Publications by authors named "Chuan Chen"

456 Publications

Co-Occurring Alteration of NOTCH and DDR Pathways Serves as Novel Predictor to Efficacious Immunotherapy in NSCLC.

Front Oncol 2021 22;11:659321. Epub 2021 Apr 22.

Cancer Center, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the most patients produce an ultra-rapid progressive disease. Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. One hundred six NSCLC patients treated with immunotherapy were combined from Rizvi et al. and Hellman et al. studies (whole exon sequencing). Two independent validation datasets consisted of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [22.1 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2-0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [Cohort 2: 13 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31-0.96; Cohort 3: 21 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18-1.1]. By analyzing TCGA cohort, we found patients with coexisting NOTCH+/co-DDR+ pathway had a higher TMB, more infiltration of CD4+T cells. Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.659321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100434PMC
April 2021

Nuclear mA reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos.

Protein Cell 2021 Apr 22. Epub 2021 Apr 22.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China.

N-methyladenosine (mA) on chromosome-associated regulatory RNAs (carRNAs), including repeat RNAs, plays important roles in tuning the chromatin state and transcription, but the intrinsic mechanism remains unclear. Here, we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs), which highly depends on the mA-binding ability. Ythdc1 is required for sufficient rRNA synthesis and repression of the 2-cell (2C) transcriptional program in ESCs, which recapitulates the transcriptome regulation by the LINE1 scaffold. Detailed analyses revealed that YTHDC1 recognizes mA on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1. Moreover, the establishment of H3K9me3 on 2C-related retrotransposons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells, which consequently increases the transcriptional activities. Our study reveals a role of mA in regulating the RNA scaffold, providing a new model for the RNA-chromatin cross-talk.
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http://dx.doi.org/10.1007/s13238-021-00837-8DOI Listing
April 2021

An artificial intelligence platform for the diagnosis and surgical planning of strabismus using corneal light-reflection photos.

Ann Transl Med 2021 Mar;9(5):374

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Strabismus affects approximately 0.8-6.8% of the world's population and can lead to abnormal visual function. However, Strabismus screening and measurement are laborious and require professional training. This study aimed to develop an artificial intelligence (AI) platform based on corneal light-reflection photos for the diagnosis of strabismus and to provide preoperative advice.

Methods: An AI platform consisting of three deep learning (DL) systems for strabismus diagnosis, angle evaluation, and operation plannings based on corneal light-reflection photos was trained and retrospectively validated using a retrospective development data set obtained between Jan 1, 2014, and Dec 31, 2018. Corneal light-reflection photos were collected to train the DL systems for strabismus screening and deviation evaluations in the horizontal strabismus while concatenated images (each composed of two photos representing different gaze states) were procured to train the DL system for operative advice regarding exotropia. The AI platform was further prospectively validated using a prospective development data set captured between Sep 1, 2019, and Jun 10, 2020.

Results: In total, 5,797 and 571 photos were included in the retrospective and prospectively development data sets, respectively. In the retrospective test sets, the screening system detected strabismus with a sensitivity of 99.1% [95% confidence interval (95% CI), 98.1-99.7%], a specificity of 98.3% (95% CI, 94.6-99.5%), and an AUC of 0.998 (95% CI, 0.993-1.000, P<0.001). Compared to the angle measured by the perimeter arc, the deviation evaluation system achieved a level of accuracy of ±6.6º (95% LoA) with a small bias of 1.0º. Compared to the real design, the operation advice system provided advice regarding the target angle within ±5.5º (95% LoA). Regarding strabismus in the prospective test set, the AUC was 0.980. The platform achieved a level of accuracy of ±7.0º (95% LoA) in the deviation evaluation and ±6.1º (95% LoA) in the target angle suggestion.

Conclusions: The AI platform based on corneal light-reflection photos can provide reliable references for strabismus diagnosis, angle evaluation, and surgical plannings.
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http://dx.doi.org/10.21037/atm-20-5442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033395PMC
March 2021

Phoenixin-14 regulates proliferation and apoptosis of vascular smooth muscle cells by modulation of KCNQ1OT1/miR-183-3p/CTNNB1 axis.

Environ Toxicol Pharmacol 2021 Apr 3;86:103655. Epub 2021 Apr 3.

Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China. Electronic address:

Phoenixin-14 has been reported to be implicated in the process of blood glucose metabolism, reproduction, lipid deposition and cardioprotection. However, the role of phoenixin-14 in vascular smooth muscle cells (VSMCs) remains unkown. In this study, we focused on the effects of phoenixin-14 on VSMCs under oxidized low-density lipoprotein (ox-LDL) treatment. The experimental results demonstrated that phoenixin-14 inhibited mRNA level and nuclear translocation of β-catenin. Functionally, phoenixin-14 inhibited cell proliferation and facilitated apoptosis of VSMCs under ox-LDL stimulation, and CTNNB1 overexpression reversed these effects. Mechanistically, KCNQ1OT1 interacted with miR-183-3p to upregulate CTNNB1 in VSMCs. Furthermore, CTNNB1 expression was negatively correlated with miR-183-3p but positively associated with KCNQ1OT1. Rescue assays indicated that KCNQ1OT1 overexpression or Lithium chloride (LiCl) treatment reversed the effects of phoenixin-14 on proliferation and apoptosis of ox-LDL-stimulated VSMCs. In summary, phoenixin-14 regulates proliferation and apoptosis of ox-LDL-treated VSMCs by regulating the KCNQ1OT1/miR-183-3p/CTNNB1 axis.
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http://dx.doi.org/10.1016/j.etap.2021.103655DOI Listing
April 2021

Low-Cost and Scalable Platform with Multiplexed Microwell Array Biochip for Rapid Diagnosis of COVID-19.

Research (Wash D C) 2021 12;2021:2813643. Epub 2021 Mar 12.

Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.

Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction between the primers and the respiratory swab RNA extracts, based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). To achieve clinically acceptable performance, we synthesized a group of six primers to identify the conserved regions of the ORF1ab gene of SARS-CoV-2. Clinical trials were conducted with 87 PCR-positive and 43 PCR-negative patient samples. The platform demonstrated both high sensitivity (95.40%) and high specificity (95.35%), showing potentials for rapid and user-friendly diagnosis of COVID-19 among many other infectious pathogens.
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http://dx.doi.org/10.34133/2021/2813643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982056PMC
March 2021

Hypertension affects the treatment of wet age-related macular degeneration.

Acta Ophthalmol 2021 Mar 31. Epub 2021 Mar 31.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Purpose: Due to population ageing as well as the high prevalence of hypertension and age-related macular degeneration (AMD) in elderly individuals, and the relationship between hypertension and AMD is unclear. Our research aimed to investigate the association between hypertension, wet AMD (wAMD) and the treatment strategy of wAMD patients affected by hypertension.

Methods: Data of wAMD patients at Zhongshan Ophthalmic Center, Sun Yat-sen University, between 1 January 2002 and 30 June 2019, were extracted from the electronic healthcare information system. wAMD patients were divided into subgroups by hypertension status, age, sex, the need for vitrectomy surgery and the number of anti-VEGF drug intravitreal injections that these were divided in 1-3 vs. >3 (available time from 1 January 2012 to 30 June 2019).

Results: A total of 3096 wAMD patients (41.7% female, 58.3% male) with an age range of 50-96 years (68.7 (SD 9.42) years) were included. wAMD was significantly associated with hypertension (p < 0.001). After adjustment for sex and age, Cox regression model showed a significant association between hypertension in wAMD patients and the number of injections (RR = 1.31, 95% CI: 1.13-1.50, p < 0.001). There was no significant association between hypertension and the need for vitrectomy (p = 0.82).

Conclusions: wet AMD was associated with hypertension status, and after the regular series of three injections, wAMD patients with hypertension were more likely to receive anti-VEGF drug intravitreal injections than those without hypertension. These results may facilitate prospective research on the prevention of wAMD and contribute to the management of wAMD patients.
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http://dx.doi.org/10.1111/aos.14791DOI Listing
March 2021

Role of residue cornstalk derived biochar for the enhanced bio-hydrogen production via simultaneous saccharification and fermentation of cornstalk.

Bioresour Technol 2021 Jun 18;330:125006. Epub 2021 Mar 18.

State Key Laboratory of Urban Water Resources and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China.

Biochar derived from residue cornstalk left after anaerobic bio-hydrogen production (RCA-biochar) was confirmed to enhance bio-hydrogen production from cornstalk hydrolysate. However, the role of RCA-biochar in simultaneous saccharification and fermentation (SSF) during bio-hydrogen production from cornstalk has not yet been revealed. This study therefore aims to fill this knowledge gap. It was observed that with the increase in RCA-biochar concentration from 0 g/L to 10.0 g/L, the maximal cumulative SSF bio-hydrogen yield varied from 24.3 ± 1.1 mL/g-substrate to 154.3 ± 3.6 mL/g substrate under varying pH values - 5.5, 6.0, 6.5, 7.0. The increasing bio-hydrogen production was observed to correlate with both RCA-biochar level and initial pH. Batch tests confirmed that the initial pH had an obvious effect an saccharification, while RCA-biochar affected anaerobic fermentation a lot. The findings revealed the role of previously unrecognized RCA-biochar in SSF bio-hydrogen production from cornstalk, which can provide an alternative approach for lignocellulosic bio-hydrogen production.
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http://dx.doi.org/10.1016/j.biortech.2021.125006DOI Listing
June 2021

Gut Microbiota and Its Metabolite Deoxycholic Acid Contribute to Sucralose Consumption-Induced Nonalcoholic Fatty Liver Disease.

J Agric Food Chem 2021 Apr 23;69(13):3982-3991. Epub 2021 Mar 23.

Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan 430071, China.

As important signal metabolites within enterohepatic circulation, bile acids (BAs) play a pivotal role during the occurrence and development of diet-induced nonalcoholic fatty liver disease (NAFLD). Here, we evaluated the functional effects of BAs and gut microbiota contributing to sucralose consumption-induced NAFLD of mice. The results showed that sucralose consumption significantly upregulated the abundance of intestinal genera and , which produced deoxycholic acid (DCA) accumulating in multiple biological matrixes including feces, serum, and liver of mice. Subsequently, elevated hepatic DCA, one of the endogenous antagonists of the farnesol X receptor (), inhibited hepatic gene expression including a small heterodimer partner () and leading to sucralose-induced NAFLD in mice. Dietary supplements with fructo-oligosaccharide or metformin markedly restored genera and abundance and the DCA level of sucralose-consuming mice, which eventually ameliorated NAFLD. These findings highlighted the effects of gut microbiota and its metabolite DCA on sucralose-induced NAFLD of mice.
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http://dx.doi.org/10.1021/acs.jafc.0c07467DOI Listing
April 2021

Simultaneous removal of carbon dioxide, sulfur dioxide and nitric oxide in a biofilter system: Optimization operating conditions, removal efficiency and bacterial community.

Chemosphere 2021 Mar 8;276:130084. Epub 2021 Mar 8.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, HeiLongjiang Province, 150090, China. Electronic address:

Anthropogenic NO, SO and CO emission from the fossil-fuel-fired power plants has aroused growing attention. This study investigated the removal performance of CO, SO and NO in flue gas as well as conversion efficiency of nitric- and sulfur-compounds in liquid phase in a biofilter. In order to develop the potential of the biofilter, simulative industry wastewater was employed as the spray solution. The satisfactory flue gas removal performance (75.23% CO, 100% SO and 82.81% NO) were achieved under the optimal operating conditions of biofilter: initial solution pH of 9 and liquid-gas ratio (L/G) of 3. The gas film mass transfer coefficients (ka) results showed that the resistance of gas mass transfer was decreased with increasing the pH value and L/G ratio, respectively. The final transformation product of NO was mostly N while about 78% SO was converted to elemental sulfur. The microbial community analysis results showed that the relative abundance of bacteria with denitrification capacity was increased by 3.05% which might have contributed to the conversion of NO intermediates products in present study. Collectively, this biofilter system achieve a better flue gas removal performance via the proper operation system, which provides an economic feasible strategy of flue gas purification and increases potential for industrial application.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130084DOI Listing
March 2021

PPAR Targeting GDF11 Inhibits Vascular Endothelial Cell Senescence in an Atherosclerosis Model.

Oxid Med Cell Longev 2021 25;2021:2045259. Epub 2021 Feb 25.

Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, China.

Atherosclerosis (AS) is a complex vascular disease that seriously harms the health of the elderly. It is closely related to endothelial cell aging, but the role of senescent cells in atherogenesis remains unclear. Studies have shown that peroxisome proliferator-activated receptor alpha (PPAR) inhibits the development of AS by regulating lipid metabolism. Our previous research showed that PPAR was involved in regulating the repair of damaged vascular endothelial cells. Using molecular biology and cell biology approaches to detect senescent cells in atherosclerosis-prone apolipoprotein E-deficient () mice, we found that PPAR delayed atherosclerotic plaque formation by inhibiting vascular endothelial cell senescence, which was achieved by regulating the expression of growth differentiation factor 11 (GDF11). GDF11 levels declined with age in several organs including the myocardium, bone, central nervous system, liver, and spleen in mice and participated in the regulation of aging. Our results showed that PPAR inhibited vascular endothelial cell senescence and apoptosis and promoted vascular endothelial cell proliferation and angiogenesis by increasing GDF11 production. Taken together, these results demonstrated that PPAR inhibited vascular endothelial cell aging by promoting the expression of the aging-related protein GDF11, thereby delaying the occurrence of AS.
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http://dx.doi.org/10.1155/2021/2045259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935606PMC
February 2021

The associations of population mobility in HIV disease severity and mortality rate in China.

Ann Transl Med 2021 Feb;9(4):315

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Human immunodeficiency virus (HIV) infection has become a chronic disease and attracted public attention globally. Population migration was considered hindering the control and management of HIV infection, but limited studies have explored how population mobility could influence the development of HIV-related complications and overall prognosis.

Methods: We enrolled hospitalized HIV patients in this cross-sectional study between January 1, 2006, and December 31, 2016. We extracted demographic, hospitalization, and patient diagnosis data. Patients were divided into three groups according to the population type: (I) resident of Guangzhou City (local resident); (II) migrant outside of Guangzhou City but within Guangdong Province (migrant within the province); and (III) migrant outside of Guangdong Province (migrant outside the province). To represent the prognosis of HIV, in-hospital death was defined as the worst outcome, whereas vision-related events were considered moderate-to-severe complications. Logistic regression models were used to analyze factors influencing the prognosis of HIV.

Results: Eight thousand and six hundred thirty-one inpatients (14,954 cases) were enrolled. The overall mortality was 7.9%, decreasing from 21.5% in 2006 to 3.8% in 2016. The prevalence of vision-related events was 14.4% between 2015 and 2016. Compared to local patients, migrant patients (within and outside the province) were younger, had significantly less access to health insurance, fewer hospitalization admissions, longer hospital stays, and a higher proportion of physical work (P<0.01). Furthermore, they had a higher prevalence of vision-related events (16.2% and 17.4% in migrant patients within the province and outside the province, respectively 9.5%) and infectious diseases, but lower in-hospital mortality (5.9% and 7.0% 12.3%) than local patients. Migrants correlated negatively with in-hospital death [odds ratio (OR) 95% CI, 0.37 (0.29-0.48) and 0.52 (0.40-0.68)] but correlated positively with vision-related events [OR (95% CI), 2.08 (1.54-2.80) and 2.03 (1.47-2.80)].

Conclusions: Migrant patients have significantly poorer access to health insurance, with an increased risk of developing moderate-to-severe HIV infection but a decreased risk of in-hospital death, indicating a trend toward withdrawing treatment in migrant patients when they have advanced diseases. Managements such as optimizing access to health insurance and improving follow-up visits for HIV infection should be considered in the context of the population mobility of HIV patients.
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http://dx.doi.org/10.21037/atm-20-4514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944320PMC
February 2021

Cotton Fiber Development Requires the Pentatricopeptide Repeat Protein GhIm for Splicing of Mitochondrial nad7 mRNA.

Genetics 2021 Mar;217(1):1-17

State Key Laboratory of Crop Genetics & Germplasm Enhancement, Hybrid Cotton R & D Engineering Research Center, Ministry of Education, Nanjing Agricultural University, Nanjing 210095, China.

Pentatricopeptide repeat (PPR) proteins encoded by nuclear genomes can bind to organellar RNA and are involved in the regulation of RNA metabolism. However, the functions of many PPR proteins remain unknown in plants, especially in polyploidy crops. Here, through a map-based cloning strategy and Clustered regularly interspaced short palindromic repeats/cas9 (CRISPR/cas9) gene editing technology, we cloned and verified an allotetraploid cotton immature fiber (im) mutant gene (GhImA) encoding a PPR protein in chromosome A03, that is associated with the non-fluffy fiber phenotype. GhImA protein targeted mitochondrion and could bind to mitochondrial nad7 mRNA, which encodes the NAD7 subunit of Complex I. GhImA and its homolog GhImD had the same function and were dosage-dependent. GhImA in the im mutant was a null allele with a 22 bp deletion in the coding region. Null GhImA resulted in the insufficient GhIm dosage, affected mitochondrial nad7 pre-mRNA splicing, produced less mature nad7 transcripts, and eventually reduced Complex I activities, up-regulated alternative oxidase metabolism, caused reactive oxygen species (ROS) burst and activation of stress or hormone response processes. This study indicates that the GhIm protein participates in mitochondrial nad7 splicing, affects respiratory metabolism, and further regulates cotton fiber development via ATP supply and ROS balance.
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http://dx.doi.org/10.1093/genetics/iyaa017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045684PMC
March 2021

Massive Open Online Courses-based blended versus face-to-face classroom teaching methods for fundamental nursing course.

Medicine (Baltimore) 2021 Mar;100(9):e24829

Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.

Abstract: An increasing number of studies focus on the effectiveness of Massive Open Online Courses (MOOC)-based blended learning, whereas none have yet studied using it for teaching fundamental nursing skills at an undergraduate level.To evaluate the effectiveness of MOOC-based blended learning versus face-to-face classroom teaching techniques within the fundamental nursing course at the Faculty of Nursing, University of Xiang Nan, China.This cluster randomized controlled trial enrolled 181 students and assigned them into either an MOOC-based blended or a face-to-face classroom teaching group, both involving the Fundamental Nursing course for undergraduate nursing students. The analyzed outcomes included test scores, critical thinking ability, and feedback received from the students on the Fundamental Nursing course.MOOC-based blended techniques versus face-to-face classroom teaching methods demonstrated higher daily performance (P = .014), operational performance (P = .001), theoretical achievements (P < .001), and final grades (P < .001) in Fundamental Nursing.Moreover, the mean change in the participants' critical thinking ability items between groups were, mostly, statistically significant. The items focusing on the feedback from the students demonstrated significant differences between the groups in terms of their satisfaction with the teaching they received (P < .001) and the overall learning effects (P = .030).This study confirmed that receiving MOOC-based blended learning was superior when compared against face-to-face classroom teaching techniques for learning within the Fundamental Nursing course.
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http://dx.doi.org/10.1097/MD.0000000000024829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939164PMC
March 2021

Novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines as potent and selective agonists of the 5-HT receptor.

Bioorg Med Chem Lett 2021 Apr 23;38:127872. Epub 2021 Feb 23.

Department of Medicinal Chemistry, Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.

A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines were identified as potent and selective agonists of the 5-HT receptor. Optimizations performed on a previously reported series of racemic tetrahydroquinoline-based tricyclic amines, delivered an advanced drug lead, (R)-4-(3,3,3-trifluoropropyl)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,8]naphthyridine, which displayed excellent in vitro and in vivo pharmacological profiles.
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http://dx.doi.org/10.1016/j.bmcl.2021.127872DOI Listing
April 2021

Superficial Temporal Artery-Posterior Cerebral Artery Bypass for the Treatment of Chronic Basilar Artery Occlusion.

World Neurosurg 2021 Feb 23. Epub 2021 Feb 23.

Department of Neurosurgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Objective: To investigate the effect of superficial temporal artery-posterior cerebral artery (STA-PCA) bypass on chronic basilar artery occlusion (CBAO).

Methods: A total of 4 patients who underwent STA-PCA bypass between January 2018 and October 2019 were enrolled in this study. Cerebral blood perfusion, ischemic events, STA diameter and blood flow changes, modified Rankin scale score (mRS), and National Institutes of Health Stroke Scale (NIHSS) score changes were recorded before and after bypass surgery.

Results: The average time from basilar artery occlusion (confirmed by cerebral angiography or computed tomography angiography) to operation was 76 ± 38.89 days (range: 30-120 days). Average scores on the NIHSS were 6.8 ± 1.26 (5-8) and 5.2 ± 2.06 (3-7) before and after treatment, respectively. mRS scores averaged 1.8 ± 0.5 (1-2) and 1.5 ± 0.58 (1-2) points, respectively. There were no obvious complications or further stroke during the follow-up. The STA diameter and flow rate were significantly increased at 12 months after operation (P < 0.05).

Conclusions: STA-PCA bypass can improve cerebral blood flow perfusion in CBAO patients. The diameter and flow of the superficial temporal artery can be increased to meet the demand of blood supply.
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http://dx.doi.org/10.1016/j.wneu.2021.02.068DOI Listing
February 2021

Impaired Intestinal Akkermansia muciniphila and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice.

mSystems 2021 Feb 23;6(1). Epub 2021 Feb 23.

Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, China

Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD. Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD. Supplementation with metformin or fructo-oligosaccharide is a potential therapeutic strategy for NAFLD treatment. In addition, we also developed a new nutritional strategy by using a natural sweetener (neohesperidin dihydrochalcone [NHDC]) as a substitute for NAS and free sugars.
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http://dx.doi.org/10.1128/mSystems.00985-20DOI Listing
February 2021

Associations Between Regional Environment and Cornea-Related Morphology of the Eye in Young Adults: A Large-Scale Multicenter Cross-Sectional Study.

Invest Ophthalmol Vis Sci 2021 Feb;62(2):35

Gansu Provincial Hospital, Lanzhou, China.

Purpose: To investigate environmental factors associated with corneal morphologic changes.

Methods: A cross-sectional study was conducted, which enrolled adults of the Han ethnicity aged 18 to 44 years from 20 cities. The cornea-related morphology was measured using an ocular anterior segment analysis system. The geographic indexes of each city and meteorological indexes of daily city-level data from the past 40 years (1980-2019) were obtained. Correlation analyses at the city level and multilevel model analyses at the eye level were performed.

Results: In total, 114,067 eyes were used for analysis. In the correlation analyses at the city level, the corneal thickness was positively correlated with the mean values of precipitation (highest r [correlation coefficient]: >0.700), temperature, and relative humidity (RH), as well as the amount of annual variation in precipitation (r: 0.548 to 0.721), and negatively correlated with the mean daily difference in the temperature (DIF T), duration of sunshine, and variance in RH (r: -0.694 to 0.495). In contrast, the anterior chamber (AC) volume was negatively correlated with the mean values of precipitation, temperature, RH, and the amount of annual variation in precipitation (r: -0.672 to -0.448), and positively associated with the mean DIF T (r = 0.570) and variance in temperature (r = 0.507). In total 19,988 eyes were analyzed at the eye level. After adjusting for age, precipitation was the major explanatory factor among the environmental factors for the variability in corneal thickness and AC volume.

Conclusions: Individuals who were raised in warm and wet environments had thicker corneas and smaller AC volumes than those from cold and dry ambient environments. Our findings demonstrate the role of local environmental factors in corneal-related morphology.
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http://dx.doi.org/10.1167/iovs.62.2.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910644PMC
February 2021

A case report of congenital idiopathic hypogonadotropic hypogonadism caused by novel mutation of GNRHR gene.

Medicine (Baltimore) 2021 Feb;100(5):e24007

Peking University Shenzhen Hospital.

Rationale: This study aimed to investigate the genetic mutation characteristics of congenital idiopathic hypogonadotropic hypogonadism (IHH) through the clinical features and genetic analysis of 2 patients with IHH in 1 pedigree.

Patient Concerns: A 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development.

Diagnoses: Combined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH.

Interventions: Whole exome and Sanger sequencing were performed to validate the mutation in family members.

Outcomes: A novel homozygous missense mutation c.521A > G (p.Q174R) in the GNRHR gene was identified in the 2 affected sisters. Familial segregation showed that the homozygous variant was inherited from their parents respectively and the eldest sister was the carrier without correlative symptom.

Lessons: We reported a novel GNRHR mutation in a pedigree with congenital idiopathic hypogonadotropic hypogonadism. Glutamine at amino acid position 174 was highly conserved among various species. The molecular structure of GNRHR protein showed that p.Q174R mutation brought in a new stable hydrogen bond between position 174 and 215, may impede conformational mobility of the TMD4 and TMD5. It suggests that the missense mutation c.521A > G related to congenital idiopathic hypogonadotropic hypogonadism was probably a causative factor for both sisters. Through high-throughput sequencing and experimental verification, we had basically determined the patient's pathogenic mutation and inheritance, which could better guide doctors for treatment.
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http://dx.doi.org/10.1097/MD.0000000000024007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870162PMC
February 2021

The trend of indirect anastomosis formation in a 2-vessel occlusion plus encephalo-myo-synangiosis rat model.

Ann Transl Med 2021 Jan;9(1):19

Department of Neurosurgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Basic research on the factors influencing indirect anastomosis formation in a 2-vessel occlusion plus encephalo-myo-synangiosis (2VO + EMS) rat model is conducive to improving the efficacy of indirect revascularization surgery in the clinic. However, the time point at which anastomosis between the rat temporal muscle (TM) and brain naturally has the greatest effect after encephalo-myo-synangiosis (EMS) remains unknown. Therefore, we conducted this study to explore the peak time of indirect anastomosis formation in the 2VO + EMS rat model.

Methods: Forty 2VO + EMS rats were randomly divided into five groups (n=8) according to the length of time (by week) after EMS, and 2VO rats were used as the control group (n=8). The expression of vascular endothelial growth factor (VEGF) and CD31 on the EMS side of the brain, perfusion ratio [improvement of cerebral blood perfusion (CBP) on the EMS side] and Morris water maze (MWM) results were compared between groups. Furthermore, the trends of the above variables were explored over weeks.

Results: Overall, the expression of VEGF and CD31, the perfusion ratio and the cognitive improvement in the 2VO + EMS rat model gradually increased over weeks after EMS. The VEGF and CD31 expression (as detected by immunofluorescence), perfusion ratio and number of times crossing the platform area peaked at 4 weeks after EMS. In addition, both the escape latency and the time spent in the target quadrant peaked in the fifth week after EMS.

Conclusions: After establishing the 2VO + EMS rat model, the degree of endothelial cell (EC) proliferation and CBP improvement on the EMS side of the brain peaked at 4 weeks after EMS, whereas the cognitive improvement peaked in the fifth week.
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http://dx.doi.org/10.21037/atm-20-2936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859809PMC
January 2021

Canidin-3-glucoside prevents nano-plastics induced toxicity via activating autophagy and promoting discharge.

Environ Pollut 2021 Apr 21;274:116524. Epub 2021 Jan 21.

Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, People's Republic of China; Zhejiang Key Laboratory for Agro-food Processing, Zhejiang University, Hangzhou, 310058, People's Republic of China; Fuli Institute of Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China; National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang University, Hangzhou, 310058, People's Republic of China. Electronic address:

Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans (C. elegans) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans, by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G's beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.
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http://dx.doi.org/10.1016/j.envpol.2021.116524DOI Listing
April 2021

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response.

Cell Host Microbe 2021 03 29;29(3):489-502.e8. Epub 2021 Jan 29.

Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China; Department of Laboratory Medicine and Department of Pediatric Infectious Diseases, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu 610041, China.

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.
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http://dx.doi.org/10.1016/j.chom.2021.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846228PMC
March 2021

Combined glycoprotein IIb/IIIa inhibitor therapy with ticagrelor for patients with acute coronary syndrome.

PLoS One 2021 2;16(2):e0246166. Epub 2021 Feb 2.

Department of Gynecology, Handan Central Hospital, Handan, China.

This study was to compare the efficacy and safety of combined glycoprotein IIb/IIIa inhibitor (GPI) and ticagrelor versus ticagrelor in patients with acute coronary syndrome (ACS). An observational study was conducted using the Improving Care for Cardiovascular Disease in China-ACS project. Totally, 13,264 patients with ACS and received combination therapy or ticagrelor therapy were analyzed. The primary outcome was the composite of major cardiovascular events (MACE: all-cause mortality, myocardial infarction [MI], stent thrombosis, cardiogenic shock, and ischemic stroke), and secondary outcomes included all-cause mortality, MI, stent thrombosis, cardiogenic shock, and ischemic stroke. The multivariable adjusted analysis indicated that combination therapy was associated with an increased risk of major cardiovascular events (MACE) (P = 0.001), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, the multivariable adjusted for propensity score-matched (PSM) analysis suggested that combination therapy produced additional risk of MACE (P = 0.014), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, PSM analysis suggested that combination therapy was associated with greater risk of stent thrombosis (P = 0.012) and intracranial bleeding (P = 0.020). Combined GPI and ticagrelor therapies did not have any beneficial effects on MACE, stent thrombosis, intracranial bleeding, any bleeding, or major bleeding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246166PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853481PMC
February 2021

Metabolomics safety assessments of microcystin exposure via drinking water in rats.

Ecotoxicol Environ Saf 2021 Apr 30;212:111989. Epub 2021 Jan 30.

CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China; Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China. Electronic address:

Drinking water exposure to microcystin-leucine-arginine (MC-LR), the most widely occurring cyanotoxins, poses a highly potential risk for human health. However, the health risk of MC-LR exposure at current guideline value in drinking water has not yet entirely evaluated. In the current study, we used H NMR-based metabolomics combined with targeted metabolic profiling by GC/LC-MS to explore the toxic effects of MC-LR exposure at environmentally relevant concentrations via drinking water in rats. The results revealed that multiple biological consequences of MC-LR exposure on host metabolism in rats. Both relatively low and high doses of MC-LR used here induced hepatic lipogenesis and inflammation. While only relatively high dose MC-LR (10 μg/L) in drinking water caused more metabolic disorders including inhibition of gluconeogenesis and promotion of β-oxidation of fatty acid. Although the dose of 1.0 μg/L MC-LR is extremely low for rats, alterations of metabolic profiles were unexpectedly found in rat liver and serum, alarming potential health risk of MC-LR at the WHO guideline level.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111989DOI Listing
April 2021

Screening and identifying hepatobiliary diseases through deep learning using ocular images: a prospective, multicentre study.

Lancet Digit Health 2021 02;3(2):e88-e97

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China; Centre for Precision Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images.

Methods: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score.

Findings: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification.

Interpretation: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool.

Funding: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S2589-7500(20)30288-0DOI Listing
February 2021

Ferroptosis in a sarcopenia model of senescence accelerated mouse prone 8 (SAMP8).

Int J Biol Sci 2021 1;17(1):151-162. Epub 2021 Jan 1.

Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, People's Republic of China.

As a systemic syndrome characterized by age-associated degenerative skeletal muscle atrophy, sarcopenia leads to a risk of adverse outcomes in the elderly. Age-related iron accumulation is found in the muscles of sarcopenia animal models and patients, but the role of iron in sarcopenia remains poorly understood. It has been recently found that iron overload in several diseases is involved in ferroptosis, an iron- dependent form of programmed cell death. However, whether this excess iron can result in ferroptosis in muscles is still unclear. In our present study, we found that ferric citrate induced ferroptosis in C2C12 cells, as well as impaired their differentiation from myoblasts to myotubes. Due to the decreased muscle mass and fiber size, 40-week-old senescence accelerated mouse prone 8 (SAMP8) mice were used as a sarcopenia model, in whose muscles the iron content and markers of ferroptosis were found to increase, compared to 8-week- old SAMP8 controls. Moreover, our results showed that iron overload upregulated the expression of P53, which subsequently repressed the protein level of Slc7a11 (solute carrier family 7, member 11), a known ferroptosis-related gene. The downregulation of Slc7a11 then induced the ferroptosis of muscle cells through the accumulation of lipid peroxidation products, which may be one of the causes of sarcopenia. The findings in this study indicate that iron plays a key role in triggering P53- Slc7a11-mediated ferroptosis in muscles, and suggest that targeting iron accumulation and ferroptosis might be a therapeutic strategy for treating sarcopenia.
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http://dx.doi.org/10.7150/ijbs.53126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757032PMC
January 2021

The value and implementation of routine ophthalmic examination in the era of HAART.

EClinicalMedicine 2021 Jan 22;31:100646. Epub 2020 Dec 22.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510000, China.

Background: The high prevalence of ocular manifestations (OMs) in patients with human immunodeficiency virus (HIV) infection and chronic diseases such as diabetes has become a global health issue. However, there is still a lack of an appropriate ophthalmic diagnostic procedure for the early detection of OMs in this population, leading to the risk of an irreversible visual impairment that substantially affects the quality of life of these patients.

Methods: The Guangzhou HIV Infection Study was a retrospective study that enrolled hospitalised HIV-infected patients in Guangzhou between January 2005 and December 2016, period corresponding to the highly active antiretroviral therapy (HAART) era in China. We collected data on OMs, systemic diseases, hospitalisation, and demographic characteristics. We classified the patients into 3 groups according to the ophthalmic examination mode they underwent: the non-ophthalmologist examination group (patients hospitalised in 2005-2011 who were only treated by infectious disease physicians), the on-demand ophthalmic examination group (patients hospitalised in 2012-2013 who were referred for a consultation with an ophthalmologist), and the routine ophthalmic examination group (patients hospitalised in 2014-2016 who routinely underwent standard ophthalmic examinations). Binary logistic regression models were used to investigate the factors related to OMs.

Findings: A total of 8,743 hospitalised HIV-infected patients were enrolled. The prevalence of detected OMs were 1.5% in the non-ophthalmologist examination group, 1.9% in the on-demand ophthalmic examination group, and 12.8% in the routine ophthalmic examination group. The odds of detection of OMs were highest in the routine ophthalmic examination group (adjusted odds ratio [aOR]=9.24, [95%CI, 6.51-13.12], compared to the non-ophthalmologist examination group). The detection of all types of OMs increased substantially, with keratitis, retinitis and vascular abnormalities increased the most (by 15.8-20.0 times). In the routine examination group, patients who were older than 50 years, males, with medical insurance, and were not resident in Guangzhou, had higher odds to have OMs. Several systemic diseases also increased the odds of OMs, with the highest odds among patients with a cytomegalovirus infection (aOR=5.59, [95%CI, 4.12-7.59]). Patients with retinitis, retinopathy and conjunctivitis had higher odds of having a CD4 T cell counts less than 200 cells/μL compared to the patients that did not have these referred OMs.

Interpretation: The implementation of a routine ophthalmic examination has improved the odds of OM detection by approximately 9 times and increased the diagnosis rates of all types of OMs. Therefore, we encourage all HIV-infected patients to undergo regular ophthalmic examinations. Patients with OMs, especially retinopathy and retinitis, need to be evaluated for immune function (such as CD4 T cell counts) and systemic diseases.
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http://dx.doi.org/10.1016/j.eclinm.2020.100646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772547PMC
January 2021

The complete plastome sequence of (Asteraceae: Cardueae), an important medicinal plant in East Asia.

Mitochondrial DNA B Resour 2020 Jan 31;5(1):951-952. Epub 2020 Jan 31.

Hangzhou Botanical Garden, Hangzhou Academy of Landscape Science, Hangzhou, China.

is one of the most commonly used herbs in China, which is famous for its high medicinal value. In this study, we analyzed and characterized the complete plastome sequence of Sequence analysis indicated that the entire genome is 153,265 bp in length, consisting of a large single-copy (LSC, 84,311 bp) and a small single-copy (SSC, 18,674 bp) region separated by a pair of inverted repeat (IR) regions of 25,140 bp for each. The genome contains 107 unique genes, including 80 different protein-coding genes, 23 tRNA genes, and 4 rRNA genes. The overall GC content of the genome is 37.7%. The phylogenetic analysis revealed a monophyletic and Cardueae. This research reports the complete plastome genome of , which provides a better understanding of this important herb.
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http://dx.doi.org/10.1080/23802359.2020.1719926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748879PMC
January 2020

Development and validation of a deep learning system to screen vision-threatening conditions in high myopia using optical coherence tomography images.

Br J Ophthalmol 2020 12 21. Epub 2020 Dec 21.

Centre of Precision Medicine, Sun Yat-sen University, Guangzhou, China.

Background/aims: To apply deep learning technology to develop an artificial intelligence (AI) system that can identify vision-threatening conditions in high myopia patients based on optical coherence tomography (OCT) macular images.

Methods: In this cross-sectional, prospective study, a total of 5505 qualified OCT macular images obtained from 1048 high myopia patients admitted to Zhongshan Ophthalmic Centre (ZOC) from 2012 to 2017 were selected for the development of the AI system. The independent test dataset included 412 images obtained from 91 high myopia patients recruited at ZOC from January 2019 to May 2019. We adopted the InceptionResnetV2 architecture to train four independent convolutional neural network (CNN) models to identify the following four vision-threatening conditions in high myopia: retinoschisis, macular hole, retinal detachment and pathological myopic choroidal neovascularisation. Focal Loss was used to address class imbalance, and optimal operating thresholds were determined according to the Youden Index.

Results: In the independent test dataset, the areas under the receiver operating characteristic curves were high for all conditions (0.961 to 0.999). Our AI system achieved sensitivities equal to or even better than those of retina specialists as well as high specificities (greater than 90%). Moreover, our AI system provided a transparent and interpretable diagnosis with heatmaps.

Conclusions: We used OCT macular images for the development of CNN models to identify vision-threatening conditions in high myopia patients. Our models achieved reliable sensitivities and high specificities, comparable to those of retina specialists and may be applied for large-scale high myopia screening and patient follow-up.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317825DOI Listing
December 2020

Short-Term Intake of Hesperetin-7--Glucoside Affects Fecal Microbiota and Host Metabolic Homeostasis in Mice.

J Agric Food Chem 2021 Feb 22;69(5):1478-1486. Epub 2020 Dec 22.

Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy of Precision Measurement Science and Technology, CAS, Wuhan 430071, China.

Hesperetin-7--glucoside (Hes-7-G) is a typical flavonoid monoglucoside isolated from Citri Reticulatae Pericarpium (CRP), which is commonly used as a food adjuvant and exhibits potential biological activities. To explore the interaction between Hes-7-G ingestion and microbiome and host metabolism, here, 16S rRNA gene sequencing was first used to analyze the alteration of fecal microbiome in mice after Hes-7-G intake. Metabolic homeostasis in mice was subsequently investigated using untargeted H NMR-based metabolomics and targeted metabolite profiling. We found that dietary Hes-7-G significantly regulated fecal microbiota and its derived metabolites, including short-chain fatty acids (SCFAs) and tryptophan metabolites (indole and its derivatives), in feces of mice. Regulation of microbiota was further confirmed by the significantly changed urinary hippurate and trimethylamine -oxide (TMAO), co-metabolites of the microbe and host. We also found that dietary Hes-7-G modulated the host tricarboxylic acid cycle (TCA) involved in energy metabolism. These findings suggested that Hes-7-G exhibits potential beneficial effects for human health.
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http://dx.doi.org/10.1021/acs.jafc.0c05921DOI Listing
February 2021