Publications by authors named "Ming Zhang"

3,113 Publications

  • Page 1 of 1

Effect of Inhibition of the JAK2/STAT3 Signaling Pathway on the Th17/IL-17 Axis in Acute Cellular Rejection After Heart Transplantation in Mice.

J Cardiovasc Pharmacol 2021 Apr 7;77(5):614-620. Epub 2021 Apr 7.

Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.

Abstract: Acute immune rejection is one of the most serious complications of heart transplantation, and its mechanism has always been a hot spot. Th17 cells and cytokine interleukin-17 (IL-17) have been proved to be involved in acute immune rejection, and the signaling pathway mechanism has attracted our interest. It has been confirmed that the Janus kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the differentiation of CD4+ T cells, so we focus on whether the JAK2/STAT3 signaling pathway is involved in the occurrence of acute immune rejection by regulating the Th17/IL-17 axis. In this study, we used Bagg's Albino c mice and C57BL/6 mice to construct heterotopic heart transplantation models, which were divided into the acute rejection group and AG490-treated group (n = 5), and donor tissue and serum were collected in 3 experimental days from the recipient mice for H&E staining analysis of paraffin sections and ELISA, Western blot, flow cytometry, and real time-polymerase chain reaction. The results showed that the acute rejection rating of the heart decreased, and the expression of related factors decreased significantly after using the inhibitor AG490, suggesting that the JAK2/STAT3 signaling pathway regulates expression of the Th17/IL-17 axis in cardiac allograft rejection.
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http://dx.doi.org/10.1097/FJC.0000000000001007DOI Listing
April 2021

Structural basis of tetanus toxin neutralization by native human monoclonal antibodies.

Cell Rep 2021 May;35(5):109070

Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China; Trinomab Biotech Co., Ltd, Zhuhai 519040, China; Institute of Biomedicine, Jinan University, Guangzhou 510632, China. Electronic address:

Four potent native human monoclonal antibodies (mAbs) targeting distinct epitopes on tetanus toxin (TeNT) are isolated with neutralization potency ranging from approximately 17 mg to 6 mg each that are equivalent to 250 IU of human anti-TeNT immunoglobulin. TT0170 binds fragment B, and TT0069 and TT0155 bind fragment AB. mAb TT0067 binds fragment C and blocks the binding of TeNT to gangliosides. The co-crystal structure of TT0067 with fragment C of TeNT at a 2.0-Å resolution demonstrates that mAb TT0067 directly occupies the W pocket of one of the receptor binding sites on TeNT, resulting in blocking the binding of TeNT to ganglioside on the surface of host cells. This study reveals at the atomic level the mechanism of action by the TeNT neutralizing antibody. The key neutralization epitope on the fragment C of TeNT identified in our work provides the critical information for the development of fragment C of TeNT as a better and safer tetanus vaccine.
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http://dx.doi.org/10.1016/j.celrep.2021.109070DOI Listing
May 2021

Biomechanical analysis of lumbar interbody fusion supplemented with various posterior stabilization systems.

Eur Spine J 2021 May 4. Epub 2021 May 4.

Interdisciplinary Division of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China.

Purpose: Biomechanical comparison between rigid and non-rigid posterior stabilization systems following lumbar interbody fusion has been conducted in several studies. However, most of these previous studies mainly focused on investigating biomechanics of adjacent spinal segments or spine stability. The objective of the present study was to compare biomechanical responses of the fusion devices when using different posterior instrumentations.

Methods: Finite-element model of the intact human lumbar spine (L1-sacrum) was modified to simulate implantation of the fusion cage at L4-L5 level supplemented with different posterior stabilization systems including (i) pedicle screw-based fixation using rigid connecting rods (titanium rods), (ii) pedicle screw-based fixation using flexible connecting rods (PEEK rods) and (iii) dynamic interspinous spacer (DIAM). Stress responses were compared among these various models under bending moments.

Results: The highest and lowest stresses in endplate, fusion cage and bone graft were found at the fused L4-L5 level with DIAM and titanium rod stabilization systems, respectively. When using PEEK rod for the pedicle screw fixation, peak stress in the pedicle screw was lower but the ratio of peak stress in the rods to yield stress of the rod material was higher than using titanium rod.

Conclusions: Compared with conventional rigid posterior stabilization system, the use of non-rigid stabilization system (i.e., the PEEK rod system and DIAM system) following lumbar interbody fusion might increase the risks of cage subsidence and cage damage, but promote bony fusion due to higher stress in the bone graft. For the pedicle screw-based rod stabilization system, using PEEK rod might reduce the risk of screw breakage but increased breakage risk of the rod itself.
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http://dx.doi.org/10.1007/s00586-021-06856-7DOI Listing
May 2021

N6-methyladenosine demethylase FTO impairs hepatic ischemia-reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation.

Cell Death Dis 2021 May 4;12(5):442. Epub 2021 May 4.

Department of Hepatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia-reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.
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http://dx.doi.org/10.1038/s41419-021-03622-xDOI Listing
May 2021

Proteomic and phosphoproteomic profiles of Sertoli cells in buffalo.

Theriogenology 2021 Apr 27;170:1-14. Epub 2021 Apr 27.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, Guangxi, China. Electronic address:

Sertoli cells provide nutrients and support for germ cell differentiation and maintain a stable microenvironment for spermatogenesis. Comprehensive identification of Sertoli cellular proteins is important in understanding spermatogenesis. In this study, we performed an integrative analysis of the proteome and phosphoproteome to explore the role of Sertoli cells in spermatogenesis. A total of 2912 and 753 proteins were identified from the proteome and phosphoproteome in Sertoli cells, respectively; 438 proteins were common to the proteome and phosphoproteome. Data are available via ProteomeXchange with identifier PXD024984. In the proteome, ACTG1, ACTB, ACTA2, MYH9 were the most abundant proteins. Gene Ontology (GO) analysis indicated that most of the proteins were involved in the processes of localization, biosynthesis, gene expression, and transport. In addition, some of the proteins related to Sertoli cell functions were also enriched. In the phosphoproteome, most of the proteins were involved in gene expression and the RNA metabolic process; the pathways mainly involved the spliceosome, mitogen-activated protein kinase signaling pathway, focal adhesion, and tight junctions. The pleckstrin homology-like domain is the most highly enriched protein domain in phosphoproteins. Cyclin-dependent kinases and protein kinases C were found to be highly active kinases in the kinase-substrate network analysis. Ten proteins most closely related to network stability were found in the analysis of the network interactions of proteins identified jointly in the phosphoproteome and proteome. Through immunohistochemistry and immunofluorescence verification of vimentin, it was found that there were localization differences between phosphorylated and non-phosphorylated vimentin in testicular tissue. This study is the first in-depth proteomic and phosphoproteomic analysis of buffalo testicular Sertoli cells. The results provide insight into the role of Sertoli cells in spermatogenesis and provide clues for further study of male reproduction.
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http://dx.doi.org/10.1016/j.theriogenology.2021.04.013DOI Listing
April 2021

Forest biomass carbon pool dynamics in Tibet Autonomous Region of China: Inventory data 1999-2019.

PLoS One 2021 3;16(5):e0250073. Epub 2021 May 3.

College of Soil and Water Conservation, Beijing Forestry University, Beijing, PR, China.

According to the forest resources inventory data for different periods and the latest estimation parameters of forest carbon reserves in China, the carbon reserves and carbon density of forest biomass in the Tibet Autonomous Region from 1999 to 2019 were estimated using the IPCC international carbon reserves estimation model. The results showed that, during the past 20 years, the forest area, forest stock, and biomass carbon storage in Tibet have been steadily increasing, with an average annual increase of 1.85×104 hm2, 0.033×107 m3, and 0.22×107 t, respectively. Influenced by geographical conditions and the natural environment, the forest area and biomass carbon storage gradually increased from the northwest to the southeast, particularly in Linzhi and Changdu, where there are many primitive forests, which serve as important carbon sinks in Tibet. In terms of the composition of tree species, coniferous forests are dominant in Tibet, particularly those containing Abies fabri, Picea asperata, and Pinus densata, which comprise approximately 45% of the total forest area in Tibet. The ecological location of Tibet has resulted in the area being dominated by shelter forest, comprising 68.76% of the total area, 64.72% of the total forest stock, and 66.34% of the total biomass carbon reserves. The biomass carbon storage was observed to first increase and then decrease with increasing forest age, which is primarily caused by tree growth characteristics. In over-mature forests, trees' photosynthesis decreases along with their accumulation of organic matter, and the trees can die. In addition, this study also observed that the proportion of mature and over-mature forest in Tibet is excessively large, which is not conducive to the sustainable development of forestry in the region. This problem should be addressed in future management and utilization activities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250073PLOS
May 2021

A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma.

Front Oncol 2021 16;11:656628. Epub 2021 Apr 16.

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.

MiR-21-5p is one of the most common oncogenic miRNAs that is upregulated in many solid cancers by inhibiting its target genes at the posttranscriptional level. However, the upstream regulatory mechanisms of miR-21-5p are still not well documented in cancers. Here, we identify a super-enhancer associated with the gene (MIR21-SE) by analyzing the genomic regulatory landscape in head and neck squamous cell carcinoma (HNSCC). We show that the MIR21-SE regulates miR-21-5p expression in different HNSCC cell lines and disruption of MIR21-SE inhibits miR-21-5p expression. We also identified that a key transcription factor, FOSL1 directly controls miR-21-5p expression by interacting with the MIR21-SE in HNSCC. Moreover, functional studies indicate that restoration of miR-21-5p partially abrogates FOSL1 depletion-mediated inhibition of cell proliferation and invasion. Clinical studies confirmed that miR-21-5p expression is positively correlated with FOSL1 expression. These findings suggest that FOSL1-SE drives miR-21-5p expression to promote malignant progression of HNSCC.
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http://dx.doi.org/10.3389/fonc.2021.656628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085558PMC
April 2021

Multi-task Learning via Adaptation to Similar Tasks for Mortality Prediction of Diverse Rare Diseases.

AMIA Annu Symp Proc 2020 25;2020:763-772. Epub 2021 Jan 25.

Department of Computer Science, Peking University, Beijing, China.

The mortality prediction of diverse rare diseases using electronic health record (EHR) data is a crucial task for intelligent healthcare. However, data insufficiency and the clinical diversity of rare diseases make it hard for deep learning models to be trained. Mortality prediction for these patients with different diseases can be viewed as a multi-task learning problem with insufficient data but a large number of tasks. On the other hand, insufficient training data makes it difficult to train task-specific modules in multi-task learning models. To address the challenges of data insufficiency and task diversity, we propose an initialization-sharing multi-task learning method (Ada-SiT). Ada-Sit can learn the parameter initialization and dynamically measure the tasks' similarities, used for fast adaptation. We use Ada-SiT to train long short-term memory networks (LSTM) based prediction models on longitudinal EHR data. The experimental results demonstrate that the proposed model is effective for mortality prediction of diverse rare diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075548PMC
January 2021

Pre-Operative Femoral Cartilage Ultrasound Characteristics Are Altered in People Who Report Symptoms at 1 year After Anterior Cruciate Ligament Reconstruction.

Ultrasound Med Biol 2021 Apr 27. Epub 2021 Apr 27.

Department of Orthopaedics, Tufts Medical Center, Boston, Massachusetts, USA.

We assessed whether pre-operative femoral cartilage thickness and echo intensity on ultrasound are different between individuals who are symptomatic (n = 6) and asymptomatic (n = 7) at 1 year after a primary unilateral anterior cruciate ligament (ACL) reconstruction (age, 23 ± 4 y; 31% women, 69% men; body mass index, 24.9 ± 3.7 kg/m). A pre-operative, bilateral ultrasound assessment was used to quantify average thickness and echo intensity in the medial, middle and lateral femoral trochlear regions. An inter-limb ratio (ACL/contralateral limb) was calculated for average thickness and echo intensity. At 1 y after ACL reconstruction, we operationally defined the presence of symptoms as scoring ≤85% on at least two Knee Injury and Osteoarthritis Outcome Score subscales. Independent-sample t-tests and Cohen's d effect sizes were used to compare ultrasound pre-operative inter-limb ratios between participants with and without symptoms at 1 y after ACL reconstruction. For medial femoral cartilage, symptomatic participants had significantly greater average cartilage thickness inter-limb ratios (p = 0.01, d = -1.65) and significantly lower echo intensity inter-limb ratios (p = 0.01, d = 1.72) compared with asymptomatic participants. Middle and lateral femoral cartilage average thickness and echo intensity were not different between symptomatic and asymptomatic participants. These findings provide preliminary evidence that a clinically feasible ultrasound assessment of the femoral trochlear cartilage may be prognostic of self-reported symptoms at 1 y after ACL reconstruction.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.03.021DOI Listing
April 2021

Spectral Analysis of Muscle Hemodynamic Responses in Post-Exercise Recovery Based on Near-Infrared Spectroscopy.

Sensors (Basel) 2021 Apr 28;21(9). Epub 2021 Apr 28.

Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong SAR 999077, China.

Spectral analysis of blood flow or blood volume oscillations can help to understand the regulatory mechanisms of microcirculation. This study aimed to explore the relationship between muscle hemodynamic response in the recovery period and exercise quantity. Fifteen healthy subjects were required to perform two sessions of submaximal plantarflexion exercise. The blood volume fluctuations in the gastrocnemius lateralis were recorded in three rest phases (before and after two exercise sessions) using near-infrared spectroscopy. Wavelet transform was used to analyze the total wavelet energy of the concerned frequency range (0.005-2 Hz), which were further divided into six frequency intervals corresponding to six vascular regulators. Wavelet amplitude and energy of each frequency interval were analyzed. Results showed that the total energy raised after each exercise session with a significant difference between rest phases 1 and 3. The wavelet amplitudes showed significant increases in frequency intervals I, III, IV, and V from phase 1 to 3 and in intervals III and IV from phase 2 to 3. The wavelet energy showed similar changes with the wavelet amplitude. The results demonstrate that local microvascular regulators contribute greatly to the blood volume oscillations, the activity levels of which are related to the exercise quantity.
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http://dx.doi.org/10.3390/s21093072DOI Listing
April 2021

The role of recombinant human brain natriuretic peptide on the cardiac output of patients with acute decompensated heart failure using Guyton venous return curve: A STROBE-compliant retrospective study.

Medicine (Baltimore) 2021 Apr;100(17):e25492

Department of Intensive Care Unit, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Abstract: rbBNP has positive cardiac effects in patients with acute decompensated heart failure, but its effects on the systemic venous circulation are not known.A single-center retrospective, self-controlled study was conducted on 14 patients undergone recombinant human brain natriuretic peptide (rhBNP) treatment between January 1, 2015 to December 31, 2018.The cardiac output (CO) significantly increased from 3.75 ± 1.14 L min-1 to 4.24 ± 0.97 L min-1 30 minutes after rbBNP infusion, and to 4.20 ± 1.19 L min-1 3 hours later. The systemic vascular resistance significantly decreased from 18.85 ± 7.66 mm Hg min L-1 to 14.62 ± 6.13 mm Hg min L-1 30 minutes. The resistance to venous return (VR) significantly decreased from 5.93 ± 4.97 mm Hg min L-1 to 4.46 ± 1.53 mmHg min L-1 3 hours later. The mean systemic filling pressure significantly decreased from 32.71 ± 20.00 mm Hg to 28.254 ± 6.09 mm Hg 3 hours later.The role of rhBNP on CO was to reduce the peripheral circulation resistance at 30 minutes after rhBNP infusion and to reduce the resistance to VR at 3 hours later.This trial is registered at ChiCTR: ID ChiCTR1900024562.
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http://dx.doi.org/10.1097/MD.0000000000025492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084054PMC
April 2021

Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease.

Exp Gerontol 2021 Apr 24;150:111376. Epub 2021 Apr 24.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

Gut microbial metabolites, SCFAs, were related with the occurrence and development of Parkinson's disease (PD). But the effects of different short-chain fatty acids (SCFAs) on PD and involving mechanisms are still undefined. In this study we evaluate the effects of three dominant SCFAs (acetate, propionate and butyrate) on motor damage, dopaminergic neuronal degeneration and underlying neuroinflammation related mechanisms in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. High (2.0 g/kg) or low doses (0.2 g/kg) of sodium acetate (NaA), sodium propionate (NaP) or sodium butyrate (NaB) were gavaged into PD mice for 6 weeks. High doses of NaA reduced the turning time of PD mice. NaB significantly reduced the turning and total time in pole test, and increased the average velocity in open field test when compared with PD mice, indicating the most effective alleviation of PD-induced motor disorder. Low and high doses of NaB significantly increased the content of tyrosine hydroxylase (TH) by 12.3% and 20.2%, while reduced α-synuclein activation by 159.4% and 132.7% in the substantia nigra pars compacta (SNpc), compared with PD groups. Butyrate reached into the midbrain SNpc and suppressed microglia over-activation. It inhibited the levels of pro-inflammatory factors (IL-6, IL-1β and TNF-α) (P < 0.01) and iNOS. Besides, butyrate inhibited the activation of NF-κB and MAPK signaling pathways in the SNpc region. Consequently, sodium butyrate could inhibit neuroinflammation and alleviate neurological damage of PD.
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http://dx.doi.org/10.1016/j.exger.2021.111376DOI Listing
April 2021

[Biomechanical analysis of ankle-foot complex during a typical Tai Chi movement-Brush Knee and Twist Step].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Feb;38(1):97-104

Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong 999077, P.R.China.

The purpose of this study is to analyze the biomechanics of ankle cartilage and ligaments during a typical Tai Chi movement-Brush Knee and Twist Step (BKTS). The kinematic and kinetic data were acquired in one experienced male Tai Chi practitioner while performing BKTS and in normal walking. The measured parameters were used as loading and boundary conditions for further finite element analysis. This study showed that the contact stress of the ankle joint during BKTS was generally less than that during walking. However, the maximum tensile force of the anterior talofibular ligament, the calcaneofibular ligament and the posterior talofibular ligament during BKTS was 130 N, 169 N and 89 N, respectively, while it was only 57 N, 119 N and 48 N during walking. Therefore, patients with arthritis of the ankle can properly practice Tai Chi. Practitioners with sprained lateral ligaments of the ankle joint were suggested to properly reduce the ankle movement range during BKTS.
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http://dx.doi.org/10.7507/1001-5515.202003003DOI Listing
February 2021

[Diagnosis, treatment and etiology analysis of nerve compression by bone fragment after lumbar spine surgery].

Zhongguo Gu Shang 2021 Apr;34(4):349-53

The Second Department of Orthopaedics, Lihuili Hospital of Ningbo Medical Center, Ningbo 315000, Zhejiang, China.

Objective: To explore the diagnosis, treatment, cause and prevention of nerve compression by bone fragment after lumbar spine surgery.

Methods: The clinical data of 23 patients with nerve compression by bone fragment after lumbar spine surgery from February 2012 to March 2019 were collected retrospectively, including 9 males and 14 females, aged 42 to 81 years with an average of (62.60±5.70) years. The surgical methods included lumbar interbody fusion in 20 cases and spinal endoscopy in 3 cases. All 23 patients experienced radiating pain on the decompression side or the contralateral limb after operation. The time of occurrence was from immediately after operation to 2 weeks after operation, with an average of (3.2±1.7) days. All patients underwent postoperative examination of lumbar spine CT or MRI to confirm residual ectopic bone fragments, and at the same time, bilateral lower extremity color Doppler ultrasound excluded thrombosis. Sources of ectopic bone fragments:14 cases of residual bone fragments caused by intervertebral fusion bone graft loss or fenestration fusion, 6 cases of fractured upper articular process head, and 3 cases of upper articular process bone remaining during spinal endoscopic surgery.

Results: The patient's hospital stay was 10 to 37 (23.4±6.2) days. All patients were followed up for 6 to 25 (13.6±3.4) months. Three patients underwent posterior open nerve root exploration for removing bone fragments on the same day or the second day after surgery, and the symptoms were relieved. Twenty patients underwent conservative treatment firstly, and 13 patients were discharged after pain relieved by conservative treatment, 7 patients failed conservative treatment, the 2 cases of failed 7 cases had undergone nerve root block surgery during conservative treatment. Two patients underwent spinal endoscopy nerve root exploration and bone mass removal, and five patients underwent posterior open nerve root exploration and bone fragmentation removal. All postoperative pain symptoms were relieved. Preoperative CT, MRI and intraoperative bone fragment removal confirmed the shape and location of the bone fragments. The most likely source of bone fragments was the loss of intervertebral fusion bone grafts or residual bone fragments resulting from fenestration fusion (14 cases), fractured upper articular process head (6 cases), and upper articular process bones remaining in endoscopic surgery (3 cases). According to the Macnab criteria in evaluating clinical outcome, 20 cases got excellent results and 3 good.

Conclusion: After the lumbar spine surgery, the nerve compression by bone fragments is treated with appropriate treatments, and good clinical results can be obtained. Timely removal of residual bone fragments during operation and careful exploration of nerve roots before closing incision can avoid such complications.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.04.011DOI Listing
April 2021

Air pollution and DNA methylation in adults: A systematic review and meta-analysis of observational studies.

Environ Pollut 2021 Apr 15;284:117152. Epub 2021 Apr 15.

Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. Electronic address:

This systematic review and meta-analysis aimed to investigate the association between air pollution and DNA methylation in adults from published observational studies. PubMed, Web of Science and Embase databases were systematically searched for available studies on the association between air pollution and DNA methylation published up to March 9, 2021. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). Meta-analysis was used to summarize the combined estimates for the association between air pollutants and global DNA methylation levels. Heterogeneity was assessed with the Cochran Q test and quantified with the I statistic. In total, 38 articles were included in this study: 16 using global methylation, 18 using candidate genes, and 11 using EWAS, with 7 studies using more than one approach. Meta-analysis revealed an imprecise but inverse association between exposure to PM and global DNA methylation (for each 10-μg/m PM, combined estimate: 0.39; 95% confidence interval: 0.97 - 0.19). The candidate-gene results were consistent for the ERCC3 and SOX2 genes, suggesting hypermethylation in ERCC3 associated with benzene and that in SOX2 associated with PM exposure. EWAS identified 201 CpG sites and 148 differentially methylated regions that showed differential methylation associated with air pollution. Among the 307 genes investigated in 11 EWAS, a locus in nucleoredoxin gene was found to be positively associated with PM in two studies. Current meta-analysis indicates that PM is imprecisely and inversely associated with DNA methylation. The candidate-gene results consistently suggest hypermethylation in ERCC3 associated with benzene exposure and that in SOX2 associated with PM exposure. The Kyoto Encyclopedia of Genes and Genomes (KEGG) network analyses revealed that these genes were associated with African trypanosomiasis, Malaria, Antifolate resistance, Graft-versus-host disease, and so on. More evidence is needed to clarify the association between air pollution and DNA methylation.
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http://dx.doi.org/10.1016/j.envpol.2021.117152DOI Listing
April 2021

Upregulating Aggregation-Induced-Emission Nanoparticles with Blood-Tumor-Barrier Permeability for Precise Photothermal Eradication of Brain Tumors and Induction of Local Immune Responses.

Adv Mater 2021 Apr 23:e2008802. Epub 2021 Apr 23.

Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, P. R. China.

Compared to other tumors, glioblastoma (GBM) is extremely difficult to treat. Recently, photothermal therapy (PTT) has demonstrated advanced therapeutic efficacy; however, because of the relatively low tissue-penetration efficiency of laser light, its application in deep-seated tumors remains challenging. Herein, bradykinin (BK) aggregation-induced-emission nanoparticles (BK@AIE NPs) are synthesized; these offer selective penetration through the blood-tumor barrier (BTB) and strong absorbance in the near-infrared region (NIR). The BK ligand can prompt BTB adenosine receptor activation, which enhances transportation and accumulation inside tumors, as confirmed by T -weighted magnetic resonance and fluorescence imaging. The BK@AIE NPs exhibit high photothermal conversion efficiency under 980 nm NIR laser irradiation, facilitating the treatment of deep-seated tumors. Tumor progression can be effectively inhibited to extend the survival span of mice after spatiotemporal PTT. NIR irradiation can eradicate tumor tissues and release tumor-associated antigens. It is observed that the PTT treatment of GBM-bearing mice activates natural killer cells, CD3 T cells, CD8 T cells, and M1 macrophages in the GBM area, increasing the therapeutic efficacy. This study demonstrates that NIR-assisted BK@AIE NPs represent a promising strategy for the improved systematic elimination of GBMs and the activation of local brain immune privilege.
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http://dx.doi.org/10.1002/adma.202008802DOI Listing
April 2021

Combined epigenetic/genetic study identified an ALS age of onset modifier.

Acta Neuropathol Commun 2021 Apr 23;9(1):75. Epub 2021 Apr 23.

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Ave., Toronto, ON, M5T 0S8, Canada.

Age at onset of amyotrophic lateral sclerosis (ALS) is highly variable (eg, 27-74 years in carriers of the GC-expansion in C9orf72). It might be influenced by environmental and genetic factors via the modulation of DNA methylation (DNAm) at CpG-sites. Hence, we combined an epigenetic and genetic approach to test the hypothesis that some common single nucleotide polymorphisms (SNPs) at CpG-sites (CpG-SNPs) could modify ALS age of onset. Our genome-wide DNAm analysis suggested three CpG-SNPs whose DNAm levels are significantly associated with age of onset in 249 ALS patients (q < 0.05). Next, genetic analysis validated the association of rs4970944 with age of onset in the discovery (n = 469; P = 0.025) and replication (n = 4160; P = 0.007) ALS cohorts. A meta-analysis of the cohorts combined showed that the median onset in AA-carriers is two years later than in GG-carriers (n = 4629; P = 0.0012). A similar association was observed with its tagging SNPs, implicating a 16 Kb region at the 1q21.3 locus as a modifier of ALS age of onset. Notably, rs4970944 genotypes are also associated with age of onset in C9orf72-carriers (n = 333; P = 0.025), suggesting that each A-allele delays onset by 1.6 years. Analysis of Genotype-Tissue Expression data revealed that the protective A-allele is linked with the reduced expression of CTSS in cerebellum (P = 0.00018), which is a critical brain region in the distributed neural circuits subserving motor control. CTSS encodes cathepsin S protein playing a key role in antigen presentation. In conclusion, we identified a 16 Kb locus tagged by rs4970944 as a modifier of ALS age of onset. Our findings support the role of antigen presenting processes in modulating age of onset of ALS and suggest potential drug targets (eg, CTSS). Future replication studies are encouraged to validate the link between the locus tagged by rs4970944 and age of onset in independent ALS cohorts, including different ethnic groups.
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http://dx.doi.org/10.1186/s40478-021-01183-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066440PMC
April 2021

Increased free water in the substantia nigra in idiopathic REM sleep behaviour disorder.

Brain 2021 Apr 21. Epub 2021 Apr 21.

Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Imaging markers sensitive to neurodegeneration in the substantia nigra are critically needed for future disease-modifying trials. Previous studies have demonstrated the utility of posterior substantia nigra free water as a marker of progression in Parkinson's disease. In this study, we tested the hypothesis that free water is elevated in the posterior substantia nigra of idiopathic REM sleep behaviour disorder, which is considered a prodromal stage of synucleinopathy. We applied free-water imaging to 32 healthy control subjects, 34 patients with idiopathic REM sleep behaviour disorder and 38 patients with Parkinson's disease. Eighteen healthy control subjects and 22 patients with idiopathic REM sleep behaviour disorder were followed up and completed longitudinal free-water imaging. Free-water values in the substantia nigra were calculated for each individual and compared among groups. We tested the associations between posterior substantia nigra free water and uptake of striatal dopamine transporter in idiopathic REM sleep behaviour disorder. Free-water values in the posterior substantia nigra were significantly higher in the patients with idiopathic REM sleep behaviour disorder patients than in the healthy control subjects, but were significantly lower in patients with idiopathic REM sleep behaviour disorder than in patients with Parkinson's disease. In addition, we observed significantly negative associations between posterior substantia nigra free-water values and dopamine transporter striatal binding ratios in the idiopathic REM sleep behaviour disorder patients. Longitudinal free-water imaging analyses were conducted with a linear mixed-effects model, and showed a significant Group × Time interaction in posterior substantia nigra, identifying increased mean free-water values in posterior substantia nigra of idiopathic REM sleep behaviour disorder over time. These results demonstrate that free water in the posterior substantia nigra is a valid imaging marker of neurodegeneration in idiopathic REM sleep behaviour disorder, which has the potential to be used as an indicator in disease-modifying trials.
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http://dx.doi.org/10.1093/brain/awab039DOI Listing
April 2021

The association of vitamin D and vitamin E levels at birth with bronchopulmonary dysplasia in preterm infants.

Pediatr Pulmonol 2021 Apr 20. Epub 2021 Apr 20.

Newborn Department, Shijiazhuang Fourth Hospital, Shijiazhuang, Hebei, China.

Background: Despite improvements made in neonatal care, bronchopulmonary dysplasia (BPD) is still the most common respiratory disease in preterm infants. The relationship between the blood contents of vitamin D/E in premature infants and BPD is still controversial.

Methods: Preterm infants were recruited as the research subjects. On the basis of the inclusion and exclusion criteria, a total of 133 eligible cases were finally included. A total of 63 preterm infants with a clear diagnosis of BPD and 5 preterm infants who died before the diagnosis of BPD were in the case group, and 65 non-BPD preterm infants with equivalent baseline characteristics were in the control group. The BPD group included 38 cases in Grade Ⅰ, 18 cases in Grade Ⅱ, and 12 cases in Grade Ⅲ. The contents of vitamin D and E in the cord blood of different groups were detected by high-performance liquid chromatography and enzyme-linked immunosorbent assay. Correlation analysis adopted the Pearson correlation analytic method.

Results: The serum vitamin D and E levels at birth were remarkably lower in the BPD group than the non-BPD group, both of which were also correlated with the severity of BPD. The vitamin D and E contents were negatively correlated with the oxygen support duration required for premature infants with BPD.

Conclusion: This study deepens our understanding of the field of BPD pathogenesis by demonstrating an association between vitamin D/E deficiency and BPD severity, suggesting that vitamin D and E might have potential clinical value in the prognosis and treatment of BPD.
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http://dx.doi.org/10.1002/ppul.25414DOI Listing
April 2021

Improving the Acceptability of Human Papillomavirus Vaccines Among Men Who Have Sex With Men According to the Associated Factors: A Systematic Review and Meta-analysis.

Front Pharmacol 2021 24;12:600273. Epub 2021 Mar 24.

Department of Dermatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

: To investigate the acceptability of human papillomavirus (HPV) vaccination among men who have sex with men (MSM) and its associated factors. : We searched studies written in English in PubMed, EMBASE, and Web of Science with no geographical or time restrictions. We evaluated the quality of the included literature. We calculated the pooled acceptability and performed meta-analysis of selected studies, including factors associated with the acceptability among MSM, using Review Manager (v5.3). : The acceptability among the 15 studies ( = 8,658) was 50% (95% CI: 0.27-0.72). The meta-analysis of seven articles ( = 4,200) indicated that having a college or higher degree (OR = 1.62, 95% CI: 1.35-1.95), disclosure of sexual orientation to healthcare professionals (HCPs; OR = 2.38, 95% CI: 1.47-3.86), vaccination with at least one dose for hepatitis A or B (OR = 2.10, 95% CI: 1.42-3.10), awareness of HPV (OR = 1.85, 95% CI: 1.21-2.83), knowledge of HPV (SMD = 0.28, 95% CI: 0.16-0.39), perceived susceptibility to HPV infection (SMD = 0.31, 95% CI: 0.11-0.50), and perceived severity of HPV-related disease (SMD = 0.40, 95% CI: 0.28-0.51) can promote acceptance of HPV vaccines. Meanwhile, people who have had unprotected anal sex or have more sex partners tend to have low acceptance of HPV vaccines. : HPV education should be actively promoted according to the factors that influence the acceptability of HPV vaccines among the MSM population. HPV education should be especially aimed at people with low academic qualifications and people with risky sexual behaviors, and should emphasize the aspects of susceptibility to and severity of HPV-related disease. More intervention trials should be conducted to increase the credibility of the results.
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http://dx.doi.org/10.3389/fphar.2021.600273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044753PMC
March 2021

Accelerated brain aging in mild traumatic brain injury: Longitudinal pattern recognition with white matter integrity.

J Neurotrauma 2021 Apr 16. Epub 2021 Apr 16.

The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, No.28 Xianning West Road, Xi'an, China, 710049;

Mild traumatic brain injury (mTBI) initiating long-term effects on white matter integrity resembles brain-aging changes, implying an aging process accelerated by mTBI. This longitudinal study aims to investigate the mTBI-induced acceleration of the brain-aging process by developing a neuroimaging model to predict brain age. The brain-age prediction model was defined using relevance vector regression based on fractional anisotropy from diffusion-tensor imaging of 523 healthy individuals. The model was used to estimate the brain-predicted age difference (brain-PAD) between the chronological and estimated brain age in 116 acute mTBI patients and 63 healthy controls. Fifty patients were followed 6~12 months to evaluate the longitudinal changes in brain-PAD. We investigated whether brain-PAD was greater in patients with elderly age, post-concussion complaints, and apolipoprotein E (APOE) ε4 genotype, and whether it had the potential to predict neuropsychological outcomes. The brain-age prediction model predicted brain age accurately ( = 0.96). The brains of mTBI in the acute phase were estimated to be "older", with greater brain-PAD (2.59 ± 5.97 years) than the healthy controls (0.12 ± 3.19 years) ( < 0.05), and remained stable 6-12 month post-injury (2.50 ± 4.54 years). Patients with older age or post-concussion complaints, rather than APOE ε4 genotype, had greater brain-PADs ( < 0.001, = 0.024). Additionally, brain-PAD in the acute phase predicted information processing speed at the 6~12 month follow-up ( = -0.36, = 0.01). In conclusion, mTBI accelerates the brain-aging process, and brain-PAD may be capable of evaluating aging-associated issues post-injury, like increased risks of neurodegeneration.
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http://dx.doi.org/10.1089/neu.2020.7551DOI Listing
April 2021

The clinical role of combined serum C1q and hsCRP in predicting coronary artery disease.

Clin Biochem 2021 Apr 13. Epub 2021 Apr 13.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address:

Objective: C1q has been shown to be associated with coronary heart disease (CAD) and can co-deposit with C-reactive protein (CRP) in atherosclerotic plaques. However, few studies have been conducted between C1q, CRP parameters and CAD. The aim of this study is to explore the relationship between C1q and CRP parameters and assess their clinical significance in CAD.

Methods: 238 total patients who underwent coronary artery angiography were enrolled and divided into control group (n = 65), stable CAD group (n = 47) and unstable angina group (UA group, n = 126). Patients' data were collected from self-administered questionnaires and electrical medical records. The severity of coronary stenosis was presented by Gensini score. The relationship between C1q, CRP parameters and CAD were evaluated by multivariate regression analysis and their predicting performance were assessed by ROC analysis and odds ratio analysis.

Results: Compared with control group, C1q was showed significantly lower in stable CAD (P = 0.004) and UA groups (P = 0.008), while hsCRP was higher in UA group (P = 0.024). Serum C1q was weakly positively associated with hsCRP (r = 0.24, P < 0.001) but not correlated with Gensini score. Logistic regression identified C1q (OR: 0.87 per 10 mg/L, 95% CI: 0.79-0.95, P = 0.001) and hsCRP (OR: 1.08 mg/L, 95% CI: 1.01-1.15, P = 0.032) as independent determinants of CAD. Furthermore, combined C1q and hsCRP level showed higher discriminatory accuracy in predicting CAD than C1q (AUC: 0.676 vs 0.585, P = 0.101; NRI: 10.4%, P = 0.049; IDI: 3.9%, P < 0.001) or hsCRP (AUC: 0.676 vs 0.585, P = 0.101; NRI: 16.7%, P = 0.006; IDI: 5.8%, P < 0.001).

Conclusions: Reduced serum C1q and increased hsCRP are independently associated with CAD and could be potential predictors for CAD diagnosis. Furthermore, combined C1q and hsCRP showed better performance in predicting CAD than using single one.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.04.004DOI Listing
April 2021

Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study.

Public Health Nutr 2021 Apr 16:1-25. Epub 2021 Apr 16.

Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China.

Objective: The impact of baseline hypertension status on the BMI-mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI-mortality association using a rural Chinese cohort.

Design: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status.

Setting: Longitudinal population-based cohort.

Participants: 17,262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China.

Results: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the HRs (95% CI) for mortality in normotensive participants were 1.92 (1.23-3.00), 1.44 (1.01-2.05), 1.14 (0.82-1.58), 0.96 (0.70-1.31), 0.96 (0.65-1.43), 1.32 (0.81-2.14), and 1.32 (0.74-2.35) respectively, and in hypertensive participants were 1.85 (1.08-3.17), 1.67 (1.17-2.39), 1.29 (0.95-1.75), 1.20 (0.91-1.58), 1.10 (0.83-1.46), 1.10 (0.80-1.52), and 0.61 (0.40-0.94) respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity versus normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants.

Conclusions: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.
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http://dx.doi.org/10.1017/S1368980021001592DOI Listing
April 2021

Supercompact Photonic Quantum Logic Gate on a Silicon Chip.

Phys Rev Lett 2021 Apr;126(13):130501

State Key Laboratory for Modern Optical Instrumentation, College of Optical Science and Engineering, Ningbo Research Institute, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou 310058, China.

To build universal quantum computers, an essential step is to realize the so-called controlled-NOT (CNOT) gate. Quantum photonic integrated circuits are well recognized as an attractive technology offering great promise for achieving large-scale quantum information processing, due to the potential for high fidelity, high efficiency, and compact footprints. Here, we demonstrate a supercompact integrated quantum CNOT gate on silicon by using the concept of symmetry breaking of a six-channel waveguide superlattice. The present path-encoded quantum CNOT gate is implemented with a footprint of 4.8×4.45  μm^{2} (∼3λ×3λ) as well as a high-process fidelity of ∼0.925 and a low excess loss of <0.2  dB. The footprint is shrunk significantly by ∼10 000 times compared to those previous results based on dielectric waveguides. This offers the possibility of realizing practical large-scale quantum information processes and paving the way to the applications across fundamental science and quantum technologies.
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http://dx.doi.org/10.1103/PhysRevLett.126.130501DOI Listing
April 2021

Dynamic Change of Thyroid Hormones With Postmenstrual Age in Very Preterm Infants Born With Gestational Age <32 Weeks: A Multicenter Prospective Cohort Study.

Front Endocrinol (Lausanne) 2020 30;11:585956. Epub 2021 Mar 30.

Department of Neonatology, Binzhou Medical University Hospital, Binzhou, China.

Background: At present, the relationship between thyrotropin (TSH) and free thyroxine (FT4) in relation to postmenstrual age (PMA) in preterm infants is still unclear, and there is no reliable standard thyroid hormone reference ranges, resulting in different diagnostic criteria for congenital hypothyroidism been used by different newborn screening programs and different countries.

Objectives: To investigate the relationship between TSH/FT4 and PMA in very preterm infants (VPIs) born with gestational age (GA) <32 weeks and to derive thyroid function reference charts based on PMA.

Methods: A prospective cohort study was performed on VPIs born with GA<32 weeks and born in or transferred to the 27 neonatal intensive care units from January 1, 2019 to December 31, 2019. Serial TSH and FT4 values were measured at the end of each week during the first month after birth and also at PMA36 weeks, PMA40 weeks and at discharge, respectively. The 2.5th, 5th, 50th, 95th, and 97.5th percentiles of TSH and FT4 of different PMA groups were calculated to draw the percentile charts based on PMA.

Results: 1,093 preterm infants were included in this study. The percentile charts of TSH and FT4 levels based on PMA were drawn respectively, and the result indicated that the percentile charts of TSH values were gradually increased initially and then decreased with increasing PMA. The 97.5th percentile chart reached the peak at PMA30 weeks (17.38μIU/ml), and then decreased gradually, reaching the same level as full-term infants (9.07μIU/ml) at PMA38-40 weeks. The 2.5th percentile chart of FT4 was at its lowest point at PMA26-27 weeks (5.23pmol/L), then increased slowly with PMA and reached the same level as full-term infants at PMA38-40 weeks (10.87pmol/L). At PMA36 weeks, the reference intervals of the 2.5th to 97.5th percentiles of TSH and FT4 were 1.18-12.3μIU/ml and 8.59-25.98pmol/L, respectively.

Conclusion: The percentile charts of TSH and FT4 in VPIs showed characteristic change with PMA. The results prompt that age-related cutoffs, instead of a single reference range, might be more useful to explain the thyroid function of VPIs. And repeated screening is necessary for preterm infants.
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http://dx.doi.org/10.3389/fendo.2020.585956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043151PMC
March 2021

Comparative analysis of DNA extraction protocols for ancient soft tissue museum samples.

Zool Res 2021 May;42(3):280-286

Key Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China.

DNA studies of endangered or extinct species often rely on ancient or degraded remains. The majority of ancient DNA (aDNA) extraction protocols focus on skeletal elements, with skin and hair samples rarely explored. Similar to that found in bones and teeth, DNA extracted from historical or ancient skin and fur samples is also extremely fragmented with low endogenous content due to natural degradation processes. Thus, the development of effective DNA extraction methods is required for these materials. Here, we compared the performance of two DNA extraction protocols (commercial and custom laboratory aDNA methods) on hair and skin samples from decades-old museum specimens to Iron Age archaeological material. We found that apart from the impact sample-specific taphonomic and handling history has on the quantity and quality of DNA preservation, skin yielded more endogenous DNA than hair of the samples and protocols tested. While both methods recovered DNA from ancient soft tissue, the laboratory method performed better overall in terms of DNA yield and quality, which was primarily due to the poorer performance of the commercial binding buffer in recovering aDNA.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.377DOI Listing
May 2021

Sexism-Related Stigma Affects Pain Perception.

Neural Plast 2021 27;2021:6612456. Epub 2021 Mar 27.

CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.

People with stigmatized characteristics tend to be devalued by others in a given society. The negative experiences related to stigma cause individuals to struggle as they would if they were in physical pain and bring various negative outcomes in the way that physical pain does. However, it is unclear whether stigma related to one's identity would affect their perception of physical pain. To address this issue, using sexism-related paradigms, we found that females had reduced pain threshold/tolerance in the Cold Pressor Test (Experiment 1) and an increased rating for nociceptive laser stimuli with fixed intensity (Experiment 2). Additionally, we observed that there was a larger laser-evoked N1, an early laser-evoked P2, and a larger magnitude of low-frequency component in laser-evoked potentials (LEPs) in the stigma condition than in the control condition (Experiment 3). Our study provides behavioral and electrophysiological evidence that sexism-related stigma affects the pain perception of females.
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http://dx.doi.org/10.1155/2021/6612456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019650PMC
March 2021

Neurovascular coupling dysfunction in end-stage renal disease patients related to cognitive impairment.

J Cereb Blood Flow Metab 2021 Apr 14:271678X211007960. Epub 2021 Apr 14.

Department of Medical Imaging, First Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, China.

We aimed to investigate the neurovascular coupling (NVC) dysfunction in end-stage renal disease (ESRD) patients related with cognitive impairment. Twenty-five ESRD patients and 22 healthy controls were enrolled. To assess the NVC dysfunctional pattern, resting-state functional MRI and arterial spin labeling were explored to estimate the coupling of spontaneous neuronal activity and cerebral blood perfusion based on amplitude of low-frequency fluctuation (ALFF)-cerebral blood flow (CBF), fractional ALFF (fALFF)-CBF, regional homogeneity (ReHo)-CBF, and degree centrality (DC)-CBF correlation coefficients. Multivariate partial least-squares correlation and mediation analyses were used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment and clinical characteristics. The NVC dysfunctional patterns in ESRD patients were significantly decreased in 34 brain regions compared with healthy controls. The decreased fALFF-CBF coefficients in the cingulate gyrus (CG) were associated positively with lower kinetic transfer/volume urea (Kt/V) and lower short-term memory scores, and were negatively associated with higher serum urea. The relationship between Kt/V and memory deficits of ESRD patients was partially mediated by the fALFF-CBF alteration of the CG. These findings reveal the NVC dysfunction may be a potential neural mechanism for cognitive impairment in ESRD. The regional NVC dysfunction may mediate the impact of dialysis adequacy on memory function.
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http://dx.doi.org/10.1177/0271678X211007960DOI Listing
April 2021