Publications by authors named "Ying Mao"

509 Publications

Embolic Stroke Model with Magnetic Nanoparticles.

ACS Appl Mater Interfaces 2021 Sep 8. Epub 2021 Sep 8.

Department of Neurosurgery, Huashan Hospital of Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.

Stroke models are vital tools in neuropharmacology and rehabilitation research. However, a classic and widely used model-the suture occlusion model-is not suitable for all research approaches, especially regarding thrombolysis. For embolic stroke models in thrombolytic research, the surgical procedures of thrombin injection in the middle cerebral artery or clot injection in the carotid artery involved are too sophisticated. Here, we report a new stroke model in mice that uses magnetic nanoparticle (MNP) cross-linked with thrombin to embolize. Briefly, after the magnet was positioned in the common carotid artery, [email protected] was injected from the tail vein. Within several minutes postinjection, the [email protected] accumulated in the carotid artery and induced thrombus formation. These complex clots were flushed into and subsequently blocked the cerebral artery. Collectively, these results suggested that this new method was a quick and easy stroke model that blocked hemisphere blood flow and damaged neural function. Importantly, this model had an excellent response to thrombolytic drugs. After urokinase injection, cerebral blood flow was restored and symptom scores were enhanced by nearly one. This method, including a quick synthesis of MNP and thrombin, provided an easy and minimally invasive process for a new stroke model that is usable in both pharmacological and rehabilitative research.
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http://dx.doi.org/10.1021/acsami.1c11377DOI Listing
September 2021

Spatial Disparities in Access to Healthcare Professionals in Sichuan: Evidence from County-Level Data.

Healthcare (Basel) 2021 Aug 16;9(8). Epub 2021 Aug 16.

School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an 710049, China.

As a southwestern province of China, Sichuan is confronted with geographical disparities in access to healthcare professionals because of its complex terrain, uneven population distribution and huge economic gaps between regions. With 10-year data, this study aims to explore the county-level spatial disparities in access to different types of healthcare professionals (licensed doctors, registered nurses, pharmacists, technologists and interns) in Sichuan using temporal and spatial analysis methods. The time-series results showed that the quantity of all types of healthcare professionals increased, especially the registered nurses, while huge spatial disparities exist in the distribution of healthcare professionals in Sichuan. The local Moran's I calculations showed that high-high clusters (significantly high healthcare professional quantity in a group of counties) were detected in Chengdu (capital of Sichuan) and relatively rich areas, while low-low clusters (significantly low healthcare professional quantity in a group of counties) were usually found near the mountain areas, namely, Tsinling Mountains and Hengduan Mountains. The findings may deserve considerations in making region-oriented policies in educating and attracting more healthcare professionals to the disadvantaged areas.
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http://dx.doi.org/10.3390/healthcare9081053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394835PMC
August 2021

Mismatch repair proteins PMS2 and MLH1 can further refine molecular stratification of IDH-mutant lower grade astrocytomas.

Clin Neurol Neurosurg 2021 Sep 10;208:106882. Epub 2021 Aug 10.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

The diagnostic role of Isocitrate Dehydrogenase (IDH) mutation status in adult lower grade astrocytomas was first formally presented within the WHO Classification of Tumours of the Central Nervous System (2016). IDH-mutant astrocytomas are not as common as IDH-wildtype astrocytomas but are of better prognosis. Our previous study provided an evident that IDH-mutant lower grade astrocytomas is not a homogeneous group and could be further stratified by PDGFRA amplification, CDK4 amplification and CDKN2A deletion. In this study, we detected the expressions of DNA mismatch repair (MMR) proteins (PMS2, MLH1, MSH2, MSH6) and PD-L1 by immunohistochemistry in 147 IDH-mutant lower grade astrocytomas and explored their clinical relevance. The loss of was identified in 28.6%, 1.4%, 8.8% and 13.6%, respectively. PD-L1 expression was detected in 1.4% of this cohort. Survival analysis revealed that loss of PMS2 was correlated with shorter OS (p < 0.001) and PFS (p = 0.005). Loss of PMS2 or MLH1 was associated with shorter OS (p < 0.001) and PFS (p = 0.008). In IDH-mutant lower grade astrocytomas without CDKN2A deletion, loss of PMS2 was associated with poorer OS (p < 0.001) and PFS (p = 0.001). Furthermore, among IDH-mutant lower grade astrocytomas lacking the three biomarkers (PDGFRA, CDK4 and CDKN2A), loss of PMS2 was also associated with a poorer OS (p < 0.001) and PFS (p = 0.003). Our data illustrated the potential application of MMR genes in stratification of IDH-mutant lower grade astrocytomas without PDGFRA, CDK4 and CDKN2A copy number alterations.
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http://dx.doi.org/10.1016/j.clineuro.2021.106882DOI Listing
September 2021

Follow the Venous Path to the Hidden Lesion: A Technical Trick in Brainstem Cavernous Malformation Surgery.

World Neurosurg 2021 Jul 22;154:44-50. Epub 2021 Jul 22.

National Center for Neurological Disorders, Shanghai, China; Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Neurosurgical Institute of Fudan University, Shanghai, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China.

Objective: Deep-seated brainstem cavernous malformations (BSCMs) pose a particular challenge for brainstem entry intraoperatively and their treatment can require comprehensive application of neuronavigation, electrophysiological brainstem mapping and monitoring, and full knowledge of safe brainstem entry zones. In the present report, we have introduced a supplementary technical trick for localizing a hidden tiny lesion inside the brainstem when a developmental venous anomaly (DVA) is present on the brainstem surface.

Methods: A retrospective analysis of a 74-case cohort treated surgically from January 2011 to December 2019 was conducted. We identified 11 patients (14.9%) whose deep-seated BSCMs were exposed and removed following a brainstem surface DVA path as a supplementary technical trick. We have presented 2 typical cases to illustrate the operative nuances.

Results: Of the 11 patients, 5 were male and 6 were female. Their average age was 38.0 ± 14.0 years (range, 15-62 years). Most BSCMs were located in the pons (n = 5; 45.5%), followed by the pontomesencephalic area (n = 3; 27.3%), midbrain (n = 2; 18.2%), and medulla oblongata (n = 1; 9.1%). All BSCMs were successfully located and completely removed. In 5 cases, the DVA was impaired after lesion removal (45.5%). However, no aggravated postoperative brainstem edema occurred in any of the 11 patients. After 3.6 ± 2.0 years of follow-up (2 patients were lost to follow-up; follow-up rate, 81.8%), no rebleeding was found, and the modified Rankin scale score of the patients had improved from 2.7 ± 1.1 preoperatively to 1.7 ± 0.9 at follow-up (P = 0.031).

Conclusions: The presented method could help surgeons trace deep-seated BSCMs with minimal brainstem parenchyma impairment, avoiding unnecessary aggressive exploration.
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http://dx.doi.org/10.1016/j.wneu.2021.07.073DOI Listing
July 2021

Microsurgical intracranial hypervascular tumor resection immediately after endovascular embolization in a hybrid operative suite: A single-center experience.

J Clin Neurosci 2021 Aug 24;90:68-75. Epub 2021 May 24.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.

Background: This study was performed to investigate the safety and outcome of one-stage hybrid endovascular and microsurgical treatment of intracranial hypervascular tumors.

Methods: The blood supply of the tumor was endovascularly embolized just before microsurgery in a one-stage fashion. Clinical data regarding the preoperative neurological status, tumor characteristics, hybrid treatment details and complications, intraoperative blood loss, and postoperative outcomes were collected prospectively and then analyzed.

Results: Beginning in July 2016, 13 patients (5 women, 8 men) with intracranial hypervascular tumors were enrolled in this study, with a mean age of 48.2 ± 10.9 years. The patients' tumors comprised seven hemangioblastomas, three hemangiopericytomas, two meningiomas, and one mesenchymal chondrosarcoma. The mean maximum tumor diameter was 54.9 ± 21.5 mm. No major procedural complications occurred except catheterization-related bleeding in one patient. The mean percentage of tumor devascularization was 65.0%±17.5%. Gross total resection was achieved in 12 patients (92.3%). The mean blood loss volume during microsurgical resection was 703.8 ± 886.8 mL (range, 150-3600 mL). Symptoms improved in three patients and remained stable in six patients.

Conclusions: One-stage hybrid embolization before intracranial hypervascular tumor resection is a safe and effective procedure to decrease intraoperative blood loss. It can prevent or treat embolization-related complications in a timely manner and avoid the risk of multiple surgical procedures.
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http://dx.doi.org/10.1016/j.jocn.2021.05.026DOI Listing
August 2021

The Evolutionary Patterns of Genome Size in Ensifera (Insecta: Orthoptera).

Front Genet 2021 23;12:693541. Epub 2021 Jun 23.

Xi'an Botanical Garden of Shaanxi Province/Institute of Botany of Shaanxi Province, Shaanxi Engineering Research Centre for Conservation and Utilization of Botanical Resources, Xi'an, China.

Genomic size variation has long been a focus for biologists. However, due to the lack of genome size data, the mechanisms behind this variation and the biological significance of insect genome size are rarely studied systematically. The detailed taxonomy and phylogeny of the Ensifera, as well as the extensive documentation concerning their morphological, ecological, behavioral, and distributional characteristics, make them a strong model for studying the important scientific problem of genome size variation. However, data on the genome size of Ensifera are rather sparse. In our study, we used flow cytometry to determine the genome size of 32 species of Ensifera, the smallest one being only 1C = 0.952 pg with the largest species up to 1C = 19.135 pg, representing a 20-fold range. This provides a broader blueprint for the genome size variation of Orthoptera than was previously available. We also completed the assembly of nine mitochondrial genomes and combined mitochondrial genome data from public databases to construct phylogenetic trees containing 32 species of Ensifera and three outgroups. Based on these inferred phylogenetic trees, we detected the phylogenetic signal of genome size variation in Ensifera and found that it was strong in both males and females. Phylogenetic comparative analyses revealed that there were no correlations between genome size and body size or flight ability in Tettigoniidae. Reconstruction of ancestral genome size revealed that the genome size of Ensifera evolved in a complex pattern, in which the genome size of the grylloid clade tended to decrease while that of the non-grylloid clade expanded significantly albeit with fluctuations. However, the evolutionary mechanisms underlying variation of genome size in Ensifera are still unknown.
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http://dx.doi.org/10.3389/fgene.2021.693541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261143PMC
June 2021

A Layer-Arranged Meshless Method for the Simulation of Additive Manufacturing with Irregular Shapes.

Micromachines (Basel) 2021 Jun 9;12(6). Epub 2021 Jun 9.

Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.

Additive manufacturing (3D Printing) has become a promising manufacturing method as it can produce parts in a flexible and efficient way, especially for very irregular parts. However, during the printing process, the material experiences a great temperature change from the melting temperature to room temperature; this causes high thermal strains and induces distinct deformations which degrade the quality of the printed parts, especially in metal 3D printing. In order to reduce possible problems and find possible solutions, a prior evaluation by simulation is often adopted. Nevertheless, since the 3D printing process generates parts in a layer-by-layer way, the analysis model should also be layer-by-layer arranged and used with a layer-by-layer based analysis process to simulate the layer-by-layer additive printing; otherwise, the simulation may not match the real behavior. In order to meet these requirements, a new meshless method is proposed to match the situations and handle these problems. As a meshless method, the modeling is not constrained by the element distribution. In addition, the analysis model generated with the proposed method can be arranged in a layer-by-layer way and combined with the proposed layer-by-layer analysis scheme, so it can then match and simulate the printing processes. Furthermore, the layer-by-layer arranged models can be automatically created, directly based on the STL (STereo-Lithography) geometry model, which is a de facto standard in the 3D printing industry. This makes the proposed approach more straightforward and efficient. To validate the proposed method, two parts with holes inside have been printed and simulated for comparison. The results show a good agreement. In addition, a highly irregular part has also been simulated to demonstrate the effectiveness and efficiency of this proposed method.
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http://dx.doi.org/10.3390/mi12060674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228000PMC
June 2021

3-Benzoylisoxazolines by 1,3-Dipolar Cycloaddition: Chloramine-T-Catalyzed Condensation of α-Nitroketones with Dipolarophiles.

Molecules 2021 Jun 8;26(12). Epub 2021 Jun 8.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilisation, Ministry of Education, School of Pharmaceutical Sciences, Shihezi University, Shihezi 832002, China.

In this study, 3-benzoylisoxazolines were synthesized by reacting alkenes with various α-nitroketones using chloramine-T as the base. The scope of α-nitroketones and alkenes is extensive, including different alkenes and alkynes to form various isoxazolines and isoxazoles. The use of chloramine-T, as the low-cost, easily handled, moderate base for 1,3-dipolar cycloaddition is attractive.
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http://dx.doi.org/10.3390/molecules26123491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227129PMC
June 2021

[Research on performance of motor-imagery-based brain-computer interface in different complexity of Chinese character patterns].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Jun;38(3):417-424

Key Laboratory of Advanced Control and Optimization for Chemical Processes, Ministry of Education, East China University of Science and Technology, Shanghai 200237, P.R. China.

The traditional paradigm of motor-imagery-based brain-computer interface (BCI) is abstract, which cannot effectively guide users to modulate brain activity, thus limiting the activation degree of the sensorimotor cortex. It was found that the motor imagery task of Chinese characters writing was better accepted by users and helped guide them to modulate their sensorimotor rhythms. However, different Chinese characters have different writing complexity (number of strokes), and the effect of motor imagery tasks of Chinese characters with different writing complexity on the performance of motor-imagery-based BCI is still unclear. In this paper, a total of 12 healthy subjects were recruited for studying the effects of motor imagery tasks of Chinese characters with two different writing complexity (5 and 10 strokes) on the performance of motor-imagery-based BCI. The experimental results showed that, compared with Chinese characters with 5 strokes, motor imagery task of Chinese characters writing with 10 strokes obtained stronger sensorimotor rhythm and better recognition performance ( < 0.05). This study indicated that, appropriately increasing the complexity of the motor imagery task of Chinese characters writing can obtain stronger motor imagery potential and improve the recognition accuracy of motor-imagery-based BCI, which provides a reference for the design of the motor-imagery-based BCI paradigm in the future.
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http://dx.doi.org/10.7507/1001-5515.202010031DOI Listing
June 2021

Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker.

Front Oncol 2021 10;11:665360. Epub 2021 Jun 10.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

, an interferon (IFN)-inducible gene, plays a promotional role in many tumors. However, its function in glioma remains unknown. In this study, bioinformatic analysis (TCGA, CGGA, Rembrandt) illustrated the upregulation and prognostic value of in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, < 0.0001). It also could be included in nomogram as a parameter to predict the 3- and 5-year survival risk (C-index = 0.86). The biological process of in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. expression had a positive association with most inflammatory-related functions, such as hematopoietic cell kinase (HCK) (R = 0.31), interferon (R = 0.72), STAT1 (R = 54), and a negative correlation with IgG (R = -0.24). Furthermore, expression tends to be positively related to multiple infiltrating immune cells, while negatively related to CD56 dim nature killer cell in glioma. Some important immune checkpoints, like , , , , and , were all positively related with (all Pearson correlation R > 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, < 0.0001) and GBM cells. These results indicated that might have important clinical significance in glioma and could serve as a potential immune therapeutic target.
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http://dx.doi.org/10.3389/fonc.2021.665360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222729PMC
June 2021

An integrative analysis of genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA detects noninvasive diagnostic markers for gliomas.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab049. Epub 2021 Apr 16.

State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, and The Collaborative Innovation Centre for Brain Science, Fudan University, Shanghai, China.

Background: Gliomas, especially the high-grade glioblastomas (GBM), are highly aggressive tumors in the central nervous system (CNS) with dismal clinical outcomes. Effective biomarkers, which are not currently available, may improve clinical outcomes through early detection. We sought to develop a noninvasive diagnostic approach for gliomas based on 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA).

Methods: We obtained genome-wide 5hmC profiles using the 5hmC-Seal technique in cfDNA samples from 111 prospectively enrolled patients with gliomas and 111 age-, gender-matched healthy individuals, which were split into a training set and a validation set. Integrated models comprised 5hmC levels summarized for gene bodies, long noncoding RNAs (lncRNAs), -regulatory elements, and repetitive elements were developed using the elastic net regularization under a case-control design.

Results: The integrated 5hmC-based models differentiated healthy individuals from gliomas (area under the curve [AUC] = 84%; 95% confidence interval [CI], 74-93%), GBM patients (AUC = 84%; 95% CI, 74-94%), WHO II-III glioma patients (AUC = 86%; 95% CI, 76-96%), regardless of (encoding isocitrate dehydrogenase) mutation status or other glioma-related pathological features such as TERT, TP53 in the validation set. Furthermore, the 5hmC biomarkers in cfDNA showed the potential as an independent indicator from mutation status and worked in synergy with mutation to distinguish GBM from WHO II-III gliomas. Exploration of the 5hmC biomarkers for gliomas revealed relevance to glioma biology.

Conclusions: The 5hmC-Seal in cfDNA offers the promise as a noninvasive approach for effective detection of gliomas in a screening program.
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http://dx.doi.org/10.1093/noajnl/vdab049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209591PMC
April 2021

Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells.

Oncoimmunology 2021 06 6;10(1):1932061. Epub 2021 Jun 6.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.

The vast majority (>90%) of glioblastoma (GBM) patients belong to the isocitrate dehydrogenase 1 wild type (IDH1) group which exhibits a poor prognosis with a median survival of less than 15 months. This study demonstrated numerous immunosuppressive genes as well as β-catenin gene, pivotal for Wnt/β-catenin signaling, were upregulated in 206 IDH1 glioma patients using the Chinese Glioma Genome Atlas (CGGA) database. The increase in microglia with an immunosuppressive phenotype and the overexpression of β-catenin protein were further verified in IDH1 GBM patients and IDH1 GL261 glioma allografts. Subsequently, we found that IDH1 GL261 cell-derived conditioned medium activated Wnt/β-catenin signaling in primary microglia and triggered their transition to an immunosuppressive phenotype. Blocking Wnt/β-catenin signaling not only attenuated microglial polarization to the immunosuppressive subtype but also reactivated immune responses in IDH1 GBM allografts by simultaneously enhancing cytotoxic CD8 T cell infiltration and downregulating regulatory T cells. Positron emission tomography imaging demonstrated enhanced proinflammatory activities in IDH1 GBM allografts after the blockade of Wnt signaling. Finally, gavage administration of a Wnt signaling inhibitor significantly restrained tumor proliferation and improved the survival of model mice bearing IDH1 GBM allografts. Depletion of CD8 T cells remarkably abrogated the therapeutic efficacy induced by the Wnt signaling inhibitor. Overall, the present work indicates that the crosstalk between IDH1 glioma cells and immunosuppressive microglia is important in maintaining the immunosuppressive glioma microenvironment. Blocking Wnt/β-catenin signaling is a promising complement for IDH1 GBM treatment by improving the hostile immunosuppressive microenvironment.
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http://dx.doi.org/10.1080/2162402X.2021.1932061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183516PMC
June 2021

The Preventive Effects of on Acute Lung Injury Induced by Lipopolysaccharide.

Indian J Microbiol 2021 Jun 1:1-13. Epub 2021 Jun 1.

the Second Affiliated Hospital of Qiqihar Medical University, No. 37 Zhonghua West Road, Jianhua DistrictHeilongjiang Province, Qiqihar City, 161000 China.

has been reported to inhibit acute lung injury (ALI). However, the molecular mechanism of () in preventing ALI has not been identified, so we investigated whether pretreatment could inhibit the activation of TLR4/MyD88/NF-κB signaling pathway following ALI. ALI model was established by intraperitoneal injection of 2 mg/kg lipopolysaccharide (LPS) to female BALB/c mice. In LC2W group, mice were intragastrically administrated LC2W for a week, before the ALI modeling. The serum of normal BALB/c mice after intragastric administration of L. casei LC2W was used for in vitro cell assays. The serum was pre-incubated with mouse macrophage cell line (RAW264.7) and human lung cell line (HLF-A), then LPS was added to co-incubate. Compared with ALI model group, LC2W pretreatment significantly reduced lung pathological damage, the number of neutrophils and total cells in bronchoalveolar lavage fluid. Besides, LC2W pretreatment could significantly reverse the abnormal expression of ICAM-1, IL-6, TNF-α and IL-10 in lung tissue and serum, plus, LC2W significantly reduced the phosphorylation levels of IRAK-1 and NF-κB p65. In vitro, the serum decreased the up-regulation of IL-6 and TNF-α in cell lines induced by LPS. In conclusion, LC2W intragastric administration pretreatment could significantly improve LPS-induced ALI in mice, probably through circulation to reach the lungs so as to inhibit the inflammatory response induced by activation of TLR4/MyD88/NF-κB signaling pathway.
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http://dx.doi.org/10.1007/s12088-021-00949-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169435PMC
June 2021

The Inhibition of B7H3 by 2-HG Accumulation Is Associated With Downregulation of VEGFA in IDH Mutated Gliomas.

Front Cell Dev Biol 2021 17;9:670145. Epub 2021 May 17.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

B7H3 (also known as CD276) is a co-stimulator checkpoint protein of the cell surface B7 superfamily. Recently, the function beyond immune regulation of B7H3 has been widely studied. However, the expression preference and the regulation mechanism underlying B7H3 in different subtypes of gliomas is rarely understood. We show here that B7H3 expression is significantly decreased in IDH-mutated gliomas and in cultured IDH1-R132H glioma cells. Accumulation of 2-HG leads to a remarkable downregulation of B7H3 protein and the activity of IDH1-R132H mutant is responsible for B7H3 reduction in glioma cells. Inhibition of autophagy by inhibitors like leupeptin, chloroquine (CQ), and Bafilomycin A1 (Baf-A1) blocks the degradation of B7H3 in glioma cells. In the meantime, the autophagy flux is more active with higher LC3B-II and lower p62 in IDH1-R132H glioma cells than in IDH1-WT cells. Furthermore, sequence alignment analysis reveals potential LC3-interacting region (LIR) motifs "F-V-S/N-I/V" in B7H3. Moreover, B7H3 interacts with p62 and CQ treatment significantly enhances this interaction. Additionally, we find that is positively correlated with and by bioinformatics analysis in gliomas. B7H3 and VEGFA are decreased in IDH-mutated gliomas and further reduced in 2-HG gliomas compared to 2-HG glioma sections by IHC staining. Our study demonstrates that B7H3 is preferentially overexpressed in IDH wild-type gliomas and could serve as a potential theranostic target for the precise treatment of glioma patients with wild-type IDH.
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http://dx.doi.org/10.3389/fcell.2021.670145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165280PMC
May 2021

Prestimulus dynamics blend with the stimulus in neural variability quenching.

Neuroimage 2021 09 28;238:118160. Epub 2021 May 28.

University of Ottawa Institute of Mental Health Research, Ottawa, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada.

Neural responses to the same stimulus show significant variability over trials, with this variability typically reduced (quenched) after a stimulus is presented. This trial-to-trial variability (TTV) has been much studied, however how this neural variability quenching is influenced by the ongoing dynamics of the prestimulus period is unknown. Utilizing a human intracranial stereo-electroencephalography (sEEG) data set, we investigate how prestimulus dynamics, as operationalized by standard deviation (SD), shapes poststimulus activity through trial-to-trial variability (TTV). We first observed greater poststimulus variability quenching in those real trials exhibiting high prestimulus variability as observed in all frequency bands. Next, we found that the relative effect of the stimulus was higher in the later (300-600ms) than the earlier (0-300ms) poststimulus period. Lastly, we replicate our findings in a separate EEG dataset and extend them by finding that trials with high prestimulus variability in the theta and alpha bands had faster reaction times. Together, our results demonstrate that stimulus-related activity, including its variability, is a blend of two factors: 1) the effects of the external stimulus itself, and 2) the effects of the ongoing dynamics spilling over from the prestimulus period - the state at stimulus onset - with the second dwarfing the influence of the first.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118160DOI Listing
September 2021

Current and emerging therapies for primary central nervous system lymphoma.

Biomark Res 2021 May 6;9(1):32. Epub 2021 May 6.

Department of Hematology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare type of extranodal lymphoma exclusively involving the CNS at the onset, with diffuse large B-cell lymphoma (DLBCL) as the most common histological subtype. As PCNSL is a malignancy arising in an immune-privileged site, suboptimal delivery of systemic agents into tumor tissues results in poorer outcomes in PCNSL than in non-CNS DLBCLs. Commonly used regimens for PCNSL include high-dose methotrexate-based chemotherapy with rituximab for induction therapy and intensive chemotherapy followed by autologous hematopoietic stem cell transplantation or whole-brain radiotherapy for consolidation therapy. Targeted agents against the B-cell receptor signaling pathway, microenvironment immunomodulation and blood-brain barrier (BBB) permeabilization appear to be promising in treating refractory/relapsed patients. Chimeric antigen receptor-T cells (CAR-T cells) have been shown to penetrate the BBB as a potential tool to manipulate this disease entity while controlling CAR-T cell-related encephalopathy syndrome. Future approaches may stratify patients according to age, performance status, molecular biomarkers and cellular bioinformation. This review summarizes the current therapies and emerging agents in clinical development for PCNSL treatment.
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http://dx.doi.org/10.1186/s40364-021-00282-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101140PMC
May 2021

Faded Critical Dynamics in Adult Moyamoya Disease Revealed by EEG and fMRI.

Oxid Med Cell Longev 2021 16;2021:6640108. Epub 2021 Apr 16.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.

Criticality is considered a dynamic signature of healthy brain activity that can be measured on the short-term timescale with neural avalanches and long-term timescale with long-range temporal correlation (LRTC). It is unclear how the brain dynamics change in adult moyamoya disease (MMD). We used BOLD-fMRI for LRTC analysis from 16 hemorrhagic ( ) and 34 ischemic ( ) patients and 25 healthy controls. Afterwards, they were examined by EEG recordings in the eyes-closed (EC), eyes-open (EO), and working memory (WM) states. The EEG data of 11 and 13 patients and 21 healthy controls were in good quality for analysis. Regarding the 4 metrics of neural avalanches (e.g., size (), duration (), value, and branching parameter ()), both MMD subtypes exhibited subcritical states in the EC state. When switching to the WM state, remained inactive, while surpassed controls and became supercritical ( < 0.05). Regarding LRTC, the amplitude envelope in the EC state was more analogous to random noise in the MMD patients than in controls. During state transitions, LRTC decreased sharply in the controls but remained chaotic in the MMD individuals ( < 0.05). The spatial LRTC reduction distribution based on both EEG and fMRI in the EC state implied that, compared with controls, the two MMD subtypes might exhibit mutually independent but partially overlapping patterns. The regions showing decreased LRTC in both EEG and fMRI were the left supplemental motor area of and right pre-/postcentral gyrus and right inferior temporal gyrus of . This study not only sheds light on the decayed critical dynamics of MMD in both the resting and task states for the first time but also proposes several EEG and fMRI features to identify its two subtypes.
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http://dx.doi.org/10.1155/2021/6640108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064775PMC
May 2021

Addressing the maldistribution of health resources in Sichuan Province, China: A county-level analysis.

PLoS One 2021 23;16(4):e0250526. Epub 2021 Apr 23.

School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Introduction: The equity of health resource allocation geographically is a contested topic. Sichuan Province, located in Southwest China, has varied topography, providing us with natural materials to explore the determinants of health resource distribution.

Materials And Methods: Spatial panel econometric models were constructed to explore the relationship between health resources and factors such as health care service demand and socioeconomic and demographic perspectives using data from Sichuan Province for eight consecutive years (2010-2017).

Results: Health care service demands were found to be a major driving force behind the distribution of health resources, showing that an increase in health care service demands draws health resources to specific counties and surrounding areas. From a socioeconomic perspective, gross domestic product per capita and the average wage show a positive association with health resources. In addition, the total population and proportion of the urban population have diverse effects in regard to health-related human resources but have the same effects on material and financial health resources.

Conclusions: Our results provide the Chinese government with evidence needed to formulate and promulgate effective policies, especially those aiming to tackle inequity among different regions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250526PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064550PMC
April 2021

Facile fabrication of phospholipid-functionalized nanofiber-based barriers with enhanced anti-adhesion efficiency.

Colloids Surf B Biointerfaces 2021 Jul 26;203:111728. Epub 2021 Mar 26.

Key Laboratory of Textile Science and Technology, Ministry of Education, College of Textiles, Donghua University, 2999 North Renmin Road, Songjiang District, Shanghai, 201620, China. Electronic address:

Electrospun nanofibrous membranes (NFMs) have attracted considerable attention as a potential physical barrier for reducing postoperative adhesion. However, no anti-adhesion barrier can completely prevent adhesion formation. In this study, phospholipid-functionalized NFMs were readily fabricated by one-step electrospinning to obtain nanofiber-based barriers with enhanced wettability and anti-adhesion efficiency. The optimized phospholipid NFMs were shown to have a fiber diameter of 831 nm ± 135 nm that is drastically decreasing, high porosity of 87.6 % ± 1.1 %, and superior hydrophilicity. Moreover, the phospholipid NFMs with excellent cytocompatibility exhibited fibroblasts being significantly reduced (≈ 51 %) after incubation of 3 days compared to that of the NFMs (≈ 96 %), confirming long-lasting anti-adhesion capability against fibroblasts. Meanwhile, less cell adhesion and proliferation of Raw 264.7 macrophages on NFM-10Lec indicated its superior anti-inflammatory effects. Thus, the facile phospholipid-functionalized nanofibers provided a promising strategy for anti-adhesion applications.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111728DOI Listing
July 2021

The Therapeutic Relationship in China: A Systematic Review and Meta-Analysis.

Int J Environ Res Public Health 2021 03 26;18(7). Epub 2021 Mar 26.

School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, China.

With a surge of conflicts between healthcare workers and patients in recent years, the therapeutic relationship (TR) in China is presently in tension. Meanwhile, consequent issues have begun to emerge, such as the distrust between healthcare workers and patients and the decline in the quality of medical services. Although many empirical studies about the TR have been conducted in China, previous studies on TR and its influencing factors have been contradictory. Therefore, this study conducted a systematic review and meta-analysis to assess the current situation of the TR and to identify factors associated with the TR in Chinese hospitals from three perspectives (healthcare worker, patient, and therapeutic interaction). Two reviewers independently searched the literature, selected researches, and extracted data through comprehensively searching of three international electronic databases and three Chinese electronic databases to identify all relevant observational studies on influencing factors for TR in China published in English and Chinese from January 2000 to January 2020. Among the 3290 records initially identified, 11 studies met the selection criteria. A total of 96,906 individuals were included in the review. The results showed that 55.73% of healthcare workers consider the TR to be tense, and 33.7% of patients hold this view. The meta-analysis indicated that healthcare workers who were male, older, less educated, working in a non-surgical department, and had a senior title were more likely to be pessimistic about the TR. Patients who were rural residents, highly educated, and had no medical insurance were more likely to be pessimistic about the TR. Furthermore, the mutual trust could improve rapport between healthcare workers and patients. The 25 other related factors related to the TR were analyzed and described using a narrative approach. The findings might deserve consideration in the design of relative policies to promote harmony between doctors and patients.
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http://dx.doi.org/10.3390/ijerph18073460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037362PMC
March 2021

The role of P62 in the development of human thyroid cancer and its possible mechanism.

Cancer Genet 2021 Aug 4;256-257:5-16. Epub 2021 Mar 4.

Thyroid Disease Diagnosis and Treatment Center, The First Affiliated Hospital of Kunming Medical University, Yunnan 650032, China. Electronic address:

Background: Thyroid cancer is the most common malignancy in human endocrine system. Increasing evidence has indicated that p62 plays a key role in tumorigenesis. The roles and underlying molecular mechanisms of P62 in thyroid cancer, however, remain to be elucidated.

Methods: The expression levels of P62 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of P62 on thyroid cancer cell proliferation, migration, invasion, cell cycle and apoptosis were measured by CCK-8 assay, transwell assay, flow cytometry and transwell assay, respectively. In terms of the mechanism, P62 could stimulate thyroid cancer progression by the activation of nuclear factor-kappa B (NF-κB) signaling pathway.

Results: P62 was highly expressed in thyroid tumor tissues. Furthermore, high expression of p62 was observed in PTC cell lines, and especially in the K1 and TPC-1 cells. In vitro, the up-regulation of p62 promoted cell proliferation, migration, and invasion of thyroid cancer cells, whereas the knockdown of p62 resulted in the opposite effect. Knock-down of P62 increased the number of cells in the G0/G1 phase but reduced it in the S and G2/M phase. Moreover, we confirmed that overexpression of p62 inactivated NF-κB pathway with sequencing analysis and bioinformatics analysis.

Conclusion: This research work suggested that p62 could promote PTC cell proliferation, migration, and invasion via NF-κB signaling pathway. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis in PTC. Its potential role as a therapeutic target for PTC is worthy of further study.
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http://dx.doi.org/10.1016/j.cancergen.2021.02.008DOI Listing
August 2021

DNA metabarcoding of zooplankton communities: species diversity and seasonal variation revealed by 18S rRNA and COI.

PeerJ 2021 19;9:e11057. Epub 2021 Mar 19.

College of Life Sciences, Shaanxi Normal University, Xian, Shaanxi, China.

Background: Zooplankton is an important component of aquatic organisms and has important biological and economical significance in freshwater ecosystems. However, traditional methods that rely on morphology to classify zooplankton require expert taxonomic skills. Moreover, traditional classification methods are time-consuming and labor-intensive, which is not practical for the design of conservation measures and ecological management tools based on zooplankton diversity assessment.

Methods: We used DNA metabarcoding technology with two different markers: the nuclear small subunit ribosomal RNA (18S rRNA) and mitochondrial cytochrome c oxidase (COI), to analyze 72 zooplankton samples collected in 4 seasons and 9 locations from the Sanmenxia Reservoir. We investigated seasonal changes in the zooplankton community and their relationship with water environmental factors.

Results: A total of 190 species of zooplankton were found, belonging to 12 phyla, 24 classes, 61 orders, 111 families, and 174 genera. Protozoa, especially ciliates, were the most diverse taxa. Richness and relative abundance of zooplankton showed significant seasonal changes. Both alpha and beta diversity showed seasonal trends: the diversity in summer and autumn was higher than that in winter and spring. The zooplankton diversity was most similar in winter and spring. By correlating metabarcoding data and water environmental factors, we proved that water temperature, chemical oxygen demand, total nitrogen and ammoniacal nitrogen were the main environmental factors driving the seasonal changes in zooplankton in the Sanmenxia Reservoir. Water temperature, followed by total nitrogen, were the most influential factors. This study highlights the advantages and some limitations of zooplankton molecular biodiversity assessment using two molecular markers.
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http://dx.doi.org/10.7717/peerj.11057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983862PMC
March 2021

Women's cancers in China: a spatio-temporal epidemiology analysis.

BMC Womens Health 2021 03 20;21(1):116. Epub 2021 Mar 20.

School of Public Policy and Administration, Xi'an Jiaotong University, 28 Xianning West Road, Beilin District, Xi'an, 710049, China.

Background: Women's cancers, represented by breast and gynecologic cancers, are emerging as a significant threat to women's health, while previous studies paid little attention to the spatial distribution of women's cancers. This study aims to conduct a spatio-temporal epidemiology analysis on breast, cervical and ovarian cancers in China, thus visualizing and comparing their epidemiologic trends and spatio-temporal changing patterns.

Methods: Data on the incidence and mortality of women's cancers between January 2010 and December 2015 were obtained from the National Cancer Registry Annual Report. Linear tests and bar charts were used to visualize and compare the epidemiologic trends. Two complementary spatial statistics (Moran's I statistics and Kulldorff's space-time scan statistics) were adopted to identify the spatial-temporal clusters.

Results: The results showed that the incidence and mortality of breast cancer displayed slow upward trends, while that of cervical cancer increase dramatically, and the mortality of ovarian cancer also showed a fast increasing trend. Significant differences were detected in incidence and mortality of breast, cervical and ovarian cancer across east, central and west China. The average incidence of breast cancer displayed a high-high cluster feature in part of north and east China, and the opposite traits occurred in southwest China. In the meantime, the average incidence and mortality of cervical cancer in central China revealed a high-high cluster feature, and that of ovarian cancer in northern China displayed a high-high cluster feature. Besides, the anomalous clusters were also detected based on the space-time scan statistics.

Conclusion: Regional differences were detected in the distribution of women's cancers in China. An effective response requires a package of coordinated actions that vary across localities regarding the spatio-temporal epidemics and local conditions.
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http://dx.doi.org/10.1186/s12905-021-01260-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981806PMC
March 2021

Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas.

Mod Pathol 2021 07 10;34(7):1245-1260. Epub 2021 Mar 10.

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts.
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http://dx.doi.org/10.1038/s41379-021-00778-xDOI Listing
July 2021

Spatial Effects of Environmental Pollution on Healthcare Services: Evidence from China.

Authors:
Ning Zhang Ying Mao

Int J Environ Res Public Health 2021 02 12;18(4). Epub 2021 Feb 12.

School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an 710049, China.

With the rapid development of urbanization and industrialization in China, environmental issues have become an urgent problem, especially issues related to air, water, and solid-waste pollution. These pollutants pose threats to the health of the population and to that of communities and have a vicious influence on the healthcare system. Additionally, pollution also exhibits spill-over effects, which means that pollution in the local region could affect the healthcare services in a neighboring region. Therefore, it is necessary to explore the relationship between pollution and healthcare. A spatial autocorrelation analysis was conducted and spatial panel econometric models were constructed to explore the characteristics of pollution and healthcare services in China and the relationship between them using data on all 31 provinces over 12 consecutive years (2006-2017). The results showed that the utilization of healthcare services and environmental pollution were not randomly distributed; unsurprisingly, air pollution and solid-waste pollution were mainly found in parts of northern China, while water pollution was highest in southern and coastal China. In addition, environmental pollution exhibited spill-over effects on healthcare services. For example, a 1% increase in solid waste in one specific geographical unit was estimated to increase the inpatient visits per capita in adjacent counties by 0.559%. Specifically, pollution showed different degrees of influence on healthcare services, which means that the impact of environmental pollution on the number of outpatient visits is greater than on the number of inpatient visits. Our results provide the government with evidence for effectively formulating and promulgating policies, especially policies aimed at tackling spill-over effects among different regions.
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http://dx.doi.org/10.3390/ijerph18041784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918594PMC
February 2021

Effects of Skin Friction on Tactile P300 Brain-Computer Interface Performance.

Comput Intell Neurosci 2021 9;2021:6694310. Epub 2021 Feb 9.

Skolkovo Institute of Science and Technology (SKOLTECH), Moscow 143026, Russia.

Tactile perception, the primary sensing channel of the tactile brain-computer interface (BCI), is a complicated process. Skin friction plays a vital role in tactile perception. This study aimed to examine the effects of skin friction on tactile P300 BCI performance. Two kinds of oddball paradigms were designed, silk-stim paradigm (SSP) and linen-stim paradigm (LSP), in which silk and linen were wrapped on target vibration motors, respectively. In both paradigms, the disturbance vibrators were wrapped in cotton. The experimental results showed that LSP could induce stronger event-related potentials (ERPs) and achieved a higher classification accuracy and information transfer rate (ITR) compared with SSP. The findings indicate that high skin friction can achieve high performance in tactile BCI. This work provides a novel research direction and constitutes a viable basis for the future tactile P300 BCI, which may benefit patients with visual impairments.
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http://dx.doi.org/10.1155/2021/6694310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886524PMC
July 2021

Spatiotemporal characteristics and meteorological determinants of hand, foot and mouth disease in Shaanxi Province, China: a county-level analysis.

BMC Public Health 2021 02 17;21(1):374. Epub 2021 Feb 17.

School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an, China.

Background: Hand, foot and mouth disease (HFMD) is one of the common intestinal infectious diseases worldwide and has caused huge economic and disease burdens in many countries. The average annual incidence rate of HFMD was 11.66% in Shaanxi during the time span from 2009 to 2018. There are distinct differences within Shaanxi, as it is a special region that crosses three temperature zones. Hence, in this study, a spatiotemporal analysis of Shaanxi was performed to reveal the characteristics of the distribution of HFMD and to explore the meteorological determinants of HFMD.

Methods: The county-level and municipal data from Shaanxi Province from 2009 to 2018 were applied to research the spatiotemporal characteristics of HFMD and its meteorological determinants. Time series and spatial autocorrelation analyses were applied to assess the spatiotemporal characteristics of HFMD. This study used spatial econometric panel models to explore the relationship between HFMD and meteorological factors based on the data of 107 counties and 10 municipalities.

Results: The incidence rate of HFMD displayed no variable trend throughout the whole research period. A high incidence rate of HFMD was observed from June to September, corresponding to a time when the climate is characterized by heavy rain, high temperature, and high humidity. The high-incidence areas were mainly located in the central region in Shaanxi, whereas the low-incidence spots were mainly found in Northern Shaanxi. Regarding the meteorological factors analysed in this study, in general, the incidence rate of HFMD in specific regions was positively associated with the rainfall, temperature and humidity.

Conclusion: These results could be applied by the government and the general public to take effective measures to prevent disease. Region-targeted policies could be enacted and implemented in the future according to specific situations in different areas and the relevant meteorological determinants. Additionally, meteorological conditions normally extend to a wide-ranging region; thus, cooperation among surrounding regions is necessary.
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http://dx.doi.org/10.1186/s12889-021-10385-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890844PMC
February 2021

How I do it? Gravity-assisted endoscopic cingulate gyrus glioma resection.

Acta Neurochir (Wien) 2021 05 16;163(5):1323-1326. Epub 2021 Feb 16.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Wulumuqi Zhong Road, Shanghai, 200040, China.

Background: The cingulate gyrus is part of the limbic system with extensive connectivity to different anatomical and functional areas. The traditional transcortical approach for a cingulate gyrus glioma contains high risk of transient or even irreversible postoperative hemiplegia.

Method: We present a case of gravity-assisted, fully endoscopic resection of a cingulate gyrus glioma with improvement of motor dysfunction while preserving the paracentral lobule, corticospinal tracts, and supplementary motor area.

Conclusion: This case demonstrates the value of gravity-assisted endoscopic resection in the dominant cingulate gyrus tumor which is surrounded by eloquent parenchyma.
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http://dx.doi.org/10.1007/s00701-021-04741-2DOI Listing
May 2021

Higher-order sensorimotor circuit of the brain's global network supports human consciousness.

Neuroimage 2021 05 12;231:117850. Epub 2021 Feb 12.

Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada; Mental Health Centre, Zhejiang University School of Medicine, Hangzhou, China.

Consciousness is a mental characteristic of the human mind, whose exact neural features remain unclear. We aimed to identify the critical nodes within the brain's global functional network that support consciousness. To that end, we collected a large fMRI resting state dataset with subjects in at least one of the following three consciousness states: preserved (including the healthy awake state, and patients with a brain injury history (BI) that is fully conscious), reduced (including the N1-sleep state, and minimally conscious state), and lost (including the N3-sleep state, anesthesia, and unresponsive wakefulness state). We also included a unique dataset of subjects in rapid eye movement sleep state (REM-sleep) to test for the presence of consciousness with minimum movements and sensory input. To identify critical nodes, i.e., hubs, within the brain's global functional network, we used a graph-theoretical measure of degree centrality conjoined with ROI-based functional connectivity. Using these methods, we identified various higher-order sensory and motor regions including the supplementary motor area, bilateral supramarginal gyrus (part of inferior parietal lobule), supragenual/dorsal anterior cingulate cortex, and left middle temporal gyrus, that could be important hubs whose degree centrality was significantly reduced when consciousness was reduced or absent. Additionally, we identified a sensorimotor circuit, in which the functional connectivity among these regions was significantly correlated with levels of consciousness across the different groups, and remained present in the REM-sleep group. Taken together, we demonstrated that regions forming a higher-order sensorimotor integration circuit are involved in supporting consciousness within the brain's global functional network. That offers novel and more mechanism-guided treatment targets for disorders of consciousness.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117850DOI Listing
May 2021
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