Publications by authors named "Yan Cai"

473 Publications

Exosome-mediated lncRNA SNHG11 Regulates Angiogenesis in Pancreatic Carcinoma Through miR-324-3p/VEGFA Axis.

Cell Biol Int 2021 Sep 14. Epub 2021 Sep 14.

Department of Hepatopancreatobiliary Surgery, the First People's Hospital of Qujing, Qujing, Yunnan, China.

Pancreatic carcinoma (PC) is one of the most common and deadly human malignancies worldwide. LncRNAs play significant roles in the occurrence and development of various cancers. LncRNA SNHG11 (SNHG11) has been found to display high expression in serum of PC patients, which implies that dysregulated SNHG11 may be related to development of PC. However, there is still a knowledge gap concerning the specific function and molecular mechanism of SNHG11 in PC. After conducting experiments with constructed models in vitro or in vivo, we found that exosomal SNHG11 promoted cell proliferation, migration and angiogenesis but impeded cell apoptosis in PC in vitro, and additionally, it facilitated tumor growth in vivo. Exosome-mediated SNHG11 regulated expression of VEGFA through sponging miR-324-3p. Rescue assays validated that the inhibitory effect of SNHG11 depletion on cell proliferation, migration and angiogenesis could be reversed by miR-324-3p down-regulation or VEGFA up-regulation, and the promoting effect of SNHG11 silence on cell apoptosis could be rescued by transfection of miR-324-3p inhibitor or pcDNA3.1-VEGFA. To conclude, exosomal-mediated SNHG11 could regulate PC progression via miR-324-3p/VEGFA axis. Our findings may provide a novel insight for understanding PC, which might contribute to development of potential PC biomarker. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/cbin.11703DOI Listing
September 2021

Selenium Deficiency Induces Apoptosis and Necroptosis Through ROS/MAPK Signal in Human Uterine Smooth Muscle Cells.

Biol Trace Elem Res 2021 Sep 4. Epub 2021 Sep 4.

Department of Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, People's Republic of China.

Selenium (Se) is one of the essential trace elements; its deficiency induces ROS production and cell death in cardiomyocytes, skeletal muscle cells, and vascular smooth muscle cells, but it is still not clear the impact of Se deficiency on human uterine smooth muscle cells (HUSMCs). To investigate the effect of low Se on the mRNA expression of selenoproteins, the mRNA and protein expression of apoptosis and necroptosis of HUSMCs and their mechanism, Se deficient HUSMCs mode was established through culturing with 1% FBS containing 0 ng/mL, 0.7 ng/mL, and 7 ng/mL Se, and 10% FBS was as the control group. Then, the apoptosis and necroptosis rates, intracellular ROS content and the expression levels of selenoproteins, apoptosis, necroptosis, MAPK pathway-related genes were examined under different Se concentrations. The results showed that Se deficiency led to the augment of cell apoptosis and necroptosis in HUSMCs (p < 0.05), downregulated (p < 0.05) 19 selenoproteins (GPX1, GPX2, GPX3, GPX4, GPX6, Dio3, Txnrd2, Txnrd3, SEPHS2, SEL15, SELH, SELI, SELM, SELN, SELO, SELS, SELT, SELV, and SELW), while Dio2, SELK, Txnrd1, and MSRB1 were not affected by Se deficiency (p ≥ 0.05). In addition, Se deficiency led to increased intracellular ROS content, p-P38 and p-JNK gene expression levels (p < 0.05), the mitochondrial apoptosis pathway Bax, Casp9 and Cle-Casp3 protein expression levels (p < 0.05), and decreased Bcl2 protein expression level (p < 0.05), simultaneously, increased necroptosis marker genes RIP1, RIP3, and MLKL protein expression levels (p < 0.05) with a dose-dependent pattern. The above results indicate that Se deficiency induces HUSMCs apoptosis and necroptosis through the ROS/MAPK pathway and is closely related to selenoproteins.
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http://dx.doi.org/10.1007/s12011-021-02910-zDOI Listing
September 2021

Role of lncRNA BCYRN1 in trophoblast cell physiology and pathogenesis of preeclampsia.

Exp Ther Med 2021 Oct 6;22(4):1137. Epub 2021 Aug 6.

Antenatal Diagnosis Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.

Long non-coding RNAs (lncRNAs) may play a key role in the pathogenesis of preeclampsia (PE). The present study investigated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in PE. A total of 30 patients with severe PE (SPE) and 30 patients with mild PE (MPE) were recruited, whilst 30 healthy pregnant individuals were enrolled as controls. Placental tissues of enrolled subjects were collected after delivery. The clinical data of pregnant women and newborns were recorded before the correlation between BCYRN1 expression and clinical characteristics was analyzed. Furthermore, HTR-8/SVneo cells were transfected with BCYRN1 overexpression plasmids and BCYRN1 small interfering (si)RNA. Cell Counting Kit-8, Transwell, flow cytometry and tube formation assays were used to detect the function of BCYRN1 in HTR-8/SVneo cells. Reverse transcription-quantitative PCR was used to detect BCYRN1 expression in placental tissues and HTR-8/SVneo cells. Western blotting was used to detect the protein expression levels of Wnt1 and β-catenin. BCYRN1 expression was lower in placenta with mild PE compared with in normal placenta, and was in turn lower in placenta with severe PE. BCYRN1 was negatively correlated with systolic blood pressure and 24-h urinary protein in patients with PE. BCYRN1 siRNA inhibited cell viability, migration, invasion and tube forming abilities whilst increasing apoptosis. By contrast, BCYRN1 overexpression conferred opposite effects. The levels of Wnt1 and β-catenin expression in the cells and placental tissues were next measured. Cells overexpressing BCYRN1 were further treated with the Wnt pathway inhibitor XAV939. Wnt1 and β-catenin expression were elevated when BCYRN1 was overexpressed, but were decreased after BCYRN1 knockdown. XAV939 attenuated the effect of BCYRN1 overexpression on HTR-8/SVneo cells. Overall, the resulted indicated that upregulation of BCYRN1 increased trophoblast viability and prevented apoptosis by activating the Wnt/β-catenin pathway to delay PE onset.
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http://dx.doi.org/10.3892/etm.2021.10571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383326PMC
October 2021

Digital Subtraction Angiography Contrast Material Transport as a Direct Assessment for Blood Perfusion of Middle Cerebral Artery Stenosis.

Front Physiol 2021 5;12:716173. Epub 2021 Aug 5.

School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China.

Digital subtraction angiography (DSA) is a fluoroscopic technique used extensively in interventional radiology for visualizing blood vessels. It has also been used to evaluate blood perfusion. However, the perfusion obtained in previous techniques was extracted from signal intensity rather than by the transport of contrast material (CM) through blood flow. The main aim of this study is to evaluate the morphological effects on the hemodynamics and the CM concentration in the middle cerebral artery (MCA) stenosis. We proposed a quantitative parameter, i.e., contrast material remaining time (CMRT), to describe the variation in the transport of CM over time. Computational fluid dynamics simulations were performed on both reconstructive synthetic and patient-derived models. In the synthetic models, we evaluated the variation of flow patterns and the transport of CM with different degrees of stenosis and the location of the lesion. It was found that an increase in the degree of stenosis (from 30 to 80%) resulted in a significant increase in CMRT at the anterior cerebral artery (ACA) outlet ( = 0.0238) and a significant decrease in CMRT at the MCA outlet ( = 0.012). The patient-derived models were reconstructed from the pre- and post-interventional DSA images of a patient with MCA stenosis. Both blood flow velocity and CMRT increased at the ACA outlet but decreased at the MCA outlet. The perfusion analysis demonstrated that the perfusion function was improved after interventional surgery. In conclusion, changes in stenotic degree at MCA may lead to apparent differences in the hemodynamic distribution and the transport of CM. CMRT could be a quantitative indicator to evaluate the changes in blood perfusion after the intervention for MCA stenosis.
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http://dx.doi.org/10.3389/fphys.2021.716173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375590PMC
August 2021

Evaluation of iodine nutritional status during pregnancy by estimated 24-h urinary iodine excretion: population variation range and individual accuracy.

Public Health Nutr 2021 Aug 12:1-11. Epub 2021 Aug 12.

Key Laboratory of Etiology and Epidemiology, National Health and Family Planning Commission, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, No.196, Baojian road, Harbin, Heilongjiang 150086, People's Republic of China.

Objective: To explore the accuracy of estimated 24-h urinary iodine excretion (24-h UIEest) in assessing iodine nutritional status.

Design: Fasting venous blood, 24-h and spot urine samples were collected during the day. The urinary iodine concentration (UIC) and urinary creatinine concentration (UCrC) were measured, and the urinary iodine-to-creatinine ratio (UI/Cr), 24-h UIEest, and 24-h urinary iodine excretion (24-h UIE) were calculated. At the population level, correlation and consistency between UIC, UI/Cr, 24-h UIEest and 24-h UIE were assessed using correlation analysis and Bland-Altman plots. At the individual level, receiver operating characteristic (ROC) curves were used to analyse the accuracy of the above indicators for evaluating insufficient and excessive iodine intake. The reference interval of 24-h UIEest was established based on percentile values.

Setting: Indicator can accurately evaluate individual iodine nutrition during pregnancy remains controversial.

Participants: Pregnant women (n 788).

Results: Using 24-h UIE as standard, the correlation coefficients of 24-h UIEest from different periods of the day ranged from 0·409 to 0·531, and the relative average differences ranged from 4·4 % to 10·9 %. For diagnosis of insufficient iodine intake, the area under the ROC curve of 24-h UIEest was 0·754, sensitivity and specificity were 79·6 % and 65·4 %, respectively. For diagnosis of excessive iodine intake, the area of 24-h UIEest was 0·771, sensitivity and specificity were 66·7 % and 82·0 %, respectively. The reference interval of 24-h UIEest was 58·43-597·65 μg.

Conclusions: Twenty-four-hour UIEest can better indicate iodine nutritional status at a relatively large sample size in a given population of pregnant women. It can be used for early screening at the individual level to obtain more lead time for pregnant women.
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http://dx.doi.org/10.1017/S1368980021003335DOI Listing
August 2021

Screening and Validation of Independent Predictors of Poor Survival in Pancreatic Cancer.

Pathol Oncol Res 2021 12;27:1609868. Epub 2021 Jul 12.

Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, China.

Pancreatic cancer is a digestive system malignant tumor with high mortality and poor prognosis, but the mechanisms of progression remain unclear in pancreatic cancer. It's necessary to identify the hub genes in pancreatic cancer and explore the novel potential predictors in the prognosis of pancreatic cancer. We downloaded two mRNA expression profiles from Gene Expression Omnibus and The Cancer Genome Atlas Pancreatic Cancer (TCGA-PAAD) datasets to screen the commonly differentially expressed genes in pancreatic cancer by limma package in R. Subsequently, measurement of the functional similarity among the 38 DEGs in common was performed to identify the hub genes using GOSemSim package. Then, survival analysis and Cox regression were applied to explore prognosis-related hub genes using the survival package. Statistics analysis by two-tailed Student's t-test or one-way based on TCGA-PAAD datasets and qPCR detection in clinical samples were performed to explore the correlations between expression of hub genes in pancreatic cancer tissues and clinical parameters. Based on integrated analysis of TCGA and GEO datasets, we screened 38 DEGs in common, which were all up-regulated. The functional similarity results showed that 10 DEGs including TSPAN1, MSLN, C1orf116, PKP3, CEACAM6, BAIAP2L1, PPL, RAB25, ERBB3, and AP1M2 in the DEGs in common, which had the higher average functional similarity, were considered as the hub genes. Survival analysis results and Cox regression analysis showed that TSPAN1, CEACAM6, as well as ERBB3 were all associated with poor overall survival of PC. qPCR results showed that the expression levels of TSPAN1 and ERBB3 were significantly upregulated in the PC tissues. The statistical analysis results revealed that TSPAN1 expression correlated significantly with histologic grade, T stage, clinical stage, and vital status by two-tailed Student's t-test or one-way ANOVA; ERBB3 expression correlated significantly with T stage, clinical stage, and vital status by two-tailed Student's t-test or one-way ANOVA. We found that TSPAN1 and ERBB3 could be independent predictors of poor survival in pancreatic cancer.
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http://dx.doi.org/10.3389/pore.2021.1609868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310909PMC
July 2021

Prevalence and characteristics of atherosclerotic plaque: Left compared with right arteries and anterior compared with posterior circulation stroke.

Eur J Radiol 2021 Sep 13;142:109862. Epub 2021 Jul 13.

Department of Radiology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Rd, Yuanjiagang, Yuzhong District, Chongqing 40016, China. Electronic address:

Purpose: To evaluate atherosclerotic plaque prevalence and characteristics between left and right cervicocephalic arteries and between anterior and posterior circulation stroke (ACS and PCS).

Methods: This retrospective study included 284 patients with acute ischemic stroke (199 ACS and 85 PCS) involving large-artery atherosclerosis or small-artery occlusion. We assessed atherosclerotic plaque prevalence and characteristics (plaque type, plaque surface morphology, plaque distribution, location of calcified nodules and plaque thickness) in each segment and their comparisons between left and right arteries and between ACS and PCS.

Results: The left subclavian artery (L-SA), common carotid artery (L-CCA) and intracranial vertebral artery (L-IVA) had significantly higher prevalence of atherosclerotic plaque than the right (R) corresponding arteries (70.1% versus 59.5%, P = 0.008), (48.1% versus 28.9%, P < 0.001), (23.9% versus 16%, P = 0.018), respectively. L-SA had a higher prevalence of mixed plaque (non-calcified > calcified) (19.6% versus 16.4%) and noncalcified plaque (51.9% versus 31.7%), and a lower prevalence of calcified plaque (8.9% versus 23.3%) and mixed plaque (calcified > non-calcified) (19.6% versus 28.6%) than R-SA, P < 0.001. The distribution of plaque type in the SA and extracranial vertebral artery (EVA) were significantly different between ACS and PCS. The soft plaque thickness of SA in PCS was significantly greater than that in ACS (3.85 ± 1.27 versus 3.51 ± 1.04, P = 0.032).

Conclusions: Atherosclerotic plaque prevalence and characteristics vary in different segments, sides and between ACS and PCS. These differences should be noted during plaque diagnosis.
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http://dx.doi.org/10.1016/j.ejrad.2021.109862DOI Listing
September 2021

MoCpa1-mediated arginine biosynthesis is crucial for fungal growth, conidiation, and plant infection of Magnaporthe oryzae.

Appl Microbiol Biotechnol 2021 Aug 22;105(14-15):5915-5929. Epub 2021 Jul 22.

Fujian Universities Key Laboratory for Plant-Microbe Interaction, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Arginine is an important amino acid involved in processes such as cell signal transduction, protein synthesis, and sexual reproduction. To understand the biological roles of arginine biosynthesis in pathogenic fungi, we used Cpa1, the carbamoyl phosphate synthase arginine-specific small chain subunit in Saccharomyces cerevisiae as a query to identify its ortholog in the Magnaporthe oryzae genome and named it MoCpa1. MoCpa1 is a 471-amino acid protein containing a CPSase_sm_chain domain and a GATase domain. MoCpa1 transcripts were highly expressed at the conidiation, early-infection, and late-infection stages of the fungus. Targeted deletion of the MoCPA1 gene resulted in a ΔMocpa1 mutant exhibiting arginine auxotrophy on minimum culture medium (MM), confirming its role in de novo arginine biosynthesis. The ΔMocpa1 mutant presented significantly decreased sporulation with some of its conidia being defective in morphology. Furthermore, the ΔMocpa1 mutant was nonpathogenic on rice and barley leaves, which was a result of defects in appressorium-mediated penetration and restricted invasive hyphal growth within host cells. Addition of exogenous arginine partially rescued conidiation and pathogenicity defects on the barley and rice leaves, while introduction of the MoCPA1 gene into the ΔMocpa1 mutant fully complemented the lost phenotype. Further confocal microscopy examination revealed that MoCpa1 is localized in the mitochondria. In summary, our results demonstrate that MoCpa1-mediated arginine biosynthesis is crucial for fungal development, conidiation, appressorium formation, and infection-related morphogenesis in M. oryzae, thus serving as an attractive target for mitigating obstinate fungal plant pathogens. KEY POINTS: • MoCpa1 is important for aerial hyphal growth and arginine biosynthesis. • MoCpa1 is pivotal for conidial morphogenesis and appressorium formation. • MoCpa1 is crucial for full virulence in M. oryzae.
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http://dx.doi.org/10.1007/s00253-021-11437-1DOI Listing
August 2021

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

J Clin Lab Anal 2021 Sep 21;35(9):e23904. Epub 2021 Jul 21.

State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background And Aims: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC.

Methods: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera.

Results: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001).

Conclusions: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.
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http://dx.doi.org/10.1002/jcla.23904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418505PMC
September 2021

Establishing cut-off scores for the self-rating AD8 based on education level.

Geriatr Nurs 2021 Jul 15;42(5):1093-1098. Epub 2021 Jul 15.

Department of Psychiatry and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

This study aimed to explore the threshold of self-rating AD8 in mild cognitive impairment (MCI) and dementia screening among community-dwelling older adults with and without education. 523 participants in Chengdu, China, were recruited: 346 with normal cognitive function, 160 with MCI and 17 with dementia. At the cut-off score of 2, the area under the receiver operator characteristic curves (AUC) of self-rating AD8 for MCI and dementia screening was 0.607 and 0.931 regardless of educational level, respectively. Grouping by educational level, the cut-off in MCI screening was 1 for literate (AUC=0.662) and 2 for illiterate individuals (AUC=0.588). For dementia screening, the cut-off was 2 for illiterate (AUC=0.912) and 4 for literate individuals (AUC=0.963). We concluded that the self-rating AD8 was ideal for dementia screening in community-dwelling older adults, with a cut-off score of 2 for illiterate and 4 for literate people, while its effectiveness for MCI screening required further evaluation.
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http://dx.doi.org/10.1016/j.gerinurse.2021.06.027DOI Listing
July 2021

Increasing wavelength-controlled steering range of an optical phased array by using two subarrays.

Appl Opt 2021 Jun;60(18):5424-5429

We demonstrate an optical phased array that consists of two subarrays based on the silicon on insulator (SOI) platform, each subarray including 16 independent channels. The demonstrated field of view of the optical phased array is 36.6×32.6 with a spot size of 1.68×0.0673. A steering range of 32.6° is achieved by combining two subarrays with different periods and tuning the wavelength from 1500 nm to 1600 nm. In another dimension, the steering is realized by introducing phase differences between channels.
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http://dx.doi.org/10.1364/AO.422721DOI Listing
June 2021

S100A8/A9 Molecular Complexes Promote Cancer Migration and Invasion via the p38 MAPK Pathway in Nasopharyngeal Carcinoma.

Bioinorg Chem Appl 2021 22;2021:9913794. Epub 2021 Jun 22.

Pharmaceutical College, Guangxi Medical University, Nanning, China.

Nasopharyngeal carcinoma (NPC) is one type of malignancy associated with migration and invasion through a currently unclear mechanism. We previously discovered S100A8/A9 levels were roughly elevated in the plasma of NPC patients as the promising biomarkers. However, their expressions and underlying functions in NPC tissues are still unknown. In the present study, we analyzed 49 NPC tissues and 20 chronic pharyngitis (CP) tissues. Immunohistochemical staining was performed in different tissues and analyzed by the Mann-Whitney test statistically. Transwell migration and invasion experiments were further performed to determine S100A8/A9 effects on NPC. Our results showed that S100A8/A9 in NPC tissues were significantly higher than those in CP tissues, closely associated with NPC clinical stages. Intriguingly, exogenous S100A8/A9 protein stimulation could dramatically enhance NPC migration and invasion abilities. In addition, p38 MAPK pathway blockade could diminish the migration and invasion of NPC cells stimulated by S100A8/A9 proteins. The downstream tumor invasion and migration associated proteins (e.g., MMP7) were also elevated in NPC tissues, consistent with S100A8/A9 overexpression. Taken together, our present findings suggest that the secreted soluble inflammatory factors S100A8/A9 might promote cancer migration and invasion via the p38 MAPK signaling pathway along with invasion/migration associated proteins overexpression in the tumor microenvironment of NPC. This may shed light on the mechanism understanding of NPC prognosis and provide more novel clues for NPC diagnosis and therapy.
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http://dx.doi.org/10.1155/2021/9913794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245251PMC
June 2021

Airway resistance variation correlates with prognosis of critically ill COVID-19 patients: A computational fluid dynamics study.

Comput Methods Programs Biomed 2021 Sep 25;208:106257. Epub 2021 Jun 25.

Department of Critical Care Medicine, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China. Electronic address:

Objective: To evaluate the quantitative changes of respiratory functions for critically ill COVID-19 patients with mechanical ventilation, computational fluid dynamics (CFD) analysis was performed based on patient-specific three-dimensional airway geometry.

Methods: 37 cases of critically ill patients with COVID-19 admitted to the ICU of Huangshi Traditional Chinese Medicine Hospital from February 1st to March 20th, 2020 were retrospectively analyzed. 5 patients whose clinical data met the specific criteria were finally cataloged into death group (2 patients) and survival group (3 patients). The patient-specific three-dimensional airways were reconstructed from the central airways down to the 4th-5th bifurcation of the tracheobronchial tree. The volume changes of bronchi were calculated during the disease progression according to the comparison of two CT scans. Additionally, the changes of air flow resistance were analyzed using numerical simulation of CFD.

Results: Pearson correlation analysis demonstrated that there was negative correlation between the change of volume (ΔV) and the change of resistance (ΔR) for all COVID-19 patients (r=-0.7025). For total airway volume, an average decrease of -11.41±15.71% was observed in death group compared to an average increase of 1.86±10.80% in survival group (p=0.0232). For air flow through airways in lower lobe, the resistance increases for death group by 10.97±77.66% and decreases for survival group by -45.49±42.04% (p=0.0246).

Conclusion: The variation of flow resistance in the airway could be used as a non-invasive functional evaluation for the prognosis and outcome of critically ill patients with COVID-19. The 'virtual' pulmonary function test by integrating follow-up CT scans with patient-derived CFD analysis could be a potentially powerful way in improving the efficiency of treatment for critically ill patients with COVID-19.
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http://dx.doi.org/10.1016/j.cmpb.2021.106257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231702PMC
September 2021

A Generalized Diagnostic Classification Modeling Framework Integrating Differential Speediness: Advantages and Illustrations in Psychological and Educational Testing.

Multivariate Behav Res 2021 Jun 21:1-20. Epub 2021 Jun 21.

Jiangxi Normal University, Nanchang, China.

To advance the theoretical foundation of incorporating response times (RTs) into diagnostic classification models (DCMs), this study attempts to further derive, test and illustrate a generalized modeling framework (known as the JVRT-LCDM) that can simultaneously analyze response accuracy and differential speediness based on an existing method (Zhan et al., , 71(2), 262-286, 2018). The JVRT-LCDM not only provides fine-grained diagnostic feedback without strict model constraints but also clarifies the specific speed trajectory of individuals. Moreover, some existing models from psychometric literatures are included in the JVRT-LCDM as special cases. The feasibility of the JVRT-LCDM is investigated via a Monte Carlo simulation study using a Bayesian estimation scheme, and two empirical datasets are then analyzed to illustrate the applicability of the JVRT-LCDM in practice. The results indicate that (1) as a generalized and flexible model, the JVRT-LCDM realizes high correct classification rates and accurate speed parameter recovery; (2) the JVRT-LCDM outperforms the existing models in terms of model-data fit, diagnostic consistency, and estimation of specific individuals in practical cognitive diagnosis assessments; and (3) the JVRT-LCDM provides reliable evidence for nonconstant speed modeling.
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http://dx.doi.org/10.1080/00273171.2021.1928474DOI Listing
June 2021

Suppression of mitochondrial ROS by prohibitin drives glioblastoma progression and therapeutic resistance.

Nat Commun 2021 06 17;12(1):3720. Epub 2021 Jun 17.

State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.

Low levels of reactive oxygen species (ROS) are crucial for maintaining cancer stem cells (CSCs) and their ability to resist therapy, but the ROS regulatory mechanisms in CSCs remains to be explored. Here, we discover that prohibitin (PHB) specifically regulates mitochondrial ROS production in glioma stem-like cells (GSCs) and facilitates GSC radiotherapeutic resistance. We find that PHB is upregulated in GSCs and is associated with malignant gliomas progression and poor prognosis. PHB binds to peroxiredoxin3 (PRDX3), a mitochondrion-specific peroxidase, and stabilizes PRDX3 protein through the ubiquitin-proteasome pathway. Knockout of PHB dramatically elevates ROS levels, thereby inhibiting GSC self-renewal. Importantly, deletion or pharmacological inhibition of PHB potently slows tumor growth and sensitizes tumors to radiotherapy, thus providing significant survival benefits in GSC-derived orthotopic tumors and glioblastoma patient-derived xenografts. These results reveal a selective role of PHB in mitochondrial ROS regulation in GSCs and suggest that targeting PHB improves radiotherapeutic efficacy in glioblastoma.
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http://dx.doi.org/10.1038/s41467-021-24108-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211793PMC
June 2021

Comparison of Psychometric Characteristics for Five Versions of the Interpersonal Needs Questionnaire in Teenagers Sample.

Front Psychol 2021 28;12:676361. Epub 2021 May 28.

School of Psychology, Jiangxi Normal University, Nanchang, China.

Interpersonal Needs Questionnaire (INQ) is a self-report measure of perceived burdensomeness and thwarted belongingness with five versions in recent studies. There are five versions of INQ. But results from studies using different versions are quite different. Current suicide behavior among teenagers has attracted much attention. But which version is more suitable for teenage samples is still uncertain. It is important to compare the potential differences in different versions of INQ to identify the most psychometrically available version to predict teenagers' acquired capability for suicide and provide them with timely help to reduce teenagers' suicide rates. This study compared the construct validity, internal consistency, validity, and average test information of each version in the sample of teenagers. Results showed the 10-item version provided the most average test information in both thwarted belongingness subscale and perceived burdensomeness subscale, and the INQ-10 is more suitable for teenage samples.
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http://dx.doi.org/10.3389/fpsyg.2021.676361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193059PMC
May 2021

MoSep3 and MoExo70 are needed for MoCK2 ring assembly essential for appressorium function in the rice blast fungus, Magnaporthe oryzae.

Mol Plant Pathol 2021 Sep 11;22(9):1159-1164. Epub 2021 Jun 11.

State Key Laboratory for Ecological Pest Control of Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, China.

Polar growth during appressorium formation is vital for the penetration peg formation in the rice blast fungus, Magnaporthe oryzae. Previous research has shown that the Sln1-septin-exocyst complex, localized at the base of the appressorium in contact with the leaf surface, forms a ring structure that influences growth polarity and affects penetration peg formation, and is necessary for pathogenicity. Our previous research showed CK2 proteins assemble another ring structure positioned perpendicular to the Sln1-septin-exocyst complex. Our research showed that the CK2 ring needs to become correctly assembled for penetration peg function and subsequent plant infection. In the present study, we found that the ring structures of CK2 are absent in the appressorium of ΔMoSep3 septin deletion mutants lacking the septin ring of the Sln1-septin-exocyst complex. Sln1 affects the septin proteins that recruit the exocyst complex that localizes as another ring at the appressorium's bottom. Destruction of the exocyst complex by mutation also causes incorrect localization of the CK2 ring structure. In conclusion, CK2 probably takes part in reestablishing the appressorium' spolarity growth necessary for penetration peg formation. We can also conclude that the correct localization and assembly of one or more CK2 ring structures in the appressorium depend on the initial assembly of the Sln1-septin-exocyst complex two rings at the base of the appressorium.
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http://dx.doi.org/10.1111/mpp.13092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358994PMC
September 2021

The molecular mechanism underlying pathogenicity inhibition by sanguinarine in Magnaporthe oryzae.

Pest Manag Sci 2021 Oct 24;77(10):4669-4679. Epub 2021 Jun 24.

Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, China.

Background: Sanguinarine (SAN) is a benzophenanthridine alkaloid that broadly targets a range of pathways in mammalian and fungal cells. In this study we set out to explore the molecular mechanism of sanguinarine inhibition of the fungal development and pathogenicity of Magnaporthe oryzae with the hope that sanguinarine will bolster the development of antiblast agents.

Results: We found that the fungus exhibited a significant reduction in vegetative growth and hyphal melanization while the spores produced long germ tubes on the artificial hydrophobic surface characteristic of a defect in thigmotropic sensing when exposed to 4, 8 and 0.5 μm sanguinarine, respectively. Consistent with these findings, we observed that the genes involved in melanin biosynthesis and the fungal hydrophobin MoMPG1 were remarkably suppressed in mycelia treated with 8 μm sanguinarine. Additionally, sanguinarine inhibited appressorium formation at a dose of 1.0 μm and this defect was restored by supplementing 5 mM of exogenous cAMP. By qRT-PCR assay we found cAMP pathway signalling genes such as MoCAP1 and MoCpkA were significantly repressed whereas MoCDTF1 and MoSOM1 were upregulated in sanguinarine-treated strains. Furthermore, we showed that sanguinarine does not selectively inhibit vegetative growth and appressorium formation of Guy11 but also other strains of M. oryzae. Finally, treatment of sanguinarine impaired the appressorium-mediated penetration and pathogenicity of M. oryzae in a dose-dependent manner.

Conclusion: Based on our results we concluded that sanguinarine is an attractive antimicrobial candidate for fungicide development in the control of rice blast disease. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6508DOI Listing
October 2021

Latamoxef-induced coagulation disorders: Incidence and risk factors.

J Clin Pharm Ther 2021 Oct 10;46(5):1382-1386. Epub 2021 Jun 10.

Department of Pharmacy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

What Is Known And Objective: To observe the effect of latamoxef on coagulation function and to analyse its risk factors.

Methods: A retrospective cohort study was performed to compare patients receiving latamoxef versus those treated with ceftazidime. Baseline characteristics and coagulation parameters were recorded and analysed to explore whether treatment with latamoxef increased the risks of coagulation disorders and bleeding.

Results And Discussion: A total number of 162 patients receiving latamoxef and 93 patients receiving ceftazidime were included. Haemorrhagic events were similar between groups, but patients receiving latamoxef had a higher risk of coagulation disorders compared to those receiving ceftazidime. Multivariate analysis revealed that the exposure of antibiotics, especially the cumulative defined daily doses (DDDs), and the nutrition risk may be the predictors of coagulation disorders.

What Is New And Conclusion: Latamoxef might induce coagulation disorders. Cumulative DDDs and the nutrition risk were linked with coagulation disorders.
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http://dx.doi.org/10.1111/jcpt.13435DOI Listing
October 2021

[Diagnostic Cut-Off Value of RDW for Screening Thalassemia and the Combined Determination of MCV, MCH, HBA and RDW].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):847-852

Department of Prenatal Diagnosis of Affiliated Hospital of North Sichuan Medical College,Nanchong 637000, Sichuan Province, China,Laboratory of Medical Examination of North Sichuan Medical College,Nanchong 637000, Sichuan Province, China,Translational Medicine Research Center of North Sichuan Medical College,Nanchong 637000, Sichuan Province, China,E-mail:

Objective: To explore the value of red cell distribution width (RDW), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin (Hb) A2 combined determination scheme for screening thalassemia.

Methods: The RDW levels of thalassemia group and healthy control group were detected and compared. The efficiency of RDW for screening thalassemia was evaluated by receiver operating characteristic (ROC) curve. The diagnostic cut-off value of RDW was also acquired by Youden index. Then, 3 groups for thalassemia screening scheme were set, including MCV+MCH+HBA , MCV+MCH+RDW(>16.0)+HBA and MCV+MCH+RDW(>15.15)+HBA . The performances of the 3 groups were evaluated through screening 621 clinical suspected cases of thalassemia.

Results: The RDW level in thalassemia group was significantly higher than that in healthy control group (P<0.05). The diagnostic cut-off value for screening thalassemia was RDW>15.15, when the Youden index was the biggest among all data. The sensitivity, specificity, positive predictive value, negative predictive value, false negative rate and consistency rate of MCV+MCH+RDW(>15.15)+HBA group was 75.46%, 48.83%, 26.50%, 89.06%, 24.54%, and 54.06%, respectively.

Conclusion: The diagnostic cut-off value of RDW for thalassemia screening has been established. The group of MCV(<82.0 fl)+MCH(<27.0 pg)+HBA (<2.5% or ≥3.5%)+RDW(>15.15) has a best efficiency among the 3 groups to screen thalassemia.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.030DOI Listing
June 2021

Inhibition of CDK9 attenuates atherosclerosis by inhibiting inflammation and phenotypic switching of vascular smooth muscle cells.

Aging (Albany NY) 2021 06 8;13(11):14892-14909. Epub 2021 Jun 8.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.

Background: Recent studies have demonstrated a key role of vascular smooth muscle cell (VSMC) dysfunction in atherosclerosis. Cyclin-dependent kinases 9 (CDK9), a potential biomarker of atherosclerosis, was significantly increased in coronary artery disease patient serum and played an important role in inflammatory diseases. This study was to explore the pharmacological role of CDK9 inhibition in attenuating atherosclerosis.

Methods: A small-molecule CDK9 inhibitor, LDC000067, was utilized to treat the high fat diet (HFD)-fed ApoE mice and human VSMCs.

Results: The results showed that inflammation and phenotypic switching of VSMCs were observed in HFD-induced atherosclerosis in ApoE mice, which were accompanied with increased CDK9 in the serum and atherosclerotic lesions where it colocalized with VSMCs. LDC000067 treatment significantly suppressed HFD-induced inflammation, proliferation and phenotypic switching of VSMCs, resulting in reduced atherosclerosis in the ApoE mice, while had no effect on plasma lipids. Further studies confirmed that LDC000067 and siRNA-mediated CDK9 knockdown reversed ox-LDL-induced inflammation and phenotypic switching of VSMCs from a contractile phenotype to a synthetic phenotype via inhibiting NF-κB signaling pathway in human VSMCs.

Conclusion: These results indicate that inhibition of CDK9 may be a novel therapeutic target for the prevention of atherosclerosis.
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http://dx.doi.org/10.18632/aging.202998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221363PMC
June 2021

Role of vascular smooth muscle cell phenotypic switching in plaque progression: A hybrid modeling study.

J Theor Biol 2021 10 1;526:110794. Epub 2021 Jun 1.

School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China; School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4001, Australia. Electronic address:

Growing genetic lineage mapping experiments have definitively shown a wide-ranging plasticity of vascular smooth muscle cells (VSMCs) in atherosclerotic plaque and suggested that VSMCs can modulate their phenotypes in response to plaque microenvironment. Here, a multiscale hybrid discrete-continuous (HDC) modeling system is established to investigate the complex role of VSMC phenotypic switching within atherosclerotic lesions. The cellular behaviors of VSMCs and macrophages, including proliferation, migration, phenotypic transformation and necrosis, are determined by cellular automata (CA) rules in discrete model. While the dynamics of plaque microenvironmental factors, such as lipid, extracellular matrix (ECM) and chemokines, are described by continuous reaction-diffusion equations in macroscopy. The simulation results demonstrate how the VSMC activities change the extracellular microenvironment and consequently affect the plaque morphology and stability. The regulation of VSMC phenotypes can affect not only the plaque morphology (necrotic core size and fibrous cap thickness) but also the deposition and distribution of microenvironmental factors (lipoprotein, ECM, and chemokines). In addition, it is found that plaque vulnerability can be inhibited by blocking VSMC transdifferentiation to a macrophage-like state and promoting it to a myofibroblastic phenotype, which suggests that targeting VSMC phenotypic switching could be a potential and promising therapeutic strategy for atherosclerosis.
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http://dx.doi.org/10.1016/j.jtbi.2021.110794DOI Listing
October 2021

Automated Test Assembly for Multistage Testing With Cognitive Diagnosis.

Front Psychol 2021 6;12:509844. Epub 2021 May 6.

School of Psychology, Jiangxi Normal University, Nanchang, China.

Computer multistage adaptive test (MST) combines the advantages of paper and pencil-based test (P&P) and computer-adaptive test (CAT). As CAT, MST is adaptive based on modules; as P&P, MST can meet the need of test developers to manage test forms and keep test forms parallel. Cognitive diagnosis (CD) can accurately measure students' knowledge states (KSs) and provide diagnostic information, which is conducive to student's self-learning and teacher's targeted teaching. Although MST and CD have a lot of advantages, many factors prevent MST from applying to CD. In this study, we first attempt to employ automated test assembly (ATA) to achieve the objectives of MST in the application of CD (called CD-MST) via heuristic algorithms. The mean correct response probability of all KSs for each item is used to describe the item difficulty of CD. The attribute reliability in CD is defined as the test quantitative target. A simulation study with the G-DINA model (generalized deterministic input noisy "and" gate model) was carried out to investigate the proposed CD-MST, and the results showed that the assembled panels of CD-MST satisfied the statistical and the non-statistical constraints.
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http://dx.doi.org/10.3389/fpsyg.2021.509844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136431PMC
May 2021

High-quality genome assembly of Pseudopestalotiopsis theae, the pathogenic fungus of tea grey blight.

Plant Dis 2021 May 12. Epub 2021 May 12.

Fujian Agriculture and Forestry University, Fujian Universities Key Laboratory for Plant-Microbe Interaction, College of Plant Protection, Fuzhou, Fujian, China;

Tea grey blight is one of the most serious foliar diseases of tea tree caused by the plant pathogenic fungus Pseudopestalotiopsis theae which can affect production and quality of tea worldwide. We generated a highly contiguous, 50.41Mbp genome assembly (N50 1.30 Mbp) of P. theae strain CYF27 by combining PacBio long-read and Illumina short-read sequencing technologies. We identified a total of 15,626 gene models, of which 1,038 genes encode putative secreted proteins. The high-quality genome assembly and annotation resource reported here will be useful for the study of fungal infection mechanisms and pathogen-host interaction.
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http://dx.doi.org/10.1094/PDIS-02-21-0318-ADOI Listing
May 2021

A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.

Nat Commun 2021 05 11;12(1):2623. Epub 2021 May 11.

Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, People's Republic of China.

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.
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http://dx.doi.org/10.1038/s41467-021-22926-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113581PMC
May 2021

Exploring boron applications in modern agriculture: A structure-activity relationship study of a novel series of multi-substitution benzoxaboroles for identification of potential fungicides.

Bioorg Med Chem Lett 2021 07 5;43:128089. Epub 2021 May 5.

Boragen, Inc., 5 Laboratory Drive, Suite 2150, Research Triangle Park, Durham, NC 27709, USA.

Several boron-containing small molecules have been approved by the US FDA to treat human diseases. We explored potential applications of boron-containing compounds in modern agriculture by pursuing multiple research and development programs. Here, we report a novel series of multi-substitution benzoxaboroles (1-36), a compound class that we recently reported as targeting geranylgeranyl transferase I (GGTase I) and thereby inhibiting protein prenylation (Kim et al., 2020). These compounds were designed, synthesized, and tested against the agriculturally important fungal pathogens Mycosphaerella fijiensis and Colletotrichum sublineolum in a structure-activity relationship (SAR) study. Compounds 13, 28, 30, 34 and 36 were identified as active leads with excellent antifungal MIC values in the range of 1.56-3.13 ppm against M. fijiensis and 0.78-3.13 ppm against C. sublineolum.
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http://dx.doi.org/10.1016/j.bmcl.2021.128089DOI Listing
July 2021

A ten N6-methyladenosine-related long non-coding RNAs signature predicts prognosis of triple-negative breast cancer.

J Clin Lab Anal 2021 Jun 2;35(6):e23779. Epub 2021 May 2.

Shanghai Research Center of Biliary Tract Disease, Shanghai, China.

Background: Patients with triple-negative breast cancer (TNBC) face a major challenge of the poor prognosis, and N6-methyladenosine-(m6A) mediated regulation in cancer has been proposed. Therefore, this study aimed to explore the prognostic roles of m6A-related long non-coding RNAs (LncRNAs) in TNBC.

Methods: Clinical information and expression data of TNBC samples were collected from TCGA and GEO databases. Pearson correlation, univariate, and multivariate Cox regression analysis were employed to identify independent prognostic m6A-related LncRNAs to construct the prognostic score (PS) risk model. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PS risk model. A competing endogenous RNA (ceRNA) network was established for the functional analysis on targeted mRNAs.

Results: We identified 10 independent prognostic m6A-related LncRNAs (SAMD12-AS1, BVES-AS1, LINC00593, MIR205HG, LINC00571, ANKRD10-IT1, CIRBP-AS1, SUCLG2-AS1, BLACAT1, and HOXB-AS1) and established a PS risk model accordingly. Relevant results suggested that TNBC patients with lower PS had better overall survival status, and ROC curves proved that the PS model had better prognostic abilities with the AUC of 0.997 and 0.864 in TCGA and GSE76250 datasets, respectively. Recurrence and PS model status were defined as independent prognostic factors of TNBC. These ten LncRNAs were all differentially expressed in high-risk TNBC compared with controls. The ceRNA network revealed the regulatory axes for nine key LncRNAs, and mRNAs in the network were identified to function in pathways of cell communication, signaling transduction and cancer.

Conclusion: Our findings proposed a ten-m6A-related LncRNAs as potential biomarkers to predict the prognostic risk of TNBC.
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http://dx.doi.org/10.1002/jcla.23779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183938PMC
June 2021

Mathematical modeling of intraplaque neovascularization and hemorrhage in a carotid atherosclerotic plaque.

Biomed Eng Online 2021 Apr 29;20(1):42. Epub 2021 Apr 29.

School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China.

Background: Growing experimental evidence has identified neovascularization from the adventitial vasa vasorum and induced intraplaque hemorrhage (IPH) as critical indicators during the development of vulnerable atherosclerotic plaques. In this study, we propose a mathematical model incorporating intraplaque angiogenesis and hemodynamic calculation of the microcirculation, to obtain the quantitative evaluation of the influences of intraplaque neovascularization and hemorrhage on vulnerable plaque development. A two-dimensional nine-point model of angiogenic microvasculature is generated based on the histology of a patient's carotid plaque. The intraplaque angiogenesis model includes three key cells (endothelial cells, smooth muscle cells, and macrophages) and three key chemical factors (vascular endothelial growth factors, extracellular matrix, and matrix metalloproteinase), which densities and concentrations are described by a series of reaction-diffusion equations. The hemodynamic calculation by coupling the intravascular blood flow, the extravascular plasma flow, and the transvascular transport is carried out on the generated angiogenic microvessel network. We then define the IPH area by using the plasma concentration in the interstitial tissue, as well as the extravascular transport across the capillary wall.

Results: The simulational results reproduce a series of pathophysiological phenomena during the atherosclerotic plaque progression. It is found that the high microvessel density region at the shoulder areas and the extravascular flow across the leaky wall of the neovasculature contribute to the IPH observed widely in vulnerable plaques. The simulational results are validated by both the in vivo MR imaging data and in vitro experimental observations and show significant consistency in quantity ground. Moreover, the sensitivity analysis of model parameters reveals that the IPH area and extent can be reduced significantly by decreasing the MVD and the wall permeability of the neovasculature.

Conclusions: The current quantitative model could help us to better understand the roles of microvascular and intraplaque hemorrhage during the carotid plaque progression.
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http://dx.doi.org/10.1186/s12938-021-00878-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082657PMC
April 2021

24 h urinary creatinine excretion during pregnancy and its application in appropriate estimation of 24 h urinary iodine excretion.

J Trace Elem Med Biol 2021 Jul 26;66:126751. Epub 2021 Mar 26.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, National Health and Family Planning Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology (23618504), Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150086 Heilongjiang, China. Electronic address:

Background: Urinary creatinine can be used to adjust urinary iodine to evaluate iodine nutritional status during pregnancy. However, the reference intervals and impact factors of urinary creatinine are unknown.

Methods: 24 h urine creatinine concentration (24 hUCr) and spot UCr at four different time periods of the day of pregnant women from Part 1 (n = 743) were measured. Linear regression analysis was performed to identify the impact factors of 24 h urinary creatinine excretion (24 hUCrE) and obtain the estimated 24 h urinary creatinine excretion (24 hUCrE). Then measured urinary iodine concentration (UIC) of 24 h and at fasting of pregnant women from Part 2 (n = 325), used spot urinary iodine to creatinine concentration ratio (UIC/UCr) and 24 hUCrE to calculate the estimated 24 h urinary iodine excretion (24 hUIE), finally checked the consistency and correlation of 24 hUIE and 24 h urinary iodine excretion (24 hUIE).

Results: In Part 1, the median 24 hUCrE was 1.24(IQR0.98-1.76)g, and the reference interval was 0.61-2.93 g. The median 24 hUCr was 0.76 (IQR0.57-1.01)g/L, and the reference interval was 0.36-1.88 g/L. Multiple linear regression results showed that pregnancy weight was an influencing factor to 24 hUCrE after adjusting by gestational weeks, age, pre-pregnancy BMI, and percentage of body fat (F = 45.029, p<0.001). In Part 2, there was no statistically significant difference between 24 hUIE and 24 hUIE (Z =-0.767, p = 0.443). Using 24hUIE as the gold standard, the relative average difference in 24hUIE was 4.2 %, the relative average differences for UIC and UIC/UCr were 32.4 % and 37.2 %. The reference interval of 24 hUIE and 24 hUIE were 88.43-585.90 μg and 50.97-700.39 μg, respectively.

Conclusions: The reference intervals of 24 hUCrE, spot UCr, 24 hUIE, and 24 hUIE during pregnancy were established. 24 hUCrE has important application value in iodine nutrition evaluation to gain more lead time for pregnant women with iodine nutrition-related diseases.
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http://dx.doi.org/10.1016/j.jtemb.2021.126751DOI Listing
July 2021
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