Publications by authors named "Lu Chen"

1,873 Publications

  • Page 1 of 1

Prognostic Value of Immune-Related lncRNA SBF2-AS1 in Diffuse Lower-Grade Glioma.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211011966

Department of Hepatopancreatobiliary Surgery, The People's Hospital of Lishui, Lishui, Zhejiang, China.

LncRNA SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1) has been proven to play an oncogenic role in various types of tumors, but the prognostic role of SBF2-AS1 in tumors, especially in diffuse lower-grade glioma (LGG), is still unclear. Here, we aimed to investigate the prognostic value of SBF2-AS1 in LGG. The LGG expression profiles from The Cancer Genome Atlas (TCGA, = 524) and Chinese Glioma Genome Atlas (CGGA, = 431) were mined by Kaplan-Meier analysis, Cox regression analysis, Chi-square test and GSEA analysis. Through Kaplan-Meier analysis, we found the prognosis of LGG patients with high expression of SBF2-AS1 were worse than that of patients with low expression (Log Rank < 0.001). Cox analysis showed SBF2-AS1 was an independent prognostic factor for poorer overall survival in LGG ( < 0.05). SBF2-AS1 was found to be significantly related to IDH mutation status and SBF2-AS1 was highly expressed in IDH wildtype group. GSEA analysis obtained a total of 126 GO terms and 6 KEGG pathways that were significantly enriched in SBF2-AS1 high expression phenotype (NOM value < 0.05). We found these 126 GO terms and KEGG pathways were mainly related to immunity. In conclusion, lncRNA SBF2-AS1 expression is an immune-related lncRNA associated with unfavorable overall survival in LGG. SBF2-AS1 could be a reliable prognostic biomarker for patients with LGG.
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http://dx.doi.org/10.1177/15330338211011966DOI Listing
June 2021

Spatial description theory of narrow-band single-carrier avalanche photodetectors.

Opt Express 2021 May;29(11):16432-16446

The avalanche is the foundation of the understanding and vast applications of the breakdown of semiconductors and insulators. Present numerical theories analyzing the avalanche photodetectors are mainly split into two categories: the macroscopic empirical model with fitting parameters and the microscopic process simulation with statistical estimations. Here, we present a parameter-free analytic theory of the avalanche for a narrow-band material, HgCdTe, originated from quantum mechanics, avoiding any fitting parameter or any statistical estimation while taking advantage of both categories. Distinct from classical theory, we propose a full spatial description of an avalanche with basic concepts such as transition rate and equation of motion modified. As a stochastic process, the probability density function (PDF) of impact ionization is utilized in a generalized history-dependent theory. On account of different carrier generation character of light and leakage current, we suggest that carrier generated at different positions should be considered separately, which is done by generalized history-dependent theory in our work. Further, in our calculation, the reason for the abnormal rise of excess noise factor (ENF) observed in the experiment in single-carrier avalanche photodetectors is clarified.
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http://dx.doi.org/10.1364/OE.418110DOI Listing
May 2021

The Interplay of Neurovasculature and Adult Hippocampal Neurogenesis.

Neurosci Lett 2021 Jun 17:136071. Epub 2021 Jun 17.

Department of Neurobiology & Behavior, SUNY at Stony Brook, Stony Brook, NY 11794, USA.

The subgranular zone of the dentate gyrus provides a local microenvironment (niche) for neural stem cells. In the adult brain, it has been established that the vascular compartment of such niches has a significant role in regulating adult hippocampal neurogenesis. More recently, evidence showed that neurovascular coupling, the relationship between blood flow and neuronal activity, also regulated hippocampal neurogenesis. Here, we review the most recent articles on addressing the intricate relationship between neurovasculature and adult hippocampal neurogenesis and a novel pathway where functional hyperemia enhances hippocampal neurogenesis. In the end, we have further reviewed recent research showing that impaired neurovascular coupling may cause declined neurogenesis and contribute to brain damage in neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.neulet.2021.136071DOI Listing
June 2021

Social Class Identity, Public Service Satisfaction, and Happiness of Residents: The Mediating Role of Social Trust.

Front Psychol 2021 1;12:659657. Epub 2021 Jun 1.

School of Economics and Management, Jiangxi Science and Technology Normal University, Nanchang, China.

Happiness is the eternal pursuit of mankind and is also the ultimate goal of social governance and national development. Based on data from the Chinese General Social Survey, this study used a structural equation model to analyze the influence of social class identity and public service satisfaction on the happiness of residents. The effect of public service satisfaction and social trust between social class identity and residents' happiness was tested using the Monte Carlo method. The empirical results show that social class identity, social trust, and public service satisfaction all had a significant positive impact on residents' happiness. The influence coefficients of social class identity on the happiness of residents and on the satisfaction degree of public service for those born in the1970s group were greater than the 1980s and 1990s groups. The influence coefficients of social class identity on the happiness and public service satisfaction of non-agricultural household residents were greater than those of agricultural household residents. Therefore, to improve the happiness of residents, we should make new breakthroughs in the equality of quality and the quality of public services, promote the integration of urban and rural areas, highlight key areas of rural development, and increase the construction of basic public services for agricultural household residents.
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http://dx.doi.org/10.3389/fpsyg.2021.659657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203815PMC
June 2021

Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes.

NPJ Genom Med 2021 Jun 17;6(1):52. Epub 2021 Jun 17.

School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China.

The emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients' prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.
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http://dx.doi.org/10.1038/s41525-021-00215-7DOI Listing
June 2021

Electrical Storm With Incessant Ventricular Tachycardia in a COVID-19 Patient: Review of Current Evidence.

Cureus 2021 Jun 11;13(6):e15604. Epub 2021 Jun 11.

Medicine and Endocrinology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, USA.

Coronavirus disease 2019 (COVID-19) is associated with various cardiovascular manifestations, including myocarditis, myocardial infarction, and arrhythmias. A prothrombotic state is the primary underlying pathogenic mechanism. While cardiac arrhythmias manifest more commonly amongst critically ill COVID-19 populations, ventricular arrhythmias have been reported only in few cases. This report describes a case of a 95-year-old African American man with COVID-19, who developed sustained monomorphic ventricular tachycardia, which progressed to an electrical storm. The case highlights the importance of high clinical suspicion, early recognition of electrical abnormalities in patients with active COVID-19 infection, and its ability to precipitate fatal ventricular arrhythmia. Also, we provide a literature review on the electrical storm in COVID-19 patients, highlighting the pathophysiologic mechanisms and the management of this deadly arrhythmia.
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http://dx.doi.org/10.7759/cureus.15604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195615PMC
June 2021

Effects of excessive nitrogen on nitrogen uptake and transformation in the wetland soils of Liaohe estuary, northeast China.

Sci Total Environ 2021 Jun 2;791:148228. Epub 2021 Jun 2.

College of Environmental Science and Engineering, Dalian Maritime University, Dalian, China.

It remains unclear whether excessive nitrogen additions lead to the degradation of Suaeda salsa (S. salsa) by affecting the nitrogen pool, enzyme activities, and bacterial community structure of wetland soils. This study investigated the effect of five added nitrogen concentrations (0, 1, 2, 4, and 6 mmol L N with NHNO = group C, group L, group M, group H, and group G, respectively) on nitrogen uptake by S. salsa and nitrogen transformation in the wetland soils of the Liaohe estuary. The height, weight, and total nitrogen (TN) of S. salsa in group G was significantly lower than in the other groups (p <0.05). The NH-N concentration in the soil tended to increase with increasing nitrogen addition, but the TN concentration in the soil tended to decrease. The nitrogenase, protease, urease, ammonia monooxygenase (AMO), nitrous oxide reductase (NOR), and dehydrogenase (DHA) activities increased with increasing nitrogen addition within the range of 0 to 4 mmol L. We identified 30 phyla and 48 known genera across all five groups. The predominant phyla were Proteobacteria (52.68%), Bacteroidetes (22.58%), and Planctomycetes (3.94%). The most abundant genus was Acinetobacter (13.38%), followed by Proteiniphilum (11.88%) and Brevundimonas (6.03%). The total number of soil bacterial species increased with increasing nitrogen addition. Group G had lower soil bacterial activity and diversity than the other groups. It was concluded that appropriate levels of nitrogen addition could promote nitrogen uptake by S. salsa and nitrogen transformation in the wetland soils of the Liaohe estuary by affecting soil enzyme activities and soil bacterial activity, diversity, abundance, and composition, while excessive nitrogen additions may be one of the reasons for the degradation of S. salsa.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148228DOI Listing
June 2021

Combination Model of Thyrotrophin Receptor Antibody and Volumetric Orbital Apex Crowding Index as an Indicator of Dysthyroid Optic Neuropathy.

Dis Markers 2021 18;2021:9964232. Epub 2021 May 18.

Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Dysthyroid optic neuropathy (DON) is one of the most serious vision-threatening complications of thyroid eye disease (TED); however, accurate and established diagnostic tools for DON are yet lacking. The present study was aimed at identifying new diagnostic factors for the accurate diagnosis of DON.

Methods: This retrospective cross-sectional study included 25 TED patients (50 eyes) with enlarged extraocular muscles, no previous anti-inflammatory therapy, and the absence of other vision-affecting diseases between May 2017 and August 2019. Baseline data, such as gender, age, ophthalmological history, thyroid disease and management, TED history including clinical features, management, and long-term results, ophthalmological examinations, serology examinations, and single-photon emission computed tomography/computed tomography (SPECT/CT) results, were extracted. The diagnostic criteria were as follows: (1) best-corrected visual acuity (BCVA) loss coexisting with either of the following-increased latency or reduction of amplitude on visual evoked potential (VEP), impaired color vision, visual field defects, contrast sensitivity impairment, and optic disk swelling-and (2) Barrett's index ≥ 60% in CT. Univariate and multivariate logistic regression analyses assessed the differences in age, gender, eyes, medical history, clinical activity, thyroid hormone and antibodies, uptake ratio (UR) of extraocular muscles in SPECT/CT, and volumetric orbital apex crowding index (VACI) using the generalized estimation equation. Consequently, the receiver operating characteristic curve (ROC) of the significant factors was constructed.

Results: Univariate analysis revealed significant differences in the clinical activity, free triiodothyronine (FT3), free thyroxine (FT4), thyrotrophin receptor antibody (TRAb) levels, the UR of superior and medial rectus, and VACI between DON and TED (without DON) groups. Multivariate regression analysis revealed that TRAb and VACI were significantly different. ROC analysis showed that the univariate models of TRAb or VACI and the multivariate model were effective indicators of DON, while the multivariate model had the highest area under the ROC curve.

Conclusion: A combination of TRAb and VACI is an effective indicator for DON.
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http://dx.doi.org/10.1155/2021/9964232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154283PMC
May 2021

Accelerating transdermal delivery of insulin by ginsenoside nanoparticles with unique permeability.

Int J Pharm 2021 Jun 8;605:120784. Epub 2021 Jun 8.

Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou 350116, China. Electronic address:

Diabetes is a metabolic disease caused by insufficient insulin secretion, action or resistance, in which insulin plays an irreplaceable role in the its treatment. However, traditional administration of insulin requires continuous subcutaneous injections, which is accompanied by inevitable pain, local tissue necrosis and hypoglycemia. Herein, a green and safe nanoformulation with unique permeability composed of insulin and ginsenosides is developed for transdermal delivery to reduce above-mentioned side effects. The ginsenosides are self-assembled to form shells to protect insulin from hydrolysis and improve the stability of nanoparticles. The nanoparticles can temporarily permeate into cells in 5 min and promptly excrete from the cell for deeper penetration. The insulin permeation is related to the disorder of stratum corneum lipids caused by ginsenosides. The skin acting as drug depot mantains the nanoparticles released continuously, therefore the body keeps euglycemic for 48 h. Encouraged by its long-lasting and effective transdermal therapy, ginsenosides-based nano-system is expected to deliver other less permeable drugs like proteins and peptides and benefit those who are with chronic diseases that need long-term medication.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120784DOI Listing
June 2021

TRDMT1 participates in the DNA damage repair of granulosa cells in premature ovarian failure.

Aging (Albany NY) 2021 Jun 8;13(11):15193-15213. Epub 2021 Jun 8.

Reproductive Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China.

The molecular mechanisms underlying premature ovarian failure, which seriously impacts the physical and psychological health of patients, are not fully understood. Here, we present the role of TRDMT1 in reactive oxygen species-induced granulosa cells death, which is considered an important cause of premature ovarian failure. We found that reactive oxygen species were increased in a HO dose-dependent manner and accompanied by the nuclear shuttling of TRDMT1, increased DNA damage and increased apoptosis of granulosa cells. In addition, reactive oxygen species-induced granulosa cells apoptosis could be prevented by the antioxidant N-acetylcysteine or overexpression of TRDMT1. Furthermore, DNA repair following reactive oxygen species induction was severely impaired/enhanced in TRDMT1 mutants, which exhibited reduced/increased RNA m5C methylation activity. Altogether, our results reveal a novel role of TRDMT1 in the regulation of premature ovarian failure through the repair of reactive oxygen species-triggered DNA damage in granulosa cells and provide an improved understanding of the mechanisms underlying granulosa cells apoptosis, which could potentially be useful for future clinical treatments of premature ovarian failure.
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http://dx.doi.org/10.18632/aging.203080DOI Listing
June 2021

pH-Dependent complexation between β-lactoglobulin and lycopene: Multi-spectroscopy, molecular docking and dynamic simulation study.

Food Chem 2021 May 28;362:130230. Epub 2021 May 28.

Department of Food Science, College of Food Science and Engineering, Jilin University, Changchun 130062, China. Electronic address:

This study aims to investigate the effect of pH levels (pH 7.0 and pH 8.1) on binding ability of β-lactoglobulin (β-LG) with lycopene (LYC) and elucidate interaction mechanisms using multi-spectroscopy and molecular docking study. β-LG at pH 8.1 showed a stronger binding affinity to lycopene than that at pH 7.0 according to binding constant, binding number, energy transfer efficiency, and surface hydrophobicity. Lycopene bound to protein mainly by van der Waals force in the form of static quenching mode and preferred to interact with β-LG at the top of barrel for both pH levels. Molecular dynamic simulation revealed that β-LG/LYC complex at pH 8.1 was more stable than at pH 7.0. β-LG/LYC complexes formed at pH 8.1 showed significantly higher ABTS radical scavenging activity than samples at pH 7.0 (p < 0.05). Data obtained may contribute valuable information for preparing a whey protein-based delivery system for lycopene.
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http://dx.doi.org/10.1016/j.foodchem.2021.130230DOI Listing
May 2021

Diagnostic Biomarker Hsa_circ_0126218 and Functioning Prediction in Peripheral Blood Monocular Cells of Female Patients With Major Depressive Disorder.

Front Cell Dev Biol 2021 20;9:651803. Epub 2021 May 20.

Psychology and Health Management Center, Harbin Medical University, Harbin, China.

Introduction: Although major depressive diroder (MDD) has brought huge burden and challenges to society globally, effective and accurate diagnoses and treatments remain inadequate. The pathogenesis that for women are more likely to suffer from depression than men needs to be excavated as well. The function of circRNAs in pathological process of depression has not been widely investigated. This study aims to explore potential diagnostic biomarker circRNA of female patients with MDD and to investigate its role in pathogenesis.

Methods: First, an expression profile of circRNAs in the peripheral blood monocular cells of MDD patients and healthy peripherals were established based on high-throughput sequencing analysis. In addition, the top 10 differentially expressed circRNAs were quantified by quantitative real-time PCR to explore diagnostic biomarkers. To further investigate the function of biomarkers in the pathogenesis of MDD, bioinformatics analysis on downstream target genes of the biomarkers was carried out.

Results: There is a mass of dysregulated circRNAs in PBMCs between female MDD patients and healthy controls. Among the top 10 differentially expressed circRNAs, hsa_circ_0126218 is more feasible as a diagnostic biomarker. The expression level of hsa_circ_0126218 displayed upregulation in patients with MDD and the area under the operating characteristic curve of hsa_circ_0126218 was 0.801 (95% CI 0.7226-0.8791, < 0.0001). To explain the competing endogenous RNA role of hsa_circ_0126218 in the pathogenesis of female MDD, a hsa_circ_0126218-miRNA-mRNA network was established. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses stated that some of the enriched pathways downstream of hsa_circ_0126218 are closely related to MDD. Moreover, we established a protein-protein network to further screen out the hub genes (PIK3CA, PTEN, MAPK1, CDC42, Lyn, YES1, EPHB2, SMAD2, STAT1, and ILK). The function of hsa_circ_0126218 was refined by constructing a verified circRNA-predicted miRNA-hub gene subnetwork.

Conclusion: hsa_circ_0126218 can be considered as a new female MDD biomarker, and the pathogenesis of female MDD by the downstream regulation of hsa_circ_0126218 has been predicted. These findings may help further improve the early detection, effective diagnosis, convenient monitoring of complications, precise treatment, and timely recurrence prevention of depression.
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http://dx.doi.org/10.3389/fcell.2021.651803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174117PMC
May 2021

Exosomal transfer of miR-429 confers chemoresistance in epithelial ovarian cancer.

Am J Cancer Res 2021 15;11(5):2124-2141. Epub 2021 May 15.

Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University Zhenjiang, Jiangsu, China.

The development of multidrug resistance during chemotherapy is the main obstacle for epithelial ovarian cancer (EOC) treatment. Exosomal transfer of carcinogenic microRNAs (miRNAs) might strengthen chemoresistance in recipient cells. Here, we identified through microarray analysis higher miR-429 expression in multidrug-resistant SKOV3 cells and their secreted exosomes (SKOV3-EXO) than in sensitive A2780 cells and their secreted exosomes. SKOV3-derived exosomes were internalized by A2780 cells, which permitted the transfer of miR-429. Exosomal miR-429 enhanced the proliferation and drug resistance of A2780 cells by targeting calcium-sensing receptor (CASR)/STAT3 pathway in vitro and in vivo. In addition, NF-κB-p65 was predicted to bind to the miR-429 promoter region, and the inhibition of NF-κB reduced the expression of miR-429 and led to the sensitivity of EOC cells. Consistently, A2780 cells co-incubated with SKOV3 pretreated with an NF-κB inhibitor or miR-429 antagomir showed sensitivity to cisplatin and exhibited attenuated cell proliferation. Based on our data, exosomal miR-429 functions as a primary regulator of the chemoresistance and malignant phenotypes of EOC by targeting CASR through a mechanism promoted by NF-κB and might be a therapeutic target for EOC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167704PMC
May 2021

Salicylic acid-based nanomedicine with self-immunomodulatory activity facilitates microRNA therapy for metabolic skeletal disorders.

Acta Biomater 2021 Jun 3. Epub 2021 Jun 3.

National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address:

Metabolic skeletal disorders remain a major clinical challenge. The complexity of this disease requires a strategy to address the net effects of both inflammation and impaired bone formation. microRNA-based gene therapy provides several therapeutic advantages to tackle these issues. Herein, we describe a microRNA-21 (miR-21) delivery system with an additional therapeutic effect from that of the delivery carrier itself. Poly (salicylic acid) (PSA) is, for the first time, synthesized via polycondensation of salicylic acid (SA), a bioactive ingredient widely used for anti-inflammation in medicine. PSA can self-assemble into nanoparticles (PSA-NPs) and can effectively deliver genes both in vitro and in vivo. The carrier was then attached to repetitive sequences of aspartate, serine, serine (DSS) for delivering miRNAs specifically to bone-formation surfaces. In vitro studies showed that [email protected] could effectively realize the intracellular delivery of miR-21 with low toxicity, while in vivo results indicated that the [email protected] prolonged blood circulation time, enhanced bone accumulation, and significantly improved the efficacy of miR-21-based bone anabolic therapy in osteoporotic mice. The constructed delivery system ([email protected]) inherited the advantages of both SA and miR-21, which could ameliorate bone-inflamed niche and rescued the impaired bone formation ability. The synergy of anti-inflammatory and pro-osteogenic effects significantly improved trabecular bone microstructure in osteoporotic mice. STATEMENT OF SIGNIFICANCE: The complexity of metabolic skeletal disorders requires a strategy to address the net effects of both inflammation and impaired bone formation. microRNA-based gene therapy provides several therapeutic advantages to tackle these issues. We develop a novel microRNA-21 delivery system with additional therapeutic effect from that of the gene carrier itself. Poly (salicylic acid) (PSA) nanoparticles, for the first time, synthesized via polycondensation of salicylic acid and can effectively deliver genes both in vitro and in vivo. The constructed delivery system ([email protected]) inherited the advantages of both SA (commonly used anti-inflammation drug in medicine) and miR-21 (a pro-osteogenic molecule), which could ameliorate bone-inflamed niche, rescued impaired bone formation ability and significantly improved trabecular bone microstructure in osteoporotic mice.
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http://dx.doi.org/10.1016/j.actbio.2021.05.024DOI Listing
June 2021

Effects of omalizumab in children with asthma: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(22):e26155

Department of Respiratory, Hunan Children's Hospital, Hunan, China.

Background: It is still controversial in the current literature whether omalizumab is beneficial for children with asthma. Given that there is no high-quality meta-analysis to incorporate existing evidence, the purpose of this protocol is to design a systematic review and meta-analysis of the level I evidence to ascertain whether omalizumab is beneficial and safe for children with asthma.

Methods: The systematic literature review is structured to adhere to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The following search terms will be used in PUBMED, Scopus, EMBASE, and Cochrane Library databases on June, 2021, as the search algorithm: (omalizumab) AND (asthma) AND (children). The primary outcome is the long-term safety and tolerability of omalizumab. The other outcomes include asthma control, quality of life, use of asthma controller medications, and spirometry measurements and emergency room visits due to asthma, and serum trough concentrations of omalizumab, free and total immunoglobulin E measured. Review Manager software (v 5.3; Cochrane Collaboration) will be used for the meta-analysis.

Results: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.

Registration Number: 10.17605/OSF.IO/G6N3P.
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http://dx.doi.org/10.1097/MD.0000000000026155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183849PMC
June 2021

Construction of a novel mRNA-miRNA-lncRNA network and identification of potential regulatory axis associated with prognosis in colorectal cancer liver metastases.

Aging (Albany NY) 2021 Jun 3;13(11):14968-14988. Epub 2021 Jun 3.

Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China.

Liver metastasis is a leading cause of death in patients with colorectal cancer (CRC). Increasing evidence demonstrates that competing endogenous RNA (ceRNA) networks play important roles in malignant cancers. The purpose of this study was to identify molecular markers and build a ceRNA network as a significant predictor of colorectal liver metastases (CRLM). By integrated bioinformatics analysis, we found that apolipoprotein C1 (APOC1) was upregulated in CRLM and associated with prognosis in patients with CRC and thereby established an APOC1-dependent ceRNA network. By survival analysis, expression analysis, and correlation analysis of each element in the ceRNA network, we identified that ZEB1-AS1, miR-335-5p and APOC1 regulated each other. We further experimentally confirmed that ZEB1-AS1 promoted a CRC progression via regulating the expression of miR-335-5p that controlled the expression of APOC1. Our findings indicate that the ZEB1-AS1-miR-335-5p-APOC1 ceRNA regulatory network is significantly valuable for better prognosis of patients with CRC and as a new therapeutic target for the treatment of CRLM.
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http://dx.doi.org/10.18632/aging.203049DOI Listing
June 2021

A Bibliometric Analysis of Research Trends of Acupuncture Therapy in the Treatment of Migraine from 2000 to 2020.

J Pain Res 2021 25;14:1399-1414. Epub 2021 May 25.

Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu Province, People's Republic of China.

Background: Migraine is the second-leading cause of disability worldwide. It is often characterized by attacks of severe, mostly unilateral, pulsating headache associated with symptoms such as photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia. Acupuncture therapy has been used worldwide for the treatment of migraine. However, no visual bibliometric analysis has been conducted on the effects of acupuncture on migraine over the past 20 years. Therefore, this study aimed to explore the current status and trends on the use of acupuncture in the treatment of migraine from 2000 to 2020.

Purpose: The objective of this study is to identify the current status and emerging trends of the global use of acupuncture on migraine from 2000 to 2020 using CiteSpace and VOSviewer.

Methods: Web of Science databases were searched for publications related to acupuncture therapy for treating migraine between 2000 and 2020. CiteSpace and VOSviewer were used to analyze the number of publications per year, countries, institutions, authors, journals, references, and keywords.

Results: A total of 572 publications were included in the final analysis. The total number of publications has continued to increase with some fluctuations over the past 20 years. The most productive country and institution in this field were the USA, and Chengdu University of Traditional Chinese Medicine, respectively. The most active and cited authors were Liang FR and Linde K, respectively. was the most productive, cited, and co-cited journal. The Linde K (2005) had the highest co-citation, citation number and centrality. The keywords "migraine" ranked first in frequency. The common type of migraine (tension-type headache), research method (randomized controlled trial, multicenter, double-blind), acupuncture's role (prophylactic, quality of life, pain), and evaluation (meta-analysis, systematic review) were the hotspots and frontier trends of acupuncture therapy on migraine between 2000 and 2020.

Conclusion: The present study examined the research-related trend in acupuncture therapy on migraine using bibliometric methods and identified the statement and research frontiers over the past two decades. This may help researchers to identify potential hotspots and new directions for future research in this field.
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http://dx.doi.org/10.2147/JPR.S306594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164719PMC
May 2021

Texture analysis of orbital magnetic resonance imaging for monitoring and predicting treatment response to glucocorticoids in patients with thyroid-associated ophthalmopathy.

Endocr Connect 2021 Jun 24;10(7):676-684. Epub 2021 Jun 24.

Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Purpose: To evaluate the value of MRI-based texture analysis of extraocular muscle (EOM) and orbital fat (OF) in monitoring and predicting the response to glucocorticoid (GC) therapy in patients with thyroid-associated ophthalmopathy (TAO).

Methods: Thirty-seven active and moderate-to-severe TAO patients (responders, n = 23; unresponders, n = 14) were retrospectively enrolled. MRI-based texture parameters (entropy, uniformity, skewness and kurtosis) of EOM and OF were measured before and after GC therapy, and compared between groups. Correlations between the changes of clinical activity score (CAS) and imaging parameters before and after treatment were assessed. Receiver operating characteristic curves were used to evaluate the predictive value of identified variables.

Results: Responsive TAOs showed significantly decreased entropy and increased uniformity at EOM and OF after GC therapy (P < 0.01), while unresponders showed no significance. Changes of entropy and uniformity at EOM and OF were significantly correlated with changes of CAS before and after treatment (P < 0.05). Responders showed significantly lower entropy and higher uniformity at EOM than unresponders before treatment (P < 0.01). Entropy and uniformity of EOM and disease duration were identified as independent predictors for responsive TAOs. Combination of all three variables demonstrated optimal efficiency (area under curve, 0.802) and sensitivity (82.6%), and disease duration alone demonstrated optimal specificity (100%) for predicting responsive TAOs.

Conclusion: MRI-based texture analysis can reflect histopathological heterogeneity of orbital tissues. It could be useful for monitoring and predicting the response to GC in TAO patients.
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http://dx.doi.org/10.1530/EC-21-0162DOI Listing
June 2021

Novel 2,3-Dialdehyde Cellulose-Based Films with Photodynamic Inactivation Potency by Incorporating the β-Cyclodextrin/Curcumin Inclusion Complex.

Biomacromolecules 2021 Jun 2. Epub 2021 Jun 2.

College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.

Antibacterial packaging film mediated by photodynamic inactivation (PDI) is a new concept in food industry. The objective of this study was to fabricate a green 2,3-dialdehyde cellulose (DAC)-based antimicrobial film with PDI potency by incorporating the β-cyclodextrin/curcumin (β-CD/Cur) complex as a photosensitizer. The PDI-mediated films were characterized by evaluating the surface morphology, chemical structure, light transmittance, mechanical properties, photochemical and thermal stability, and water solubility. The results showed that the DAC-CD/Cur films were soluble in water and mechanically strong with a tensile strength of 63.87 MPa and an elongation break of 1.32%, which was attributed to the formation of hydrogen bonds between DAC and β-CD/Cur molecules. Meanwhile, the composite films possessed a good light transmittance but impeded the penetration of ultraviolet light and efficiently delayed the degradation of curcumin. More importantly, the PDI-mediated films exhibited a broad-spectrum ability to kill , , and in pure culture. Notably, they also potently inactivated these harmful bacteria on ready-to-eat salmon with a maximum of ∼4 Log CFU/g (99.99%) reduction after 60 min irradiation (13.68 J/cm). Therefore, the PDI-mediated DAC-CD/Cur films are novel and promising antimicrobial food packaging films in food industry.
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http://dx.doi.org/10.1021/acs.biomac.1c00165DOI Listing
June 2021

Subcellular localization of the mouse PRAMEL1 and PRAMEX1 reveals multifaceted roles in the nucleus and cytoplasm of germ cells during spermatogenesis.

Cell Biosci 2021 Jun 1;11(1):102. Epub 2021 Jun 1.

Department of Animal Science, Center for Reproductive Biology and Health (CRBH), College of Agricultural Sciences, The Pennsylvania State University, 324 Henning Building, University Park, PA, 16802, USA.

Background: Preferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen (CTA) that is predominantly expressed in normal gametogenic tissues and a variety of tumors. Members of the PRAME gene family encode leucine-rich repeat (LRR) proteins that provide a versatile structural framework for the formation of protein-protein interactions. As a nuclear receptor transcriptional regulator, PRAME has been extensively studied in cancer biology and is believed to play a role in cancer cell proliferation by suppressing retinoic acid (RA) signaling. The role of the PRAME gene family in germline development and spermatogenesis has been recently confirmed by a gene knockout approach. To further understand how PRAME proteins are involved in germ cell development at a subcellular level, we have conducted a systematic immunogold electron microscopy (IEM) analysis on testis sections of adult mice with gene-specific antibodies from two members of the mouse Prame gene family: Pramel1 and Pramex1. Pramel1 is autosomal, while Pramex1 is X-linked, both genes are exclusively expressed in the testis.

Results: Our IEM data revealed that both PRAMEL1 and PRAMEX1 proteins were localized in various cell organelles in different development stages of spermatogenic cells, including the nucleus, rER, Golgi, mitochondria, germ granules [intermitochondrial cement (IMC) and chromatoid body (CB)], centrioles, manchette, and flagellum. Unlike other germ cell-specific makers, such as DDX4, whose proteins are evenly distributed in the expressed-organelle(s), both PRAMEL1 and PRAMEX1 proteins tend to aggregate together to form clusters of protein complexes. These complexes were highly enriched in the nucleus and cytoplasm (especially in germ granules) of spermatocytes and spermatids. Furthermore, dynamic distribution of the PRAMEL1 protein complexes were observed in the microtubule-based organelles, such as acroplaxome, manchette, and flagellum, as well as in the nuclear envelope and nuclear pore. Dual staining with PRAMEL1 and KIF17B antibodies further revealed that the PRAMEL1 and KIF17B proteins were co-localized in germ granules.

Conclusion: Our IEM data suggest that the PRAMEL1 and PRAMEX1 proteins are not only involved in transcriptional regulation in the nucleus, but may also participate in nucleocytoplasmic transport, and in the formation and function of germ cell-specific organelles during spermatogenesis.
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http://dx.doi.org/10.1186/s13578-021-00612-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170798PMC
June 2021

Synthetic Iowaite Can Effectively Remove Inorganic Arsenic from Marine Extract.

Molecules 2021 May 20;26(10). Epub 2021 May 20.

College of Pharmacology, Nanjing University of Chinese Medicine, Nanjing 210023, China.

For the removal of arsenic from marine products, iowaite was prepared and investigated to determine the optimal adsorption process of arsenic. Different chemical forms of arsenic (As(III), As(V)) with varying concentrations (0.15, 1.5, 5, 10, 15, and 20 mg/L) under various conditions including pH (3, 5, 7, 9, 11) and contact time (1, 2, 5, 10, 15, 30, 60, 120, 180 min) were exposed to iowaite. Adsorption isotherms and metal ions kinetic modeling onto the adsorbent were determined based on Langmuir, Freundlich, first- and second-order kinetic models. The adsorption onto iowaite varied depending on the conditions. The adsorption rates of standard solution, As(III) and As(V) exceeded 95% under proper conditions, while high complexity was noted with marine samples. As(III) and As(V) from extraction all decreased when exposed to iowaite. The inclusion morphology and interconversion of organic arsenic limit adsorption. Iowaite can be efficiently used for inorganic arsenic removal from wastewater and different marine food products, which maybe other adsorbent or further performance of iowaite needs to be investigated for organic arsenic.
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http://dx.doi.org/10.3390/molecules26103052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160602PMC
May 2021

Model-based analysis uncovers mutations altering autophagy selectivity in human cancer.

Nat Commun 2021 05 31;12(1):3258. Epub 2021 May 31.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.
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http://dx.doi.org/10.1038/s41467-021-23539-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166871PMC
May 2021

Exposure to biomass smoke induces pulmonary Th17 cell differentiation by activating TLR2 on dendritic cells in a COPD rat model.

Toxicol Lett 2021 Sep 28;348:28-39. Epub 2021 May 28.

National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China. Electronic address:

Almost three billion people in developing countries are exposed to biomass smoke (BS), which predisposes them to developing chronic obstructive pulmonary disease (COPD). COPD is associated with abnormal innate and adaptive immune responses in the lungs and systemic circulation, but the mechanisms underlying BS-COPD development are uncertain. We investigated the role of dendritic cells (DCs) and interleukin (IL)-17A in BS-COPD. We investigated T helper cell responses in the BS-exposed COPD rat model by flow cytometry, quantitative PCR, and enzyme-linked immunosorbent assays. We conducted ex vivo experiments to determine which antigen-presenting cells induce Th17 cell responses. We evaluated the in vitro effects of BS-related particulate matter (BRPM) (2.5 μm) on the function of bone marrow-derived dendritic cells (BMDCs). We found that BS exposure enhanced Th17 responses in the lungs of the COPD-modelled rats, and the stimulated DCs (but not the macrophages) were sufficient to induce naïve CD4 + T cells to produce IL-17A in ex vivo experiments. BRPM significantly enhanced the maturation and activation of DCs through Toll-like receptor 2 (TLR2), but not TLR4, and induced Th17 responses. Therefore, BS activated lung DCs through TLR2, which led to Th17 responses and emphysema in the rats. This process is possibly therapeutically targetable.
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http://dx.doi.org/10.1016/j.toxlet.2021.05.010DOI Listing
September 2021

Loading Gentamicin and Zn on TiO Nanotubes to Improve Anticoagulation, Endothelial Cell Growth, and Antibacterial Activities.

Stem Cells Int 2021 3;2021:9993247. Epub 2021 May 3.

Faculty of Mechanical and Material Engineering, Huaiyin Institute of Technology, Huai'an 223003, China.

Titanium and its alloys are widely used in blood-contacting implantable and interventional medical devices; however, their biocompatibility is still facing great challenges. In the present study, in order to improve the biocompatibility and antibacterial activities of titanium, TiO nanotubes were firstly in situ prepared on the titanium surface by anodization, followed by the introduction of polyacrylic acid (PAA) and gentamicin (GS) on the nanotube surface by layer-by-layer assembly, and finally, zinc ions were loaded on the surface to further improve the bioactivities. The nanotubes displayed excellent hydrophilicity and special nanotube-like structure, which can selectively promote the albumin adsorption, enhance the blood compatibility, and promote the growth of endothelial cells to some degree. After the introduction of PAA and GS, although the superhydrophilicity cannot be achieved, the results of platelet adhesion, cyclic guanosine monophosphate (cGMP) activity, hemolysis rate, and activated partial thromboplastin time (APTT) showed that the blood compatibility was improved, and the blood compatibility was further enhanced after zinc ion loading. On the other hand, the modified surface showed good cytocompatibility to endothelial cells. The introduction of PAA and zinc ions not only promoted the adhesion and proliferation of endothelial cells but also upregulated expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO). The slow and continuous release of GS and Zn over 14 days can significantly improve the antibacterial properties. Therefore, the present study provides an effective method for the surface modification of titanium-based blood-contacting materials to simultaneously endow with good blood compatibility, endothelial growth behaviors, and antibacterial properties.
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http://dx.doi.org/10.1155/2021/9993247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112940PMC
May 2021

Mesenchymal Stem Cells in Preclinical Infertility Cytotherapy: A Retrospective Review.

Stem Cells Int 2021 17;2021:8882368. Epub 2021 May 17.

First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.

Infertility is a global reproductive disorder which is caused by a variety of complex diseases. Infertility affects the individual, family, and community through physical, psychological, social and economic consequences. The results from recent preclinical studies regarding stem cell-based therapies are promising. Stem cell-based therapies cast a new hope for infertility treatment as a replacement or regeneration strategy. The main features and application prospects of mesenchymal stem cells in the future of infertility should be understood by clinicians. Mesenchymal stem cells (MSCs) are multipotent stem cells with abundant source, active proliferation, and multidirectional differentiation potential. MSCs play a role through cell homing, secretion of active factors, and participation in immune regulation. Another advantage is that, compared with embryonic stem cells, there are fewer ethical factors involved in the application of MSCs. However, a number of questions remain to be answered prior to safe and effective clinical application. In this review, we summarized the recent status of MSCs in the application of the diseases related to or may cause to infertility and suggest a possible direction for future cytotherapy to infertility.
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http://dx.doi.org/10.1155/2021/8882368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143877PMC
May 2021

Pre-supplementary motor network connectivity and clinical outcome of magnetic stimulation in obsessive-compulsive disorder.

Hum Brain Mapp 2021 May 29. Epub 2021 May 29.

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, The School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China.

A large proportion of patients with obsessive-compulsive disorder (OCD) respond unsatisfactorily to pharmacological and psychological treatments. An alternative novel treatment for these patients is repetitive transcranial magnetic stimulation (rTMS). This study aimed to investigate the underlying neural mechanism of rTMS treatment in OCD patients. A total of 37 patients with OCD were randomized to receive real or sham 1-Hz rTMS (14 days, 30 min/day) over the right pre-supplementary motor area (preSMA). Resting-state functional magnetic resonance imaging data were collected before and after rTMS treatment. The individualized target was defined by a personalized functional connectivity map of the subthalamic nucleus. After treatment, patients in the real group showed a better improvement in the Yale-Brown Obsessive Compulsive Scale than the sham group (F  = 6.0, p = .019). To show the neural mechanism involved, we identified an "ideal target connectivity" before treatment. Leave-one-out cross-validation indicated that this connectivity pattern can significantly predict patients' symptom improvements (r = .60, p = .009). After real treatment, the average connectivity strength of the target network significantly decreased in the real but not in the sham group. This network-level change was cross-validated in three independent datasets. Altogether, these findings suggest that personalized magnetic stimulation on preSMA may alleviate obsessive-compulsive symptoms by decreasing the connectivity strength of the target network.
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http://dx.doi.org/10.1002/hbm.25468DOI Listing
May 2021

PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway.

Cell Death Dis 2021 May 28;12(6):552. Epub 2021 May 28.

Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, China.

Some studies have reported that activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1 is a critical ribosome rarely reported in human tumors. This study aimed to explore the molecular mechanisms of PNO1 in HCC. Using 150 formalin-fixed and paraffin-embedded samples and 8 fresh samples, we found high PNO1 expression in HCC tumor tissues through Western blotting and RT-PCR. Moreover, the higher PNO1 expression was associated with poor HCC prognosis patients. In vitro and in vivo experiments indicated that PNO1 overexpression promoted the proliferation and depressed the apoptosis of HCC cells. High PNO1 expression also increased the autophagy of HCC cells. The molecular mechanisms underlying PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results showed that PNO1 promoted HCC progression through the MAPK signaling pathway. Therefore, PNO1 was overexpressed in HCC, promoted autophagy, and inhibited the apoptosis of HCC cells through the MAPK signaling pathway.
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http://dx.doi.org/10.1038/s41419-021-03837-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163843PMC
May 2021

Addressing People's Vaccine Hesitancy Will Be Helpful for COVID-19 Vaccination in China.

Asia Pac J Public Health 2021 May 28:10105395211018175. Epub 2021 May 28.

Peking University, Beijing, China.

The latest news about global vaccine research and development shows that we have made great progress in vaccine development. However, in China, a large population of people are hesitant to get vaccinated due to various reasons. In this article, we focus on how to address people's hesitancy on the coronavirus disease 2019 (COVID-19) vaccine. It is important that governments fully prepare for both pre-risk prevention and post-event relief to promote the vaccination program's smooth implementation. In particular, the government should establish and improve a national vaccine injury compensation program in response to COVID-19's adverse events following immunization. Only through multilateral efforts and comprehensive measures can the people's confidence in vaccination improve and their worries about the future be relatively eased.
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http://dx.doi.org/10.1177/10105395211018175DOI Listing
May 2021

Trends in the clinical features of amyotrophic lateral sclerosis: A 14-year Chinese cohort study.

Eur J Neurol 2021 May 28. Epub 2021 May 28.

Department of Neurology, Peking University Third Hospital, Haidian District, 49 North Garden Road, Beijing, 100191, China.

Objectives: To determine the transitional patterns in the clinical characteristics, treatments and comorbidities in amyotrophic lateral sclerosis (ALS) patients over the past 14 years using data from a large clinical cohort in mainland China.

Methods: Sporadic ALS patients who visited the Peking University Third Hospital from January 2005 to December 2018 were included in this study. The 14 years were divided into three periods, and changes in the baseline characteristics of the participants were analyzed at 5-year intervals.

Results: In total, 3 410 patients with sporadic ALS were recruited: 2 181 were male, and 1 229 were female. The proportion of patients with bulbar-onset ALS increased from 13.0% in 2005-2009 to 19.5% in 2015-2018 (P <0.001). The mean [standard deviation (SD)] age at onset increased from 49.5 (11.4) years in 2005-2009 to 53.0 (11.0) years in 2015-2018 (P <0.001). ALS patients with diabetes or hypertension showed a delay in ALS onset, and the delay was even more apparent when the patients had both comorbidities. The proportion of riluzole users increased approximately 2.5-fold from 2005-2009 to 2015-2018 (P <0.001).

Conclusions: In the context of the lack of clinical data on ALS in mainland China, this study evaluated a large cohort of patients diagnosed over a 14-year period. The age at onset and percentage of patients who used riluzole both increased over the study period. Additionally, we found that patients with comorbidities such as diabetes and hypertension had a delayed age at ALS onset.
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http://dx.doi.org/10.1111/ene.14943DOI Listing
May 2021

Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ-UCP2 cascade.

FASEB J 2021 Jun;35(6):e21555

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Preeclampsia (PE) is a life-threatening disease of pregnant women associated with severe hypertension, proteinuria, or multi-organ injuries. Mitochondrial-mediated placental oxidative stress plays a key role in the pathogenesis of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, regulating placental mitochondrial reactive oxygen species (ROS). We showed that Rnd3 is down-regulated in primary trophoblasts isolated from PE patients. Loss of Rnd3 in trophoblasts resulted in excessive ROS generation, cell apoptosis, mitochondrial injury, and proton leakage from the respiratory chain. Moreover, Rnd3 overexpression partially rescues the mitochondrial defects and oxidative stress in human PE primary trophoblasts. Rnd3 physically interacts with the peroxisome proliferators-activated receptor γ (PPARγ) and promotes the PPARγ-mitochondrial uncoupling protein 2 (UCP2) cascade. Forced expression of PPARγ rescues deficiency of Rnd3-mediated mitochondrial dysfunction. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPARγ-UCP2 signaling and highlight that downregulation of Rnd3 is a potential factor involved in PE pathogenesis.
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http://dx.doi.org/10.1096/fj.202002639RRRDOI Listing
June 2021