Publications by authors named "Ying Han"

1,192 Publications

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Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy.

Ann Transl Med 2021 Aug;9(16):1288

Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Background: This study aimed to investigate radiation-induced lymphopenia and its potential risk factors in patients with breast cancer receiving adjuvant radiotherapy.

Methods: Breast cancer patients received adjuvant radiotherapy (RT) at our hospital with peripheral lymphocyte counts (PLC) at pre-and immediately after RT (post-RT) were eligible. The primary endpoints were any grade of lymphopenia post-RT and nadir-PLC/pre-PLC <0.8. Patient characteristics, tumor factors, and treatment factors were collected for risk assessment. Data are presented as mean and 95% confidence interval (CI) unless otherwise specified. Matched analysis was used to compare the statistical significance between different RT techniques.

Results: A total of 735 consecutive patients met the study criteria. The mean PLC was 1.58×10/L before and 0.99×10/L post-RT (P<0.001). At the end of RT, 60.5% of patients had lymphopenia. Univariate and multivariable logistic analyses showed that RT technique involving RapidArc, mean lung dose, and chemotherapy were significant risk factors (P<0.05) for lymphopenia. RT technique was the only significant risk factor (P<0.05) for nadir-PLC/pre-PLC <0.8. Patients treated with RapidArc had a significantly greater reduction of PLC along with greater V5 of the lungs, even after matching mean lung dose and radiated volume.

Conclusions: Lymphopenia is common in patients with breast cancer after adjuvant RT. RT technique is the only significant factor for lymphopenia and nadir-PLC/pre-PLC <0.8, suggesting the significance of RT technique choice to minimize lymphopenia and improve treatment outcomes.
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http://dx.doi.org/10.21037/atm-21-2150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422134PMC
August 2021

Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: A systematic review, meta-analysis and call for action.

EClinicalMedicine 2021 Oct 8;40:101111. Epub 2021 Sep 8.

National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China.

Background: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19.

Methods: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832).

Finding: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis.

Interpretation: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations.

Funding: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.
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http://dx.doi.org/10.1016/j.eclinm.2021.101111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424080PMC
October 2021

Evolution of Intestinal Microbiota of Asphyxiated Neonates Within 1 Week and Its Relationship With Neural Development at 6 Months.

Front Pediatr 2021 23;9:690339. Epub 2021 Aug 23.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Asphyxia is an emergent condition in neonates that may influence the function of the nervous system. Research has shown that intestinal microbiota is very important for neurodevelopment. Studies regarding the association between gut microbiota and neurodevelopment outcome in asphyxiated newborns remain scarce. To study the microbial characteristics of asphyxiated neonates within 1 week of life and to investigate their relationship with neural development at 6 months. The feces produced on days 1, 3, and 5, and the clinical data of full-term neonates with asphyxia and without asphyxia, delivered from March 2019 to October 2020 at Peking University First Hospital, were collected. We used 16S ribosomal deoxyribonucleic acid amplicon sequencing to detect the intestinal microbiota of asphyxiated neonates and neonates in the control group. We followed up asphyxiated neonates for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate their development. A total of 45 neonates were enrolled in the study group and 32 were enrolled in the control group. On day 1, the diversity and richness of the microflora of the study group were more than those of the control group. Non-metric multidimensional scaling analysis showed significant differences in the microbiota of the two groups on days 1, 3, and 5. At the phylum level, the main microflora of the two groups were not different. At the genus level, the study group had increased relative abundance of , etc. on day 1. On day 3, the relative abundance of , etc. was still greater than that of the control group, and the relative abundance of was less than that of the control group. On day 5, the relative abundance of and was still higher than that of the control group, and the relative abundance of in the study group was significantly increased. At the species level, on day 3, the relative abundance of in the study group was less than that in the control group. Linear discriminant analysis effect size showed that the microbiota of the study group mainly consisted of and on day 1 and on day 3. In the control group, was the dominant bacterium on day 3. Neonates in the study group were followed up for 6 months, and the communication score of ASQ-3 was negatively correlated with the relative abundance of and on day 1. The diversity and richness of the microbiota of asphyxiated neonates on the first day of life were significantly increased and mainly consisted of pathogenic flora. and found in neonates with asphyxia on day 1 of life may be related to neural development at 6 months.
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http://dx.doi.org/10.3389/fped.2021.690339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419515PMC
August 2021

Divergent Connectivity Changes in Gray Matter Structural Covariance Networks in Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

Front Aging Neurosci 2021 16;13:686598. Epub 2021 Aug 16.

School of Biological Science and Medical Engineering, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China.

Alzheimer's disease (AD) has a long preclinical stage that can last for decades prior to progressing toward amnestic mild cognitive impairment (aMCI) and/or dementia. Subjective cognitive decline (SCD) is characterized by self-experienced memory decline without any evidence of objective cognitive decline and is regarded as the later stage of preclinical AD. It has been reported that the changes in structural covariance patterns are affected by AD pathology in the patients with AD and aMCI within the specific large-scale brain networks. However, the changes in structural covariance patterns including normal control (NC), SCD, aMCI, and AD are still poorly understood. In this study, we recruited 42 NCs, 35 individuals with SCD, 43 patients with aMCI, and 41 patients with AD. Gray matter (GM) volumes were extracted from 10 readily identifiable regions of interest involved in high-order cognitive function and AD-related dysfunctional structures. The volume values were used to predict the regional densities in the whole brain by using voxel-based statistical and multiple linear regression models. Decreased structural covariance and weakened connectivity strength were observed in individuals with SCD compared with NCs. Structural covariance networks (SCNs) seeding from the default mode network (DMN), salience network, subfields of the hippocampus, and cholinergic basal forebrain showed increased structural covariance at the early stage of AD (referring to aMCI) and decreased structural covariance at the dementia stage (referring to AD). Moreover, the SCN seeding from the executive control network (ECN) showed a linearly increased extent of the structural covariance during the early and dementia stages. The results suggest that changes in structural covariance patterns as the order of NC-SCD-aMCI-AD are divergent and dynamic, and support the structural disconnection hypothesis in individuals with SCD.
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http://dx.doi.org/10.3389/fnagi.2021.686598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415752PMC
August 2021

The selective deprotonation of carbon quantum dots for fluorescence detection of phosphate and visualization of latent fingerprints.

Nanoscale 2021 Aug 22;13(30):13057-13064. Epub 2021 Jul 22.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.

We developed a water-soluble, stable and selective "turn-on" fluorescence sensing platform based on carbon quantum dots (CQDs) for rapid determination of phosphate (Pi) in aqueous solutions and for visualization of latent fingerprints on paper. The hydroxyl groups on the surface of the synthesized CQDs can be deprotonated by Pi to trigger the intramolecular charge transfer (ICT) process and the inhibition of excited-state proton transfer (ESPT), achieving a turn-on emission response. CQDs demonstrated the capability to selectively detect Pi over other common ions and biomolecules with the linear fluorescence intensity change in the range from 0 to 100 μM. Moreover, the paper sprayed with the CQD solution showed a remarkable blue emission speckle and a fingerprint upon addition of Pi solution and finger touching, respectively. Notably, the fingerprint images including level 3 details (crossover, bifurcation, termination, and island and sweat pores) are also clearly identified and distinguished, indicating their potential application in document security. We believe that the as-synthesized CQDs will provide a new tool for Pi detection in aqueous media and paper document security.
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http://dx.doi.org/10.1039/d1nr02432aDOI Listing
August 2021

Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex.

Int J Nanomedicine 2021 24;16:5755-5776. Epub 2021 Aug 24.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China.

Background: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.

Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.

Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and -15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6 orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.

Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.
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http://dx.doi.org/10.2147/IJN.S318266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403987PMC
August 2021

Low-dose transscleral cyclophotocoagulation with subsequent phacoemulsification in the treatment of prolonged acute primary angle closure.

Br J Ophthalmol 2021 Aug 30. Epub 2021 Aug 30.

Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Background: To explore the outcomes and mechanisms of intraocular pressure (IOP) control using low-dose transscleral cyclophotocoagulation (LDTSCP) followed by phacoemulsification in patients with prolonged acute primary angle closure (APAC).

Methods: Patients with prolonged APAC refractory to all other treatment modalities were prospectively recruited, and underwent LDTSCP (10 shots, 2 s duration, 120° treatment with the energy starting at 1500 mW and titrated to the level with audible burst but not exceeding 2000 mW) and anterior chamber paracentesis 1 week prior to phacoemulsification with intraocular lens implantation and viscogoniosynechiolysis. Postoperative IOP, vision, anatomic changes on anterior segment optical coherence tomography and complications were recorded.

Results: Twenty eyes with prolonged APAC were recruited. Median follow-up was 12 months (range 9-18), at which point the vision in all eyes had improved and IOP was ≤17 mm Hg on no antiglaucoma medications. Following LDTSCP at postoperative day (POD) 1, IOP decreased in all eyes to a median 15 mm Hg (range: 6-28 mm Hg). Post-LDTSCP supraciliary effusion (SCE) occurred in 90% of eyes on POD1 or POD7 and ciliary body defect (CBD) was detected in 30% of eyes and resolved in all cases by postoperative month 1. Lower post-LDTSCP IOP was associated with more number of bursts (r=-0.558, p=0.011) and higher grade of SCE (r=-0.877, p<0.001), but not with total energy (p=0.240). Eyes with CBD (p=0.018) and a higher number of bursts (r=0.657, p=0.002) had higher grade SCE.

Conclusions: LDTSCP-induced SCE may explain the post-LDTSCP IOP reduction seen in eyes with prolonged APAC. LDTSCP instead of traditional more extensive treatment, was sufficient to provide a relatively safe and effective bridge therapy prior to phacoemulsification.

Trial Registration Number: Chinese Clinical Trials Registry (ChiCTR1900023567).
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http://dx.doi.org/10.1136/bjophthalmol-2021-318880DOI Listing
August 2021

The diagnosis of amnestic mild cognitive impairment by combining the characteristics of brain functional network and support vector machine classifier.

J Neurosci Methods 2021 Aug 21;363:109334. Epub 2021 Aug 21.

School of Electrical Engineering, Yanshan University, Qinhuangdao, China; Measurement Technology and Instrumentation Key Lab of Hebei Province, Qinhuangdao, China.

Background: Amnestic mild cognitive impairment (aMCI) is an essential stage of early detection and potential intervention for Alzheimer's disease (AD). Patients with aMCI exhibit partially abnormal functional brain connectivity and it is suggested that these features may represent a new diagnostic marker of early AD.

New Method: In this paper, we constructed two brain network models, a phase synchronization index (PSI) undirected network and a directed transfer function (DTF) directed network, to evaluate the cognitive function in patients with aMCI. We then built SVM classification models using the network clustering coefficient, global efficiency and average node degree as features to distinguish between aMCI patients and controls.

Results: Our results reveal a classification accuracy and AUC of 66.6 ± 1.7% and 0.7475 and 80.0 ± 2.2% and 0.7825, respectively, for the two network models (PSI and DTF). As the directed network model performed better than the undirected model, we introduced an improved graph theory feature, efficiency density, which resulted in an increased classification accuracy and AUC value 86.6 ± 2.6% and 0.8295, respectively.

Comparison With Existing Methods: The analysis of network models and the directionality of information flow is suitable for analysis of nonlinear EEG signals for assessment of the functional state of the brain. Compared with traditional network features, our proposed improved features more comprehensively evaluate transmission efficiency and density of the brain.

Conclusion: In this study, we demonstrate that an improved efficiency density feature is helpful for enhancing classification the accuracy of aMCI. Moreover, directed brain network models exhibit better classification for aMCI diagnosis than undirected networks.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109334DOI Listing
August 2021

Hypoxia-Inducible Factor 2-Alpha Mediated Gene Sets Differentiate Pulmonary Arterial Hypertension.

Front Cell Dev Biol 2021 5;9:701247. Epub 2021 Aug 5.

College of Veterinary Medicine, Northwest A&F University, Xianyang, China.

Objectives: HIF2α is of vital importance in the regulation of endothelial dysfunction, cell proliferation, migration, and pulmonary vascular remodeling in pulmonary hypertension. Our previous studies demonstrated that conditional and inducible deletion of HIF2α in mouse lung endothelial cells, dramatically protected the mice against vascular remodeling and the development of pulmonary arterial hypertension (PAH). Here, we provide a novel transcriptome insight into the impact of HIF2α in PAH pathogenesis and the potential to use HIF2α-mediated gene sets to differentiate PAH human subjects.

Methods: Using transcriptome data, we first tapped the value of the difference in gene expression profile between wild type (WT) and knockdown (KD) cell lines. We considered the deregulated genes between WT and -KD cells as HIF2α influenced genes. By examining the lung tissue transcriptome data set with nine controls and eight PAH patients, we evaluated the HIF2α regulatory network in PAH pathogenesis to further determine the identification ability of HIF2α-mediated gene sets in human PAH subjects. On the other hand, using peripheral blood mononuclear cells (PBMCs) transcriptome data from PAH patients and healthy controls, we further validated the potential of the HIF2α-mediated PBMC gene sets as a possible diagnostic tool for PAH. To verify the ability of HIF2α-mediated gene sets for the identification of PAH, endothelial cell-specific knockout mice with spontaneous pulmonary hypertension were used for reverse validation experiments.

Results: 19 identified GO biological process terms were significantly correlated with the genes down-regulated in -KD cells, all of which are strongly related to the PAH pathogenesis. We further assessed the discriminative power of these HIF2α-mediated gene sets in PAH human subjects. We found that the expression profile of the HIF2α-mediated gene sets in lung tissues and PBMCs were differentiated both between controls and PAH patients. Further, a significant positive correlation was observed between hypoxia and deficiency mediated gene set expression profiles. As expected, 7 of the 19 significantly down-regulated GO terms in -KD cells were found to overlap with the up-regulated GO gene sets in mice compared to WT controls, suggesting opposing effects of HIF2α and PHD2 on PAH pathogenesis.

Conclusion: HIF2αmediated gene sets may be used to differentiate pulmonary arterial hypertension.
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http://dx.doi.org/10.3389/fcell.2021.701247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375387PMC
August 2021

Knockdown of Salusin- Improves Cardiovascular Function in Myocardial Infarction-Induced Chronic Heart Failure Rats.

Oxid Med Cell Longev 2021 10;2021:8896226. Epub 2021 Aug 10.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Salusin- is a biologically active peptide with 20 amino acids that exerts several cardiovascular activity-regulating effects, such as regulating vascular endothelial function and the proliferation of vascular smooth muscle cells. However, the regulatory effects of salusin- in myocardial infarction-induced chronic heart failure (CHF) are still unknown. The current study is aimed at investigating the effects of silencing salusin- on endothelial function, cardiac function, vascular and myocardial remodeling, and its underlying signaling pathways in CHF rats induced by coronary artery ligation. CHF and sham-operated (Sham) rats were subjected to tail vein injection of adenoviral vectors encoding salusin- shRNA or a control-shRNA. The coronary artery (CA), pulmonary artery (PA), and mesenteric artery (MA) were isolated from rats, and isometric tension measurements of arteries were performed. Compared with Sham rats, the plasma salusin-, leptin and visfatin levels and the salusin- protein expression levels of CA, PA, and MA were increased, while the acetylcholine- (ACh-) induced endothelium-dependent vascular relaxation of CA, PA, and MA was attenuated significantly in CHF rats and was improved significantly by salusin- gene knockdown. Salusin- knockdown also improved cardiac function and vascular and myocardial remodeling, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels, and decreased NAD(P)H oxidase activity, NOX-2 and NOX-4 expression, and reactive oxygen species (ROS) levels in arteries in CHF rats. The effects of salusin- knockdown in CHF rats were attenuated significantly by pretreatment with the NOS inhibitor L-NAME. These results indicate that silencing salusin- contributes to the improvement of endothelial function, cardiac function, and cardiovascular remodeling in CHF by inhibiting NAD(P)H oxidase-ROS generation and activating eNOS-NO production.
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http://dx.doi.org/10.1155/2021/8896226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373485PMC
August 2021

Ggct (γ-glutamyl cyclotransferase) plays an important role in erythrocyte antioxidant defense and red blood cell survival.

Br J Haematol 2021 Aug 18. Epub 2021 Aug 18.

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

The expression of GGCT (γ-glutamyl cyclotransferase) is upregulated in various human cancers. γ-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), but the physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mice leads to splenomegaly and progressive anaemia phenotypes, due to elevated oxidative damage and the shortened life span of Ggct RBCs. Ggct RBCs have increased reactive oxygen species (ROS), and are more sensitive to H O -induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor l-cysteine are decreased in Ggct RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.
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http://dx.doi.org/10.1111/bjh.17775DOI Listing
August 2021

Combined Support Vector Machine Classifier and Brain Structural Network Features for the Individual Classification of Amnestic Mild Cognitive Impairment and Subjective Cognitive Decline Patients.

Front Aging Neurosci 2021 30;13:687927. Epub 2021 Jul 30.

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.

Objective: Individuals with subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI) represent important targets for the early detection and intervention of Alzheimer's disease (AD). In this study, we employed a multi-kernel support vector machine (SVM) to examine whether white matter (WM) structural networks can be used for screening SCD and aMCI.

Methods: A total of 138 right-handed participants [51 normal controls (NC), 36 SCD, 51 aMCI] underwent MRI brain scans. For each participant, three types of WM networks with different edge weights were constructed with diffusion MRI data: fiber number-weighted networks, mean fractional anisotropy-weighted networks, and mean diffusivity (MD)-weighted networks. By employing a multiple-kernel SVM, we seek to integrate information from three weighted networks to improve classification performance. The accuracy of classification between each pair of groups was evaluated via leave-one-out cross-validation.

Results: For the discrimination between SCD and NC, an area under the curve (AUC) value of 0.89 was obtained, with an accuracy of 83.9%. Further analysis revealed that the methods using three types of WM networks outperformed other methods using single WM network. Moreover, we found that most of discriminative features were from MD-weighted networks, which distributed among frontal lobes. Similar classification performance was also reported in the differentiation between subjects with aMCI and NCs (accuracy = 83.3%). Between SCD and aMCI, an AUC value of 0.72 was obtained, with an accuracy of 72.4%, sensitivity of 74.5% and specificity of 69.4%. The highest accuracy was achieved with features only selected from MD-weighted networks.

Conclusion: White matter structural network features help machine learning algorithms accurately identify individuals with SCD and aMCI from NCs. Our findings have significant implications for the development of potential brain imaging markers for the early detection of AD.
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http://dx.doi.org/10.3389/fnagi.2021.687927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361326PMC
July 2021

Evaluation of the Brain Function State During Mild Cognitive Impairment Based on Weighted Multiple Multiscale Entropy.

Front Aging Neurosci 2021 30;13:625081. Epub 2021 Jul 30.

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

The mild cognitive impairment (MCI) stage plays an essential role in preventing the progression of older adults to Alzheimer's disease. In this study, neurofeedback training (NFT) is applied to improve MCI brain cognitive function. To assess the improvement effect, a novel algorithm called Weighted Multiple Multiscale Entropy (WMMSE) is proposed to extract and analyze the electroencephalogram (EEG) features of patients with MCI. To overcome the information loss problem of traditional multiscale entropy (MSE), WMMSE fully considered the correlation of the sequence and the contribution of each sequence to the total entropy. The experimental group composed of 39 patients with MCI was subjected to NFT for 10 days during two sessions. The control group included 21 patients with MCI without any intervention. The Lempel-Ziv complexity (LZC) was used for primary assessment, and WMMSE was used to accurately analyze the effect of NFT. The results show that the WMMSE values of F4, C3, C4, O1, and T5 channels post-NFT are higher compared with pre-NFT and significant differences ( < 0.05). Moreover, the cognitive subscale of the Montreal Cognitive Assessment (MoCA) results shows that the post-NFT score is higher than the pre-NFT in the vast majority of the patients with MCI and significant differences ( < 0.05). When compared with the control group, the WMMSE values of the experimental group increased in each channel. Therefore, the NFT intervention method contributes to brain cognitive functional recovery, and WMMSE can be used as a biomarker to evaluate the state of MCI brain cognitive function.
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http://dx.doi.org/10.3389/fnagi.2021.625081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362600PMC
July 2021

Chemotherapy is a risk factor of lymphopenia before adjuvant radiotherapy in breast cancer.

Cancer Rep (Hoboken) 2021 Aug 14:e1525. Epub 2021 Aug 14.

Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Background: Lymphopenia can decrease immune function of the host and is a known risk factor for poor prognosis in malignant tumors. Radiation induced lymphopenia was common in patients with breast cancer and was also reported to have a negative effect on long-term outcome.

Aims: Lymphopenia may be associated with baseline immune status before radiotherapy (RT). This study aimed to explore the rate and risk factors of lymphopenia before start of the adjuvant RT in patients with breast cancer.

Methods: Patients with invasive breast cancer treated from March 2015 to February 2020 and with peripheral lymphocyte counts (PLC) available within 7 days from the beginning of RT were eligible for this study. Data were presented as mean and 95% confidence interval unless otherwise specified. The risk factors of low PLC before RT were identified using univariate and multivariable linear regressions.

Results: A total of 1012 consecutive patients met the study criteria. The mean PLC before RT commencement was 1.58*10 /L (95%CI: 1.55-1.62*10 /L) with 15.2% (95%CI: 13.1%-17.6%) CTCAE defined lymphopenia, rendering 12.3%, 2.6%, 0.3%, and 0% for grade 1, 2, 3 and 4 respectively. Univariate and multivariable linear regression showed prior chemotherapy was the most significant risk factor (p < .001) for low PLC, while age, menopausal status and lymph node stage were not (all ps > .05). A total of 912 (90.1%, 95%CI: 88.1%-91.9%) patients had chemotherapy before adjuvant RT in this study. In patients with HR+/HER2- breast cancer, 69.0% (95%CI: 63.0%-74.5%) N0 and 98.1% (95%CI: 95.1%-99.5%) N1 had also received chemotherapy.

Conclusions: Patients with breast cancer might have lymphopenia from prior chemotherapy at the start of adjuvant RT which could have negative effect on long-term outcome. It is also noted that most of the patients with HR+/HER2-, early-stage breast cancer were treated with aggressive chemotherapy without knowing the risk of chemotherapy induced lymphopenia. Future study on predictive or prognostic multigene assays is warranted to avoid unnecessary chemotherapy and subsequent lymphopenia in patients with low risk breast cancer.
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http://dx.doi.org/10.1002/cnr2.1525DOI Listing
August 2021

The influence of the gut microbiota on the bioavailability of oral drugs.

Acta Pharm Sin B 2021 Jul 28;11(7):1789-1812. Epub 2020 Sep 28.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
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http://dx.doi.org/10.1016/j.apsb.2020.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343123PMC
July 2021

Ferritin as a diagnostic, differential diagnostic, and prognostic marker for immune-related adverse events.

Cancer Biol Med 2021 Aug 11. Epub 2021 Aug 11.

Department of Immunology and Biotherapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.

Objective: Distinguishing immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) from the AEs caused by chemotherapy, targeted therapy, or infection is highly difficult. This study offers new insights into evaluating the diagnosis, differential diagnostic, and prognostic value of ferritin for irAEs induced by ICIs.

Methods: From December 1, 2018, to April 1, 2019, we examined 318 patients with malignant tumors who received serum ferritin monitoring. The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy, and 87 patients treated with chemotherapy. Of the 231 patients, 90 had irAEs (irAE group), 70 had non-irAEs (non-irAE group), 67 had no AEs (no irAE-non irAE group), and 4 had unclassified AEs. In the 87 patients, 60 had AEs (AE group), and 27 had no AEs (no AE group). Statistical analyses were conducted with nonparametric Mann-Whitney tests.

Results: At the onset of AEs in the irAE group, ferritin (normal range, 35-150 μg/L) rose to a median of 927 μg/L (range, 117-17,825 μg/L) from 86 μg/L at baseline (range, 29-421 μg/L) ( < 0.001). Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group (median, 81 μg/L; range, 32-478 μg/L) ( < 0.001) and the AE group (median, 103 μg/L; range, 23-712 μg/L) ( < 0.001). After treatment in the irAE group, ferritin continuously decreased to a normal range in recovered patients, showed no significant changes in stable patients, and continued to rise in patients who died.

Conclusions: Ferritin can be used as a diagnostic, differential diagnostic, and prognostic marker for irAEs in patients treated with ICIs.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2021.0037DOI Listing
August 2021

Saucer[n]arenes: Synthesis, Structure, Complexation, and Guest-Induced Circularly Polarized Luminescence Property.

Angew Chem Int Ed Engl 2021 Aug 10. Epub 2021 Aug 10.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Macrocycles denoted as saucer[n]arenes (n=4,5) were easily synthesized by the one-pot condensation of 2,7-dimethoxynaphthalene (2,7-DMN) and paraformaldehyde in the presence of TFA or catalytic BF ⋅OEt . With 1,1-dimethylpiperidin-1-ium as the template, saucer[4]arene was selectively obtained. Crystal structures show that saucer[n]arenes are all composed of 2,7-DMN moiety bridged by the methylene groups at 1,6-positions: all of the 7-methoxy groups lie on one face, and all of the 2-methoxy groups lie on the other. Saucer[n]arenes exhibit strong fluorescence properties with the quantum yields of 19.6 % and 23.4 %. They form 1:1 complexes with ammonium salts in both solution and solid state (association constant up to 10  M in CDCl ). Chiral quaternary ammonium salts can induce the chirality of the dynamically racemic inherently chiral saucer[n]arenes in solution, and thus show mirror-imaged circular dichroism signals and circularly polarized luminescence (CPL) properties.
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http://dx.doi.org/10.1002/anie.202108209DOI Listing
August 2021

Unraveling the effects of arbuscular mycorrhizal fungi on cadmium uptake and detoxification mechanisms in perennial ryegrass (Lolium perenne).

Sci Total Environ 2021 Jul 22;798:149222. Epub 2021 Jul 22.

School of Life Sciences and Engineering, Southwest University of Science and Technology, Mianyang 621010, China; Joint Research Unit CTFC-AGROTECNIO-CERCA Center, Lleida 25198, Spain; Department of Crop and Forest Sciences, Universitat de Lleida, Lleida 25198, Spain. Electronic address:

Cadmium (Cd) is a major environmental pollutant and one of the most toxic metals in the environment. Arbuscular mycorrhizal fungi (AMF) assisted phytoremediation can be used to remove Cd from polluted soils but the role of AMF, which mediate in Cd accumulation and tolerance, remains poorly understood. Here we inoculated Lolium perenne with two different AMF species (Glomus etunicatum and Glomus mosseae). Mycorrhizal L. perenne and non-mycorrhizal controls were exposed to Cd stress and we tested the effects of AMF mycorrhization on Cd uptake and subsequent tolerance, as well as the underlying mechanisms. Mycorrhizal infection increased root Cd uptake and we observed that net Cd influx was coupled with net Ca influx. The inactivation of Ca transporter channels decreased Cd uptake in non-inoculated roots to a greater extent than in inoculated roots, indicating that AMF activates additional ion transport channels. In consequence, inoculated plants exhibited higher Cd accumulation in both roots and shoots than non-inoculated controls. However, AMF-inoculated plants showed higher chlorophyll concentrations, photosynthesis, and growth under Cd, indicating lower Cd toxicity in AMF-inoculated plants, despite the increase in Cd uptake. We observed that AMF-inoculated favored the isolation of Cd within cell walls and vacuoles, and had higher concentrations of superoxide dismutase activity and glutathione concentration in roots than non-inoculated plants, consequently experiencing less stress upon Cd exposure. Our results highlight the potential and mechanism of AMF for enhancing phytoremediation of L. perenne in heavy metal contaminated environments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149222DOI Listing
July 2021

Gut microbiota enhances the chemosensitivity of hepatocellular carcinoma to 5-fluorouracil in vivo by increasing curcumin bioavailability.

Phytother Res 2021 Aug 10. Epub 2021 Aug 10.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union medical college, Beijing, China.

5-Fluorouracil (5-Fu) is efficient for hepatocellular carcinoma (HCC) treatment, but fast-emerging resistance limits its usage. Curcumin is being investigated for its potential chemosensitivity, but its low oral bioavailability hinders its chemosensitivity effect in vivo. Gut microbiota modulation is considered to contribute to its bioactivities in vivo. In the current study, we demonstrate that curcumin can enhance 5-Fu chemosensitivity in HCC cells in vitro, increase the apoptosis rate, arrest the cell cycle at G2/M phase, and block the PI3k/AKT/mTOR signalling pathway by inhibiting the phosphorylation of PI3K and its downstream protein kinases. Curcumin also remarkably sensitized H22 cells to 5-Fu, allowing it to inhibit tumour growth in vivo. 16S rDNA sequencing suggests that curcumin in combination with 5-Fu significantly alters the gut microbiota composition based on alpha and beta diversity analysis compared to drug treatment alone. Gut microbiota depletion abolished curcumin's chemosensitivity effect in vivo. A pharmacodynamics study suggested that the gut microbiota increased the oral bioavailability of curcumin (AUC 15.24 ± 0.77 μM/h [wt] vs. 3.04 ± 0.18 μM/h [gut microbiota depleted]). In conclusion, curcumin can increase the chemosensitivity of HCC to 5-Fu in vitro and in vivo, and gut microbiota plays a key role in its effect in vivo.
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http://dx.doi.org/10.1002/ptr.7240DOI Listing
August 2021

Comparing N-acetylcysteine to sodium thiosulfate for relieving symptoms caused by Lugol's iodine chromoendoscopy: a randomized, double-blind trial.

Gastrointest Endosc 2021 Aug 6. Epub 2021 Aug 6.

Xijing Hospital of Digestive Diseases, Air Force Medical University (Fourth Military Medical University), Xian, China. Electronic address:

Background And Aims: Lugol's iodine chromoendoscopy is an important method to detect esophageal squamous cell carcinoma. Sodium thiosulfate solution (STS) was used to neutralize iodine after Lugol's chromoendoscopy; nonetheless, it is not available in many medical centers. The aim of the current study was to assess the efficacy of N-acetylcysteine solution (NAC) for relieving symptoms caused by Lugol's iodine chromoendoscopy.

Methods: Patients were randomized to receive either STS or NAC after spraying Lugol's iodine solution on the esophagus. The neutralizing effects for residual iodine in esophagus and gastric mucus pool were observed. The primary endpoint was the intensity of retrosternal pain and/or heartburn measured by a visual analogue scale (VAS) score 30 minutes after chromoendoscopy. The secondary endpoints were the rate of patients with any adverse symptom, the rate of moderate to severe retrosternal discomfort occurred, and the heart rate variability between timepoints before and after chromoendoscopy.

Results: The neutralization rates for residual iodine between the NAC and STS groups were not significantly different (P > .999). The difference of median VAS scores between the NAC and STS groups 30 minutes after chromoendoscopy was 0.0 (P = .719; 95% CI, 0.0 - 0.0), and the 95% CI higher limit was 0.0, which was less than our prespecified margin of 0.5, concluding to noninferiority of NAC with regard to STS. There was no significant difference between the 2 groups regarding the rate of patients with any adverse symptom, the rate of moderate to severe retrosternal discomfort, or heart rate variability at 5 minutes or 30 minutes after chromoendoscopy.

Conclusion: As a very easily accessible reagent in clinical circumstances, NAC can also alleviate mucosal irritation symptoms induced by Lugol's chromoendoscopy at similar efficacy as STS and can be routinely recommended.
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http://dx.doi.org/10.1016/j.gie.2021.07.025DOI Listing
August 2021

Anterior Segment OCT in Primary Angle Closure Compared to Normal Subjects with Similar Shallow Anterior Chamber.

J Glaucoma 2021 Aug 9. Epub 2021 Aug 9.

College of Letters & Science, University of California, Berkeley, Berkeley, CA Department of Ophthalmology, University of California, San Francisco, San Francisco, CA Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China Ophthalmology Section, Surgical Service, San Francisco Veterans Affairs Medical Center, San Francisco, California.

Prcis: Compared with normal subjects with similar shallow ACD, patients with PACD had narrower angle structures measured by SS-OCT at 250▒μm from scleral spur (very root of iris), especially along oblique and vertical axis.

Purpose: To examine anterior segment structures in normal subjects whose anterior chamber depth (ACD) was shallow on slit lamp exam but did not meet the diagnostic criteria of primary angle closure disease (PACD), and to compare them with PACD patients with similar ACD.

Methods: Patients were recruited from glaucoma clinic at Zhongshan Ophthalmic Center. A total of 40 eyes from 29 PACD patients and 40 eyes from 34 normal subjects received full ophthalmic examination and CASIA SS-1000 OCT tests. PACD eyes and control eyes were 1:1 matched for ACD at 0 degree of scan. Generalized linear model that accounted for inter-eye correlation was used to compare differences between the two groups for intraocular pressure (IOP) and SS-OCT parameters. P values were adjusted for multiple comparisons using the Bonferroni method.

Results: The PACD and control groups had similar age, but the PACD group had a significantly higher IOP (18.4 vs. 14.0▒mmHg, P=0.005). Angle parameters, representative of angle area, such as angle recess area (ARA) and trabecular iris space area (TISA) measured at 250▒μm along axes of 90°, 135°, 225° and 315° were significantly smaller in PACD group than those of control group (adjusted P<0.05), while most of angle parameters at 500▒μm and 750▒μm, volume parameters, and anterior chamber parameters, were similar (adjusted P>0.05).

Conclusions: In PACD patients compared to normal subjects with similar anterior chamber shallowing, OCT findings measured at the iris root 250▒μm from the scleral spur, especially in the oblique and vertical axes, including ARA and TISA, may match gonioscopic findings more closely and provide further insight into mechanisms of PACD.
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http://dx.doi.org/10.1097/IJG.0000000000001915DOI Listing
August 2021

Synergistic Effects of Eu-MOF on Perovskite Solar Cells with Improved Stability.

Adv Mater 2021 Aug 8:e2102947. Epub 2021 Aug 8.

Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, MIIT Key Laboratory for Low-dimensional Quantum Structure and Devices, Experimental Center of Advanced Materials, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China.

Enhancing device lifetime is one of the essential challenges in perovskite solar cells. The ultrathin Eu-MOF layer is introduced at the interface between the electron-transport layer and the perovskite absorber to improve the device stability. Both Eu ions and organic ligands in the MOF can reduce the defect concentration and improve carrier transport. Moreover, due to the Förster resonance energy transfer effect, Eu-MOF in perovskite films can improve light utilization and reduce the decomposition under ultraviolet light. Meanwhile, Eu-MOF also turns tensile strain to compressive strain in the perovskite films. As a result, the corresponding devices achieve a champion power conversion efficiency (PCE) of 22.16%. In addition, the devices retain 96% of their original PCE after 2000 h under the relative humidity of 30% and 91% of their original PCE after 1200 h after continuous 85 °C aging condition in N .
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http://dx.doi.org/10.1002/adma.202102947DOI Listing
August 2021

A comprehensive analysis of the efficacy and safety of COVID-19 vaccines.

Mol Ther 2021 09 6;29(9):2794-2805. Epub 2021 Aug 6.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China. Electronic address:

The numbers of cases and deaths from coronavirus disease 2019 (COVID-19) are continuously increasing. Many people are concerned about the efficacy and safety of the COVID-19 vaccines. We performed a comprehensive analysis of the published trials of COVID-19 vaccines and the real-world data from the Vaccine Adverse Event Reporting System. Globally, our research found that the efficacy of all vaccines exceeded 70%, and RNA-based vaccines had the highest efficacy of 94.29%; moreover, Black or African American people, young people, and males may experience greater vaccine efficacy. The spectrum of vaccine-related adverse drug reactions (ADRs) is extremely broad, and the most frequent ADRs are pain, fatigue, and headache. Most ADRs are tolerable and are mainly grade 1 or 2 in severity. Some severe ADRs have been identified (thromboembolic events, 21-75 cases per million doses; myocarditis/pericarditis, 2-3 cases per million doses). In summary, vaccines are a powerful tool that can be used to control the COVID-19 pandemic, with high efficacy and tolerable ADRs. In addition, the spectrum of ADRs associated with the vaccines is broad, and most of the reactions appear within a week, although some may be delayed. Therefore, ADRs after vaccination need to be identified and addressed in a timely manner.
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http://dx.doi.org/10.1016/j.ymthe.2021.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342868PMC
September 2021

Platelet 3D Preservation Using a Novel Biomimetic Nanofiber Peptide for Reduced Apoptosis and Easy Storage.

ACS Appl Mater Interfaces 2021 Aug 4;13(32):38040-38049. Epub 2021 Aug 4.

Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, 27(1) Taiping Road, Beijing 100850, China.

Human platelets (PLTs) are vulnerable to unfavorable conditions, and their adequate supply is limited by strict transportation conditions. We report here that PLTs preserved under three-dimensional (3D) conditions using novel biomimetic nanofiber peptides showed reduced apoptosis compared with classical PLTs stored at 22 °C and facilitated the storage and transportation of PLTs. The mechanism of PLT 3D preservation involves the formation of cross-links and a 3D nanofibrous network by a self-assembled peptide scaffold material at physiological conditions after initiation by triggers in plasma. PLTs adhere to the surface of the nanofibrous network to facilitate the 3D distribution of PLTs. The 3D microstructure, rheological properties, and effect on the inflammatory response and hemolysis were evaluated. Compared to traditional PLTs stored at 22 °C, PLTs subjected to 3D preservation showed similar morphology, number, aggregation activity, and reduced apoptosis. The detection of the reactive oxygen species (ROS) levels demonstrated that both reduced intracellular and mitochondrial ROS levels were correlated with reduced apoptosis. This study reveals a new 3D preservation method for PLTs based on the use of novel biomimetic nanofiber peptides that presents an attractive opportunity for various biomedical applications.
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http://dx.doi.org/10.1021/acsami.1c08394DOI Listing
August 2021

Development of an optimal protocol for isolation and purification of human granulosa cells in patients with different ovarian reserves.

Exp Ther Med 2021 Sep 1;22(3):938. Epub 2021 Jul 1.

Department of Center for Reproductive Medicine, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin 300100, P.R. China.

The aim of the current study was to develop an accurate and reproducible method for isolation of granulosa cells (GCs) in patients with different ovarian reserves. The cells of healthy individuals and patients with polycystic ovary syndrome (PCOS) were isolated using a modified two-step Percoll density gradient centrifugation. The cells of patients with poor ovarian response (POR) were isolated using a one-step method suitable for samples containing few cells. Cells extracted using these purification techniques were compared regarding cell yield, viability and purity using immunocytochemistry, flow cytometry, Cell Counting Kit-8, western blotting and RNA integrity analysis. The purity and activity of the cells in the POR group were comparable with those in the healthy and PCOS groups and no statistically significant differences were identified. Furthermore, isolated cells analyzed for RNA integrity indicated good quality RNA and presented an RNA integrity number of 8-10, demonstrating that the technique enabled the isolation of GCs from different types of patients. Thus, a reliable and reproducible technique for the isolation of pure GCs with high yield is described in the present study. This protocol provides an efficient method targeted to patients with different ovarian reserve functions that enables the preparation of GCs for evaluating their molecular functions.
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http://dx.doi.org/10.3892/etm.2021.10370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290409PMC
September 2021

Women Exhibit Lower Global Left Frontal Cortex Connectivity Among Cognitively Unimpaired Elderly Individuals: A Pilot Study from SILCODE.

J Alzheimers Dis 2021 Jul 27. Epub 2021 Jul 27.

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

Background: Mounting evidence suggests that sex differences exist in cognitive reserve (CR) for cognitively unimpaired (CU) elderly individuals. Global left frontal connectivity (gLFC connectivity) is a reliable neural substrate of CR.

Objective: The purpose of this study was to explore sex differences in gLFC connectivity among CU elderly individuals.

Methods: One hundred thirteen normal controls (NCs) (women = 66) and 132 individuals with subjective cognitive decline (SCD) (women = 92) were recruited from the Sino Longitudinal Study on Cognitive Decline (SILCODE) (data 1). Among them, 88 subjects underwent amyloid-β (Aβ) imaging, including 32 Aβ+ and 56 Aβ-subjects. Forty-six subjects underwent another rs-fMRI examination (data 2) to validate the repeatability of the calculation of gLFC connectivity, which was determined through seed-based functional connectivity between the LFC and voxels throughout the whole brain. Independent-sample t-tests were used to evaluate the sex differences in gLFC connectivity across different subgroups (NC versus SCD, Aβ+ versus Aβ-). Partial correlation analysis was used to calculate the correlations between gLFC connectivity and cognitive assessments.

Results: Women exhibited lower gLFC connectivity in both the NC (p = 0.001) and SCD (p = 0.020) subgroups than men. Women also exhibited lower gLFC connectivity in both the Aβ-(p = 0.006) and Aβ+ (p = 0.025) groups. However, the significant difference disappeared in the Aβ+ group when considering the covariates of age, education, total intracranial volume, and APOE4-carrying status. In addition, gLFC connectivity values were negatively correlated with Geriatric Depression Scale scores in the SCD group (r = -0.176, p = 0.047).

Conclusion: Women showed lower gLFC connectivity among CU elderly individuals.
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http://dx.doi.org/10.3233/JAD-210376DOI Listing
July 2021

Catalytic Clusterbody for Enhanced Quantitative Protein Immunoblot.

Anal Chem 2021 08 30;93(31):10807-10815. Epub 2021 Jul 30.

Department of Chemistry and Biology, Faculty of Environment and Life Science, Beijing University of Technology, Beijing 100124, China.

To assess low-abundance protein biomarkers associated with tumor progression, we have developed artificial catalytic antibodies based on well-defined metal clusters modified with rationally designed peptides, termed clusterbodies. Such clusterbodies possess favorable integrated features of matched ultrasmall sizes, intrinsic fluorescence, and enzyme-like catalytic and selective recognition properties that are inaccessible to traditional antibodies. Consequently, a quantitative assay with high accuracy and high sensitivity is established by measuring the fluorescence and catalytic chemiluminescence of metal clusters preferentially recognizing the protein biomarker, which is confirmed by the molecular-weight marker references of immunoblotting. The results of quantitative immunoblotting are highly close to that derived from the enzyme-linked immunosorbent assay, implying the reliability of this protocol. Remarkably, the detection limit of the aimed protein achieved is as low as 1.0 pg, one magnitude lower than that of the conventional immunoassay. The significant variation of expression levels of the biomarker in tumor cells evidently indicates their distinguished invasion ability. This platform has potential application in analyzing low-abundance protein biomarkers in complex biological matrixes, which is essential to corroborate tumor malignancy in early stage. It inspires the construction of clusterbody-based precise bioprobes with customized structures and integrative functions for advanced quantitative biosensing.
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http://dx.doi.org/10.1021/acs.analchem.1c00779DOI Listing
August 2021

The competence of village clinicians in the diagnosis and management of childhood epilepsy in Southwestern China and its determinants: A cross-sectional study.

Lancet Reg Health West Pac 2020 Oct 23;3:100031. Epub 2020 Sep 23.

Peking University People's Hospital, Beijing, China.

Background: Due to lack of neurologists in low- and middle-income countries, communities of patients living with epilepsy are calling for task-shifting of diagnosis and management from physicians to paramedical providers in the primary health care systems to narrow the huge treatment gap. Evidence to guide this work has been limited. This study assesses the competence of village clinicians (VC)- mostly paramedical providers- in the diagnosis and management of a presumptive case of childhood epilepsy and its determinants.

Methods: A cross-sectional study was conducted in rural areas of a province in Southwestern China from July 2017 to January 2018. We randomly selected 370 VCs who practiced Western medicine and assumed the main responsibility of providing medical services in his/her clinic. A standardized clinical vignette based on national clinical practice guidelines was used to evaluate clinicians' competence in three domains: number and proportion of recommended (and essential) checklist (questions, examinations, and tests) completed, correctness of diagnosis, and correctness of case management.

Findings: Though VCs completed 14•3% (IQR 9•5%-19•1%) of the recommended checklist, 63•2% (234/370, 95%CI 58•2%-68•0%) provided a correct diagnosis. Only 1•6% of VCs (6/370, 95%CI 0•7%-3•5%) gave correct management with both correct medication and referral, however 90•3% (334/370, 95%CI 86•8%-92•9%) provided partially correct management by referring patients to upper-level health facilities (89•5%, 331/370, 95%CI 85•9%-92•2%) or prescribing anti-epileptic drugs (AEDs) correctly (0•8%, 3/370, 95%CI 0•3%-2•4%). Around 1/4 VCs referred patients to Township Health Centers which usually were not staffed with pediatric neurologists. Fewer provided helpful medical advice to patients for daily management. The heuristic process was found to be negatively associated with the proportion of the recommended checklist that VCs completed, which is positively associated with correctness of diagnosis.

Interpretation: Most VCs could diagnose and refer childhood epilepsy patients correctly; however, they lacked competence when it came to assuming the responsibility of primary care providers, referring efficiently, refilling AEDs, as well as supervising and instructing daily management of patients.

Funding: HY received the funding for this study from the "" of the Business Development Center of the RCSC (Beijing) and UCB (Belgium). UCB provided support in the form of a salary for author DET.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315368PMC
October 2020

Influencing factors and decoupling analysis of carbon emissions in China's manufacturing industry.

Environ Sci Pollut Res Int 2021 Jul 27. Epub 2021 Jul 27.

School of Business Administration, Northeastern University, Shenyang, 110169, China.

The manufacturing industry directly reflects national productivity, and it is also an industry with high energy consumption and severe carbon emissions. This study decomposes the influential factors on carbon emissions in China's manufacturing industry from 1995 to 2018 into industry value added, energy consumption, fixed asset investment, carbon productivity, energy structure, energy intensity, investment carbon intensity, and investment efficiency by Generalized Divisia Index Model. The decoupling analysis of carbon emissions and industry value added is carried out to investigate the states of the manufacturing industry under the pressure of "low carbon" and "economy." Results show that first, fixed asset investment is the driving force of carbon emissions, followed by industry value added; investment carbon intensity, carbon productivity, investment efficiency, and energy intensity are the mitigating factors; simultaneously, the impacts of energy consumption and energy structure are fluctuating. Second, the decoupling of manufacturing has improved, especially in the light industry. Third, the decoupling of carbon emissions and economic development is mainly dominated by the decoupling of energy consumption and industry added value. Therefore, reducing the proportion of coal consumption and optimizing the energy structure are significant ways to promote the low-carbon development of the manufacturing industry.
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http://dx.doi.org/10.1007/s11356-021-15548-0DOI Listing
July 2021

Feature level-based group lasso method for amnestic mild cognitive impairment diagnosis.

Comput Methods Programs Biomed 2021 Sep 16;208:106286. Epub 2021 Jul 16.

School of Biological Science and Medical Engineering, Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing 100083, China; State Key Lab of Cognition Neuroscience and Learning, Beijing Normal University, Beijing 100875, China. Electronic address:

Background And Objective: Previous studies have indicated that brain morphological measures change in patients with amnestic mild cognitive impairment (aMCI). However, most existing classification methods cannot take full advantage of these measures. In this study, we improve traditional multitask learning framework by fully considering the relevance among related tasks and supplementary information from other unrelated tasks at the same time.

Methods: We propose a feature level-based group lasso (FL-GL) method in which a feature represents the average value of each ROI for each measure. First, we design a correlation matrix in which each row represents the relationship among different measures for each ROI. And this matrix is used to guide the feature selection based on a group lasso framework. Then, we train specific support vector machine (SVM) classifiers with the selected features for each measure. Finally, a weighted voting strategy is applied to combine these classifiers for a final prediction of aMCI from normal control (NC).

Results: We use the leave-one-out cross-validation strategy to verify our method on two datasets, the Xuan Wu Hospital dataset and the ADNI dataset. Compared with the traditional method, the results show that the classification accuracies can be improved by 6.12 and 4.92% with the FL-GL method on the two datasets.

Conclusions: The results of an ablation study indicated that feature level-based group sparsity term was the core of our method. So, considering correlation at the feature level could improve the traditional multitask learning framework and our FL-GL method obtained better classification performance of patients with MCI and NCs.
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http://dx.doi.org/10.1016/j.cmpb.2021.106286DOI Listing
September 2021
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