Publications by authors named "Weiguo Li"

212 Publications

Early recognition of necrotizing pneumonia in children based on non-contrast-enhanced computed tomography radiomics signatures.

Transl Pediatr 2021 Jun;10(6):1542-1551

National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.

Background: Necrotizing pneumonia (NP) is an infrequent but severe complication of pneumonia in children. In the early stages of NP, CT imaging shows lung consolidation, which cannot be detected in time. This study aimed to explore the ability of non-contrast-enhanced CT radiomics features to recognize NP in early stage.

Methods: This was a retrospective study, and 250 patients who presented with lung consolidation on initial CT images were included in this study. After a follow-up period of 1-3 weeks, 116 patients developed NP, whose CT or X-ray shows cavitation or liquefied necrosis. Manual segmentation of lesion sites in the initial non-contrast-enhanced CT scans was performed with RadCloud (Huiying Medical Technology Co., Ltd., China), and 1,409 radiomics features were extracted. We used Variance threshold (0.8), SelectKBest, and the least absolute shrinkage and selection operator (LASSO) methods for feature dimension reduction. Three machine learning algorithms, k-nearest neighbor (KNN), support vector machine (SVM), and logistic regression (LR) models, were established to recognize NP early. To assess the recognition performance, the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and other indicators were used in the validation cohort.

Results: Radiomics features helped to recognize NP in early stage in both the training and validation cohorts. The AUC (sensitivity, specificity) for the training and validation cohorts were 0.81 (0.73, 0.68) and 0.71 (0.61, 0.65) for KNN, respectively; 0.81 (0.72, 0.70) and 0.77 (0.66, 0.65) for SVM, respectively; and 0.82 (0.73, 0.73) and 0.76 (0.63, 0.70) for LR, respectively. Recall and F1-scores determined that LR performed better at diagnosing early NP, with the values of the above two indexes being 0.70 and 0.67, respectively.

Conclusions: Non-contrast-enhanced CT-based radiomics models may be helpful for recognizing NP in early stage.
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http://dx.doi.org/10.21037/tp-20-241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261593PMC
June 2021

Impact of the Malnutrition on Mortality in Elderly Patients Undergoing Percutaneous Coronary Intervention.

Clin Interv Aging 2021 14;16:1347-1356. Epub 2021 Jul 14.

Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.

Purpose: Malnutrition has been shown to be related to adverse clinical outcomes in patients with heart failure, hypertension, atrial fibrillation and other cardiovascular diseases. However, in the patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI), especially in the elderly, the association of nutritional state and all-cause mortality remains unknown. We aimed to investigate the association of malnutrition with all-cause mortality in the elder patients undergoing PCI.

Patients And Methods: Based on the largest retrospective and observational cohort study from January 2007 to December 2017, the Controlling Nutritional Status (CONUT) score was applied to 21,479 consecutive patients with age ≥60 who undergoing PCI for nutritional assessment. Participants were classified as absent, mild, moderate and severe malnutrition by CONUT score. The Kaplan-Meier method was used to compare all-cause mortality among the above four groups. Multivariable Cox proportional hazard regression analyses were performed to examine the association of malnutrition with all-cause mortality.

Results: According to the CONUT score, 48.19%, 15.08% and 0.94% patients were mildly, moderately and severely malnourished, respectively. During a median follow-up of 5.16 years (interquartile range: 3.02 to 7.89 years), 3173 (14.77%) patients died. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with a worse nutritional status. Compared with normal nutritional state, malnutrition was associated with significantly increased risk for all-cause mortality (adjusted hazard ratio for mild, moderate and severe degrees of malnutrition, respectively: 1.20 [95% confidence interval (CI): 1.09 to 1.33], 1.32 [95% CI: 1.17 to 1.49] and 1.76 [95% CI: 1.33 to 2.33]).

Conclusion: Malnutrition is prevalent among elderly patients with CAD undergoing PCI, and is strongly related to the all-cause mortality increasing. For elderly patients with CAD undergoing PCI, it is necessary to assess the status of nutrition, and evaluate the efficacy of nutritional interventions.
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http://dx.doi.org/10.2147/CIA.S308569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286965PMC
July 2021

Establishing a patient registry study database of dust mite allergic asthma in children: design, methodology and preliminary exploration.

Ann Transl Med 2021 Jun;9(12):993

Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

Background: Asthma is a heterogeneous disease with different phenotypes, endotypes and responses to treatment. Dust mite allergic asthma (DMAA) is the most common type in children. Compared with randomized control trials, a patient registry study (PRS) can reflect the real physical condition and clinical diagnosis more comprehensively.

Methods: Children who visited the asthma clinic of the Children's Hospital of Chongqing Medical University between August 2018 and August 2020, and met the inclusion criteria and also agreed to participate, were enrolled in the registry study. Clinical information, laboratory tests and peripheral blood samples were collected after informed consent was given by guardians.

Results: To date, 208 children have been enrolled in the patient registry database of DMAA. They are mainly male, with >50% having a history of allergic rhinitis, cesarean section, positive family history and passive smoking. Eosinophils and total immunoglobulin E levels were all significantly higher than normal. According to results for the childhood asthma control test (c-ACT) and ratio of forced expiratory volume in 1 s to predicted value after inhaled corticosteroid treatment, the uncontrolled group had higher hemoglobin (Hb) levels than the control group. The group exhibiting abnormal pulmonary function was older, and had longer disease duration, higher fractional exhaled nitric oxide and Hb than the group in which pulmonary function was restored.

Conclusions: We have preliminarily established a registered study database of children with DMAA. By cluster analysis and using blood samples, we can further study the different pathophysiological mechanisms in order to provide more individualized and targeted treatments for all children.
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http://dx.doi.org/10.21037/atm-21-2566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267296PMC
June 2021

Deciphering variation of 239 elite japonica rice genomes for whole genome sequences-enabled breeding.

Genomics 2021 Jul 6;113(5):3083-3091. Epub 2021 Jul 6.

Huazhi Biotech Co. Ltd., Changsha, Hunan 410125, China; China Southern Regional Collaborative Innovation Center for Cereal and Oil Crops, College of Agriculture, Hunan Agricultural University, Changsha, Hunan 410125, China. Electronic address:

Revealing genomic variation of representative and diverse germplasm is the cornerstone of deploying genomics information into genetic improvement programs of species of agricultural importance. Here we report the re-sequencing of 239 japonica rice elites representing the genetic diversity of japonica germplasm in China, Japan and Korea. A total of 4.8 million SNPs and PAV of 35,634 genes were identified. The elites from Japan and Korea are closely related and relatively less diverse than those from China. A japonica rice pan-genome was constructed, and 35 Mb non-redundant novel sequences were identified, from which 1131 novel genes were predicted. Strong selection signals of genomic regions were detected on most of the chromosomes. The heading date genes Hd1 and Hd3a have been artificially selected during the breeding process. The results from this study lay the foundation for future whole genome sequences-enabled breeding in rice and provide a paradigm for other species.
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http://dx.doi.org/10.1016/j.ygeno.2021.07.002DOI Listing
July 2021

Molecular and Functional Evolution of the Spermatophyte Sesquiterpene Synthases.

Int J Mol Sci 2021 Jun 14;22(12). Epub 2021 Jun 14.

Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Sesquiterpenes are important defense and signal molecules for plants to adapt to the environment, cope with stress, and communicate with the outside world, and their evolutionary history is closely related to physiological functions. In this study, the information of plant sesquiterpene synthases (STSs) with identified functions were collected and sorted to form a dataset containing about 500 members. The phylogeny of spermatophyte functional STSs was constructed based on the structural comparative analysis to reveal the sequence-structure-function relationships. We propose the evolutionary history of plant sesquiterpene skeletons, from chain structure to small rings, followed by large rings for the first time and put forward a more detailed function-driven hypothesis. Then, the evolutionary origins and history of spermatophyte STSs are also discussed. In addition, three newly identified STSs , and were analyzed in this functional evolutionary system, and their germacrene D products were consistent with the functional prediction. This demonstrates an application of the structure-based phylogeny in predicting STS function. This work will help us to understand evolutionary patterns and dynamics of plant sesquiterpenes and STSs and screen or design STSs with specific product profiles as functional elements for synthetic biology application.
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http://dx.doi.org/10.3390/ijms22126348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232007PMC
June 2021

Deep Brain Stimulation Complications in Patients With Parkinson's Disease and Surgical Modifications: A Single-Center Retrospective Analysis.

Front Hum Neurosci 2021 11;15:684895. Epub 2021 Jun 11.

Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.

Background: As a complication-prone operation, deep brain stimulation (DBS) has become the first-line surgical approach for patients with advanced Parkinson's disease (PD). This study aimed to evaluate the incidence and risk factors of DBS-associated complications.

Methods: We have reviewed a consecutive series of patients with PD undergoing DBS procedures to describe the type, severity, management, and outcome of postoperative complications from January 2011 to December 2018. Both univariate and multivariate analyses were performed to identify statistically significant risk factors. We also described our surgical strategies to minimize the adverse events.

Results: A total of 225 patients underwent 229 DBS implantation procedures (440 electrodes), of whom 20 patients experienced 23 DBS-associated complications, including ten operation-related complications and 13 hardware-related ones. Univariate analysis elucidated that comorbid medical conditions ( = 0.024), hypertension ( = 0.003), early-stage operation ( < 0.001), and unilateral electrode implantation ( = 0.029) as risk factors for overall complications, or more specifically, operation-related complications demonstrated in the stratified analysis. In contrast, no risk factor for hardware-related complications was identified. Statistical significances of hypertension (OR = 3.33, 95% CI: 1.14-9.71, = 0.027) and early-stage (OR = 11.04, 95% CI: 2.42-50.45, = 0.002) were further validated via multivariate analysis. As the annual number of DBS procedures increased, the incidence of complications gradually decreased ( = -0.699, < 0.01). Additionally, there was a strong correlation between surgical complications and unplanned readmission ( = 0.730, < 0.01).

Conclusion: The importance of cumulative experience and relevant technique modifications should be addressed to prevent DBS-associated complications and unplanned readmission.
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http://dx.doi.org/10.3389/fnhum.2021.684895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226223PMC
June 2021

Malnutrition and the risk for contrast-induced acute kidney injury in patients with coronary artery disease.

Int Urol Nephrol 2021 Jun 25. Epub 2021 Jun 25.

Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.

Purpose: Malnutrition is a common comorbidity of coronary artery disease (CAD) and is often associated with adverse events. The malnutrition often means lower cholesterol, albumin and high lymphocyte, as risk factors of Contrast-Induced Acute Kidney Injury (CI-AKI). We aim to evaluate the association between malnutrition and CI-AKI following coronary angiography (CAG) in CAD patients.

Methods: We analyzed 3170 CAD patients with variables of nutritional status (Controlling Nutritional Status score (CONUT)) from the prospective multicenter study, REICIN (NCT01402232) including 4,271 consecutive patients undergoing CAG from January 2013 to February 2016. Patients were divided into the normal group (CONUT score 0-1) and malnutrition group (CONUT score > 1). The association of malnutrition and the risk of CI-AKI was examined in all CAD patients using multivariable logistics regression analysis.

Results: Among the 3170 patients (mean age: 63.1 ± 10.7 years), 1865 (58.8%) suffered from malnutrition, 111 (3.5%) developed CI-AKI, including 23 (1.76%) in normal group and 88 (4.72%) in malnutrition group (p < 0.01). The malnourished patients were older, and likely had anemia and worse cardiorenal function. After adjustment for confounders, the risk of CI-AKI was 1.04 times higher in the malnutrition group than in the normal group (adjusted OR: 2.04, 95% CI 1.28-3.38, p < 0.01).

Conclusions: Among CAD patients undergoing CAG, malnutrition is extremely common and associated with a double risk of CI-AKI. Further studies are needed to investigate the potential renal protection of intervening malnutrition in CAD patients.
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http://dx.doi.org/10.1007/s11255-021-02915-6DOI Listing
June 2021

Duramycin radiosensitization of MCA-RH 7777 hepatoma cells through the elevation of reactive oxygen species.

J Cancer Res Ther 2021 Apr-Jun;17(2):543-546

Department of Radiology, Northwestern University, Chicago, Illinois, USA.

Objective: The objective of this study is to explore the radiosensitization effects of duramycin against the liver cancer hepatoma cells and relationship to reactive oxygen species (ROS) generation.

Materials And Methods: MCA-RH 7777 cells were treated with various combinations of duramycin concentrations and radiation doses. After the treatment, cell viabilities were determined by a cell proliferation assay; intracellular ROS levels were detected with the flow cytometric method.

Results: MCA-RH 7777 cell viability was found significantly reduced after combining duramycin and radiation exposure (comparing to that of either treatment alone). Increased intracellular ROS levels were observed in cells treated with combinations of duramycin and radiation.

Conclusion: Duramycin increased the intracellular ROS generation and also increased the radiosensitivity of MCA-RH 7777 cells.
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http://dx.doi.org/10.4103/jcrt.JCRT_284_18DOI Listing
June 2021

Interspecies competition between Scrippsiella acuminata and three marine diatoms: Growth inhibition and allelopathic effects.

Aquat Toxicol 2021 Aug 28;237:105878. Epub 2021 May 28.

College of Life Science and Technology, Jinan University, Guangzhou 510632, China. Electronic address:

Interactions between Scrippsiella acuminata and three diatoms, Chaetoceros curvisetus, Phaeodactylum tricornutum, and Skeletonema dohrnii, were investigated using bi-algal co-cultures and cell-free and sonicated-cell filtrates in this study. Volatile aldehydes in sonicated filtrates of the three diatoms were analyzed by GC/MS. Furthermore, effects of 2E, 4E-decadienal (2,4-D) on the growth and the photosynthetic efficiency of the four microalgal species were studied. The growth of Sc. acuminata was significantly inhibited by the three diatoms in all co-cultures, and the inhibitory effects were higher under nutrient-rich conditions. Both cell-free and sonicated-cell filtrates of the three diatoms showed significant inhibitions on the growth of Sc. acuminata, which highlighted that diatoms produce allelopathic compounds not only to the surrounding environments but also inside the cells. Fifteen aldehydes were detected in the sonicated-cell filtrates of the three diatoms, and 5, 5, and 12 types of aldehydes were detected in C. curvisetus, P. tricornutum, and Sk. dohrnii, respectively. Polyunsaturated aldehydes (PUAs) composition differed among the three diatom species. Phenylglyoxal (CHO) dominated in C. curvisetus, 2,4-D (CHO) predominated in P. tricornutum, and high proportions of 2-hexenal (CHO), 2E, 4E-heptadienal (CHO), and 2,4-D were detected in Sk. dohrnii. 2,4-D showed significantly inhibitory effects on the growth of algal cells including diatoms themselves in a dose-dependent manner, and photosynthetic efficiency was significantly decreased as well. Sc. acuminata was the most sensitive species. The 96 h EC values of 2,4-D on the growth of the four microalgae were 1.64 μmol/L for Sc. acuminata, 3.09 μmol/L for C. curvisetus, 4.93 μmol/L for P. tricornutum, and 8.54 μmol/L for Sk. dohrnii, respectively. The results suggest that PUAs produced by diatoms may help them to take the competitive advantages in phytoplankton community, and thus to sustain diatom-dominated community structure in nutrient rich coastal waters.
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http://dx.doi.org/10.1016/j.aquatox.2021.105878DOI Listing
August 2021

Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation.

J Vasc Interv Radiol 2021 Aug 9;32(8):1103-1112.e12. Epub 2021 Apr 9.

Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL.

Purpose: To investigate the feasibility, safety, and absorbed-dose distribution of prostatic artery radioembolization (RE) in a canine model.

Materials And Methods: Fourteen male castrated beagles received dihydroandrosterone/estradiol to induce prostatic hyperplasia for the duration of the study. Each dog underwent fluoroscopic prostatic artery catheterization. Yttrium-90 (Y) microspheres (TheraSphere; Boston Scientific, Marlborough, Massachusetts) were delivered to 1 prostatic hemigland (dose escalation from 60 to 200 Gy), with the contralateral side serving as a control. Assessments for adverse events were performed throughout the follow-up (Common Terminology Criteria for Adverse Events v5.0). Positron emission tomography/magnetic resonance (MR) imaging provided a confirmation after the delivery of absorbed-dose distribution. MR imaging was performed before and 3, 20, and 40 days after RE. Tissue harvest of the prostate, rectum, bladder, urethra, penis, and neurovascular bundles was performed 60 days after RE.

Results: All the animals successfully underwent RE. Positron emission tomography/MR imaging demonstrated localization to and good coverage of only the treated hemigland. No adverse events occurred. The MR imaging showed a significant dose-dependent decrease in the treated hemigland size at 40 days (25%-60%, P < .001). No extraprostatic radiographic changes were observed. Necropsy demonstrated no gross rectal, urethral, penile, or bladder changes. Histology revealed RE-induced changes in the treated prostatic tissues of the highest dose group, with gland atrophy and focal necrosis. No extraprostatic RE-related histologic findings were observed.

Conclusions: Prostate Y RE is safe and feasible in a canine model and leads to focal dose-dependent changes in the gland without inducing unwanted extraprostatic effects. These results suggest that an investigation of nonoperative prostate cancer is warranted.
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http://dx.doi.org/10.1016/j.jvir.2021.01.282DOI Listing
August 2021

Data Augmentation: Using Channel-Level Recombination to Improve Classification Performance for Motor Imagery EEG.

Front Hum Neurosci 2021 11;15:645952. Epub 2021 Mar 11.

Tianjin Artificial Intelligence Innovation Center (TAIIC), Tianjin, China.

The quality and quantity of training data are crucial to the performance of a deep-learning-based brain-computer interface (BCI) system. However, it is not practical to record EEG data over several long calibration sessions. A promising time- and cost-efficient solution is artificial data generation or data augmentation (DA). Here, we proposed a DA method for the motor imagery (MI) EEG signal called brain-area-recombination (BAR). For the BAR, each sample was first separated into two ones (named half-sample) by left/right brain channels, and the artificial samples were generated by recombining the half-samples. We then designed two schemas (intra- and adaptive-subject schema) corresponding to the single- and multi-subject scenarios. Extensive experiments using the classifier of EEGnet were conducted on two public datasets under various training set sizes. In both schemas, the BAR method can make the EEGnet have a better performance of classification ( < 0.01). To make a comparative investigation, we selected two common DA methods (noise-added and flipping), and the BAR method beat them ( < 0.05). Further, using the proposed BAR for augmentation, EEGnet achieved up to 8.3% improvement than a typical decoding algorithm CSP-SVM ( < 0.01), note that both the models were trained on the augmented dataset. This study shows that BAR usage can significantly improve the classification ability of deep learning to MI-EEG signals. To a certain extent, it may promote the development of deep learning technology in the field of BCI.
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http://dx.doi.org/10.3389/fnhum.2021.645952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990774PMC
March 2021

Relationship between electrode position of deep brain stimulation and motor symptoms of Parkinson's disease.

BMC Neurol 2021 Mar 17;21(1):122. Epub 2021 Mar 17.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.

Background: To investigate the relationship between the position of bilateral STN-DBS location of active contacts and the clinical efficacy of STN-DBS on motor symptoms in Parkinson's disease (PD) patients.

Methods: Retrospectively analyze the clinical data of 57 patients with PD who underwent bilateral STN-DBS from March 2018 to December 2018. Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) score, levodopa equivalent day dose (LEDD), Parkinson's Disease Quality of Life Scale (PDQ-39) before operation and within 6 months after operation, determine the location of activated contacts and volume of tissue activated (VTA) in the Montreal Neurological Institute (MNI) space, and analyze their correlation with the improvement rate of motor symptoms (UPDRS-III score improvement rate).

Results: After 6 months of follow up, the UPDRS-III scores of 57 patients (Med-off) were improved by 55.4 ± 18.9% (P<0.001) compared with that before operation. The improvement rate of PDQ-39 scores [(47.4 ± 23.2)%, (P < 0.001)] and the reduction rate of LEDD [(40.1 ± 24.3)%, (P < 0.01)] at 6 months postoperation were positively correlated with the improvement rate of motor symptoms (Med-off)(PDQ-39:r = 0.461, P<0.001; LEDD: r = 0.354, P = 0.007), the improvement rate of UPDRS-III (Med-off) and the Z-axis coordinate of the active contact in the MNI space were positively correlated (left side: r = 0.349,P = 0.008;right side: r = 0.369,P = 0.005). In the MNI space, there was no correlation between the UPDRS-III scores improvement rate (Med-off) at 6 months after operation and bilateral VTA in the STN motor subregion, STN associative subregion and STN limbic subregion of the active electrode contacts of 57 patients (all P > 0.05). At 6 months after surgery, the difference between the Z-axis coordinate in the different improvement rate subgroups(<25, 25 to 50%, and>50%) in the MNI space was statistically significant (left side: P = 0.030; right side: P = 0.024). In the MNI space, there was no statistically significant difference between the groups in the VTA of the electrode active contacts (all P > 0.05).

Conclusion: STN-DBS can improve the motor symptoms of PD patients and improve the quality of life. The closer the stimulation is to the STN dorsolateral sensorimotor area, the higher the DBS is to improve the motor symptoms of PD patients.
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http://dx.doi.org/10.1186/s12883-021-02148-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972210PMC
March 2021

Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression miR-185-5p/miR-214-3p.

Front Oncol 2020 19;10:617105. Epub 2021 Feb 19.

Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Clear cell renal cell carcinoma (ccRCC) comprises approximately 75% of renal cell carcinomas, which is one of the most common and lethal urologic cancers, with poor quality of life for patients and is a huge economic burden to health care systems. It is imperative we find novel prognostic and therapeutic targets for ccRCC clinical intervention. In this study, we found that the expression of the long noncoding RNA (lncRNA) ASB16-AS1 was downregulated in ccRCC tissues compared with non-diseased tissues and was also associated with advanced tumor stage and larger tumors. By constructing cell and mouse models, it was found that downregulated lncRNA ASB16-AS1 enhanced cell proliferation, migration, invasion, and promoted tumor growth and metastasis. Furthermore, by performing bioinformatics analysis, biotinylated RNA pull-downs, AGO2-RIP, and luciferase reporter assays, our findings showed that downregulated ASB16-AS1 decreased La-related protein 1 (LARP1) expression by inhibiting miR-185-5p and miR-214-3p. Furthermore, it was found that overexpression of LARP1 reversed the promotive effects of downregulated ASB16-AS1 on ccRCC cellular progression. Our results revealed that downregulated ASB16-AS1 promotes ccRCC progression a miR-185-5p-miR-214-3p-LARP1 pathway. We suggest that this pathway could be used to monitor prognosis and presents therapeutic targets for ccRCC clinical management.
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http://dx.doi.org/10.3389/fonc.2020.617105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933513PMC
February 2021

Guidelines for the Management of Children and Adolescent with COVID-19: protocol for an update.

Transl Pediatr 2021 Jan;10(1):177-182

Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Background: Coronavirus disease 2019 (COVID-19) has become a constant threat to people's lives, bringing huge challenges to the global public health and medical service system. In order to ensure the timeliness and reliability of the recommendations in guidelines, the working group of the Rapid Advice Guidelines for Management of Children with COVID-19 decided to update the guideline to incorporate the latest evidence to guide the management of COVID-19 in children and adolescent.

Methods: We will update the guidelines, originally developed as a rapid advice guideline, into a standard guideline. We will follow the clinical practice guideline (CPG) update manuals of the National Institute for Health and Clinical Excellence (NICE) and the Spanish National Health System (SNHS). The updated guidelines will also follow the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist and Checklist for the Reporting of Updated Guidelines (CheckUp).

Discussion: Through systematic search, evaluation and grading of the best available relevant clinical evidence, combined with the experience of frontline clinical experts in the fight against the epidemic and the wishes of patients and their caretakers, we will update our previous rapid advice guidelines into a high-quality, implementable standard guidelines for the management of COVID-19 in children and adolescent.

Trial Registration: The standard guideline update has been registered at the International Practice Guidelines Registry Platform (http://guidelines-registry.cn/?lang=en, registration No. IPGRP-2020CN101).
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http://dx.doi.org/10.21037/tp-20-290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882303PMC
January 2021

Multisystem inflammatory syndrome in children during the coronavirus disease 2019 (COVID-19) pandemic: a systematic review of published case studies.

Transl Pediatr 2021 Jan;10(1):121-135

Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.

Background: Many cases have been reported recently on multisystem inflammatory syndrome in children (MIS-C), a newly emerged disease that seemed to correlate with coronavirus disease 2019 (COVID-19). The aim of this review was to describe the clinical features, treatment and outcomes of MIS-C, as well as to assess the risk of bias of published case studies, analyzing their reporting quality.

Methods: We searched all articles reporting on multisystem inflammatory condition in children and adolescents in the context of COVID-19 through MEDLINE (via PubMed), Web of Science, China Biology Medicine disc (CBM) and China National Knowledge Infrastructure (CNKI) from their inception to June 17, 2020. We used CARE and IHE checklists to evaluate the risk of bias and quality of the included studies. We combined the data of clinical manifestations, imaging findings, treatments and outcomes using STATA version 15.

Results: Twenty-four studies were included, with a total of 270 participants. Most cases were from Europe and the United States, and the terms of MIS-C in different articles were varied. Fever and gastrointestinal symptoms were the most experienced symptoms. Shock, rash, conjunctivitis, lips or oral cavity changes, hand and feet anomalies, and lymphadenopathy were observed, while respiratory symptoms seemed relatively infrequent. Seventy-eight percent to 100% of patients had evidence of SARS-CoV-2 infection, and patients positive for SARS-CoV-2 by serology [86% (95% CI: 78%, 95%)] were more than those by RT-PCR [36% (95% CI: 26%, 46%)]. Most patients had one or more increased inflammatory markers including C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), ferritin, interleukin-6 (IL-6), and D-dimer, accompanied by neutrophilia and lymphopenia. Impaired cardiac function was seen from elevated biomarkers and abnormal echocardiography. Intravenous immunoglobulin (IVIG), anticoagulants, inotropic agents and glucocorticoids were the main treatments, along with other intensive supportive care. Overall, the outcomes of MIS-C were favorable, and only one death was recorded. In terms of the quality assessment of included studies, most of the case studies did not follow the standard reporting checklist, so that they failed to get higher scores in the risk of bias assessment.

Conclusions: Patients with MIS-C present with symptoms more severe than children with COVID-19, with fever and gastrointestinal symptoms as the primary manifestations and multisystem involvement, particularly cardiovascular system. Longer follow-up and further researches for the pathophysiology of MIS-C are urgently needed. In addition, attention should be paid to the quality of case studies to improve the completeness and transparency of scientific reports.
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http://dx.doi.org/10.21037/tp-20-188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882293PMC
January 2021

Family exposure and the impact of containment measures to children with coronavirus disease 2019 outside Hubei, China: a cross-sectional study.

Transl Pediatr 2021 Jan;10(1):92-102

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Background: In response to the ongoing epidemic of coronavirus disease 2019 (COVID-19), China has carried out restrictive disease containment measures across the country.

Methods: In this cross-sectional study, we collected demographic and epidemiological data of 376 laboratory-confirmed cases of COVID-19 among children younger than 18 years of age. Using descriptive statistics and odds ratios, we described the odds of exposure outside the family after the implementation of control measures compared to before.

Results: Children diagnosed on or after February 4, 2020, had a lower odds of exposure to COVID-19 outside of the family compared to those diagnosed before February 3, 2020 (OR =0.594, 95% CI: 0.391 to 0.904). In the stratified analysis, children aged 0 to 5 years had the lowest odds of exposure outside of the family (OR =0.420, 95% CI: 0.196 to 0.904) compared to the other age groups assessed.

Conclusions: Our study on the children infected with COVID-19 as well as their exposure within family provided evidence that the implementation of containment measures was effective in reducing the odds of exposure outside of the family, especially for preschool children. Continuation of these efforts, coupled with tailored prevention and health education messaging for younger aged children, may help to reduce the transmission of COVID-19 among children until other therapeutic interventions or vaccines are available.
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http://dx.doi.org/10.21037/tp-20-214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882296PMC
January 2021

Comparative transcriptome analysis of sesquiterpene biosynthesis and functional characterization of sesquiterpene synthases in Leonurus sibiricus L.

Planta 2021 Feb 18;253(3):71. Epub 2021 Feb 18.

Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, People's Republic of China.

Main Conclusion: Two sesquiterpene synthases were identified through comparative transcriptome analysis of Leonurus sibiricus. LsSqTPS2 could produce high titer of δ-cadinene in vivo which suggests the terpene specificity of L. sibiricus. Leonurus sibiricus L., a medicinal herb, is widely used in China due to its pharmacological activities. Cadinene type sesquiterpenes, one of major bioactive components mainly present in aerial parts of L. sibiricus, showed antibacterial, anti-inflammatory, antioxidant and antiproliferative properties. However, there is no report about the sesquiterpene biosynthesis in L. sibiricus. This study identified L. sibiricus sesquiterpene synthases (LsSqTPSs) through comparative transcriptome analysis of L. sibiricus leaf and root samples using the BGISEQ-500 sequencing technique. A total of 83,244 unigenes were obtained with an average length of 1025 bp. Among them, 50,356 unigenes (60.49%) acquired annotations according to the BLAST searching results. A total of 68 differentially expressed genes (DEGs) were potentially involved in the sesquiterpene biosynthesis. Furthermore, four candidate DEGs encoding LsSqTPSs were characterized. The enzymatic characterization in engineered yeast showed that LsSqTPS1 produced α-farnesene as the single product and LsSqTPS2 mainly produced 76.23 mg/L of δ-cadinene, which constituted the major component of L. sibiricus leaf essential oil. This work contributes to the investigation of sesquiterpene biosynthesis in L. sibiricus.
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http://dx.doi.org/10.1007/s00425-021-03586-4DOI Listing
February 2021

Characterization of -Nerolidol Synthase from Maxim and Production of -Nerolidol in Engineered .

J Agric Food Chem 2021 Feb 15;69(7):2236-2244. Epub 2021 Feb 15.

Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Volatile terpenoids are a large group of important secondary metabolites and possess many biological activities. The acyclic sesquiterpene -nerolidol is one of the typical representatives and widely used in cosmetics and agriculture. Here, the accumulation of volatile terpenes in different tissues of was investigated, and two -nerolidol synthases, CaNES1 and CaNES2, were identified and characterized by enzymatic assays. Both genes are differentially transcribed in different tissues of . Next, we constructed a cell factory to enable high-level production of -nerolidol. Glucose was the sole carbon source to sequentially control gene expression between the competitive squalene and -nerolidol pathways. Finally, the -nerolidol production of recombinant strain LWG003- was 7.01 g/L by fed-batch fermentation in a 5 L bioreactor. The results clarify volatile terpenoid biosynthesis in and provide a promising potential for industrial production of -nerolidol in .
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http://dx.doi.org/10.1021/acs.jafc.0c06084DOI Listing
February 2021

Why multisystem inflammatory syndrome in children has been less commonly described in Asia?

Transl Pediatr 2020 Dec;9(6):873-875

Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.

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http://dx.doi.org/10.21037/tp-20-151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804475PMC
December 2020

Design, synthesis and evaluation of 1-benzyl-1H-imidazole-5-carboxamide derivatives as potent TGR5 agonists.

Bioorg Med Chem 2021 02 27;32:115972. Epub 2020 Dec 27.

Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, People's Hospital of Hebi, School of Medicine, Henan University, Henan, China; Key Laboratory of Molecular Pathology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot, China. Electronic address:

TGR5 is emerging as an important and promising target for the treatment of diabetes, obesity and other metabolic syndromes. A series of novel 1-benzyl-1H-imidazole-5-carboxamide derivatives was designed, synthesized and evaluated in vitro and in vivo. The most potent compounds 19d and 19e exhibited excellent agonistic activities against hTGR5, which was superior to those of the reference drugs INT-777 and LCA. In addition, compounds 19d and 19e exhibited good selectivity against FXR and presented significant glucose-lowering effects in vivo. Compound 19d could stimulate GLP-1 secretion by activating of TGR5.
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http://dx.doi.org/10.1016/j.bmc.2020.115972DOI Listing
February 2021

De novo assembly of the Mylia taylorii transcriptome and identification of sesquiterpene synthases.

Arch Biochem Biophys 2021 02 25;698:108742. Epub 2020 Dec 25.

Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, PR China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, PR China; SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300072, PR China. Electronic address:

Mylia taylorii is an ancient nonseed land plant that accumulates various sesquiterpenes with insecticidal and antibacterial activities. Recently, microbial-type sesquiterpene synthases (STSs) with atypical aspartate-rich metal ion binding motifs have been identified in some liverworts. Here, transcriptome analysis of M. taylorii was performed to identify M. taylorii sesquiterpene synthases (MtSTSs) that are potentially involved in sesquiterpene biosynthesis and diversity. A total of 255,669 unigenes were obtained with an average length of 963 bp in the transcriptome data of M. taylorii, among which 148,093 (57.92%) unigenes had BLAST results. Forty-eight unigenes were related to the sesquiterpene backbone biosynthesis according to KEGG annotation. In addition, MtSTS1, MtSTS2 and MtSTS3 identified from putative MtSTSs display sesquiterpene catalytic activities on the basis of functional characterizations in yeast. Interestingly, MtSTSs exhibit a noncanonical metal ion binding motif and the structural composition of a single α-domain, which are features of microbial STSs instead of archetypical plant STSs. This study revealed new microbial-type STS members of nonseed plants, and functionally identified that MtSTSs may contribute to the investigation of the biosynthesis and biological role of sesquiterpenes in M. taylorii.
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http://dx.doi.org/10.1016/j.abb.2020.108742DOI Listing
February 2021

Analysis of the immunoglobin E molecular sensitization profile in children with allergic asthma and predictive factors for the efficacy of allergy immunotherapy.

Ann Transl Med 2020 Nov;8(21):1459

Department of Respiratory Medicine Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

Background: As the incidence of allergic asthma in children increases, the immunoglobin E (IgE) molecular sensitization profile of allergic asthma remains underreported while the level of total IgE (tIgE) and sIgE/tIgE have not been studied as predictors of efficacy of allergen immunotherapy (AIT) for allergic asthma, specifically in children.

Methods: Starting from August 2018 to March 2019 in the Respiratory Department of the Children's Hospital of Chongqing Medical University, asthmatic children, with positive skin prick tests to Der p or Der f, were enrolled in this study. Total IgE, allergen serum-specific IgE (sIgE) of Der p, Der f, (Blo t), cat dander, dog dander, egg white, milk, cockroach, shrimp, and crab, along with Der p allergen components, Der p1 and Der p2, were measured by ImmunoCAP™ assay.

Results: A total of 142 children with allergic asthma were enrolled, all of whom showed positive IgE for Der p, Der p1, Der p2, and Der f; meanwhile, the positive rates of Blo t, cat dander, dog dander, egg white, milk, cockroach, shrimp, and crab were 91.84%, 10.96%, 7.32%, 9.15%, 11.58%, 17.03%, 18.90%, and 18.28% respectively. A significantly high correlation was found between total IgE and the sIgE of Der f, Der p, Der p 1, and Der p 2. Asthmatic children with a family history of allergy displayed higher total IgE and unknown IgE levels than those patients without a family history of allergy. The ratios of Der f sIgE/tIgE and Der p sIgE/tIgE were higher in the negative family history of allergy group than in the positive family history of allergy group. Furthermore, total IgE and unknown IgE were higher in the polysensitized group than in the in monosensitized group. The ratios of Der f sIgE/tIgE and Der p sIgE/tIgE were higher in the monosensitized group than in the polysensitized group.

Conclusions: From this study, we noticed that dust mites are the main cause of asthma in children investigated. Our findings indicate patients with no family history of allergy and monosensitized patients have a higher ratio of sIgE/tIgE, and those patients may benefit more from AIT.
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http://dx.doi.org/10.21037/atm-20-7314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723661PMC
November 2020

Anxiety and Depression Among Imaging Doctors in Post-COVID-19 Period.

SN Compr Clin Med 2020 Nov 23:1-5. Epub 2020 Nov 23.

Institute of Radiation Medicine, Shangdong Academy of Medical Sciences, Jinan, 250062 China.

To investigate the mental state of medical imaging staff in Shandong Province, China, who have been on the forefront of the COVID-19 epidemic during its late stage in China. Questionnaires designed to assess anxiety and depression were administered on-location, and 5331 complete results were collected. SPSS software was used for statistical descriptions and analysis. Rates of anxiety disorders and depression among medical imaging workers in Shandong Province, China, were 6.1% and 6.5%, respectively, higher than those of anxiety and depression in Chinese residents before the epidemic. The outbreak in Xinjiang, China; virus mutation in Japan; and spread of the epidemic due to occupational errors were the primary reported causes of anxiety and depression among image workers. Medical imaging workers showed evidence of psychological abnormalities during the late stage of the epidemic in China.
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http://dx.doi.org/10.1007/s42399-020-00654-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681194PMC
November 2020

Correlation and Agreement of Yttrium-90 Positron Emission Tomography/Computed Tomography with Ex Vivo Radioembolization Microsphere Deposition in the Rabbit VX2 Liver Tumor Model.

J Vasc Interv Radiol 2021 01 12;32(1):23-32.e1. Epub 2020 Nov 12.

Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.

Purpose: To demonstrate a stronger correlation and agreement of yttrium-90 (Y) positron emission tomography (PET)/computed tomography (CT) measurements with explant liver tumor dosing compared with the standard model (SM) for radioembolization.

Materials And Methods: Hepatic VX2 tumors were implanted into New Zealand white rabbits, with growth confirmed by 7 T magnetic resonance imaging. Seventeen VX2 rabbits provided 33 analyzed tumors. Treatment volumes were calculated from manually drawn volumes of interest (VOI) with three-dimensional surface renderings. Radioembolization was performed with glass Y microspheres. PET/CT imaging was completed with scatter and attenuation correction. Three-dimensional ellipsoid VOI were drawn to encompass tumors on fused images. Tumors and livers were then explanted for inductively coupled plasma (ICP)-optical emission spectroscopy (OES) analysis of microsphere content. Y PET/CT and SM measurements were compared with reference standard ICP-OES measurements of tumor dosing with Pearson correlation and Bland-Altman analyses for agreement testing with and without adjustment for tumor necrosis.

Results: The median infused activity was 33.3 MBq (range, 5.9-152.9). Tumor dose was significantly correlated with Y PET/CT measurements (r = 0.903, P < .001) and SM estimates (r = 0.607, P < .001). Bland-Altman analyses showed that the SM tended to underestimate the tumor dosing by a mean of -8.5 Gy (CI, -26.3-9.3), and the degree of underestimation increased to a mean of -18.3 Gy (CI, -38.5-1.9) after the adjustment for tumor necrosis.

Conclusions: Y PET/CT estimates were strongly correlated and had better agreement with reference measurements of tumor dosing than SM estimates.
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http://dx.doi.org/10.1016/j.jvir.2020.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086791PMC
January 2021

Diabetic rats are more susceptible to cognitive decline in a model of microemboli-mediated vascular contributions to cognitive impairment and dementia.

Brain Res 2020 12 28;1749:147132. Epub 2020 Sep 28.

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, United States.

Vascular disease plays an important role in all kinds of cognitive impairment and dementia. Diabetes increases the risk of vascular disease and dementia. However, it is not clear how existing vascular disease in the brain accelerates the development of small vessel disease and promotes cognitive dysfunction in diabetes. We used microemboli (ME) injection model in the current study to test the hypothesis that cerebrovascular dysfunction in diabetes facilitates entrapment of ME leading to inflammation and cognitive decline. We investigated cognitive function, axonal/white matter (WM) changes, neurovascular coupling, and microglial activation in control and diabetic male and female Wistar rats subjected to sham or low/high dose ME injection. Diabetic male animals had cognitive deficits, WM demyelination and greater microglial activation than the control animals even at baseline. Functional hyperemia gradually declined in diabetic male animals after ME injection. Both low and high ME injection worsened WM damage and increased microglial activation in diabetic male and female animals. Low ME did not cause cognitive decline in controls, while promoting learning/memory deficits in diabetic female rats and no further decline in diabetic male animals. High ME led to cognitive decline in control male rats and exacerbated the deficits in diabetic cohort. These results suggest that the existing cerebrovascular dysfunction in diabetes may facilitate ME-mediated demyelination leading to cognitive decline. It is important to integrate comorbidities/sex as a biological variable into experimental models for the development of preventive or therapeutic targets.
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http://dx.doi.org/10.1016/j.brainres.2020.147132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606832PMC
December 2020

On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures.

Biomaterials 2021 01 24;265:120408. Epub 2020 Sep 24.

Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60607, USA; Department of Biomedical Engineering, McCormick School of Engineering, Evanston, IL, 60208, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 60611, USA. Electronic address:

Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673262PMC
January 2021

Resequencing of 1,143 indica rice accessions reveals important genetic variations and different heterosis patterns.

Nat Commun 2020 09 22;11(1):4778. Epub 2020 Sep 22.

Huazhi Biotech Co. Ltd, 410125, Changsha, China.

Obtaining genetic variation information from indica rice hybrid parents and identification of loci associated with heterosis are important for hybrid rice breeding. Here, we resequence 1,143 indica accessions mostly selected from the parents of superior hybrid rice cultivars of China, identify genetic variations, and perform kinship analysis. We find different hybrid rice crossing patterns between 3- and 2-line superior hybrid lines. By calculating frequencies of parental variation differences (FPVDs), a more direct approach for studying rice heterosis, we identify loci that are linked to heterosis, which include 98 in superior 3-line hybrids and 36 in superior 2-line hybrids. As a proof of concept, we find two accessions harboring a deletion in OsNramp5, a previously reported gene functioning in cadmium absorption, which can be used to mitigate rice grain cadmium levels through hybrid breeding. Resource of indica rice genetic variation reported in this study will be valuable to geneticists and breeders.
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http://dx.doi.org/10.1038/s41467-020-18608-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508829PMC
September 2020

Follow-up Study of Long-time Positive RT-PCR in Stool Specimens From Asymptomatic Children Infected With SARS-CoV-2.

Pediatr Infect Dis J 2020 10;39(10):e315-e317

From the Department of Respiratory Medicine.

In the current study, we report on 4 children with confirmed SARS-CoV-2 infection, of which 3 of them were asymptomatic. These patients had both pharyngeal swabs and anal swabs testing during hospital or after discharge. All the 4 children showed long-time positive viral RNA in the stool specimens after pharyngeal swabs turned negative during the follow-up stage, especially in the asymptomatic children. The positive RNA in stool specimens of asymptomatic children last for more than 54 days after admission or 30 days after discharge.
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http://dx.doi.org/10.1097/INF.0000000000002837DOI Listing
October 2020

Deferoxamine Treatment Prevents Post-Stroke Vasoregression and Neurovascular Unit Remodeling Leading to Improved Functional Outcomes in Type 2 Male Diabetic Rats: Role of Endothelial Ferroptosis.

Transl Stroke Res 2021 08 1;12(4):615-630. Epub 2020 Sep 1.

Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

It is a clinically well-established fact that patients with diabetes have very poor stroke outcomes. Yet, the underlying mechanisms remain largely unknown. Our previous studies showed that male diabetic animals show greater hemorrhagic transformation (HT), profound loss of cerebral vasculature in the recovery period, and poor sensorimotor and cognitive outcomes after ischemic stroke. This study aimed to determine the impact of iron chelation with deferoxamine (DFX) on (1) cerebral vascularization patterns and (2) functional outcomes after stroke in control and diabetic rats. After 8 weeks of type 2 diabetes induced by a combination of high-fat diet and low-dose streptozotocin, male control and diabetic animals were subjected to thromboembolic middle cerebral artery occlusion (MCAO) and randomized to vehicle, DFX, or tPA/DFX and followed for 14 days with behavioral tests. Vascular indices (vascular volume and surface area), neurovascular remodeling (AQP4 polarity), and microglia activation were measured. Brain microvascular endothelial cells (BMVEC) from control and diabetic animals were evaluated for the impact of DFX on ferroptotic cell death. DFX treatment prevented vasoregression and microglia activation while improving AQP4 polarity as well as blood-brain barrier permeability by day 14 in diabetic rats. These pathological changes were associated with improvement of functional outcomes. In control rats, DFX did not have an effect. Iron increased markers of ferroptosis and lipid reactive oxygen species (ROS) to a greater extent in BMVECs from diabetic animals, and this was prevented by DFX. These results strongly suggest that (1) HT impacts post-stroke vascularization patterns and recovery responses in diabetes, (2) treatment of bleeding with iron chelation has differential effects on outcomes in comorbid disease conditions, and (3) iron chelation and possibly inhibition of ferroptosis may provide a novel disease-modifying therapeutic strategy in the prevention of post-stroke cognitive impairment in diabetes.
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http://dx.doi.org/10.1007/s12975-020-00844-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917163PMC
August 2021

Revealing the toxicity of dimethyl phthalate (DMP) to the oxygen-carrying function of red blood cells (RBCs): The iron release mechanism.

Chemosphere 2021 Jan 19;263:128017. Epub 2020 Aug 19.

School of Marine Science and Technology, Harbin Institute of Technology, Weihai, Weihai, 264209, PR China.

Phthalic acid esters (PAEs), as typical hormone pollutants, do harms to human health after enrichment over a long term exposure, causing the loss of oxygen-carrying function of red blood cells (RBCs). This study has investigated the mechanism for the toxicity of dimethyl phthalate (DMP) on the oxygen-carrying function of RBCs by measuring the iron release content of hemoglobin (Hb) in vivo and in vitro. The hematologic examination showed that the high dose of DMP at 1000 mg/kg significantly reduced the Hb content and increased the granulocyte content, whereas such toxicity was not relatively observed at a low (50 mg/kg) or a medium (250 mg/kg) dose of DMP. The in vitro experiments showed that DMP, incubated with RBCs, increased the iron release content as a function of DMP concentration. Interestingly, such a phenomenon was not observed when DMP was incubated with Hb alone, indicating that the release of hemoglobin iron could not directly caused by the combination of DMP and hemoglobin. The in vivo experiments indicated that DMP induced iron release and oxidative stress for rat RBCs. Moreover, vitamin C and E was found to reduce the level of iron release by recovering erythrocytes from the oxidative stress induced by DMP. This work has revealed that the oxidative stress induced by DMP, causing the release of Hb iron from RBCs, is the reason for the toxicity of DMP to the oxygen-carrying function.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128017DOI Listing
January 2021
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