Publications by authors named "Shu Li"

1,203 Publications

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Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance.

Nat Commun 2021 Oct 22;12(1):6154. Epub 2021 Oct 22.

Gehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.

Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that the CBFB-MYH11 (CM) fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduces AML rate and extends survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibits AML cell survival, reduces leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. The combination of miRisten with chemotherapy further enhances the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a therapeutic approach for inv(16) AML.
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http://dx.doi.org/10.1038/s41467-021-26420-7DOI Listing
October 2021

Biological Control of f. sp. Tropical Race 4 Using Natively Isolated spp. YN0904 and YN1419.

J Fungi (Basel) 2021 Sep 24;7(10). Epub 2021 Sep 24.

Yunnan Key Laboratory of Green Prevention and Control of Agricultural Transboundary Pests, Agricultural Environment and Resources Institute, Yunnan Academy of Agricultural Sciences, 2238 Beijing Road, Kunming 650205, China.

Fusarium wilt of banana (FWB) is the main threatening factor for banana production worldwide. To explore bacterial biocontrol resources for FWB, the antagonistic effective strains were isolated from banana-producing areas in Yunnan Province, China. Two isolates (YN0904 and YN1419) displaying strong antagonism against Tropical Race 4 (TR4) were identified from a total of 813 strains of endophytic bacteria. TR4 inhibition rates of YN0904 and YN1419 were 79.6% and 81.3%, respectively. By looking at morphological, molecular, physiological and biochemical characteristics, YN0904 was identified as , while YN1419 was identified as . The control effects of YN0904 and YN1419 on TR4 in greenhouse experiments were 82.6% and 85.6%, respectively. Furthermore, YN0904 obviously promoted the growth of banana plantlets. In addition, biocontrol marker genes related to the biosynthesis of antibiotics synthesized and auxin key synthetase genes could be detected in YN0904. Surprisingly, the marker gene could be exclusively detected in YN1419, while other marker genes were all absent. Molecular characterization results could provide a theoretical basis for expounding the biocontrol mechanisms of these two strains. We concluded that natively antagonistic strains derived from local banana plantations could provide new biological control resources for FWB.
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http://dx.doi.org/10.3390/jof7100795DOI Listing
September 2021

Deep learning predicts epidermal growth factor receptor mutation subtypes in lung adenocarcinoma.

Med Phys 2021 Oct 20. Epub 2021 Oct 20.

School of Medical Informatics, China Medical University, Liaoning, Shenyang, 110122, China.

Purpose: This study aimed to explore the predictive ability of deep learning (DL) for the common epidermal growth factor receptor (EGFR) mutation subtypes in patients with lung adenocarcinoma.

Methods: A total of 665 patients with lung adenocarcinoma (528/137) were recruited from two different institutions. In the training set, an 18-layer convolutional neural network (CNN) and 5-fold cross-validation strategy were used to establish a CNN model. Subsequently, an independent external validation cohort from the other institution was used to evaluate the predictive efficacy of the CNN model. Grad-weighted class activation mapping (Grad-CAM) technology was used for the visual interpretation of the CNN model. In addition, this study also compared the prediction abilities of the radiomics and CNN models. Receiver operating characteristic (ROC) curves, accuracy and precision values, and recall and F1-score were used to evaluate the effectiveness of the CNN model and compare its performance with that of the radiomics model.

Results: In the validation set, the micro- and macro-average values of the area under the ROC curve of the CNN model to identify the three EGFR subtypes were 0.78 and 0.79, respectively. All evaluation indicators of the CNN model were better than those of the radiomics model.

Conclusions: Our study confirmed the potential of DL for predicting the EGFR mutation status in lung adenocarcinoma. The imaging phenotypes of the three mutation subtypes were found to be different, which can provide a basis for choosing more accurate and personalized treatment in patients with lung adenocarcinoma. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mp.15307DOI Listing
October 2021

Enhanced and sustainable control of Myzus persicae by repellent plants in organic pepper and eggplant greenhouses.

Pest Manag Sci 2021 Oct 17. Epub 2021 Oct 17.

Institute of Plant and Environment Protection, Beijing Academy of Agriculture and Forestry Sciences, Beijing, 100097, China.

Background: Repellent plants (RPs), generally used to keep pests away from crops in integrated pest management, have been shown to reduce the need for synthetic insecticide sprays in various agroecosystems. However, few studies have evaluated the pest control efficiency of RPs during the entire growth period of crops. To evaluate the effect of RPs against Myzus persicae and explore the application and management modes of RPs in the field, we planted mint (Mentha haplocalyx), mung bean (Vigna radiata), celery (Apium graveolens), and coriander (Coriandrum sativum) near the ventilation openings of commercial greenhouses.

Results: Five-month sampling results showed that mung bean and mint treatments significantly reduced the M. persicae population levels during the entire growth period, while celery and coriander reduced aphid infestations during the main harvest period of eggplant. The four RPs species showed the strongest repellence during their fast-growth periods. Mung bean and mint shortened the activity period of M. persicae in pepper by delaying the pest from reaching its peak activity. Celery and coriander reduced aphid density on eggplant during their main activity period. Mint, celery, and coriander inhibited the population growth of M. persicae in the laboratory, revealing the potential value of RPs in reducing M. persicae population levels in the field.

Conclusion: Mint, mung bean, celery, and coriander planted near the ventilation openings of greenhouses could be used to control M. persicae infestations in commercial greenhouses. Early planting and timely replanting of RPs is a more effective, environmentally friendly, and suitable method for organic pest control than chemical pesticides. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ps.6681DOI Listing
October 2021

Identification of Immune Subtypes for Predicting the Prognosis of Patients in Head and Neck Squamous Cell Carcinoma.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211045823

12589Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with poor prognosis and immune response, which plays an important role in tumor progression. Recently, immunotherapies have revolutionized the therapeutic means of malignancies including HNSCC. However, the relationship between immunophenotypes of HNSCC and its clinical response to immune-checkpoint inhibitors remains unclear. We aim to identify molecular subtyping related to distinct immunophenotypes in HNSCC. Consensus clustering algorithm was conducted for subtyping. Immunophenotypes between subtypes were compared according to infiltrating immunocytes, immune reactions, major histocompatibility complex (MHC) family, immunoinhibitory, immunostimulatory and immune scores. The relationship between immunophenotype and genotype was investigated from gene mutation and tumor mutation burden. The potential response of Immune-checkpoint blockade (ICB) therapy was estimated with TIDE and ImmuCellAI algorithms, and immune-checkpoint genes. The immune characteristics were also investigated. Biological functions were annotated by the gene-set enrichment analysis (GSEA) algorithm. Two distinct immune subtypes of HNSCC with different survival outcomes, biological characteristics, immunophenotype, and ICB response were identified. The subtype-1 was featured with better prognosis, more infiltrated immunocytes, stronger immune reaction, higher immune-related gene expression, higher immune-checkpoint gene expression (PD-1, PD-L1, and CTLA-4), and better ICB response. A higher immune response in subtype-1 was also revealed by GSEA. Subtype-1 possessed a higher immune response and more sensitivity to ICB therapy leading to a better prognosis. These findings may shed promising light on the immunotherapy strategy in HNSCC.
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http://dx.doi.org/10.1177/15330338211045823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521413PMC
October 2021

Huntingtin CAG expansion impairs germ layer patterning in synthetic human 2D gastruloids through polarity defects.

Development 2021 Oct 5;148(19). Epub 2021 Oct 5.

Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG repeats in the huntingtin gene (HTT). Although HD has been shown to have a developmental component, how early during human embryogenesis the HTT-CAG expansion can cause embryonic defects remains unknown. Here, we demonstrate a specific and highly reproducible CAG length-dependent phenotypic signature in a synthetic model for human gastrulation derived from human embryonic stem cells (hESCs). Specifically, we observed a reduction in the extension of the ectodermal compartment that is associated with enhanced activin signaling. Surprisingly, rather than a cell-autonomous effect, tracking the dynamics of TGFβ signaling demonstrated that HTT-CAG expansion perturbs the spatial restriction of activin response. This is due to defects in the apicobasal polarization in the context of the polarized epithelium of the 2D gastruloid, leading to ectopic subcellular localization of TGFβ receptors. This work refines the earliest developmental window for the prodromal phase of HD to the first 2 weeks of human development, as modeled by our 2D gastruloids.
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http://dx.doi.org/10.1242/dev.199513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513611PMC
October 2021

Performance of cryogenic demountable indium seal at high pressures.

Rev Sci Instrum 2021 Sep;92(9):093905

Chengdu Xinliantong Cryogenic Equipment Co., Ltd., Chengdu 610200, China.

An essential challenge in seal design is to provide an ultra-low leak rate at cryogenic temperatures and high pressures. In this paper, the performance of demountable indium seals under a charging pressure of 8.5 MPa A and at cryogenic temperatures down to -190 °C was investigated. Three indium seal structures with a diameter of 30 mm were specifically designed and tested. All three structures went through both room temperature and cryogenic temperature tests in cycles with a pressure of up to 8.5 MPa A. In addition, leak rate experiments regarding the creep relaxation effect of the indium ring were conducted. The results showed that the leak rates of all three structures were lower than 1 × 10 Pa m s at both room temperature and cryogenic temperature with the pressure up to 8.5 MPa A when the torque was 8 or 12 N m. It was concluded that the linear loads for achieving a successful indium seal were 163, 171, and 220 N mm alongside its circumference for the 2 mm indium M-T structure, the 3 mm indium M-T structure, and the Z-shaped seal structure, respectively. Furthermore, although the torque slightly dropped after the assembly due to the creep relaxation effect, the leak rates of the structure were still lower than 1 × 10 Pa m s three days after the assembly. The present work is helpful for designing ultra-low leak rate demountable indium seals at cryogenic temperatures and high pressures.
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http://dx.doi.org/10.1063/5.0051279DOI Listing
September 2021

Trend Analysis and Intervention Effect Starting Point Detection of COVID-19 Epidemics Using Recalibrated Time Series Models - Worldwide, 2020.

China CDC Wkly 2021 May;3(20):417-422

Center of Clinical Big Data and Analytics, Second Affiliated Hospital and Department of Big Data Health Science School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

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http://dx.doi.org/10.46234/ccdcw2021.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392971PMC
May 2021

Unintentional Medication Discrepancies at Admission Among Elderly Inpatients with Chronic Medical Conditions in Vietnam: A Single-Centre Observational Study.

Drugs Real World Outcomes 2021 Sep 29. Epub 2021 Sep 29.

School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia.

Background: Elderly patients are at high risk of unintentional medication discrepancies during transition of care as they are more likely to have multiple comorbidities and chronic diseases that require multiple medications.

Objective: The aim of the study was to assess the frequency of unintentional medication discrepancies and identify the associated risk factors and potential clinical impact of them in elderly inpatients during hospital admission.

Patients And Methods: A prospective observational study was conducted from July to December 2018 in an 800-bed geriatric hospital in Hanoi, North Vietnam. Patients over 60 years of age, admitted to one of selected internal medicine wards, taking at least one chronic medication before admission, and staying at least 48 h were eligible for enrollment. Medication discrepancies of chronic medications before and after admission of each participant were identified by a pharmacist using a step-by-step protocol for the medication reconciliation process. The identified discrepancies were then classified as intentional or unintentional by an assessment group comprising a pharmacist and a physician. A logistic regression model was used to identify risk factors of medication discrepancies.

Results: Among 192 enrolled patients, 328 medication discrepancies were identified, with 87 (26.5%) identified as unintentional. Nearly a third of enrolled patients (32.3%) had at least one unintentional medication discrepancy. The most common unintentional medication discrepancy was omission of drugs (75.9% of 87 medication discrepancies). The logistic regression analysis revealed a positive association between the number of discrepancies at admission and the type of treatment wards.

Conclusions: Medication discrepancies are common at admission among Vietnamese elderly inpatients. This study highlights the importance of obtaining a comprehensive medication history at hospital admission and supports implementing a medication reconciliation program to reduce the negative impact of medication discrepancy, especially for the elderly population.
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http://dx.doi.org/10.1007/s40801-021-00274-3DOI Listing
September 2021

Frailty Phenotype and Mortality: A Prospective Cohort Study.

J Am Med Dir Assoc 2021 Sep 25. Epub 2021 Sep 25.

School of Public Health, Tianjin Medical University, Tianjin, China. Electronic address:

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http://dx.doi.org/10.1016/j.jamda.2021.08.030DOI Listing
September 2021

Mice lacking the proton channel Hv1 exhibit sex-specific differences in glucose homeostasis.

J Biol Chem 2021 Sep 20;297(4):101212. Epub 2021 Sep 20.

Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, PR China; Biomedical Research Center, Qilu Institute of Technology, Shandong, PR China. Electronic address:

Sex as a physiologic factor has a strong association with the features of metabolic syndrome. Our previous study showed that loss of the voltage-gated proton channel Hv1 inhibits insulin secretion and leads to hyperglycemia and glucose intolerance in male mice. However, there are significant differences in blood glucose between male and female Hv1-knockout (KO) mice. Here, we investigated the differences in glucose metabolism and insulin sensitivity between male and female KO mice and how sex steroids contribute to these differences. We found that the fasting blood glucose in female KO mice was visibly lower than that in male KO mice, which was accompanied by hypotestosteronemia. KO mice in both sexes exhibited higher expression of gluconeogenesis-related genes in liver compared with WT mice. Also, the livers from KO males displayed a decrease in glycolysis-related gene expression and an increase in gluconeogenesis-related gene expression compared with KO females. Furthermore, exogenous testosterone supplementation decreased blood glucose levels in male KO mice, as well as enhancing insulin signaling. Taken together, our data demonstrate that knockout of Hv1 results in higher blood glucose levels in male than female mice, despite a decreased insulin secretion in both sexes. This sex-related difference in glucose homeostasis is associated with the glucose metabolism in liver tissue, likely due to the physiological levels of testosterone in KO male mice.
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http://dx.doi.org/10.1016/j.jbc.2021.101212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503595PMC
September 2021

The type II histidine triad protein HtpsC facilitates invasion of epithelial cells by highly virulent Streptococcus suis serotype 2.

J Microbiol 2021 Oct 7;59(10):949-957. Epub 2021 Sep 7.

College Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, Jiangsu, P. R. China.

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that presents a significant threat both to pigs and to workers in the pork industry. The initial steps of S. suis 2 pathogenesis are unclear. In this study, we found that the type II histidine triad protein HtpsC from the highly virulent Chinese isolate 05ZYH33 is structurally similar to internalin A (InlA) from Listeria monocytogenes, which plays an important role in mediating listerial invasion of epithelial cells. To determine if HtpsC and InlA function similarly, an isogenic htpsC mutant (ΔhtpsC) was generated in S. suis by homologous recombination. The htpsC deletion strain exhibited a diminished ability to adhere to and invade epithelial cells from different sources. Double immunofluorescence microscopy also revealed reduced survival of the ΔhtpsC mutant after co-cultivation with epithelium. Adhesion to epithelium and invasion by the wild type strain was inhibited by a monoclonal antibody against E-cadherin. In contrast, the htpsC-deficient mutant was unaffected by the same treatment, suggesting that E-cadherin is the host-cell receptor that interacts with HtpsC and facilitates bacterial internalization. Based on these results, we propose that HtpsC is involved in the process by which S. suis 2 penetrates host epithelial cells, and that this protein is an important virulence factor associated with cell adhesion and invasion.
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http://dx.doi.org/10.1007/s12275-021-1129-1DOI Listing
October 2021

Co-overexpression of RIOK1 and AKT1 as a prognostic risk factor in glioma.

J Cancer 2021 25;12(19):5745-5752. Epub 2021 Jul 25.

Department of Pathology, College of Basic Medical Sciences, Shenyang Medical College, Shenyang City, Liaoning Province 110034, P.R. China.

Glioblastoma multiforme (GBM) is one of the most frequent primary malignancies of the brain. Although the treatment strategy has significantly improved, patient prognosis remains poor. studies have shown that the right open reading frame kinase 1/protein kinase B (RIOK1-AKT) signaling pathway plays an important role in the malignant phenotype of glioma cells. This study aimed to investigate the co-expression of RIOK1 and ATK in glioma tissues and its clinical significance. Compared with normal tissues, RIOK1 and AKT1 expression were significantly upregulated in glioma tissues. In addition, patients with higher World Health Organization staging grades had increased RIOK1 and AKT1 expression levels, and RIOK1 and AKT1 expression were positively correlated. Notably, both RIOK1 and AKT1 expressions were correlated with poor prognosis. experiments showed that silencing RIOK1 inhibited the proliferation, migration, and invasion of glioma cell lines by suppressing AKT and c-Myc expression. These results indicate that the RIOK1-AKT1 axis could play an important role in GBM progression.
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http://dx.doi.org/10.7150/jca.60596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408104PMC
July 2021

Vaccinated or not? Survey on attitude toward 'approach-avoidance conflict' under uncertainty.

Hum Vaccin Immunother 2021 Sep 2:1-6. Epub 2021 Sep 2.

The School of Communication and Design, Sun Yat-Sen University, Guangzhou, China.

Vaccinated or not? This is an attitude survey for 'approach-avoidance conflict' under uncertainty. Therefore, measuring people's attitude toward COVID-19 vaccination is relatively distinctive from an attitude over a general conflict. An online survey of 3123 respondents from 30 provincial-level regions - out of 31 - on the Chinese mainland was conducted from January 22 to 27, 2021 to measure their willingness to be vaccinated. We found that over half of the respondents chose the options 'not to be vaccinated now' and 'wait and see before making a vaccination decision,' thereby indicating that people's willingness to be vaccinated is not as optimistic as anticipated in the early stage of vaccination in China. Hence, investigators should carefully select the measuring method to assess the 'true' levels of willingness to accept COVID-19 vaccines. Lastly, the relevant departments should fully predict obstacles to achieve immunity coverage and prepare for the 'vaccine hesitancy' of people in need.
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http://dx.doi.org/10.1080/21645515.2021.1967038DOI Listing
September 2021

Applications of Membranes for Sustainability.

Membranes (Basel) 2021 Aug 16;11(8). Epub 2021 Aug 16.

Department of Chemical Engineering, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates.

Applications of membranes in water and wastewater treatment, desalination, as well as other purification processes, have become more widespread over the past few decades [...].
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http://dx.doi.org/10.3390/membranes11080629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402074PMC
August 2021

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis.

Stem Cells Int 2021 10;2021:1439563. Epub 2021 Aug 10.

Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China.

Objective: Osteoporosis is an abnormal bone metabolism disease characterized by microstructural degeneration of bone tissue and reduction in bone mass, resulting in increased brittleness of bone tissue and susceptibility to fracture. Due to the tissue regenerative potential of stem cell transplantation, it is now used in the treatment of various disease models such as osteoporosis. The purpose of this work is to carry out a systematic review and meta-analysis of the efficacy of stem cell therapy in ovariectomized (OVX) osteoporotic rats.

Methods: PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang Databases were used to search for articles that met the inclusion criteria. Two researchers independently screened the articles that met the inclusion criteria. RevMan 5.3 and STATA 16.0 were used for data analysis. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202150017.

Results: Thirteen eligible studies were selected, including 405 rats. The sources of stem cells are divided into four main categories: bone marrow mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), amniotic membrane mesenchymal stem cells (AM-MSCs), and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Compared with the OVX group, both stem cell transplantation groups had higher bone mineral density (BMD) (BMSCs: SMD = 2.01, 95% CI: [1.38, 2.63], < 0.001, = 76.6%; ADSCs: SMD = 2.24, 95% CI: [0.79, 3.69], = 0.003, = 86.7%) and bone volume/total volume (BV/TV) (hUCB-MSCs: SMD = 1.71, 95% CI: [0.97, 2.44], < 0.001, = 0%; ADSCs: SMD = 2.16, 95% CI: [0.27, 4.04], = 0.025, = 82.6%). In the BMSC treatment groups, the trabecular numbers (Tb.N) (SMD = 4.28, 95% CI: [0.91, 7.64], = 0.013, = 94.9%) were significantly higher, whereas the results for trabecular thickness (Tb.Th) (SMD = 2.7, 95% CI: [-0.34, 5.73], = 0.081, = 95.4%) and trabecular spacing (Tb.Sp) (SMD = -3.08, 95% CI: [-6.55, 0.38], = 0.081, = 96.3%) were not statistically significant compared to those of the OVX group. The stem cell transplantation group had a low BMD, BV/TV, and Tb.N compared to the sham operation group.

Conclusion: Stem cell therapy may increase bone strength, bone volume, and the number of trabeculae in OVX osteoporotic rats. The results of this meta-analysis showed the potential therapeutic effect of stem cell transplantation in OVX osteoporotic rats, bringing new therapeutic ideas and directions to the clinical treatment of osteoporosis. Due to the limited number and quality of studies related to some outcomes, more high-quality RCTs are still needed in the future to complement the existing findings.
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http://dx.doi.org/10.1155/2021/1439563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380498PMC
August 2021

Association of coffee and genetic risk with incident dementia in middle-aged and elderly adults.

Nutr Neurosci 2021 Aug 23:1-10. Epub 2021 Aug 23.

School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China.

Background: Prior evidence suggests that coffee might be related to dementia, however, little is known about coffee and dementia in individuals with elevated genetic susceptibility for dementia. Additionally, most previous studies have focused on total coffee instead of examining coffee types separately.

Methods: This study included 203,776 participants (60-73 years old) from the UK Biobank who were initially free of dementia. Polygenic risk scores for dementia were divided into quintile to stratify individuals into low (lowest quintile), intermediate (quintile 2-4), and high (highest quintile) genetic risk categories. Coffee intake was assessed at baseline and included total, instant, ground, and decaffeinated coffee.

Results: During a median follow-up of 11.4 years, 4405 cases of dementia occurred (1856 Alzheimer's disease [AD], 1105 vascular dementia). Compared to non-coffee drinking, heavy instant coffee drinking (> 6 cups/day) and moderate decaffeinated coffee drinking (1-3 cups/day) were associated with a higher risk of dementia (hazard ratio [HR] 1.19-1.34) and AD (HR 1.41-1.51), while moderate ground coffee drinking was associated with a lower risk of dementia (HR, 0.78; = 0.001) and vascular dementia (HR, 0.58; < 0.001). Among participants at high genetic risk, heavy coffee drinking was associated with a 95% (HR; 1.95, 95% CI, 1.21-3.16) higher risk of AD than non-coffee drinking. We found an interaction between coffee and genetic risk in relation to AD (= 0.038).

Conclusion: The association of dementia and coffee varied by coffee types. Heavy coffee consumption was associated with a higher risk of AD in individuals with high genetic risk for dementia.
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http://dx.doi.org/10.1080/1028415X.2021.1966868DOI Listing
August 2021

Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and Older Adults.

Drugs Aging 2021 10 18;38(10):921-930. Epub 2021 Aug 18.

School of Public Health, Tianjin Medical University, Tianjin, 300070, China.

Background: There is ongoing debate about the associations between drug therapies targeting the renin-angiotensin-aldosterone system (RAAS) and adverse outcomes in coronavirus disease 2019 (COVID-19).

Objective: This study aims to examine the associations between using medications for the cardiovascular system and the risks associated with COVID-19 in middle-aged and older adults.

Methods: A total of 77,221 participants (aged 50-86 years) from UK Biobank were tested for SARS-CoV-2 RNA. The medications included angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), β-blockers, calcium channel blockers (CCB), statins, and aspirin. COVID-19 outcomes comprised a positive test result and severity of COVID-19 (defined as mild, hospitalization or death). We evaluated the risk among total participants and for sub-groups based on sex. Propensity score matching was performed 1:1 and logistic regression models were used.

Results: Among the middle- and older aged participants, no significant associations between any class of medications and the likelihood of COVID-19 infection were observed. ACEI were associated with a higher mortality risk from COVID-19 (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.32) and CCB were associated with a lower hospitalization risk for COVID-19 (OR 0.87, 95% CI 0.79-0.96) among the male patients with COVID-19, while a lower mortality risk from COVID-19 (OR 0.67, 95% CI 0.47-0.96) was observed with ARB among the female patients with COVID-19.

Conclusions: The study suggested sex differences in the risk of death from COVID-19 with the use of ACEI and ARB among middle-aged and older adults. Sex differences in the risk of hospitalization for COVID-19 with the use of CCB was observed as well. It is of clinical importance that clinicians adopt different CVD treatment approaches for female and male patients with COVID-19.
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http://dx.doi.org/10.1007/s40266-021-00886-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370833PMC
October 2021

[Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19~+B cells regulating FAK/CAPN/PI3K pathway].

Zhongguo Zhong Yao Za Zhi 2021 Jul;46(14):3705-3711

Graduate School of Anhui University of Chinese Medicine Hefei 230031,China.

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β,IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β,IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201120.501DOI Listing
July 2021

Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Jun;50(3):352-360

Clinical Colloge of Wannan Medical College.

To investigate the effects of salt-inducible kinase 2 (SIK2) on energy metabolism in rats with cerebral ischemia-reperfusion. Adult SD male rats were divided into 5 groups: sham group, ischemia group, reperfusion group, adenovirus no-load group, and SIK2 overexpression group with 5 animals in each group. The middle cerebral artery occlusion (MCAO) was induced with the modified Zea-Longa line thrombus method to establish the cerebral ischemia reperfusion model. Eight days before the MCAO, SIK2 overexpression was induced by injecting 7 μL adenovirus in the right ventricle, then MCAO was performed for followed by reperfusion HE staining was used to observe the pathological changes of cerebral tissue in rats; TTC staining was used to observe the volume of cerebral infarct. The levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in rat brain tissue were detected by ELISA; the levels of SIK2 and hypoxia-inducible factor 1α (HIF-1α) in the rat brain tissues were detected by RT-qPCR and Western blotting. Compared with the sham group, SIK2 level was decreased in the ischemia group, and it was further declined in the reperfusion group (<0.05). Compared with the sham group and ischemic group, the pathological injury in reperfusion group were more severe, and the infarct size was larger; compared with the reperfusion group and adenovirus no-load group, the pathological injury of the SIK2 overexpression group was milder, and the infarct size is less. Compared with the sharn group, HIF-1α was increased in both ischemia group and reperfusion group, especially in ischemia group (all <0.05); HIF-1α level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05). ATP level in ischemia group and reperfusion group was lower than that in the sham group, and the reperfusion group decreased more significantly than the ischemia group (<0.05); ADP content was increased in the ischemia and reperfusion group, and the ADP content in reperfusion group was significantly higher than that in the ischemia group (<0.05). ATP level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05), and ADP was decreased in the SIK2 overexpression group (all <0.05). SIK2 can up-regulate the ATP level and down-regulate the ADP level in rat brain tissue and alleviate cerebral ischemia-reperfusion injury by increase the level of HIF-1α.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0164DOI Listing
June 2021

Relationship between the Metabolic Associated Fatty Liver Disease and Endometrial Thickness in Postmenopausal Women: A Cross-sectional Study in China.

Int J Med Sci 2021 22;18(14):3082-3089. Epub 2021 Jun 22.

Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

To determine the relationship between the endometrial thickness (ET) and metabolic associated fatty liver disease (MAFLD) in the postmenopausal women who have a comprehensive health examination. This was a population-based, retrospective observational study of the prevalence of MAFLD in 8594 postmenopausal women with different ET in the Quality Control Center of Health Examination in Chongqing, China. Binary and multivariable logistic regression analyses were used to obtain odds ratios and 95% confidence intervals for patients of different ET with MAFLD after adjusting for age. The incidences of MAFLD were 28.6% (1352), 30.3% (1058), 34.9% (133) in postmenopausal women with ET of < 3 mm, 3 mm ≤ & < 5 mm, and ≥ 5 mm, respectively. Compared with a baseline ET of less than 5.0 mm, the risk of MAFLD in patients with ET of ≥5.0 mm is higher (OR=1.291, 95% CI: 1.041-1.603, P<0.05). After adjustment for age, a statistically significant positive correlation was still observed. The increased prevalence of MAFLD in patients with ET of 3 mm ≤ &<5 mm (OR=1.110, 95% CI: 1.008-1.223) and ≥5 mm (OR=1.383, 95% CI: 1.109-1.724) achieved statistical significance, respectively. In addition, multiple logistic analyses controlling for age also confirmed the finding of positive correlation among body mass index (BMI) and ET. Our results suggest that there is a positive correlation between MAFLD and ET in postmenopausal women. In addition, increased BMI is also associated with an increased risk of thickened endometrium.
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http://dx.doi.org/10.7150/ijms.60780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364468PMC
June 2021

Analysis of IVF/ICSI Outcomes in Endometriosis Patients With Recurrent Implantation Failure: Influence on Cumulative Live Birth Rate.

Front Endocrinol (Lausanne) 2021 30;12:640288. Epub 2021 Jul 30.

State Key Laboratory of Reproductive Medicine, Center of Clinic Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital/Jiangsu Women and Children Health Hospital, Nanjing, China.

Objective: To study the influence of endometriosis activity on the pregnancy outcomes of patients with recurrent implantation failure (RIF) in fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles. The pregnancy outcomes were compared between RIF patients with endometriosis who received treatment at different occasions to explore the appropriate treatment plan for these patients and to optimize the pregnancy-support strategies.

Design: Ambispective cohort study.

Methods: A total of 330 patients with endometriosis were enrolled from 2008 to 2018 and included 1043 IVF/ICSI cycles. All patients were diagnosed with RIF after IVF/ICSI. Patients were assigned to three subtypes according to different control states of endometriosis, including the untreated, early-treatment, and late-treatment groups. The clinical pregnancy rate, live birth rate, and cumulative live birth rate of endometriosis patients with RIF were the main outcomes; additionally, the fertilization rate, available embryonic rate, and high-quality embryonic rate were also compared.

Results: The early-treatment and late-treatment groups showed higher cumulative live birth rate than the untreated group (early-treated 43.6% . late-treated 46.3% . untreated 27.7%, P<0.001), though patients in the two treatment groups had higher rates of adenomyosis and ovarian surgery. The two treatment group showed a better laboratory result than the untreated and especially, the early-treatment group. The untreated group (46.24%) had a lower IVF fertilization rate than the treated group (early-treated [64.40%] and late-treated [60.27%] (P<0.001). In addition, the rates of available embryos and high-quality embryos in the early-treated group were much higher those that in the untreated group (90.30% . 85.20%, 76.50% . 64.47%). Kaplan-Meier curve showed that patients in the untreated group needed a mean of 23.126 months to achieve one live birth; whereas those in the treated group needed a comparatively shorter duration (early-treated: 18.479 ± 0.882 months and late-treated: 14.183 ± 1.102 months, respectively).

Conclusion: Endometriosis has a negative influence on IVF/ICSI outcome. The control of endometriosis activity can result in a higher cumulative live birth rate in patients. It is necessary for endometriosis patients to receive medical treatment to achieve a better prognosis especially for those with RIF.
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http://dx.doi.org/10.3389/fendo.2021.640288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362597PMC
July 2021

Modulation of Xenogeneic T Cell Proliferation by B7 and mTOR Blockade of T cells and Porcine Endothelial Cells.

Transplantation 2021 Aug 11. Epub 2021 Aug 11.

Department of Surgery, Duke University School of Medicine, Durham, NC, USA.

Background: Activation of porcine endothelial cells (PECs) is the mechanistic centerpiece of xenograft rejection. This study sought to characterize the immuno-phenotype of human T cells in response to PECs and to explore the immuno-modulation of B7 and mTOR blockade of T cells and/or PECs during xeno-responses.

Methods: Rapid memory T-cell (TM) responses to PECs were assessed by an intracellular cytokine staining. T-cell proliferation to PEC with or without belatacept or rapamycin were evaluated by a mixed lymphocyte-endothelial cell reaction (MLER). Additionally, rapamycin-pretreated PECs were used in MLER. Cell phenotypes were analyzed by flow cytometry.

Results: TNF-α/IFN-γ producers were detected in CD8+ cells stimulated by human endothelium but not PECs. MLER showed proliferation of CD4+ and CD8+ cells with predominantly memory subsets. Purified memory and naïve cells proliferated following PEC-stimulation with an increased frequency of TM in PEC-stimulated naïve cells. Proliferating cells upregulated PD-1 and CD2 expression. Belatacept partially inhibited T-cell proliferation with reduced CD2 expression and frequency of the CD8+CD2highCD28- subset. Rapamycin dramatically inhibited PEC-induced T cell proliferation, and rapamycin-preconditioned PECs failed to induce T-cell proliferation. PD-1 blockade did not restore T-cell proliferation to rapamycin-preconditioned PECs.

Conclusions: Humans lack rapid TM-mediated responses to PECs, but induce T-cell proliferative responses characterized largely as TM with increasing CD2 and PD-1 expression. B7-CD28 and mTOR blockade of T cells exhibit dramatic inhibitory effects in altering xeno-proliferating cells. Rapamycin alter PEC xeno-immunogenicity leading to inhibition of xeno-specific T-cell proliferation independent of PD-1-PD ligand interaction.
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http://dx.doi.org/10.1097/TP.0000000000003920DOI Listing
August 2021

Disrupted resting-state interhemispheric functional connectivity in systemic lupus erythematosus patients with and without neuropsychiatric lupus.

Neuroradiology 2021 Aug 11. Epub 2021 Aug 11.

Department of Radiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, Zhuang Autonomous Region, China.

Purpose: The aim of the study is to explore interhemispheric homotopic functional connectivity alterations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric lupus (NPSLE and non-NPSLE, respectively) and their potential correlations with clinical characteristics and neuropsychological performance.

Methods: Based on resting-state functional MRI (rs-fMRI) data collected from SLE patients and matched healthy controls (HCs), the voxel-mirrored homotopic connectivity (VMHC) analysis was conducted to measure functional homotopy. Subsequently, correlations between altered functional homotopy and clinical/neuropsychological data were analyzed.

Results: Compared with the HC group, both NPSLE and non-NPSLE groups showed attenuated homotopic connectivity in middle temporal gyrus (MTG), cuneus (CUN), middle occipital gyrus (MOG), angular gyrus (ANG), and postcentral gyrus (PoCG). NPSLE patients also exhibited decreased homotopic connectivity in inferior parietal gyrus (IPG) and middle frontal gyrus (MFG). Compared with non-NPSLE patients, NPSLE patients showed weaker interhemispheric homotopic functional connectivity in MOG. Decreased homotopic functional connectivity in PoCG, IPG, and MOG were associated with the anxiety state of SLE patients.

Conclusions: Our findings revealed attenuated functional homotopy in both NPSLE and non-NPSLE groups compared to the HC group, which appeared to be more severe in patients with comorbid neuropsychiatric lupus. Interhemispheric homotopy dysconnectivity may participate in the neuropathology of anxiety symptoms in SLE.
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http://dx.doi.org/10.1007/s00234-021-02750-7DOI Listing
August 2021

[Effects of ERα gene overexpression on bone mineral density and calcium and phosphorus metabolism inovariectomized osteoporosis mice].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 May;37(3):332-336

Xiangnan University Medical Imaging Examination and Rehabilitation College, Chenzhou 423000.

To investigate the effects of estrogen receptor α (ERα) gene overexpression on bone metabolism and calcium and phosphorus metabolism in ovariectomized osteoporosis mice, and to provide experimental basis for targeted gene therapy of osteoporosis. Thirty SPF female mice were randomly divided into sham operation group, model group and ERα overexpression group with 10 mice in each group. After the model was established, the ERα overexpression group was transfected with recombinant adenovirus vector carrying mouse ERα gene by intraspinal injection. The model group was transfected with empty virus, and the sham operation group was not treated. The expression of ERα gene in bone tissue of mice was detected by quantitative Real-time PCR (RT-PCR). Bone mineral density (BMD) of mouse femur was measured after modeling. Trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular segregation (Tb.Sp), bone volume fraction (BV/TV) and biomechanical strength of femur were measured by micro-CT scanning. Serum levels of calcium (Ca), phosphorus (P), osteocalcin (BGP) and alkaline phosphatase (ALP) were measured by automatic biochemical analyzer. The expressions of tissue inhibitor of metalloproteinases 1 (TIMP-1) and monocyte chemotactic protein 1 (MCP-1) in bone homogenate were detected by Immunohistochemistry. Compared with sham operation group, the expression level of ERα gene in bone tissue of model group was decreased significantly, the levels of BMD, BV/TV, Tb. Th, maximum load, rigidity coefficient, Ca and P were decreased, while the levels of Tb. Sp, BGP and ALP were increased significantly (<0.05). Compared with the sham operation group, the expression level of TIMP-1 protein in the bone tissue of the model group was significantly decreased, while that of MCP-1 protein was increased, while that of the ERα overexpression group was increased while that of MCP-1 was decreased (<0.05).The levels of ERα gene expression, BMD, BV/TV, TB. Th, maximum load, rigidity coefficient, Ca and P in the ERα overexpression group were significantly higher than those in the model group, while Tb. Sp, BGP and ALP were significantly lower (<0.05). Compared with the sham operation group, mean optical density of TIMP-1 in the bone tissue of the model group was significantly decreased, while that of MCP-1 was significantly increased, and that of the ERα overexpression group was significantly increased while that of MCP-1 was significantly decreased (<0.05). ERα gene overexpression can improve osteoporosis by regulating bone mineral density, bone parameters, bone metabolism, calcium and phosphorus metabolic indicators and the expression levels of TIMP-1 and MCP-1 in tissues.
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http://dx.doi.org/10.12047/j.cjap.6028.2021.002DOI Listing
May 2021

[Effect of transcutaneous electrical acupoint stimulation on lung function and risks of exacerbation for patients with chronic obstructive pulmonary disease].

Zhen Ci Yan Jiu 2021 Jul;46(7):598-604

Department of Traditional Chinese Medicine, Chengdu Fifth People's Hospital, Chengdu 611130, China.

Objective: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on lung function, clinical symptoms, exercise tolerance and risk of acute exacerbation in patients with chronic obstructive pulmonary disease (COPD).

Methods: A total of 49 outpatients with COPD were randomly divided into TEAS group and control group by using a digital table. The clinical trials were conducted by using randomized, single-blinded and placebo-controlled method. Patients in the TEAS group were treated by TEAS of Feishu (BL13), Dingchuan (EX-B1), Zusanli (ST36) and Pishu (BL20) for 40 min, once every other day for 4 weeks, while patients in the control group were treated with placebo TEAS which the electrode plates were adhered to the same acupoints but without electrical current outputs. The treatment was conducted every 3 months in one year. In addition, patients of the two groups had no restriction on their original treatment with conventional western medicines and Chinese Materia medica. The lung function (forced expiratory volume in 1 second predicted,FEV1%, forced vital capacity predicted,FVC%) was detected using a spirometer), clinical symptom scores (CAT) for coughing, phlegm, chest tightness, climbing, family activities, out-door activities, sleeping and energy status were given. The patient's exercise tolerance was assessed using walking distance in 6 min, and the risks of acute exacerbation (times of exacerbation and hospitalization in 1 year) were recorded.

Results: Correlative analysis showed a negative correlation between the risks of acute exacerbation and the levels of FEV1% and FVC% (<0.01) and a positive correlation between the risks of acute exacerbation and CAT score (<0.01). Self-comparison showed that 1 month after the treatment, the FEV1% and FVC% levels, 6MWD in the control group were significantly decreased (<0.001, <0.01), while the CAT score in the control group, and FEV1% and 6MWD in the TEAS group were obviously increased in comparison with their own pretreatment (<0.05, <0.001), but FVC% in the TEAS group and the times of exacerbation and hospitalization in the control group had no obvious changes in comparison with their own pre-treatment (>0.05). One year (1 year) after the treatment, FEV1% and FVC% levels, 6MWD in the control group, and CAT score and times of exacerbations and hospitalization in the TEAS group were significantly decreased (<0.001, <0.01, <0.05), while CAT score in the control group and 6MWD in the TEAS group were markedly increased (<0.05, <0.01), but FEV1% in the TEAS group and the times of exacerbation and hospitalization in the control group had no significant change compared with their own pretreatment (>0.05). Comparison between two groups showed that after the treatment, the FEV1% (1 month) and FVC% (1 month and 1 year), 6MWD (1 month and 1 year) were significantly higher in the TEAS group than in the control group (<0.05), while the CAT (1 month and 1 year) and times of exacerbation and hospitalization (1 year) were significantly lower in the TEAS group than in the control group (<0.05, <0.01, <0.001), without significant difference in the FEV1% (1 year) level (>0.05).

Conclusion: TEAS can improve the lung function, clinical symptoms, exercise tolerance, and reduce the risks of acute exacerbation in patients with COPD.
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http://dx.doi.org/10.13702/j.1000-0607.200646DOI Listing
July 2021

Targeted Temperature Management for In-hospital Cardiac Arrest Caused by Thyroid Storm: A Case Report.

Front Cardiovasc Med 2021 21;8:634987. Epub 2021 Jul 21.

Department of Emergency Medicine, Peking University Third Hospital, Beijing, China.

Malignant ventricular arrhythmias caused by thyroid storm, such as ventricular tachycardia (VT) or ventricular fibrillation (VF), which are life-threatening, are rare. We report the case of a patient who suffered from cardiac arrest caused by thyroid storm and the rare VF; the patient showed a favorable neurologic outcome after receiving targeted temperature management (TTM) treatment by intravascular cooling measures. A 24-year-old woman who had lost 20 kg in the preceding 2 months presented to the emergency department with diarrhea, vomiting, fever, and tachycardia. Thyroid function testing showed increased free triiodothyronine (FT3) and free thyroxine (FT4), decreased thyroid-stimulating hormone (TSH), and positive TSH-receptor antibody (TRAB). She was diagnosed with hyperthyroidism and had experienced sudden cardiac arrest (SCA) due to ventricular fibrillation (VF) caused by thyroid storm. The patient was performed with targeted temperature management (TTM) by intravascular cooling measures. Regular follow-up in the endocrinology department showed a good outcome. Our case not only suggests a new method of cooling treatment for thyroid storm, but also provides evidence for the success of TTM on patients resuscitated from in-hospital cardiac arrest (IHCA) who remain comatose after return of spontaneous circulation (ROSC).
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http://dx.doi.org/10.3389/fcvm.2021.634987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333705PMC
July 2021

Altered Functional Brain Network in Systemic Lupus Erythematosus Patients Without Overt Neuropsychiatric Symptoms Based on Resting-State Functional Magnetic Resonance Imaging and Multivariate Pattern Analysis.

Front Neurol 2021 21;12:690979. Epub 2021 Jul 21.

Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

This study aims to investigate the alterations in functional brain network in systemic lupus erythematosus patients without overt neuropsychiatric symptoms [neuropsychiatric systemic lupus erythematosus (non-NPSLE)] from the perspective of degree centrality (DC) and functional connectivity (FC) using resting-state functional magnetic resonance imaging (MRI) and multivariate pattern analysis (MVPA) approach. DC analysis was performed based on the resting-state functional MRI data derived from 47 non-NPSLE patients and 47 healthy controls (HCs). Nodes with abnormal DC were utilized as seeds for further FC analysis. The correlation between MRI variables and clinical or neuropsychological data was analyzed using Pearson correlation analysis. Finally, MVPA classification based on DC was performed. When compared with the HCs, the non-NPSLE patients exhibited remarkably higher DC in the bilateral hippocampus (HIP), right insula (INS), and lower DC in the left superior parietal gyrus. Furthermore, the patients displayed significantly higher FC between the left HIP and the left INS/left dorsolateral middle frontal gyrus/left supramarginal gyrus and higher FC between the right HIP and the right middle temporal gyrus/right dorsolateral middle frontal gyrus/right dorsolateral inferior frontal gyrus/right supramarginal gyrus (all imaging variables mentioned earlier underwent cluster-level false discovery rate corrections, the voxel threshold was < 0.001, cluster threshold was < 0.05). Correlation analysis revealed significantly negative correlations between DC values of the right INS and disease activity and the DC values of the right HIP and the Montreal Cognitive Assessment scores. The accuracy, sensitivity, and specificity of MVPA classification based on DC were 72.34, 63.83, and 80.85%, respectively. The most discriminative power brain regions were chiefly located within the temporal, parietal, and frontal regions. Patients with non-NPSLE exhibited abnormal DC and FC in the brain network. MVPA based on DC possessed commendable classification ability. Our study may provide a novel perspective on the neuropathological mechanisms underlying subclinical brain damage in non-NPSLE.
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http://dx.doi.org/10.3389/fneur.2021.690979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333697PMC
July 2021
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