Publications by authors named "Zheng Wen"

361 Publications

Despite vaccination, China needs non-pharmaceutical interventions to prevent widespread outbreaks of COVID-19 in 2021.

Nat Hum Behav 2021 Jun 22. Epub 2021 Jun 22.

Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China.

COVID-19 vaccination is being conducted in over 200 countries and regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remains a key question for policy makers. To address this, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable of keeping the reproduction number (R) around 1.3, the synergetic effect of NPIs and vaccination could reduce the COVID-19 burden by up to 99% and bring R below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.
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http://dx.doi.org/10.1038/s41562-021-01155-zDOI Listing
June 2021

A merged method for targeted analysis of amino acids and derivatives using parallel reaction monitoring combined with untargeted profiling by HILIC-Q-Orbitrap HRMS.

J Pharm Biomed Anal 2021 Sep 15;203:114208. Epub 2021 Jun 15.

Frontiers Science Center for Disease-related Molecular Network, Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

With continuously increased scan rate and sensitivity, high resolution mass spectrometry (HRMS) allows for both reliable targeted analysis (e.g., parallel reaction monitoring, PRM) and a global overview for discovery-based untargeted profiling (e.g., data dependent acquisition, DDA) to be performed. Based on previous study on PRM for large scale targeted metabolomics quantification, we developed an innovative method merged targeted and untargeted approaches in a single run. In our workflow, the scheduled PRM for targeted analysis of amino acids and derivatives combined with the full scan was acquired in every sample injection by hydrophilic interaction liquid chromatography tandem quadrupole-Orbitrap high resolution mass spectrometry (HILIC-Q-Orbitrap HRMS). The identification of metabolic features from full scan was further performed with DDA methodology on grouped quality control (QC) samples and matched with available database. Specifically, 20 amino acids and 40 derivatives were selected for targeted analysis with optimal chromatographic separation and PRM parameters. All isomers within the selected metabolites were totally separated in the robust HILIC condition. 36 of selected metabolites were well-detected and showed a good linearity and reproducibility in NIST SRM 1950 plasma. Moreover, the absolute quantification performance of targeted PRM method was systematically validated using 10 amino acids with the corresponding stable isotope-labeled internal standards (SIL-IS). Finally, the newly developed method was successfully applied to analysis of the plasma samples from patients of pancreatic benign tumor and pancreatic cancer. The significant reduction of circulating amino acids in patients with pancreatic malignancy was confirmed by targeted PRM method and other amino acids modifications as well as polar metabolites were identified with untargeted profiling. Therefore, we have established a workflow that combines specifically and reliably targeted PRM method as well as broad-coverage untargeted profiling, which provides an innovative strategy for basic and clinical metabolomics study.
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http://dx.doi.org/10.1016/j.jpba.2021.114208DOI Listing
September 2021

Temporal Bacterial Community Diversity in the Rhizosphere Over Years of Continuous Monocropping.

Front Microbiol 2021 25;12:641643. Epub 2021 May 25.

Panxi Crops Research and Utilization Key Laboratory of Sichuan Province, College of Agriculture Science, Xichang University, Xichang, China.

Long-term continuous monocropping negatively influences the physicochemical and biological characteristics of cultivated soil, especially for the economically important crop of flue-cured tobacco that is intolerant to continuous monocropping. The underlying mechanism of soil sickness under continuous monoculture and the temporal dynamic changes over the tobacco life cycle among different monoculture time spans remain poorly characterized. In this study, high-throughput sequencing targeting the 16S rRNA gene phylogenetic marker was performed on 60 soil samples of rhizosphere soil from flue-cured tobacco in the replanting, growth and harvest period across 5, 10, and 20 years of a continuous monocropping system. Bacterial community diversity decreased with the increase in duration of continuous monocropping, and the rhizosphere microbiota was highly dynamic in the harvest period. The random forests algorithm identified 17 taxa as biomarkers and a model was established to correlate root microbiota with continuous monocropping time of flue-cured tobacco. Molecular ecological network analysis elaborated the differences and interactions in bacterial co-occurrence patterns under different monocropping systems. The co-occurrence microbial network was larger in size but there were fewer interactions among microbial communities with the increase in continuous monocropping duration. These results provide insights into the changes of flue-cured tobacco root microbiome diversity in response to continuous monocropping and suggest a model for successional dynamics of the root-associated microbiota over continuous monocropping time and development stage. This study may help elucidate the theoretical basis underlying obstacles to continuous monocropping and could contribute to improving guidance for tobacco production.
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http://dx.doi.org/10.3389/fmicb.2021.641643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186668PMC
May 2021

Developing a Subjective Evaluation Scale for Assessing the Built Environments of China's Hygienic City Initiative.

Biomed Environ Sci 2021 May;34(5):372-378

Office of Epidemiology, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Objective: To develop a preliminary subjective evaluation scale for assessing the built environments of China's Hygienic City Initiative and to evaluate its reliability and validity.

Methods: The initial items of the scale were determined based on a review of policy documents and consultations with experts. The final items of the scale were confirmed through individual interviews with residents combined with the discretetrend method, critical ratio method, correlation coefficient method, and factor analysis method. Then, the dimensions of the scale were determined using exploratory factor analysis (EFA). The Cronbach's coefficient, split-half reliability coefficient, and confirmatory factor analysis (CFA) were used to assess the reliability and validity of the scale.

Results: A scale containing five dimensions with 22 items was established, including urban lifestyle, governance, basic functions, environmental sanitation, and amenities. The Cronbach's coefficient of the scale was 0.876, and the split-half reliability coefficient was 0.796. The CFA results indicate that each inspection level was within the standard limit.

Conclusion: The preliminarily subjective evaluation scale for assessing the built environments of China's Hygienic City Initiative demonstrates a high level of reliability and validity. Additional empirical studies should be carried out to further verify the value of the scale in terms of practical application.
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http://dx.doi.org/10.3967/bes2021.049DOI Listing
May 2021

CHA2DS2-VASc score predicts the slow flow/no-reflow phenomenon in ST-segment elevation myocardial infarction patients with multivessel disease undergoing primary percutaneous coronary intervention.

Medicine (Baltimore) 2021 May;100(21):e26162

Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, Beijing, China.

Abstract: ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) have a higher incidence of slow-flow/no-reflow (SF-NR) phenomenon during primary percutaneous coronary intervention (PPCI) than those with single vessel disease. Currently, no effective tools exist to predict the risk of SF-NR in this population. The present study aimed to evaluate whether CHA2DS2-VASc score can be used as a simple tool to predict this risk.This study consecutively included STEMI patients hospitalized in Beijing Anzhen Hospital from January 2005 to January 2015. Among these patients, 1032 patients with MVD were finally enrolled. Patients were divided into SF-NR (+) group and SF-NR (-) group according to whether SF-NR occurred during PPCI. SF-NR was defined as the thrombolysis in myocardial infarction (TIMI) grade ≤2.There were 134 patients (13%) in the SF-NR (+) group. Compared with the SF-NR (-) group, patients in the SF-NR (+) group are elder, with lower left ventricular ejection fraction and higher CHA2DS2-VASc score. Multiple logistic regression analysis indicated that CHA2DS2-VASc score ≥3 (odds ratio [OR], 2.148; 95% confidence interval [CI], 1.389-3.320; P = .001), current smoking (OR, 1.814; 95% CI, 1.19-2.764; P = .006), atrial fibrillation (OR, 2.892; 95% CI, 1.138-7.350; P = .03), complete revascularization (OR, 2.307; 95% CI, 1.202-4.429; P = .01), and total length of stents ≥40 mm (OR, 1.482; 95% CI, 1.011-2.172; P = .04) were independent risk factors of SF-NR. The incidence of SF-NR in patients with CHA2DS2-VASc score ≥3 was 1.7 times higher than that in patients with CHA2DS2-VASc score <3. Additionally, patients with CHA2DS2-VASc score ≥3 plus ≥2 risk factors have 3 times higher incidence of SF-NR than those with CHA2DS2-VASc score ≥3 plus 0 to 1 risk factor.CHA2DS2-VASc score ≥3 can be used as a simple and sensitive indicator to predict SF-NR phenomenon and guide the PPCI strategy in STEMI patients with MVD.
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http://dx.doi.org/10.1097/MD.0000000000026162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154372PMC
May 2021

TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis.

Cell Metab 2021 May 17. Epub 2021 May 17.

State Key Laboratory of Membrane Biology, Peking University, Beijing 100871, China; Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China; Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address:

How amphipathic phospholipids are shuttled between the membrane bilayer remains an essential but elusive process, particularly at the endoplasmic reticulum (ER). One prominent phospholipid shuttling process concerns the biogenesis of APOB-containing lipoproteins within the ER lumen, which may require bulk trans-bilayer movement of phospholipids from the cytoplasmic leaflet of the ER bilayer. Here, we show that TMEM41B, present in the lipoprotein export machinery, encodes a previously conceptualized ER lipid scramblase mediating trans-bilayer shuttling of bulk phospholipids. Loss of hepatic TMEM41B eliminates plasma lipids, due to complete absence of mature lipoproteins within the ER, but paradoxically also activates lipid production. Mechanistically, scramblase deficiency triggers unique ER morphological changes and unsuppressed activation of SREBPs, which potently promotes lipid synthesis despite stalled secretion. Together, this response induces full-blown nonalcoholic hepatosteatosis in the TMEM41B-deficient mice within weeks. Collectively, our data uncovered a fundamental mechanism safe-guarding ER function and integrity, dysfunction of which disrupts lipid homeostasis.
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http://dx.doi.org/10.1016/j.cmet.2021.05.006DOI Listing
May 2021

New strategy of color and power doppler sonography combined with DMSA in the assessment of acute pyelonephritis in infants.

BMC Nephrol 2021 May 17;22(1):181. Epub 2021 May 17.

Department of Rheumatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China.

Background: The purpose of this study was to evaluate the clinical value of color and power doppler sonography (CPDS) when combined it with 99mTc-dimercaptosuccinic acid scintigraphy (DMSA) in assessment of acute pyelonephritis (APN) in infants.

Methods: A total of 79 children with APN admitted to our hospital from June 2016 to Jan 2019 were enrolled, including 52 boys and 27 girls, age range 1 month to 3 years old. All cases followed the diagnostic criteria for acute pyelonephritis and excluded anatomical abnormalities of urinary system. All 79 patients were examined by urinary ultrasonography (US), CPDS, and DMSA within 48 h of fever and analyzed the clinical value of combining the two methods in the assessment of APN in infants.

Results: Among 79 children, urinary ultrasonography revealed 2 cases of renal cortical echo changes, both located in the upper pole of the kidney, 24 cases of kidney enlargement, and 1 case of left kidney shrinkage. Ninety-five kidneys were shown to be diseased with DMSA, while 105 kidneys abnormal by CPDS. The sensitivity of CPDS was 69.4%, and the specificity was 38.1%. In children younger than 6 months, the sensitivity of CPDS was 56.9%, which was 84.2% in childeren between 6 months to 1 year, and 94.4% from 1 to 3 years old, respectively. The corresponding specificity of CPDS was 44.1, 26.7, and 35.7%. There was no significant correlation between CPDS levels and DMSA positive results. The abnormal rate of intermediate part in the kidneys was significantly lower than that in the upper and lower poles. Children with abnormal CPDS have a greater risk of renal scarring(p < 0.05).

Conclusion: Abnormalities detected by CPDS in a cohort of infants with APN poorly correlated with DMSA findings. But the sensitivity of CPDS is highly age-related, it can be used as a non-invasive helpful tool for early diagnosis of acute pyelonephritis in infants older than 6 months old.
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http://dx.doi.org/10.1186/s12882-021-02390-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130442PMC
May 2021

Corrigendum: Digenic Variants in the and Genes Co-segregating With a Limb-Girdle Muscular Dystrophy in a Han Chinese Family.

Front Neurosci 2021 21;15:678618. Epub 2021 Apr 21.

Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.

[This corrects the article DOI: 10.3389/fnins.2021.601757.].
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http://dx.doi.org/10.3389/fnins.2021.678618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098658PMC
April 2021

The impact of relaxing interventions on human contact patterns and SARS-CoV-2 transmission in China.

Sci Adv 2021 05 7;7(19). Epub 2021 May 7.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Nonpharmaceutical interventions to control SARS-CoV-2 spread have been implemented with different intensity, timing, and impact on transmission. As a result, post-lockdown COVID-19 dynamics are heterogeneous and difficult to interpret. We describe a set of contact surveys performed in four Chinese cities (Wuhan, Shanghai, Shenzhen, and Changsha) during the pre-pandemic, lockdown and post-lockdown periods to quantify changes in contact patterns. In the post-lockdown period, the mean number of contacts increased by 5 to 17% as compared to the lockdown period. However, it remains three to seven times lower than its pre-pandemic level sufficient to control SARS-CoV-2 transmission. We find that the impact of school interventions depends nonlinearly on the intensity of other activities. When most community activities are halted, school closure leads to a 77% decrease in the reproduction number; in contrast, when social mixing outside of schools is at pre-pandemic level, school closure leads to a 5% reduction in transmission.
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http://dx.doi.org/10.1126/sciadv.abe2584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104862PMC
May 2021

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial.

Front Med 2021 Apr 28. Epub 2021 Apr 28.

Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
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http://dx.doi.org/10.1007/s11684-021-0853-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079840PMC
April 2021

Effects of metabolic memory on inflammation and fibrosis associated with diabetic kidney disease: an epigenetic perspective.

Clin Epigenetics 2021 Apr 21;13(1):87. Epub 2021 Apr 21.

Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

Diabetic kidney disease (DKD) is one of the most common microvascular complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and the leading cause of end-stage renal disease (ESRD) worldwide. Persistent inflammation and subsequent chronic fibrosis are major causes of loss of renal function, which is associated with the progression of DKD to ESRD. In fact, DKD progression is affected by a combination of genetic and environmental factors. Approximately, one-third of diabetic patients progress to develop DKD despite intensive glycemic control, which propose an essential concept "metabolic memory." Epigenetic modifications, an extensively studied mechanism of metabolic memory, have been shown to contribute to the susceptibility to develop DKD. Epigenetic modifications also play a regulatory role in the interactions between the genes and the environmental factors. The epigenetic contributions to the processes of inflammation and fibrogenesis involved in DKD occur at different regulatory levels, including DNA methylation, histone modification and non-coding RNA modulation. Compared with genetic factors, epigenetics represents a new therapeutic frontier in understanding the development DKD and may lead to therapeutic breakthroughs due to the possibility to reverse these modifications therapeutically. Early recognition of epigenetic events and biomarkers is crucial for timely diagnosis and intervention of DKD, and for the prevention of the progression of DKD to ESRD. Herein, we will review the latest epigenetic mechanisms involved in the renal pathology of both type 1 (T1DN) and type 2 diabetic nephropathy (T2DN) and highlight the emerging role and possible therapeutic strategies based on the understanding of the role of epigenetics in DKD-associated inflammation and fibrogenesis.
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http://dx.doi.org/10.1186/s13148-021-01079-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061201PMC
April 2021

Investigation of Obesity-Alleviation Effect of on Mice Fed with a High-Fat Diet through Metabolomics Revealed Enhanced Decomposition and Inhibition of Accumulation of Lipids.

J Proteome Res 2021 05 15;20(5):2714-2724. Epub 2021 Apr 15.

Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, 88 Keyuan South Road, Hi-Tech Zone, Chengdu 610041, China.

The metabolic and bioactivity effects of () in obesity treatment were studied in mice fed with a high-fat diet using a metabolomics approach. Aqueous extracts of were obtained via grinding, dissolving, and freeze-drying. The hepatic steatosis effect of was characterized by hematoxylin and eosin histological staining. External performance of the obesity-alleviation effect was monitored by measuring body and food weight. In addition, the metabolomics analysis of the -mice interaction system was performed using the established platform combining liquid chromatography-tandem mass spectrometry with statistical analysis. The presence and spatial distribution patterns of differential molecules were further evaluated through desorption electrospray ionization-mass spectrometry imaging. The results showed that played a vital role in downregulating lipid accumulation (especially triacylglycerols) and fatty acids biosynthesis together with enhanced lipid decomposition and healing in Bagg albino mice. During such a process, mainly induced metabolomic alterations of amino acids, organic acids, phospholipids, and glycerolipids. Moreover, under the experimental concentrations, induced more fluctuations of aqueous-soluble metabolites in the plasma and lipids in the liver than in the kidneys. This study provides an advanced alternative to traditional -based studies for evaluating the metabolic effects and bioactivity of through metabolomics technology, revealing potential technological improvement and clinical application.
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http://dx.doi.org/10.1021/acs.jproteome.1c00015DOI Listing
May 2021

Structure-guided improvement in the enantioselectivity of an Aspergillus usamii epoxide hydrolase for the gram-scale kinetic resolution of ortho-trifluoromethyl styrene oxide.

Enzyme Microb Technol 2021 May 19;146:109778. Epub 2021 Mar 19.

Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, PR China. Electronic address:

Microtuning the substrate-binding pocket (SBP) of EHs has emerged as an effective approach to manipulate their enantio- or regio-selectivities and activities towards target substrates. Here, the enantioselectivity (enantiomeric ratio, E) of AuEH2 towards a racemic (rac-) ortho-trifluoromethyl styrene oxide (o-TFMSO) was improved via microtuning its SBP. Based on the analysis on the crystal structure of AuEH2, its specific residues I192, Y216, R322 and L344 lining the SBP in close to the catalytic triad were identified for site-saturation mutagenesis. After screening, five single-site mutants were selected with E values elevated from 8 to 12-25 towards rac-o-TFMSO. To further improve E, four double-site mutants were constructed by combinatorial mutagenesis of AuEH2 separately with AuEH2, AuEH2, AuEH2 and AuEH2. Among all the mutants, AuEH2 possessed the largest E of 83 with activity of 67 U/g wet cell. The kinetic resolution of 200 mM rac-o-TFMSO was conducted at 0 °C for 5.5 h using 80 mg/mL wet cells of E. coli/Aueh2, a transformant expressing AuEH2, retaining (S)-o-TFMSO with 98.4 % ee and 49.3 % yield. Furthermore, the molecular docking simulation analysis indicated that AuEH2 more enantiopreferentially attacks the terminal carbon (C) in the oxirane ring of (R)-o-TFMSO than AuEH2.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109778DOI Listing
May 2021

Flexoelectric Thin-Film Photodetectors.

Nano Lett 2021 Apr 24;21(7):2946-2952. Epub 2021 Mar 24.

College of Physics and Center for Marine Observation and Communications, Qingdao University, Qingdao 266071, P.R. China.

The flexoelectric effect, which manifests itself as a strain-gradient-induced electrical polarization, has triggered great interest due to its ubiquitous existence in crystalline materials without the limitation of lattice symmetry. Here, we propose a flexoelectric photodetector based on a thin-film heterostructure. This prototypical device is demonstrated by epitaxial LaFeO thin films grown on LaAlO substrates. A giant strain gradient of the order of 10/m is achieved in LaFeO thin films, giving rise to an obvious flexoelectric polarization and generating a significant photovoltaic effect in the LaFeO-based heterostructures with nanosecond response under light illumination. This work not only demonstrates a novel self-powered photodetector different from the traditional interface-type structures, such as the p-n and Schottky junctions but also opens an avenue to design practical flexoelectric devices for nanoelectronics applications.
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http://dx.doi.org/10.1021/acs.nanolett.1c00055DOI Listing
April 2021

Vitamin D status and its dietary and lifestyle factors in children during the first 5 years of life: A cross-sectional multicentre Jiangsu bone study.

J Hum Nutr Diet 2021 Mar 10. Epub 2021 Mar 10.

Department of Child Health Care, Xinghua Maternity and Child Health Care Hospital, Xinghua, China.

Background: To explore the vitamin D status with its demographic and lifestyle factors including dietary, supplementation, and physical activity in 0-5 years old children.

Methods: This was a large population-based cross-sectional multicentre study in which the children were recruited from 12 Children's Health Care Centers by a stratified cluster random-sampling method in 10 cities in Jiangsu Province, China.

Results: A total number of 5289 children were investigated. The prevalence of vitamin D deficiency was 30.1%. The concentration of 25 hydroxyvitamin D was 64.0 (46.3-83.0) nmol mL after adjustment for covariates. Children with higher risk of vitamin D deficiency were more likely to be at older age, girls, survey conducted in spring, location in southern Jiangsu province, residence in urban, outdoor activity < 2 h day (all p < 0.05). Moreover, those with lower risk were more likely to be the number of parity ≥ 2 times, vitamin D supplementation from birth to 6 months, the initial time of vitamin D supplementation after birth ≤ 1 months, vitamin D and calcium supplementation in the last 3 months, and dose of vitamin D supplementation > 400 IU day (all p < 0.05). Children with preferences for sweets, meat consumption > 150.0 g day , milk consumption < 250 mL day , time of sleeping < 10 h day had higher risks of vitamin D deficiency. However, these relationships were affected by demographics.

Conclusions: Vitamin D status during the first five years of life was suboptimal and was associated with demographic and lifestyle determinants including milk, meat, sweets, vitamin D and calcium supplementation, sleeping and outdoor activity.
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http://dx.doi.org/10.1111/jhn.12883DOI Listing
March 2021

Infectivity, susceptibility, and risk factors associated with SARS-CoV-2 transmission under intensive contact tracing in Hunan, China.

Nat Commun 2021 03 9;12(1):1533. Epub 2021 Mar 9.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1178 potential SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts.
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http://dx.doi.org/10.1038/s41467-021-21710-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943579PMC
March 2021

Digenic Variants in the and Genes Co-segregating With a Limb-Girdle Muscular Dystrophy in a Han Chinese Family.

Front Neurosci 2021 4;15:601757. Epub 2021 Mar 4.

Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.

Limb-girdle muscular dystrophies (LGMD) are hereditary genetic disorders characterized by progressive muscle impairment which predominantly include proximal muscle weaknesses in the pelvic and shoulder girdles. This article describes an attempt to identify genetic cause(s) for a LGMD pedigree via a combination of whole exome sequencing and Sanger sequencing. Digenic variants, the titin gene () c.19481T>G (p.Leu6494Arg) and the trafficking protein particle complex 11 gene () c.3092C>G (p.Pro1031Arg), co-segregated with the disease phenotype in the family, suggesting their possible pathogenicity.
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http://dx.doi.org/10.3389/fnins.2021.601757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969792PMC
March 2021

Identification of α-glucosidase inhibitors from Cortex Lycii based on a bioactivity-labeling high-resolution mass spectrometry-metabolomics investigation.

J Chromatogr A 2021 Apr 4;1642:462041. Epub 2021 Mar 4.

Frontiers Science Center for Disease-related Molecular Network, Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Cortex Lycii, as a kind of traditional Chinese medicines, have shown prospects in the prevention of diabetes and its complications. However, there is comparatively little information regarding the characterization of potentially hypoglycemic compounds derived from Cortex Lycii. In this study, we performed a global non-selective investigation of α-glucosidase inhibitors in Cortex Lycii based on a bioactivity-labeling high-resolution mass spectrometry-metabolomics method. Samples of Cortex Lycii were collected from different Chinese provinces and their ethyl acetate extracts were analyzed using an in vitro α-glucosidase inhibition assay for bioactivity-labeling. The ethyl acetate extracts were also subjected to liquid chromatography-mass spectrometry analysis and multivariate data analysis was subsequently conducted to identify correlations between the bioactivity measured from the enzyme-involved test and the profiles obtained based on high-resolution mass spectrometry. The variables contributing significantly to the separation of the more-active from the less-active samples were considered to indicate the potential target ions of active compounds. MS/MS fragment patterns and nuclear magnetic resonance analyses were used to identify the potential target ions. The developed platform mentioned above facilitated rapid identification of four α-glucosidase inhibitors, namely, N-p-trans-coumaroyltyramine (1), N-trans-caffeoyl-tyramine (2), (9R,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (3a), and (9S,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (3b) from Cortex Lycii. The α-glucosidase inhibitory activities of compounds 3a and 3b with IC values of 1.0413±0.0551 and 1.0423±0.0049 mM, respectively, are reported here for the first time. Enzyme kinetics revealed that both 3a and 3b were non-competitive inhibitors of α-glucosidase, with Ki values of 2.20 and 2.24 mM, respectively. In short, the presented work identified compounds 3a and 3b as potential α-glucosidase inhibitors with higher inhibitory activity and a different mode of inhibition compared to the standard α-glucosidase inhibitor, acarbose. The integrated approach adopted in this study can be extended as a normalized procedure to rapidly identify active compounds, even from complex extracts, and can readily be adapted for the study of other natural products.
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http://dx.doi.org/10.1016/j.chroma.2021.462041DOI Listing
April 2021

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China.

Chin Med J (Engl) 2021 Jan 14;134(5):524-531. Epub 2021 Jan 14.

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Background: Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.

Methods: We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI.

Results: The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56-4.52, P < 0.001), low body mass index (BMI) (OR 0.91, 95% CI 0.84-0.98, P = 0.013), not being married (OR 0.29, 95% CI 0.17-0.49, P < 0.001), history of myocardial infarction (MI) (OR 2.59, 95% CI 1.33-5.04, P = 0.005), higher heart rate (HR) (OR 1.02, 95% CI 1.01-1.03, P = 0.002), cardiac shock in the ED (OR 5.03, 95% CI 1.48-17.08, P = 0.010), pre-hospital delay (>12 h) (OR 3.31, 95% CI 1.83-6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27-0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals.

Conclusions: Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.
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http://dx.doi.org/10.1097/CM9.0000000000001171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929575PMC
January 2021

Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.

Signal Transduct Target Ther 2021 Feb 26;6(1):94. Epub 2021 Feb 26.

Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The arachidonic acid (AA) pathway plays a key role in cardiovascular biology, carcinogenesis, and many inflammatory diseases, such as asthma, arthritis, etc. Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes to a spectrum of bioactive mediators that includes prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases (CVD), cancers, and inflammatory diseases. This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2. Thus, we herein present a synopsis of AA metabolism in human health, cardiovascular and cancer biology, and the signaling pathways involved in these processes. To explore the role of the AA metabolism and potential therapies, we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.
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http://dx.doi.org/10.1038/s41392-020-00443-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910446PMC
February 2021

Distribution of chimeric antigen receptor-modified T cells against CD19 in B-cell malignancies.

BMC Cancer 2021 Feb 25;21(1):198. Epub 2021 Feb 25.

Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.

Background: The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19 B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo.

Methods: NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry.

Results: CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7-21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients.

Conclusions: CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects.

Trial Registration: The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421 .
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http://dx.doi.org/10.1186/s12885-021-07934-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908740PMC
February 2021

Natural variations in a pectin acetylesterase gene, MdPAE10, contribute to prolonged apple fruit shelf life.

Plant Genome 2021 03 18;14(1):e20084. Epub 2021 Feb 18.

College of Horticulture, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing, 100193, China.

Room-temperature shelf life is a key factor in fresh market apple (Malus domestica Borkh.) quality and commercial value. To investigate the genetic and molecular mechanism underlying apple shelf life, quantitative trait loci (QTL) were identified using bulked segregant analysis via sequencing (BSA-seq). Ethylene emission, flesh firmness, or crispness of apple fruit from 1,273 F plants of M. asiatica Nakai 'Zisai Pearl' × M. domestica 'Golden Delicious' were phenotyped prior to and during 6 wk of room-temperature storage. Segregation of ethylene emission and the flesh firmness or crispness traits was detected in the population. Thirteen QTL, including three major ones, were identified on chromosome 03, 08, and 16. A candidate gene encoding pectin acetylesterase, MdPAE10, from the QTL Z16.1 negatively affected fruit shelf life. A 379-bp deletion in the coding sequence of MdPAE10 disrupted its function. A single nucleotide polymorphism (SNP) in the MdPAE10 promoter region reduced its transcription activity. These findings provided insight into the genetic control of fruit shelf life and can be potentially used in apple marker-assisted selection.
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http://dx.doi.org/10.1002/tpg2.20084DOI Listing
March 2021

Lichen sclerosus successfully treated with baricitinib plus psoralen and ultraviolet A.

Dermatol Ther 2021 05 2;34(3):e14896. Epub 2021 Mar 2.

Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, China.

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http://dx.doi.org/10.1111/dth.14896DOI Listing
May 2021

The double face of miR-320: cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction.

Signal Transduct Target Ther 2021 Feb 18;6(1):69. Epub 2021 Feb 18.

Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China.

MicroRNAs (miRNAs) are aberrantly expressed in the pathophysiologic process of heart failure (HF). However, the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported, which might be covered by the globe effects of it on the heart. In the current study, Langendorff system was applied to isolate cardiomyocytes (CMs) and cardiac fibroblasts (CFs) from transverse aortic constriction (TAC)-induced mice. Slight increase of miR-320 expression was observed in the whole heart tissue of TAC mice. Interestingly, miR-320 was significantly elevated in CMs but decreased in CFs from TAC mice at different time points. Then, recombinant adeno-associated virus 9 with cell-type-specific promoters were used to manipulate miR-320 expressions in vivo. Both in vitro and in vivo experiments showed the miR-320 overexpression in CMs exacerbated cardiac dysfunction, whereas overexpression of miR-320 in CFs alleviated cardiac fibrosis and hypertrophy. Mechanically, downstream signaling pathway analyses revealed that miR-320 might induce various effects via targeting PLEKHM3 and IFITM1 in CMs and CFs, respectively. Moreover, miR-320 mediated effects could be abolished by PLEKHM3 re-expression in CMs or IFITM1 re-expression in CFs. Interestingly, miR-320 treated CFs were able to indirectly affect CMs function, but not vice versa. Meanwhile, upstream signaling pathway analyses showed that miR-320 expression and decay rate were rigorously manipulated by Ago2, which was regulated by a cluster of cell-type-specific TFs distinctively expressed in CMs and CFs, respectively. Together, we demonstrated that miR-320 functioned differently in various cell types of the heart during the progression of HF.
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http://dx.doi.org/10.1038/s41392-020-00445-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890065PMC
February 2021

Can a COVID-19 vaccination program guarantee the return to a pre-pandemic lifestyle?

Res Sq 2021 Feb 9. Epub 2021 Feb 9.

COVID-19 vaccination programs have been initiated in several countries to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as vaccination builds up and how to update priority groups for vaccination in real-time remain key questions for policy makers. To address these questions, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent local outbreaks to escalate to major widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs be capable to keep the reproduction number (Rt) around 1.3, a vaccination program could reduce up to 99% of COVID-19 burden and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.
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http://dx.doi.org/10.21203/rs.3.rs-200069/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885929PMC
February 2021

Can a COVID-19 vaccination program guarantee the return to a pre-pandemic lifestyle?

medRxiv 2021 Feb 5. Epub 2021 Feb 5.

COVID-19 vaccination has been initiated in several countries to control SARS-CoV-2 transmission. Whether and when non-pharmaceutical interventions (NPIs) can be lifted as vaccination builds up remains key questions. To address them, we built a data-driven SARS-CoV-2 transmission model for China. We estimated that, to prevent local outbreaks to escalate to major widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs be capable to keep the reproduction number (Rt) around 1.3, vaccination could reduce up to 99% of COVID-19 burden and bring Rt below the epidemic threshold in 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed, especially in large populations with little natural immunity.
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http://dx.doi.org/10.1101/2021.02.03.21251108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872368PMC
February 2021

Who should be prioritized for COVID-19 vaccination in China? A descriptive study.

BMC Med 2021 02 10;19(1):45. Epub 2021 Feb 10.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Background: All countries are facing decisions about which population groups to prioritize for access to COVID-19 vaccination after the first vaccine products have been licensed, at which time supply shortages are inevitable. Our objective is to define the key target populations, their size, and priority for a COVID-19 vaccination program in the context of China.

Methods: On the basis of utilitarian and egalitarian principles, we define and estimate the size of tiered target population groups for a phased introduction of COVID-19 vaccination, considering evolving goals as vaccine supplies increase, detailed information on the risk of illness and transmission, and past experience with vaccination during the 2009 influenza pandemic. Using publicly available data, we estimated the size of target population groups, and the number of days needed to vaccinate 70% of the target population. Sensitivity analyses considered higher vaccine coverages and scaled up vaccine delivery relative to the 2009 pandemic.

Results: Essential workers, including staff in the healthcare, law enforcement, security, nursing homes, social welfare institutes, community services, energy, food and transportation sectors, and overseas workers/students (49.7 million) could be prioritized for vaccination to maintain essential services in the early phase of a vaccination program. Subsequently, older adults, individuals with underlying health conditions and pregnant women (563.6 million) could be targeted for vaccination to reduce the number of individuals with severe COVID-19 outcomes, including hospitalizations, critical care admissions, and deaths. In later stages, the vaccination program could be further extended to target adults without underlying health conditions and children (784.8 million), in order to reduce symptomatic infections and/or to stop virus transmission. Given 10 million doses administered per day, and a two-dose vaccination schedule, it would take 1 week to vaccinate essential workers but likely up to 7 months to vaccinate 70% of the overall population.

Conclusions: The proposed framework is general but could assist Chinese policy-makers in the design of a vaccination program. Additionally, this exercise could be generalized to inform other national and regional strategies for use of COVID-19 vaccines, especially in low- and middle-income countries.
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http://dx.doi.org/10.1186/s12916-021-01923-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872877PMC
February 2021

Combination of acupuncture and medical training therapy on tension type headache: Results of a randomised controlled pilot study.

Cephalalgia 2021 Jul 9;41(8):879-893. Epub 2021 Feb 9.

Department for Rehabilitation Medicine, Hannover Medical School, Hannover, Germany.

Objectives: The aim of this study was to compare the effects of acupuncture and medical training therapy alone and in combination with those of usual care on the pain sensation of patients with frequent episodic and chronic tension-type headache.

Design: This was a prospective single-centre randomised controlled trial with four balanced treatment arms. The allocation was carried out by pre-generated randomisation lists in the ratio 1:1:1:1 with different permutation block sizes.

Setting: The study was undertaken in the outpatient clinic of Rehabilitation Medicine of the Hannover Medical School. Ninety-six adult patients with tension-type headache were included and randomised into usual care (n = 24), acupuncture (n = 24), medical training (n = 24), and combination of acupuncture and medical training (n = 24). One patient was excluded from analysis because of withdrawing her/his consent, leaving 95 patients for intention to treat analysis. Each therapy arm consisted of 6 weeks of treatment with 12 interventions. Follow-up was at 3 and 6 months.

Main Outcome Measures: Pain intensity (average, maximum and minimum), frequency of headache, responder rate (50% frequency reduction), duration of headache and use of headache medication. The combination of acupuncture and medical training therapy significantly reduced mean pain intensity compared to usual care (mean = -38%, standard deviation = 25%,  = 0.012). Comparable reductions were observed for maximal pain intensity (-25%, standard deviation = 20%, 0.014) and for minimal pain intensity (-35%, standard deviation = 31%, 0.03). In contrast, neither acupuncture nor medical training therapy differed significantly from usual care. No between-group differences were found in headache frequency, mean duration of headache episodes, and pain medication intake. At 3 months, the majority of all patients showed a reduction of at least 50% in headache frequency. At 6 months, significantly higher responder rates were found in all intervention groups compared to usual care.

Conclusions: In contrast to monotherapy, only the combination of acupuncture and medical training therapy was significantly superior in reduction of pain intensity compared to usual care. Registered on 11 February 2019. German Clinical Trials Register, DRKS00016723.
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http://dx.doi.org/10.1177/0333102421989620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217893PMC
July 2021