Publications by authors named "Weiqi Chen"

106 Publications

Nattokinase Attenuates Retinal Neovascularization Via Modulation of Nrf2/HO-1 and Glial Activation.

Invest Ophthalmol Vis Sci 2021 May;62(6):25

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China.

Purpose: Nattokinase (NK), an active ingredient extracted from traditional food Natto, has been studied for prevention and treatment of cardiovascular diseases due to various vasoprotective effects, including fibrinolytic, antihypertensive, anti-atherosclerotic, antiplatelet, and anti-inflammatory activities. Here, we reported an antineovascular effect of NK against experimental retinal neovascularization.

Methods: The inhibitory effect of NK against retinal neovascularization was evaluated using an oxygen-induced retinopathy murine model. Expressions of Nrf2/HO-1 signaling and glial activation in the NK-treated retinae were measured. We also investigated cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) after NK administration.

Results: NK treatment significantly attenuated retinal neovascularization in the OIR retinae. Consistently, NK suppressed VEGF-induced cell proliferation and migration in a concentration-dependent manner in cultured vascular endothelial cells. NK ameliorated ischemic retinopathy partially via activating Nrf2/HO-1. In addition, NK orchestrated reactive gliosis and promoted microglial activation toward a reparative phenotype in ischemic retina. Treatment of NK exhibited no cell toxicity or anti-angiogenic effects in the normal retina.

Conclusions: Our results revealed the anti-angiogenic effect of NK against retinal neovascularization via modulating Nrf2/HO-1, glial activation and neuroinflammation, suggesting a promising alternative treatment strategy for retinal neovascularization.
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http://dx.doi.org/10.1167/iovs.62.6.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164371PMC
May 2021

Ocular symptoms as the initial clinical manifestations in patients with extraocular tumors.

Ann Transl Med 2021 Mar;9(6):497

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China.

Background: Due to the variety of clinical presentation, some tumors may be concealed and easily misdiagnosed, leading to delays in management. We report a series of patients who initially presented to an Ophthalmic Clinic with ocular symptoms and were subsequently diagnosed with extraocular tumors.

Methods: Patients who presented to the ophthalmic outpatient clinic at the Joint Shantou International Eye Center with ocular symptoms between April 2013 and December 2019 and were subsequently diagnosed with intracranial or systemic tumors were reviewed retrospectively. Clinical data, including ocular symptoms and signs, ophthalmic and systemic imaging examinations, and the results of tumor biopsies were collected and analyzed.

Results: Twenty-three patients were included in this study, of which 16 were female (69.6%) and 7 were male (30.4%). Chief complaints at the first visit included visual loss (n=20), proptosis (n=2), and diplopia (n=1). Ocular examination revealed disc pallor (n=8) and swelling (n=3), choroidal mass with or without chorioretinal detachment (n=5), and proptosis (n=2). Visual field (VF) examination was performed in 11 patients of which hemianopia (n=4) and non-specific field loss (n=7) were noted. Brain CT or MRI, together with histopathological findings from surgical biopsies confirmed the diagnosis of the intracranial tumors in 18 cases, including pituitary adenoma (n=7), meningioma (n=2), oligodendroglioma (n=1), sellar tumor (n=1), suprachiasmatic arteriovenous aneurysm (n=1), orbital glioma (n=1), multiple intracranial tumors (n=1), and sphenoid ossifying fibroma (n=1). Nasopharyngeal carcinoma (NPC) (n=3) was diagnosed with brain MRI and nasal endoscopy. Five patients were confirmed as choroidal metastasis secondary to lung cancer (n=3), hepatoma (n=1), and breast cancer (n=1).

Conclusions: Patients with extraocular tumors may present initially to an ophthalmologist with ocular symptoms. It is important to identify and appropriately manage these patients to avoid unnecessary delays in future treatment.
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http://dx.doi.org/10.21037/atm-21-830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039673PMC
March 2021

Carbon dioxide hydrate in a microfluidic device: Phase boundary and crystallization kinetics measurements with micro-Raman spectroscopy.

J Chem Phys 2021 Mar;154(11):114710

Center for Hydrate Research, Chemical and Biological Engineering Department, Colorado School of Mines, Golden, Colorado 80401, USA.

Various emerging carbon capture technologies depend on being able to reliably and consistently grow carbon dioxide hydrate, particularly in packed media. However, there are limited kinetic data for carbon dioxide hydrates at this length scale. In this work, carbon dioxide hydrate propagation rates and conversion were evaluated in a high pressure silicon microfluidic device. The carbon dioxide phase boundary was first measured in the microfluidic device, which showed little deviation from bulk predictions. Additionally, measuring the phase boundary takes on the order of hours compared to weeks or longer for larger scale experimental setups. Next, propagation rates of carbon dioxide hydrate were measured in the channels at low subcoolings (<2 K from phase boundary) and moderate pressures (200-500 psi). Growth was dominated by mass transfer limitations until a critical pressure was reached, and reaction kinetics limited growth upon further increases in pressure. Additionally, hydrate conversion was estimated from Raman spectroscopy in the microfluidics channels. A maximum value of 47% conversion was reached within 1 h of a constant flow experiment, nearly 4% of the time required for similar results in a large scale system. The rapid reaction times and high throughput allowed by high pressure microfluidics provide a new way for carbon dioxide gas hydrate to be characterized.
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http://dx.doi.org/10.1063/5.0039533DOI Listing
March 2021

Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 and Major Adverse Cardiovascular Events, Stroke, and All-Cause Mortality: Systemic Review and Meta-Analysis.

Front Cardiovasc Med 2021 2;8:617249. Epub 2021 Mar 2.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal protein in low-density lipoprotein cholesterol metabolism, has been validated to be an established target for cardiovascular (CV) risk reduction. Nevertheless, prospective studies concerning the associations between circulating PCSK9 and the risk of CV events and mortality have yielded, so far, inconsistent results. Herein, we conducted a meta-analysis to evaluate the association systemically. Pertinent studies were identified from PubMed, EMBASE, and Cochrane Library database through July 2020. Longitudinal studies investigating the value of circulating PCSK9 for predicting major adverse cardiovascular events (MACEs) or stroke or all-cause mortally with risk estimates and 95% confidence intervals (CI) were included in the analyses. Dose-response meta-analysis was also applied to evaluate circulating PCSK9 and risk of MACEs in this study. A total of 22 eligible cohorts comprising 28,319 participants from 20 eligible articles were finally included in the study. The pooled relative risk (RR) of MACEs for one standard deviation increase in baseline PCSK9 was 1.120 (95% CI, 1.056-1.189). When categorizing subjects into tertiles, the pooled RR for the highest tertile of baseline PCSK9 was 1.252 (95% CI, 1.104-1.420) compared with the lowest category. This positive association between PCSK9 level and risk of MACEs persisted in sensitivity and most of the subgroup analyses. Twelve studies were included in dose-response meta-analysis, and a linear association between PCSK9 concentration and risk of MACEs was observed (x2 test for non-linearity = 0.31, P non-linearity = 0.575). No significant correlation was found either on stroke or all-cause mortality. This meta-analysis added further evidence that high circulating PCSK9 concentration significantly associated with increased risk of MACEs, and a linear dose-response association was observed. However, available data did not suggest significant association either on stroke or all-cause mortality. Additional well-designed studies are warranted to further investigate the correlations between PCSK9 concentration and stroke and mortality.
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http://dx.doi.org/10.3389/fcvm.2021.617249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960648PMC
March 2021

Comparison of VerifyNow, thromboelastography, and PL-12 in patients with minor ischemic stroke or transient ischemic attack.

Aging (Albany NY) 2021 03 3;13(6):8396-8407. Epub 2021 Mar 3.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

High on-treatment platelet reactivity (HOPR) is associated with stroke recurrence. It is important to find a reliable method to assess HOPR. We aimed to compare the correlations between VerifyNow™ system, thromboelastography (TEG), and Aggrestar platelet function analyzer (PL-12) on platelet activity in patients with minor ischemic stroke or transient ischemic attack (TIA) after dual antiplatelet therapy for 7 days. About 276 patients were included. Spearman's correlation coefficient and the kappa coefficient were adopted to evaluate associations among the three test methods. An obvious correlation between VerifyNow and TEG on HOPR-ADP (r=0.64, p<0.001) was found. The correlations of HOPR-ADP between PL-12 and the other two platelet function analyzers were moderate (PL-12 versus VerifyNow, r=0.47, p<0.001; PL-12 versus TEG, r=0.25, p<0.001). The correlations of HOPR-AA were limited among these three platelet function analyzers (VerifyNow versus TEG, r=0.09, p=0.14; VerifyNow versus PL-12, r=0.15, p=0.01; PL-12 versus TEG, r=0.10, p=0.09). Correlations among different platelet function analyzers were varied. VerifyNow and TEG were more correlative than PL-12 on HOPR-ADP. The consistence of HOPR-AA was limited among VerifyNow, TEG and PL-12. The proportion of stroke recurrence and composite events in patients with HOPR-ADP assessing by PL-12 was higher than VerifyNow and TEG.
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http://dx.doi.org/10.18632/aging.202650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034945PMC
March 2021

Machine learning classifiers for predicting 3-year progression-free survival and overall survival in patients with gliomas after surgery.

J Cancer 2021 15;12(6):1604-1615. Epub 2021 Jan 15.

Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

To develop machine-learning based models to predict the progression-free survival (PFS) and overall survival (OS) in patients with gliomas and explore the effect of different feature selection methods on the prediction. We included 505 patients (training cohort, n = 354; validation cohort, n = 151) with gliomas between January 1, 2011 and December 31, 2016. The clinical, neuroimaging, and molecular genetic data of patients were retrospectively collected. The multi-causes discovering with structure learning (McDSL) algorithm, least absolute shrinkage and selection operator regression (LASSO), and Cox proportional hazards regression model were employed to discover the predictors for 3-year PFS and OS, respectively. Eight machine learning classifiers with 5-fold cross-validation were developed to predict 3-year PFS and OS. The area under the curve (AUC) was used to evaluate the prognostic performance of classifiers. McDSL identified four causal factors (tumor location, WHO grade, histologic type, and molecular genetic group) for 3-year PFS and OS, whereas LASSO and Cox identified wide-range number of factors associated with 3-year PFS and OS. The performance of each machine learning classifier based on McDSL, LASSO, and Cox was not significantly different. Logistic regression yielded the optimal performance in predicting 3-year PFS based on the McDSL (AUC, 0.872, 95% confidence interval [CI]: 0.828-0.916) and 3-year OS based on the LASSO (AUC, 0.901, 95% CI: 0.861-0.940). McDSL is more reproducible than LASSO and Cox model in the feature selection process. Logistic regression model may have the highest performance in predicting 3-year PFS and OS of gliomas.
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http://dx.doi.org/10.7150/jca.52183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890310PMC
January 2021

Concurrency of Early-Age Exposure to Chinese Famine and Diabetes Increases Recurrence of Ischemic Stroke.

Front Neurol 2020 20;11:520633. Epub 2021 Jan 20.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Early age exposure to the Chinese Great Leap Forward famine (1959-1961) is associated with the incidence of risk factors for ischemic stroke. This study aims to examine the relationship between early age famine exposure and 12-month stroke recurrence. We sought to explore the interaction between famine exposure status and metabolic phenotypes on stroke recurrence and how the adherence of crucial evidence-based key performance indicators (KPI) would modify this interaction. We analyzed data of patients who were born between 1953 and 1964 in the China National Stroke Registry II (CNSR-II). The study population was further divided into five subgroups for comparing 12-month stroke recurrence. A multivariate Cox proportional hazard regression model was used in analyzing the impact of the concurrence of metabolic phenotypes-type 2 diabetes (T2D) or metabolic syndrome (MetS)-and early-age famine exposure on recurrent risk. The influence of the adherence to predefined KPI and concurrency of metabolic phenotype was also evaluated. Concurrent T2D and early age famine exposure was associated with an increased recurrence risk of ischemic stroke with 12 months [adjusted hazard ratio (HR): 1.63, 95% confidence interval (CI) 1.28-2.07]. Optimal adherence to KPI was not associated with significantly reduced risk of 12-month stroke recurrence (adjusted HR: 0.80, 95% CI: 0.51-1.26). Concurrency of early-age famine exposure and diabetes mellitus was associated with a higher risk of stroke recurrence within 12 months, and adherence to evidence-based KPI did not reduce the risk significantly.
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http://dx.doi.org/10.3389/fneur.2020.520633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855705PMC
January 2021

Clinical Utility of a Nomogram for Predicting 30-Days Poor Outcome in Hospitalized Patients With COVID-19: Multicenter External Validation and Decision Curve Analysis.

Front Med (Lausanne) 2020 23;7:590460. Epub 2020 Dec 23.

Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Early detection of coronavirus disease 2019 (COVID-19) patients who are likely to develop worse outcomes is of great importance, which may help select patients at risk of rapid deterioration who should require high-level monitoring and more aggressive treatment. We aimed to develop and validate a nomogram for predicting 30-days poor outcome of patients with COVID-19. The prediction model was developed in a primary cohort consisting of 233 patients with laboratory-confirmed COVID-19, and data were collected from January 3 to March 20, 2020. We identified and integrated significant prognostic factors for 30-days poor outcome to construct a nomogram. The model was subjected to internal validation and to external validation with two separate cohorts of 110 and 118 cases, respectively. The performance of the nomogram was assessed with respect to its predictive accuracy, discriminative ability, and clinical usefulness. In the primary cohort, the mean age of patients was 55.4 years and 129 (55.4%) were male. Prognostic factors contained in the clinical nomogram were age, lactic dehydrogenase, aspartate aminotransferase, prothrombin time, serum creatinine, serum sodium, fasting blood glucose, and D-dimer. The model was externally validated in two cohorts achieving an AUC of 0.946 and 0.878, sensitivity of 100 and 79%, and specificity of 76.5 and 83.8%, respectively. Although adding CT score to the clinical nomogram (clinical-CT nomogram) did not yield better predictive performance, decision curve analysis showed that the clinical-CT nomogram provided better clinical utility than the clinical nomogram. We established and validated a nomogram that can provide an individual prediction of 30-days poor outcome for COVID-19 patients. This practical prognostic model may help clinicians in decision making and reduce mortality.
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http://dx.doi.org/10.3389/fmed.2020.590460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785751PMC
December 2020

Antiplatelet effect of ticagrelor with aspirin in acute minor stroke and transient ischemic attack stratified by metabolizer status: subgroup analysis of the PRINCE trial.

Aging (Albany NY) 2020 12 19;13(3):3994-4006. Epub 2020 Dec 19.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Studies on antiplatelet effect of ticagrelor/aspirin and clopidogrel/aspirin in patients with acute minor stroke and transient ischemic attack (TIA) stratified by metabolizer status is limited. We gained data from the Platelet Reactivity In Non-disabling Cerebrovascular Events study. Platelet reactivity was tested at baseline, 2 hours, 24 hours, 7 days and 90 days after initial dose, including high on-treatment platelet reactivity (HOPR), which was defined as P2Y12 reaction unit >208, and percentage inhibition of platelet aggregation (IPA). A total of 365 patients were included. There were 199 (54.5%) individuals classified as carriers of loss-of-function alleles. For carriers and non-carriers, the proportions of HOPR were significantly lower in those with ticagrelor/aspirin compared with those with clopidogrel/aspirin at 2 hours, 24 hours, 7 days, respectively (all p<0.05). IPA was higher at all time points except at baseline in patients with ticagrelor/aspirin compared with those with clopidogrel/aspirin in both carriers and non-carriers of lose-of-function alleles (all p<0.05). Our findings showed that ticagrelor/aspirin therapy possessed greater platelet inhibition and more rapid onset in platelet inhibition compared with clopidogrel/aspirin therapy both in carriers and non-carriers of lose-of-function alleles with acute minor stroke or TIA.
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http://dx.doi.org/10.18632/aging.202366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906170PMC
December 2020

Heavy metal poisoning resistance of a Co-modified 3Mn10Fe/Ni low-temperature SCR deNOx catalyst.

Environ Sci Pollut Res Int 2021 Mar 19;28(12):14546-14554. Epub 2020 Nov 19.

School of Petroleum Engineering, Changzhou University, Changzhou, 213164, Jiangsu, People's Republic of China.

Heavy metals have a great influence on the deNO efficiency of catalysts. The 3Mn10Fe/Ni catalyst that used nickel foam (Ni) as the carrier, Mn and Fe as the active components, and Co as a trace auxiliary was prepared using an impregnation method. The catalysts poisoned by Pb or Zn and Co-modified catalysts with Pb or Zn poisoning were studied. The addition of Pb or Zn significantly decreases the deNO activity of the 3Mn10Fe/Ni catalyst due to the decrease in the content of high-valence metal elements such as Fe and Mn, lattice oxygen concentration, reduction performance, acidity, and the number of acid sites. However, after Co modification, the deNO activity of the poisoned catalysts can be improved effectively because the strong interaction between Pb or Zn and lattice oxygen is weakened, and the contents of lattice oxygen, high valence metal elements, reduction ability, and the number of acid sites increase.
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http://dx.doi.org/10.1007/s11356-020-11667-2DOI Listing
March 2021

Glycemic traits and Alzheimer's disease: a Mendelian randomization study.

Aging (Albany NY) 2020 11 16;12(22):22688-22699. Epub 2020 Nov 16.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Previous observational studies have reported an association between impaired glucose metabolism and Alzheimer's disease. This study aimed to examine the causal association of glycemic traits with Alzheimer's disease. We used a two-sample Mendelian randomization approach to evaluate the causal effect of six glycemic traits (type 2 diabetes, fasting glucose, fasting insulin, hemoglobin A1c, homeostasis model assessment- insulin resistance and HOMA-β-cell function) on Alzheimer's disease. Summary data on the association of single nucleotide polymorphisms with these glycemic traits were obtained from genome-wide association studies of the DIAbetes Genetics Replication And Meta-analysis and Meta-Analyses of Glucose and Insulin-related traits Consortium. Summary data on the association of single nucleotide polymorphisms with Alzheimer's disease were obtained from the International Genomics of Alzheimer's Project. The Mendelian randomization analysis showed that 1-standard deviation higher fasting glucose and lower HOMA-β-cell function (indicating pancreatic β-cell dysfunction) were causally associated with a substantial increase in risk of Alzheimer's disease (odds ratio=1.33, 95% confidence interval: 1.04-1.68, p=0.02; odds ratio=1.92, 95% confidence interval: 1.15-3.21, p=0.01). However, no significant association was observed for other glycemic traits. This Mendelian randomization analysis provides evidence of causal associations between glycemic traits, especially high fasting glucose and pancreatic β-cell dysfunction, and high risk of Alzheimer's disease.
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http://dx.doi.org/10.18632/aging.103887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746331PMC
November 2020

Development and characterization of rat duodenal organoids for ADME and toxicology applications.

Toxicology 2020 12 24;446:152614. Epub 2020 Oct 24.

Bristol-Myers Squibb R&D, Pharmaceutical Candidate Optimization, Rt. 206 and Province Line Road, Princeton, NJ, 08648, United States. Electronic address:

Many in vitro gastrointestinal models have been developed with the hope that they will continue to improve in their similarity to the organs from which they were isolated. Intestinal organoids isolated from various species are now being used to investigate physiology and pathophysiology. In this study, intestinal stem cells were isolated from adult rat duodenum and culture conditions were optimized to promote the growth, differentiation and development of 3D organoids. We optimized and characterized rat duodenal organoids with light and electron microscopy, immunofluorescence and notably, global mRNA expression. The metabolic capacity of these cultures was investigated using probe substrates for multiple phase I and phase II drug metabolizing enzymes and found to be in line with previous results from intestinal primary cultures and a significant improvement over immortalized cell lines. Over the course of differentiation, the gene expression profiles of the rat duodenal organoids were consistent with expected trends in differentiation to various cell lineages reflecting the duodenum in vivo. Further, incubations of these cultures with naproxen and celecoxib resulted in cytotoxicity consistent with the direct cytotoxic effects of these drugs to duodenum in vivo. Based on these characteristics, the rat duodenal organoids described herein will provide a novel platform for investigating a wide variety of mechanistic questions.
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http://dx.doi.org/10.1016/j.tox.2020.152614DOI Listing
December 2020

Effect of ticagrelor versus clopidogrel on platelet reactivity measured by thrombelastography in patients with minor stroke or TIA.

Aging (Albany NY) 2020 10 16;12(20):20085-20094. Epub 2020 Oct 16.

Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

In this study, we tested the effect of ticagrelor versus clopidogrel on platelet reactivity in patients with minor stroke or transient ischemic attack (TIA). A pre-specified subgroup analysis of a randomized controlled trial was conducted. Platelet reactivity was assessed by thrombelastography (TEG) platelet mapping. Patients were divided into carriers and non-carriers according to the carrier status of loss-of-function (LOF) alleles. The primary outcome was the proportion of patients with high on-treatment platelet reactivity (HOPR) (defined as maximum amplitude induced by adenosine diphosphate > 47mm) at 90±7 days. Clinical outcomes within 90±7 days were followed up. Among 339 patients, 170 were randomized to ticagrelor/aspirin and 169 to clopidogrel/aspirin. Compared with clopidogrel/aspirin, the proportion of HOPR at 90±7 days in ticagrelor/aspirin was significantly lower (12.2% versus 30.0%, < 0.001). Ticagrelor/aspirin had a lower proportion of HOPR among carriers (11.0% versus 35.6%, < 0.001), but not among non-carriers (13.5% versus 22.4%, = 0.17). Ticagrelor was superior to clopidogrel in inhibiting platelet reactivity measured by TEG platelet mapping among patients with acute minor stroke or TIA, particularly in carriers of the LOF alleles. Large randomised controlled trials are needed to confirm our findings.
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http://dx.doi.org/10.18632/aging.103452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655198PMC
October 2020

Which risk predictors are more likely to indicate severe AKI in hospitalized patients?

Int J Med Inform 2020 11 11;143:104270. Epub 2020 Sep 11.

Department of Internal Medicine, Division of Medical Informatics, University of Kansas Medical Center, Kansas City, 66160, USA. Electronic address:

Objectives: Acute kidney injury (AKI) is a sudden episode of kidney failure or damage and the risk of AKI is determined by the complex interactions of patient factors. In this study, we aimed to find out which risk factors in hospitalized patients are more likely to indicate severe AKI.

Methods: We constructed a retrospective cohort of adult patients from all inpatient units of a tertiary care academic hospital between November 2007 and December 2016. AKI predictors included demographic information, admission and discharge dates, medications, laboratory values, past medical diagnoses and admission diagnosis. We developed a machine learning-based knowledge mining model and a screening framework to analyze which risk predictors are more likely to imply severe AKI in hospitalized populations.

Results: Among the final analysis cohort of 76,957 hospital admissions, AKI occurred in 7,259 (9.43 %) with 6,396 (8.31 %) at stage 1, 678 (0.88 %) at stage 2, and 185 (0.24 %) at stage 3. We compared the non-AKI (without AKI) vs any AKI (stages 1-3), and mild AKI (stage 1) vs severe AKI (stages 2 and 3), where the best cross-validated area under the receiver operator characteristic curve (AUC) were 0.81 (95 % CI, 0.79-0.82) and 0.66 (95 % CI, 0.62-0.71), respectively. Using the developed knowledge mining model and screening framework, we identified 33 risk predictors indicating that severe AKI may occur.

Conclusions: This study screened out 33 risk predictors that are more likely to indicate severe AKI in hospitalized patients, which would help strengthen the early care and prevention of patients.
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http://dx.doi.org/10.1016/j.ijmedinf.2020.104270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127080PMC
November 2020

Concurrent intracranial and extracranial artery stenosis and the prognosis of transient ischaemic symptoms or imaging-negative ischaemic stroke.

Stroke Vasc Neurol 2021 Mar 13;6(1):33-40. Epub 2020 Aug 13.

Department of Neurology, Beijing Tiantan Hospital, Beijing, China

Background And Purpose: Transient ischaemic attack (TIA), transient symptoms with infarction (TSI) and diffusion-weighted imaging (DWI)-negative acute ischaemic stroke (AIS) share similar aetiologies but are considered to have a rather benign prognosis. We intended to investigate the association between intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and the prognosis of patients with TIA, TSI and DWI-negative AIS.

Methods: Clinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study, according to symptom duration, acute infarction on DWI and discharge diagnosis. Based on the severity and location of arterial atherosclerosis, we categorised the study population into four groups: no or <50% ICAS and no ECAS; ≥50% ICAS but no ECAS; no or <50% ICAS with ECAS; and concurrent ≥50% ICAS and ECAS. Using multivariable Cox regression models, we analysed the relationship between the severity and distribution of large artery atherosclerosis and the prognosis of TIA, TSI and DWI-negative AIS.

Results: A total of 806 patients were included, 67.3% of whom were male. The median age of the study participants was 63 years. Patients in the concurrent ≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate (adjusted HR 3.4 (95% CI 1.15 to 10.04), p=0.027) and a higher risk of composite vascular events (adjusted HR 3.82 (95% CI 1.50 to 9.72), p=0.005).

Conclusions: Concurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events. Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS. Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.
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http://dx.doi.org/10.1136/svn-2020-000377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005902PMC
March 2021

Validation of the NEOS score in Chinese patients with anti-NMDAR encephalitis.

Neurol Neuroimmunol Neuroinflamm 2020 09 5;7(5). Epub 2020 Aug 5.

From the Department of Neurology, Beijing Tong Ren Hospital, Capital Medical University (Y.P., F.D., L. Liu, Y.L., C.L., L.C., Y.Z., L. Li, Q.M., J.W.); Medical Research Center, Beijing Tong Ren Hospital, Capital Medical University (Y.P., F.D., L. Liu, Y.L., C.L., L.C., Y.Z., L. Li, Q.M., J.W.); Department of Neurology, Beijing Tiantan Hospital, Capital Medical University (W.C., H.Y., X.Z.); Department of Neurology, Xuanwu Hospital, Capital Medical University (A.L.), Beijing; Beijing Children Hospital, Capital Medical University (X.W.); Department of Neurology, the Second Hospital of Hebei Medical University (J.H.), Shijiazhuang; China National Clinical Research Center for Neurological Diseases (W.C., H.Y.), Beijing; Center of Stroke, Beijing Institute for Brain Disorders (W.C., H.Y.); and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease (W.C., H.Y.), China.

Objective: The performance of anti-NMDAR Encephalitis One-Year Functional Status (NEOS) in predicting the 1-year functional status in Chinese patients with anti-NMDAR encephalitis is unknown.

Methods: We recruited patients with anti-NMDAR encephalitis from the Multicenter and Prospective Clinical Registry Study of Anti-NMDAR Encephalitis in Beijing Area. Patients were followed up for 1 year. We defined the poor functional status as a modified Rankin Scale score of more than 2 and good functional status as a modified Rankin Scale score of no more than 2. We performed a receiver-operator characteristic analysis to assess the discriminatory power of the NEOS score in predicting the 1-year functional status by using the area under the curve (AUC). Calibration was assessed by Pearson correlation coefficient and Hosmer-Lemeshow tests.

Results: Among the 111 patients with anti-NMDAR encephalitis recruited from 364 potentially eligible participants, 87 (78.4%) had good functional status at 1 year, whereas the remaining 24 (21.6%) had poor functional status. The AUC of the NEOS score for 1-year poor functional status was 0.86 (95% CI 0.78-0.93, < 0.001). The increased NEOS was associated with higher risk of 1-year poor functional status in patients with anti-NMDAR encephalitis.

Conclusions: The NEOS score is considered a reliable predictor of the risk of 1-year poor functional status in Chinese patients with anti-NMDAR encephalitis. This score could help to estimate the velocity of clinical improvement in advance.

Clinicaltrialgov Identifier: NCT02443350.

Classification Of Evidence: This study provides Class III evidence that in patients with anti-NMDAR encephalitis, the NEOS score predicts 1-year functional status.
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http://dx.doi.org/10.1212/NXI.0000000000000860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413709PMC
September 2020

Changing relative risk of clinical factors for hospital-acquired acute kidney injury across age groups: a retrospective cohort study.

BMC Nephrol 2020 08 2;21(1):321. Epub 2020 Aug 2.

Department of Internal Medicine, Division of Medical Informatics, University of Kansas Medical Center, Kansas City, 66160, USA.

Background: Likelihood of developing acute kidney injury (AKI) increases with age. We aimed to explore whether the predictability of AKI varies between age groups and assess the volatility of risk factors using electronic medical records (EMR).

Methods: We constructed a retrospective cohort of adult patients from all inpatient units of a tertiary care academic hospital and stratified it into four age groups: 18-35, 36-55, 56-65, and > 65. Potential risk factors collected from EMR for the study cohort included demographics, vital signs, medications, laboratory values, past medical diagnoses, and admission diagnoses. AKI was defined based on the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria. We analyzed relative importance of the risk factors in predicting AKI using Gradient Boosting Machine algorithm and explored the predictability of AKI across age groups using multiple machine learning models.

Results: In our cohort, older patients showed a significantly higher incidence of AKI than younger adults: 18-35 (7.29%), 36-55 (8.82%), 56-65 (10.53%), and > 65 (10.55%) (p < 0.001). However, the predictability of AKI decreased with age, where the best cross-validated area under the receiver operating characteristic curve (AUROC) achieved for age groups 18-35, 36-55, 56-65, and > 65 were 0.784 (95% CI, 0.769-0.800), 0.766 (95% CI, 0.754-0.777), 0.754 (95% CI, 0.741-0.768), and 0.725 (95% CI, 0.709-0.737), respectively. We also observed that the relative risk of AKI predictors fluctuated between age groups.

Conclusions: As complexity of the cases increases with age, it is more difficult to quantify AKI risk for older adults in inpatient population.
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http://dx.doi.org/10.1186/s12882-020-01980-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397647PMC
August 2020

Effect of sex differences on prognosis of intravenous thrombolysis: data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China).

Stroke Vasc Neurol 2021 Mar 8;6(1):10-15. Epub 2020 Jul 8.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Background And Purpose: Previous studies have reported conflicting results as to whether women have poorer functional outcome than men after thrombolytic therapy. This study aims to investigate the relationship between sex differences and the prognosis of intravenous thrombolysis in Chinese patients with acute ischaemic stroke.

Methods: The patients enrolled in this study were from the Chinese Acute Ischemic Stroke Thrombolysis Monitoring and Registration study. The primary outcome was poor functional outcome, defined as a 3-month modified Rankin score of 3-6. The safe outcome was symptomatic intracranial haemorrhage (SICH) and mortality within 7 days and 90 days. Multiple Cox regression model was used to correct the potential covariates to evaluate the association between sex disparities and prognosis. Furthermore, the interaction of preonset Rankin scores, baseline National Institute of Health Stroke Scale (NIHSS) scores and Trial of Org 10172 in Acute Stroke Treatment (TOAST) types was statistically analysed.

Results: A total of 1440 patients were recruited, including 541 women and 899 men. The baseline information indicated that women were older at the time of onset (66.2±11.2 years vs 61.0±11.3 years, p<0.001), and more likely to have a history of atrial fibrillation (25.3% vs 11.2%, p<0.001), and had a higher NIHSS score on admission (12.3±6.8 vs 11.6±6.7, p=0.04). According to the prognosis analysis of unsatisfactory functional recovery, there was no significant difference between women and men (45.9% vs 37.1%; adjusted OR 1.01, 95% CI 0.75 to 1.37). As for the safe outcome, the proportion of SICH and mortality in women is relatively high but did not reach statistical significance. There was no significant interaction with sex, age, preonset Rankin score, NIHSS score, TOAST classification and the prognosis of intravenous thrombolysis.

Conclusions: For Chinese patients with ischaemic stroke, although women are older and more severe at the time of onset, the prognosis after intravenous thrombolysis is not significantly different from men.
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http://dx.doi.org/10.1136/svn-2020-000351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005908PMC
March 2021

Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Reactivity in Patients With Minor Stroke or TIA.

Front Neurol 2020 10;11:534. Epub 2020 Jun 10.

Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

The combination of clopidogrel and aspirin is recommended for the treatment of patients with acute minor stroke or transient ischemic attack (TIA). However, with varied clopidogrel resistance (often due to loss-of-function (LOF) alleles), alternatives like ticagrelor have been suggested. Previous studies showed that ticagrelor had a lower platelet reactivity assessed by VerifyNow P2Y12 assay than clopidogrel. We aimed to compare the effect of ticagrelor vs. clopidogrel on platelet reactivity assessed by a different method (Aggrestar platelet function analyzer) and analyze whether genotypes were involved. A pre-specified subgroup analysis of a randomized controlled trial- Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) was conducted. Patients with minor stroke or TIA were randomized for treatment with ticagrelor plus aspirin or clopidogrel plus aspirin. Platelet reactivity was assessed by Aggrestar (PL) platelet function analyzer and high on-treatment platelet reactivity (HOPR) on ticagrelor or clopidogrel was compared. Clinical outcomes included any stroke, composite vascular events and bleeding events within 90 days. Patients were categorized into carriers and non-carriers according to the carrier status of LOF alleles. Among 675 patients enrolled in the PRINCE trial, 387 patients were included in this subgroup: 197 were randomized to ticagrelor plus aspirin and 190 to clopidogrel plus aspirin. At 90 ± 7 days, compared with clopidogrel/aspirin group, the proportion of HOPR in ticagrelor/aspirin group was significantly lower (19.6 vs. 40.8%, < 0.001). No significant treatment-by-genotype interactions were found ( for interaction = 0.12). Within 90 days, a trend toward a lower risk of new stroke in ticagrelor/aspirin compared to clopidogrel/aspirin was observed (4.6 vs. 9.5%, HR 0.47, 95% CI 0.21-1.05, = 0.06). Ticagrelor is superior to clopidogrel in inhibiting platelet reactivity measured by the PL platelet function analyzer among patients with acute minor stroke or TIA. Our study confirmed the finding of the main analysis of PRINCE trial in a different assay. Large randomized controlled trials are needed to evaluate our findings. Clinicaltrials.gov NCT02506140.
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http://dx.doi.org/10.3389/fneur.2020.00534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298086PMC
June 2020

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases.

Stroke Vasc Neurol 2020 06 18;5(2):159-176. Epub 2020 Jun 18.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Aim: Stroke is the leading cause of disability and death in China. Ischaemic stroke accounts for about 60%-80% of all strokes. It is of considerable significance to carry out multidimensional management of ischaemic cerebrovascular diseases. This evidence-based guideline aims to provide the latest detailed and comprehensive recommendations on the diagnosis, treatment and secondary prevention of ischaemic cerebrovascular diseases.

Methods: We had performed comprehensive searches of MEDLINE (via PubMed) (before 30 June 2019), and integrated the relevant information into charts and distributed to the writing group. Writing group members discussed and determined the recommendations through teleconference. We used the level of evidence grading algorithm of Chinese Stroke Association to grade each recommendation. The draft was reviewed by the Guideline Writing Committee of Chinese Stroke Association Stroke and finalised. This guideline is fully updated every 3 years.

Results: This evidence-based guideline is based on the treatment, care and prevention of ischaemic cerebrovascular diseases, which emphasises on pathogenesis evaluation, intravenous thrombolysis, endovascular therapy, antiplatelet therapy, prevention and treatment of complications, and risk factor management.

Conclusions: This updated guideline presents a framework for the management of ischaemic cerebrovascular diseases. Timely first-aid measures, professional care in the acute stage, and proactive secondary prevention will be helpful to patients.
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http://dx.doi.org/10.1136/svn-2020-000378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337371PMC
June 2020

Surgical outcomes of macular hole and epimacular membrane treatment in patients with intraoperative amaurosis under sub-Tenon's anesthesia.

J Int Med Res 2020 May;48(5):300060520925705

Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, China.

Objective: Some patients have been found to develop intraoperative amaurosis under sub-Tenon's anesthesia. We explored whether these patients have poor surgical outcomes during mid- to long-term postoperative follow-up.

Methods: In this case series, 74 of 85 patients with macular diseases who underwent phacoemulsification combined with vitrectomy under sub-Tenon's anesthesia developed intraoperative amaurosis. The surgical outcomes at the 2- and 4-month follow-ups in these patients were investigated and compared with the outcomes in patients without amaurosis using best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and pattern visual evoked potential (PVEP).

Results: Both BCVA and the OCT-based macular structure in patients with intraoperative amaurosis showed significant postoperative improvement comparable with that of patients without amaurosis. The presence of intraoperative amaurosis was not associated with either macular hole closure or macular edema regression. PVEP revealed no significant changes in the wave latency or amplitude before and after surgery.

Conclusion: Intraoperative amaurosis following sub-Tenon's block is commonly seen but does not predict a poor surgical prognosis. When a patient develops amaurosis during surgery, the surgeon should increase patient comfort through verbal communication rather than perform an additional intervention to help relieve the patient's anxiety.
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http://dx.doi.org/10.1177/0300060520925705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243398PMC
May 2020

Causal associations of insulin resistance with coronary artery disease and ischemic stroke: a Mendelian randomization analysis.

BMJ Open Diabetes Res Care 2020 05;8(1)

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Introduction: The relationship between insulin resistance (IR) and cardiovascular diseases is unclear. We aimed to examine the causal associations of IR with cardiovascular diseases, including coronary artery disease, myocardial infarction, ischemic stroke and its subtypes, using Mendelian randomization.

Research Design And Methods: Due to low sample size for gold standard measures and in order to well reflect the underlying phenotype of IR, we used 53 single nucleotide polymorphisms associated with IR phenotypes (ie, fasting insulin, high-density lipoprotein cholesterol and triglycerides) from recent genome-wide association studies (GWASs) as instrumental variables. Summary-level data from four GWASs of European individuals were used. Data on IR phenotypes were obtained from meta-analysis of GWASs of up to 188 577 individuals and data on the outcomes from GWASs of up to 446 696 individuals. Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, simple and weighted-median approaches and MR-Egger regression was used to explore pleiotropy.

Results: Genetically predicted 1-SD increase in IR phenotypes were associated with a substantial increase in risk of coronary artery disease (OR=1.79, 95% CI: 1.57 to 2.04, p<0.001), myocardial infarction (OR=1.78, 95% CI: 1.54 to 2.06, p<0.001), ischemic stroke (OR=1.21, 95% CI: 1.05 to 1.40, p=0.007) and the small-artery occlusion subtype of stroke (OR=1.80, 95% CI: 1.30 to 2.49, p<0.001), but not associated with the large-artery atherosclerosis and cardioembolism subtypes of stroke. There was no evidence of pleiotropy. Results were broadly consistent in sensitivity analyses using simple and weighted-median approaches accounting for potential genetic pleiotropy.

Conclusions: This study provides evidence to support that IR was causally associated with risk of coronary artery disease, myocardial infarction, ischemic stroke and the small-artery occlusion subtype of stroke.
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http://dx.doi.org/10.1136/bmjdrc-2020-001217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223029PMC
May 2020

Correlation between sub-Tenon's anesthesia and transient amaurosis during ophthalmic surgery.

Int Ophthalmol 2020 Aug 21;40(8):1955-1962. Epub 2020 Apr 21.

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, 515041, Guangdong Province, China.

Purpose: To verify the correlation between sub-Tenon's anesthesia and intraoperative visual loss in ophthalmic surgery.

Methods: Sixty-four patients underwent phacoemulsification combined pars plana vitrectomy under sub-Tenon's anesthesia. Participants were investigated about their light perception at several time points: before anesthesia, immediately after anesthesia, 10 min after anesthesia without any surgical intervention or microscope illumination, and after the whole surgery. Intraoperative amaurosis was determined as that a patient could not see any light from their operative eye. The incidence rate of amaurosis at different time points and among different anesthetists was analyzed.

Results: The rate of intraoperative amaurosis was 0%, 1.56%, 48.44%, and 95.31% at several time points, respectively: before anesthesia, immediately after anesthesia, 10 min after anesthesia without any surgical intervention or microscope light exposure during the interval, and immediately after the whole surgery, presenting a significantly time-dependent increase (P < 0.01). There was no correlation between the amaurosis and different diseases and anesthesiologists. The amaurosis was transient, and all operative eyes could perceive light on the first postoperative day.

Conclusions: Sub-Tenon's anesthesia contributes to the intraoperative amaurosis during operation. Temporary interruption of optic nerve conduction by the anesthetic could be a credible explanation. The amaurosis is transient and reversible, requires no additional treatment, and should not be considered as a surgical complication.
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http://dx.doi.org/10.1007/s10792-020-01369-6DOI Listing
August 2020

COL2A1 protective variant reduces sporadic rhegmatogenous retinal detachment severity.

Exp Eye Res 2020 02 31;191:107907. Epub 2019 Dec 31.

Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, China. Electronic address:

Rhegmatogenous retinal detachment (RRD) is the most common type of RD, the separation of neurosensory retina from the underlying retinal pigment epithelium. The RRD patients can be benefited from appropriate treatment if detected early, especially for the people predicted at high risk. In this study, we aimed to investigate the genetic association and clinical correlation of collagen type II alpha 1 (COL2A1) variants with sporadic RRD in a southern Chinese population. Totally 156 RRD patients and 254 control subjects were recruited, and 12 COL2A1 tag single nucleotide polymorphisms were genotyped by the TaqMan assay. The RRD patients had poorer visual acuity (P < 0.001) and lower intraocular pressure (IOP; P < 0.001) in their surgical eyes compared to the fellow eyes. The COL2A1 rs1793958 variant was significantly associated with RRD in the genotypic (P = 0.024), allelic (P = 0.011, odds ratio (OR) = 0.669), recessive (P = 0.011, OR = 0.384) and homozygous models (P = 0.007, OR = 0.348). RRD patients carrying the rs1793958 G allele had smaller retinal detachment area (P = 0.041) and smaller IOP differences (P = 0.046) between the surgical and fellow eyes compared to those carrying the wildtype AA genotype. In summary, this study revealed that the COL2A1 rs1793958 variant is associated with reduced risk of sporadic RRD, and patients carrying rs1793958 G allele have lower RRD severity.
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http://dx.doi.org/10.1016/j.exer.2019.107907DOI Listing
February 2020

Response to Comment on: Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study.

Eye (Lond) 2020 08 30;34(8):1485. Epub 2019 Oct 30.

Joint Shantou International Eye Center, Shantou University & the Chinese University of Hong Kong, Shantou, China.

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http://dx.doi.org/10.1038/s41433-019-0660-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468269PMC
August 2020

An automated microfluidic system for the investigation of asphaltene deposition and dissolution in porous media.

Lab Chip 2019 11 13;19(21):3628-3640. Epub 2019 Sep 13.

Department of Chemical and Biomolecular Engineering, New York University, Brooklyn, NY 11201, USA.

Asphaltenes, among the most complex components of crude oil, vary in their molecular structure, composition, and self-assembly in porous media. This complexity makes them challenging in laboratory characterization methods. In the present work, a novel microfluidic device was designed to access in situ transient, high-fidelity information on asphaltene deposition and dissolution within porous media. The automated microfluidic device features three independent 4.5 μL packed-bed microreactors on the same chip. The deposition of asphaltenes was investigated at five different temperatures (ranging from 25-65 °C) in addition to dissociation with xylenes. Our findings demonstrate a decrease in the dispersity of asphaltene nanoaggregates in the porous media when the deposition temperature is increased. Furthermore, the direct quantification of the dissociation solvent was made possible by in situ Raman spectroscopy. The average occupancy of xylenes and xylene-free porous media (or unrecognized sites) was estimated to be 0.41 and 0.66, respectively. It was observed that asphaltenes deposited at higher deposition temperatures are more difficult to dissociate by xylenes than those deposited at lower temperatures. In order to develop efficient remediation treatments in energy production operations, the convoluted behaviours of asphaltenes in porous media must be understood on a molecular level. Automated microfluidic systems have the potential to streamline treatment designs, improve their efficiency, and enable the design of green chemistry in conventional energy production operations.
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http://dx.doi.org/10.1039/c9lc00671kDOI Listing
November 2019

Prognostic factors associated with visual outcome of salvageable eyes with posttraumatic endophthalmitis.

Sci Rep 2019 09 3;9(1):12678. Epub 2019 Sep 3.

Joint Shantou International Eye Center, Shantou University & the Chinese University of Hong Kong, Shantou, China.

The purpose of this study is to evaluate the prognostic factors associated with visual outcomes in the salvageable eyes with posttraumatic endophthalmitis. We retrospectively reviewed the medical records of all patients diagnosed with posttraumatic endophthalmitis in our hospital between 2008 and 2015. The following information was collected: age, sex, etiology, past medical history, clinical manifestations, wound location, microbiology, blood leukocyte counts, types of interventions, initial visual acuities and final visual acuities. Univariate and multivariate analyses were used to explore the factors associated with final best-corrected visual acuity. In total, 98 eyes of 98 patients were included in our study. Fifty-seven eyes underwent vitrectomy, 27 of them had silicone oil tamponade, 38 eyes received intravitreal ceftazidime only and 3 eyes received intracameral ceftazidime. In univariate analysis, poor initial visual acuity, presence of intraocular foreign body, number of intravitreal injections, retinal detachment and Zone 3 injury were associated with poor visual outcome. In multivariable analysis, poor initial visual acuity, presence of intraocular foreign body and number of intravitreal injections were independently associated with poor visual outcome. The silicone oil group had fewer repeated intravitreal injections than the group without oil tamponade. We concluded that the visual outcome of salvageable eyes with posttraumatic endophthalmitis is associated with initial visual acuity, presence of intraocular foreign body and number of intravitreal antibiotic injections.
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http://dx.doi.org/10.1038/s41598-019-49117-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722068PMC
September 2019

Enhanced and Persistent Inhibition of Organic Cation Transporter 1 Activity by Preincubation of Cyclosporine A.

Drug Metab Dispos 2019 11 19;47(11):1352-1360. Epub 2019 Aug 19.

Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Princeton, New Jersey

Recent pharmacogenetic evidence indicates that hepatic organic cation transporter (OCT) 1 can serve as the locus of drug-drug interactions (DDIs) with significant pharmacokinetic and pharmacodynamic consequences. We examined the impact of preincubation on the extent of OCT1 inhibition in transfected human embryonic kidney 293 (HEK293) cells. Following 30-minute preincubation with an inhibitor, approximately 50-fold higher inhibition potency was observed for cyclosporine A (CsA) against OCT1-mediated uptake of metformin compared with coincubation, with IC values of 0.43 ± 0.12 and 21.6 ± 4.5 M, respectively. By comparison, only small shifts (≤2-fold) in preincubation IC versus coincubation were observed for quinidine, pyrimethamine, ritonavir, and trimethoprim. The shift in CsA OCT1 IC was substrate dependent since it ranged from >1.2- to 50.2-fold using different experimental substrates. The inhibition potential of CsA toward OCT1 was confirmed by fenoterol hepatocyte uptake experiment. Furthermore, no shift in CsA IC was observed with HEK293 cells transfected with OCT2 and organic anion transporter (OAT) 1 and OAT3. Short exposure (30 minutes) to 10 M CsA produced long-lasting inhibition (at least 120 minutes) of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA were maintained long after the removal of the compound from the incubation buffer. The potent and persistent inhibitory effect after exposure to CsA warrants careful consideration in the design and interpretation of clinical OCT1 DDI studies. SIGNIFICANCE STATEMENT: Preincubation of OATP1B1 and OATP1B3 with their inhibitor may result in the enhancement of the inhibitory potency in a cell-based assay. However, limited data are available on potentiation of OCT1 inhibition by preincubation, which is a clinically relevant drug transporter. For the first time, we observed a 50-fold increase in CsA inhibitory potency against OCT1-mediated transport of metformin following a preincubation step. The CsA preincubation effect on OCT1 inhibition is substrate dependent. Moreover, the inhibition potential of CsA toward OCT1 is confirmed by hepatocyte uptake experiment. This study delivers clear evidences about the potent and persistent inhibitory effect on OCT1 after exposure to CsA. Further studies are needed to assess the effect of CsA on OCT1 drug substrates in vivo.
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http://dx.doi.org/10.1124/dmd.119.087197DOI Listing
November 2019

Identification and characterization of a novel promoter variant in placental growth factor for neovascular age-related macular degeneration.

Exp Eye Res 2019 10 1;187:107748. Epub 2019 Aug 1.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China. Electronic address:

Purpose: Intronic variants in the placental growth factor (PGF) gene have been associated with neovascular age-related macular degeneration (AMD). This study is to discover and characterize rare variants in the PGF gene for neovascular AMD.

Methods: The promoter region, coding sequences and splicing regions of the PGF gene were sequenced in a Hong Kong southern Chinese cohort of 235 neovascular AMD patients and 435 controls. A detected 18 base-pair deletion variant in the promoter region of PGF was analyzed in a Shantou southern Chinese cohort of 189 neovascular AMD patients and 846 controls. The transcription activity of this disease-associated promoter variant was determined in human ARPE-19 cells by promoter-luciferase analysis.

Results: A novel 18-base-pair deletion mutation in the promoter region of PGF was identified in 3 (1.28%) patients and 1 (0.23%) control subject (OR = 5.61; 95% CI 0.58-54.26) in the Hong Kong cohort, and in 2 (1.06%) patients and 2 (0.24%) controls (OR = 4.51; 95% CI: 0.63-32.25) in the Shantou cohort. In the combined southern Chinese sample, this deletion had a significant association with neovascular AMD (P = 0.026; OR = 5.08, 95% CI: 1.21-21.36). The 18-base-pair deletion was predicted to alter the transcription factor binding sites in the PGF promoter, and higher luciferase expression was detected in ARPE-19 cells transfected with the deletion variant plasmid than those transfected with wild type plasmid (P = 0.0002).

Conclusions: This study identified a rare, functional promoter variant in the PGF gene that increases PGF transcription activity and confers a 5-fold risk to neovascular AMD.
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http://dx.doi.org/10.1016/j.exer.2019.107748DOI Listing
October 2019

Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study.

Eye (Lond) 2020 03 18;34(3):595-596. Epub 2019 Jul 18.

Joint Shantou International Eye Center, Shantou University & the Chinese University of Hong Kong, Shantou, China.

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http://dx.doi.org/10.1038/s41433-019-0537-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042233PMC
March 2020