modified by reperfusion therapy (p for interaction = 0.010), with no significant association between RDW and HT among patients underwent reperfusion therapy.

Conclusions: Elevated RDW level was related to increased risk of HT among AIS patients without reperfusion therapy.
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http://dx.doi.org/10.1159/000504742DOI Listing
May 2020

C-reactive Protein, Infection, and Outcome After Acute Ischemic Stroke: A Registry and Systematic Review.

Curr Neurovasc Res 2019 ;16(5):405-415

Department of Neurology, Center of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Background: A number of studies have explored the prognostic role of CRP in patients with acute ischemic stroke, however, the results have been inconclusive. The aim of our study was to investigate the impact of infection on the association between CRP and 3-month functional outcome by performing a registry study and systematic review.

Methods: Patients admitted within 24 hours of acute ischemic stroke onset and had CRP measured within 24 hours after admission were included. Patients admitted between June 2016 and December 2018 in Chengdu Stoke Registry were enrolled. The PubMed database was searched up to July 2019 to identify eligible studies. Poor outcome was defined as modified Rankin Scale scores at 3-month more than 3.

Results: Totally, 368 patients in the registry and 18 studies involving 15238 patients in the systematic review were included. A statistically significant association between CRP values on admission and 3-month poor outcome in patients without infection was found, both in our registry (CRP per 1-mg/L increment, OR 1.04, 95% CI 1.01 to 1.07, p=0.008) and meta-analysis (CRP per 1-mg/dL increment, OR 1.66 [95% CI 1.37 to 2.01, p<0.001]). In patients with infection, CRP was not associated with a 3-month poor outcome according to registry data (OR 1.00, 95% CI 0.99 to 1.01, p=0.663) and meta-analysis (OR 1.01, 95% CI 0.99 to 1.01, p=0.128).

Conclusion: High CRP value was independently associated with a 3-month poor outcome after stroke in patients without infection. Further studies are required to examine the value of infection on CRP measures and long-term functional outcomes.
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http://dx.doi.org/10.2174/1567202616666191026122011DOI Listing
October 2020

Effectiveness of tailored communication intervention in increasing colonoscopy screening rates amongst first-degree relatives of individuals with colorectal cancer: A systematic review and meta-analysis.

Int J Nurs Stud 2020 Jan 16;101:103397. Epub 2019 Aug 16.

The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, 6/F, Esther Lee Building, Shatin, N.T., Hong Kong SAR, China.

Objectives: Ensuring that the first-degree relatives of patients with colorectal cancer are properly screened is critical to reduce disease incidence and mortality rate. Tailored communication intervention is a promising method to induce health-related behavioural changes. However, evidence of the effects of tailored communication interventions on the screening rate of populations at an increased familial risk of colorectal cancer is lacking. This review aimed to identify, appraise and examine existing evidence of the effectiveness of tailored communication interventions in increasing colonoscopy screening rates amongst the first-degree relatives of people with colorectal cancer.

Design: Systematic review and meta-analysis.

Data Sources: Twelve electronic English and Chinese databases [Medline, EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Review, CINAHL, Scopus, Global Health, British Journal Index, China National Knowledge Infrastructure (CNKI), Wan Fang Data and China Biology Medicine (CBM)] were searched to identify eligible clinical trials that were published over period of 1995 to October 2018.

Review Methods: Studies were selected by using key words, such as 'colorectal cancer', 'screening', 'colonoscop*', 'first degree relative*', 'uptake or adhere*' and 'cost'. Two reviewers independently assessed the eligibility of each study and extracted the data. The Cochrane Risk of Bias Tool was applied to evaluate the risk of bias amongst included studies. Meta-analysis was performed when possible. Subgroup analysis was performed for types of communication channels. Sensitivity analysis was conducted to explore the influence of random units on the primary outcome.

Results: Four studies that adopted tailored communication interventions to increase colonoscopy screening rates were identified. Pooled analysis showed that tailored communication had a beneficial effect on improving colonoscopy use in the colorectal cancer screening context (OR: 2.21, 95% CI: 1.71-2.85, p < 0.01). Furthermore, subgroup analysis showed that repeated tailored communication delivered via print plus telephone call had a significant effect on increasing colonoscopy screening rates (OR: 2.39, 95% CI: 1.78-3.21, p < 0.01). The results of sensitivity analysis indicated that types of randomisation units did not influence outcomes.

Conclusion: Tailored communication is a beneficial approach for increasing colonoscopy screening rates amongst first-degree relatives who are at increased familial risk of colorectal cancer. The effective components of tailored communication were repeated contacts, combined verbal and written communication and important tailored variables. Future studies with rigorous designs are recommended to develop an integrated tailoring assessment decision system with the support of Internet-based communication channels.
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http://dx.doi.org/10.1016/j.ijnurstu.2019.103397DOI Listing
January 2020

Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: A cohort study and systematic review.

J Neurol Sci 2019 Nov 31;406:116445. Epub 2019 Aug 31.

Center of Cerebrovascular Disease, Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background And Purpose: The relationship between neutrophil to lymphocyte ratio (NLR) and prognosis after acute ischemic stroke (AIS) remains controversial. The aim of this cohort study and systematic review was to ascertain the association of admission NLR with major clinical poor outcomes after AIS.

Methods: We analyzed data from Chengdu stroke registry and performed a systematic review for previous literature. The outcomes were hemorrhagic transformation (HT), parenchymal hematoma (PH), symptomatic intracranial hemorrhage (sICH), 3-month death or disability (modified Rankin Scale≥3), and 3-month death. Odds ratios (ORs) and 95% confidence intervals (CIs) of NLR as a continuous and categorical variable and poor outcomes were pooled separately. We also calculated the predictive accuracy of admission NLR in different outcomes.

Results: We included 808 patients from registry database and 9563 patients from previous studies. Our registry data showed that NLR ≥5 was associated with HT (OR 2.03, 95%CI 1.19-3.46), PH (OR 2.54, 95%CI 1.20-5.35) and 3-month death (OR 5.55, 95%CI 1.41-21.89); meta-analysis with our data and other observational studies indicated that higher NLR was associated with HT (OR 1.99, 95% CI 1.45-2.73), sICH (OR 2.22, 95% CI 1.60-3.09), 3-month death or disability (OR 1.68, 95% CI 1.18-2.38), and 3-month death (OR 2.79, 95% CI 1.57, 4.94). NLR had the highest predictive accuracy for 3-month death.

Conclusions: Higher NLR is positively associated with the risk of HT and 3-month death after stroke. Considering the limited predictive ability of a single biomarker, more studies should validate the role of NLR in prognostic models.
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http://dx.doi.org/10.1016/j.jns.2019.116445DOI Listing
November 2019

ANKLE1 N -Methyladenosine-related variant is associated with colorectal cancer risk by maintaining the genomic stability.

Int J Cancer 2020 06 6;146(12):3281-3293. Epub 2019 Nov 6.

Key Laboratory for Environment and Health (Ministry of Education), Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

The N -Methyladenosine (m A) modification plays an important role in many biological processes, especially tumor development. However, little is still known about how it affects colorectal cancer (CRC) carcinogenesis. Here, we first systematically investigate the association of variants related to m A modification with the CRC risk in 1,062 CRC cases and 2,184 controls by using our exome-wide association data and followed by two replication sets including 7,341 CRC cases and 7,902 controls. The variant rs8100241 located in ANKLE1 was significantly associated with CRC risk (odds ratio = 0.88, 95% confidence interval = 0.84-0.92, p = 4.85 × 10 ) in 8,403 cases and 10,086 controls. This variant was previously identified to be associated with the susceptibility of breast cancer with BRCA1 mutation triple negative breast cancer. Further functional analysis indicated that overexpression of the rs8100241[A] allele significantly increased the ANKLE1 m A level and facilitated the ANKLE1 protein expression compared to that of rs8100241[G] allele. We further found the ANKLE1 m A modification was catalyzed by the "writer" complex (METTL3, METTL14, or WTAP) and recognized by the "reader" YTHDF1. Mechanistically, we found that the ANKLE1 functions as a potential tumor suppressor that inhibits cell proliferation and facilitates the genomic stability. An elevated frequency of micronucleated cells, increased cell proliferation, and colony formation ability were observed when ANKLE1 knockdown. Our study illustrated that the germline missense variant can increase CRC risk by influencing ANKLE1 m A level, highlighting a clinical potential of variants-associated m A modification as a risk marker for CRC prevention.
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http://dx.doi.org/10.1002/ijc.32677DOI Listing
June 2020

Effects of the blood urea nitrogen to creatinine ratio on haemorrhagic transformation in AIS patients with diabetes mellitus.

BMC Neurol 2019 Apr 13;19(1):63. Epub 2019 Apr 13.

Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: The effect of the blood urea nitrogen (BUN) to creatinine (Cr) ratio (henceforth BUN/Cr) on haemorrhagic transformation (HT) of acute ischaemic stroke (AIS) patients is unclear.

Methods: AIS patients in the West China Hospital, Sichuan University, Chengdu, China, admitted within seven days from stroke onset (2012-2016) were included in the study. Baseline data, including BUN and Cr levels, were collected. The outcome was defined as HT during hospitalization.

Results: In this study, 1738 participants with an average age of 62.7 ± 14.0 years were included. After adjusting potential confounders (age, blood platelet, albumin, stroke severity, triglycerides and low-density lipoprotein [LDL]), multivariate logistic regression analyses indicated that BUN/Cr is independently associated with HT. The nonlinear relation between BUN/Cr and HT was explored in a dose-dependent manner, with an apparent inflection point of 30.71. On the left and right sides of the inflection point, the odds ratio (OR) and 95% confidence interval (CI) were 1.05 (1.02-1.08) and 0.96 (0.88-1.05), respectively. Interaction between BUN/Cr and diabetes mellitus (DM) and HT (P for interaction = 0.0395) was noted. BUN/Cr showed positive correlation with HT in DM patients (OR = 1.07; 95% CI: [1.02, 1.12]) but no significant relationship with HT in patients without DM.

Conclusion: BUN/Cr is significantly associated with HT in AIS patients in a linear fashion, with an apparent cut point demarcating the HT difference. When the patients have DM, BUN/Cr is positively correlated with HT. These results support a revision in how we anticipate the prognosis for AIS patients.
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http://dx.doi.org/10.1186/s12883-019-1290-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463662PMC
April 2019
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