Publications by authors named "Xiaofeng Li"

642 Publications

Association between vitamin D receptor polymorphisms and acute pancreatitis: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 Apr;100(16):e25508

Department of Emergency.

Background: Several studies have been performed to investigate the association between vitamin D receptor (VDR) gene polymorphism and acute pancreatitis, but the results are inconclusive. We conducted this meta-analysis for a precise estimation of the association between BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570) polymorphisms and acute pancreatitis.

Methods: Appropriate studies were retrieved by searching Web of Science, PubMed, Scopus, and Google scholar databases, until January 31, 2021. Two reviewers independently conducted data extraction and literature quality evaluation. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association.All of the data were analyzed with Stata 16.0.

Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusions: This meta-analysis will summarize the association between BsmI, ApaI, TaqI, and FokI polymorphisms and the risk of acute pancreatitis.

Ethics And Dissemination: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.

Osf Registration Number: DOI 10.17605/OSF.IO/83W7R.
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http://dx.doi.org/10.1097/MD.0000000000025508DOI Listing
April 2021

The association between interleukin-8 gene-251 A/T polymorphism and sepsis: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 Apr;100(15):e25483

Department of Emergency, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China.

Background: Emerging evidence has indicated that interleukin-8 (IL-8) gene-251A/T polymorphism may affect individual susceptibility to sepsis. However, the results of published studies are inconclusive. The aim of this meta-analysis was to elucidate the association between this polymorphism and the risk and mortality of sepsis.

Methods: Relevant publications were searched from PubMed, EmBase, and Web of Science databases up to January 31, 2021, with studies only in English. The reference lists of the retrieved studies were investigated as well. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to figure out the relationship between IL-8-251 A/T polymorphisms and the risk and mortality of sepsis. All of the data were analyzed with Stata 16.0.

Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusion: This meta-analysis will summarize the relationship between IL-8-251 A/T polymorphism and the risk and mortality of sepsis.
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http://dx.doi.org/10.1097/MD.0000000000025483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052005PMC
April 2021

Inhibition of lung cancer by vitamin D depends on downregulation of histidine-rich calcium-binding protein.

J Adv Res 2021 Mar 27;29:13-22. Epub 2020 Aug 27.

Department of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Introduction: Intrinsic vitamin D affects the proliferation, apoptosis, invasion, metastasis, and tumorigenesis of lung cancer by regulating tumor signaling pathways. Histidine-rich calcium-binding protein (HRC) maintains Ca homeostasis, which plays crucial roles in the occurrence and development of cancer.

Objectives: Our study aims to investigate the ability of vitamin D in the regulation of HRC and the role of HRC playing in lung cancer.

Methods: We investigated the effects of vitamin D on lung cancer and the underlying mechanisms, by measuring HRC and vitamin D receptor (VDR) expression in lung cancer, paracancer, and normal tissues from patients using immunohistochemistry, western blotting, and real time RT-PCR. We transfected H460 lung cancer cells (supplemented or not with vitamin D) with PX458-HRC and pcDNA3.1-HRC plasmids and injected mice with lung cancer cells harboring pcDNA3.1-vector or pcDNA3.1-HRC plasmids.

Results: Vitamin D inhibited HRC expression and H460 cell migration and proliferation, and promoted apoptosis compared with controls. The expression of HRC and VDR was significantly upregulated and downregulated, respectively, in lung cancer versus paracancer or normal tissues. Cell proliferation and migration were reduced, apoptotic cells were more and tumors were smaller in mice treated with vitamin D/cholecalciferol cholesterol emulsion (CCE) than in vitamin D/CCE+HRC mice.

Conclusion: Vitamin D inhibited lung cancer tumor growth, migration, and proliferation by downregulating HRC.
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http://dx.doi.org/10.1016/j.jare.2020.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020154PMC
March 2021

Frontiers of Autoantibodies in Autoimmune Disorders: Crosstalk Between Tfh/Tfr and Regulatory B Cells.

Front Immunol 2021 26;12:641013. Epub 2021 Mar 26.

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Balance of Tfh/Tfr cell is critically important for the maintenance of immune tolerance, as evidenced by the fact that T follicular helper (Tfh) cells are central to the autoantibodies generation through providing necessary help for germinal center (GC) B cells, whereas T follicular regulatory (Tfr) cells significantly inhibit autoimmune inflammation process through restraining Tfh cell responses. However, signals underlying the regulation of Tfh and Tfr cells are largely undefined. Regulatory B cells (Bregs) is a heterogeneous subpopulation of B cells with immunosuppressive function. Considerable advances have been made in their functions to produce anti-inflammatory cytokines and to regulate Th17, Th1, and Treg cells in autoimmune diseases. The recent identification of their correlations with dysregulated Tfr/Tfh cells and autoantibody production makes Bregs an important checkpoint in GC response. Bregs exert profound impacts on the differentiation, function, and distribution of Tfh and Tfr cells in the immune microenvironment. Thus, unraveling mechanistic information on Tfh-Breg and Tfr-Breg interactions will inspire novel implications for the establishment of homeostasis and prevention of autoantibodies in diverse diseases. This review summarizes the dysregulation of Tfh/Tfr cells in autoimmune diseases with a focus on the emerging role of Bregs in regulating the balance between Tfh and Tfr cells. The previously unsuspected crosstalk between Bregs and Tfh/Tfr cells will be beneficial to understand the cellular mechanisms of autoantibody production and evoke a revolution in immunotherapy for autoimmune diseases.
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http://dx.doi.org/10.3389/fimmu.2021.641013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033031PMC
March 2021

Antityrosinase Mechanism and Antimelanogenic Effect of Arbutin Esters Synthesis Catalyzed by Whole-Cell Biocatalyst.

J Agric Food Chem 2021 Apr 6;69(14):4243-4252. Epub 2021 Apr 6.

Department of Spine Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics of Guangdong Province, Guangzhou 510630, China.

Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog values = 0.27-5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 μM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.
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http://dx.doi.org/10.1021/acs.jafc.0c07379DOI Listing
April 2021

Image Analysis of Surface Porosity Mortar Containing Processed Spent Bleaching Earth.

Materials (Basel) 2021 Mar 28;14(7). Epub 2021 Mar 28.

Faculty of Mechanical Engineering and Computer Science, Częstochowa University of Technology, 42-214 Częstochowa, Poland.

Image analysis techniques are gaining popularity in the studies of civil engineering materials. However, the current established image analysis methods often require advanced machinery and strict image acquisition procedures which may be challenging in actual construction practices. In this study, we develop a simplified image analysis technique that uses images with only a digital camera and does not have a strict image acquisition regime. Mortar with 10%, 20%, 30%, and 40% pozzolanic material as cement replacement are prepared for the study. The properties of mortar are evaluated with flow table test, compressive strength test, water absorption test, and surface porosity based on the proposed image analysis technique. The experimental results show that mortar specimens with 20% processed spent bleaching earth (PSBE) achieve the highest 28-day compressive strength and lowest water absorption. The quantified image analysis results show accurate representation of mortar quality with 20% PSBE mortar having the lowest porosity. The regression analysis found strong correlations between all experimental data and the compressive strength. Hence, the developed technique is verified to be feasible as supplementary mortar properties for the study of mortar with pozzolanic material.
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http://dx.doi.org/10.3390/ma14071658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037207PMC
March 2021

Composition and exposure characteristics of PM on subway platforms and estimates of exposure reduction by protective masks.

Environ Res 2021 Mar 19;197:111042. Epub 2021 Mar 19.

Department of Building Science, School of Architecture, Tsinghua University, Beijing, 100084, China.

There is limited information on exposure to metallic constituents of fine particulate matter in subway stations. We characterized the concentrations and composition of airborne fine particulate pollution on six subway platforms in Nanjing, China in both summer and winter of 2019. A microenvironment exposure model was used to evaluate the concentrations of elements in fine particulate matter and the contribution of exposure duration (time spent in the subway station) to overall daily exposure of subway workers and commuters with and without the use of N95 respirators, surgical masks, and cotton masks. We found that airborne fine particulate pollution on station platforms was much higher than in an urban reference site of ambient air, and the same was true for metallic constituents of the particles, such as iron, copper, manganese, strontium, and vanadium. Subway workers were exposed to higher levels of these airborne metals than commuters. The average daily exposure concentration of fine particulate matter was 73.5 μg/m for subway workers and 61.8 μg/m for commuters, while the average daily exposure to iron was 15.5 μg/m for subway workers and 2.0 μg/m for commuters. Subway workers were exposed to iron, copper, manganese, and strontium/vanadium at levels approximately eight-fold, four-fold, three-fold, and two-fold greater than the exposure sustained by commuters, respectively. We calculated that wearing N95 respirators or surgical masks can reduce the exposure to these airborne metallic particles significantly for both subway workers and commuters. Overall, we estimate that personal exposure to airborne fine particulate matter on subway platforms can be reduced through the use of N95 respirators or properly fitting masks.
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http://dx.doi.org/10.1016/j.envres.2021.111042DOI Listing
March 2021

Immune-related genes of the larval Holotrichia parallela in response to entomopathogenic nematodes Heterorhabditis beicherriana LF.

BMC Genomics 2021 Mar 17;22(1):192. Epub 2021 Mar 17.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Yuanmingyuan West Road, Beijing, 100193, China.

Background: Entomopathogenic nematodes (EPNs) emerge as compatible alternatives to conventional insecticides in controlling Holotrichia parallela larvae (Coleoptera: Scarabaeidae). However, the immune responses of H. parallela against EPNs infection remain unclear.

Results: In present research, RNA-Seq was firstly performed. A total of 89,427 and 85,741 unigenes were achieved from the midgut of H. parallela larvae treated with Heterorhabditis beicherriana LF for 24 and 72 h, respectively; 2545 and 3156 unigenes were differentially regulated, respectively. Among those differentially expressed genes (DEGs), 74 were identified potentially related to the immune response. Notably, some immune-related genes, such as peptidoglycan recognition protein SC1 (PGRP-SC1), pro-phenoloxidase activating enzyme-I (PPAE-I) and glutathione s-transferase (GST), were induced at both treatment points. Bioinformatics analysis showed that PGRP-SC1, PPAE-I and GST were all involved in anti-parasitic immune process. Quantitative real-time PCR (qRT-PCR) results showed that the three immune-related genes were expressed in all developmental stages; PGRP-SC1 and PPAE-I had higher expressions in midgut and fat body, respectively, while GST exhibited high expression in both of them. Moreover, in vivo silencing of them resulted in increased susceptibility of H. parallela larvae to H. beicherriana LF.

Conclusion: These results suggest that H. parallela PGRP-SC1, PPAE-I and GST are involved in the immune responses to resist H. beicherriana LF infection. This study provides the first comprehensive transcriptome resource of H. parallela exposure to nematode challenge that will help to support further comparative studies on host-EPN interactions.
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http://dx.doi.org/10.1186/s12864-021-07506-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967997PMC
March 2021

Primary empty sella: The risk factors and associations with the cerebral small vessel diseases-An observational study.

Clin Neurol Neurosurg 2021 Apr 5;203:106586. Epub 2021 Mar 5.

Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, China. Electronic address:

Objective: To investigate the risk factors of primary empty sella (PES) and its associations with cerebral small vessel diseases (CSVD).

Methods: A total of 132 consecutive patients were recruited from Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University from December 2018 to January 2020, including 69 cases of PES, and age, gender-matched 63 subjects without PES. Demographics and clinical characteristics were recorded. Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH), which are image markers for CSVD, were assessed. Univariate logistic regression models and multivariate logistic regression models were performed to predict the independent risk factors of PES.

Results: There was a significant difference in baseline characteristics in terms of hypertension (p < 0.001) and pregnancy (p = 0.019) between PES and the control group; among markers of CSVD, whole WMH (p = 0.030) and periventricular hyperintensities (PVH) (p = 0.027) were significantly different; however, no significant differences concerning deep WMH, total PVS, basilar ganglia-PVS and centrum semiovale-PVS (p > 0.05). After adjusting relevant potential confounders, multivariate logistic regression revealed hypertension (OR=3.158, 95 %CI: 1.452∼6.865, p = 0.004) and pregnancy (OR=2.236, 95 %CI: 1.036-4.826, p = 0.040) were independent risk factors for PES.

Conclusion: Hypertension and pregnancy are independent risk factors of PES. There is a possible correlation between PES and WMH, especially PVH, however, further studies are required to confirm these findings.
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http://dx.doi.org/10.1016/j.clineuro.2021.106586DOI Listing
April 2021

A selective NLRP3 inflammasome inhibitor attenuates behavioral deficits and neuroinflammation in a mouse model of Parkinson's disease.

J Neuroimmunol 2021 May 8;354:577543. Epub 2021 Mar 8.

Department of Neurology, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, No. 22-1, Taoyuan Road, China. Electronic address:

Nod-like receptor pyrin containing (NLRP)3 inflammasome-mediated neuroinflammation is involved in the pathology of Parkinson's disease (PD), but the roles of other inflammasomes in PD remain unclear. The NLRP3 inhibitor MCC950 exerts neuroprotective effects in several neurological diseases. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-induced mouse model with or without intraperitoneal MCC950 administration, we assessed whether specifically the NLRP3 inflammasome is activated in the nigrostriatal system and whether MCC950 has therapeutic potential in this PD model. Western blots were used to determine the nigrostriatal expression of inflammasome-specific proteins, including NLRP1, NLRP2, NLRP3, nod-like receptor CARD containing 4 (NLRC4), and absent in melanoma 2 (AIM2). The pole, hanging, and swimming tests were used to assess functional deficits, western blots and immunostainings were used to analyze dopaminergic neuronal degeneration, as well as activation of glial cells and the NLRP3 inflammasome. NLRP3 expression in the nigrostriatal system of MPTP-induced mice was significantly increased compared to control, whereas NLRP1, NLRP2, NLRC4, and AIM2 expression in the nigrostriatal system, as well as NLRP3 expression in the cerebral cortex and hippocampus, were similar in the two groups. Furthermore, MPTP-induced mice exhibited behavioral dysfunctions, dopaminergic neuronal degeneration, and activation of glial cells and the NLRP3 inflammasome. MCC950 treatment of MPTP-induced mice improved behavioral dysfunctions, reduced dopaminergic neuronal degeneration, and inhibited the activation of glial cells and the NLRP3 inflammasome. In conclusion, these findings indicated that NLRP3, not NLRP1, NLRP2, NLRC4, and AIM2, may be the key inflammasome that promotes MPTP-induced pathogenesis. MCC950 protects against MPTP-induced nigrostriatal damage and may be a novel promising therapeutic approach in treating MPTP-induced PD.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577543DOI Listing
May 2021

Correlation between uniocular deviation and duction changes following different decompression surgeries in thyroid eye disease.

BMC Ophthalmol 2021 Mar 12;21(1):134. Epub 2021 Mar 12.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Background: Postoperative ocular imbalance is an important problem for orbital decompression surgery in thyroid eye disease (TED). The aim of this study was to evaluate the changes in unilateral ocular deviation and duction following orbital decompression and discuss the biomechanics of ocular imbalance.

Methods: Fifty-four TED patients who underwent unilateral orbital decompression were included. Fifteen patients underwent 1-wall (deep lateral wall) decompression, 18 patients underwent 2-wall (deep lateral and medial wall) decompression and 21 patients underwent 3-wall (deep lateral, medial and inferior wall) decompression. Objective and subjective deviation of the operated eyes were evaluated using the prism test and synoptophore, respectively. Ocular ductions were measured using Hirschberg's method. The diameters of the extraocular rectus were measured by computed tomography.

Results: Ocular deviation and duction showed no significant difference after 1-wall decompression (p = 0.25-0.89). Esotropia increased after 2-wall decompression (p = 0.001-0.02), and hypotropia increased after 3-wall decompression (p = 0.02). Adduction increased but abduction decreased following 2-wall and 3-wall decompression (p < 0.05). Infraduction increased following 3-wall decompression (p < 0.001). Additionally, the increase in esotropia was significantly correlated with the increase in adduction and with the decrease in abduction (r = 0.37-0.63, p < 0.05). There were significant correlations between the diameter of the medial rectus and the increase in esotropia, the increase in adduction and the decrease in abduction postoperatively (r = 0.35-0.48, p < 0.05).

Conclusions: The changes in ocular deviation and duction were different after 1-wall, 2-wall and 3-wall orbital decompression. The increased contractile force of the rectus may be an important reason for strabismus changes after orbital decompression surgery.
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http://dx.doi.org/10.1186/s12886-021-01892-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955663PMC
March 2021

PCTR1 Enhances Repair and Bacterial Clearance in Skin Wounds.

Am J Pathol 2021 Mar 6. Epub 2021 Mar 6.

Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

Tissue injury elicits an inflammatory response that facilitates host defense. Resolution of inflammation promotes the transition to tissue repair and is governed in part by specialized pro-resolving mediators (SPM). The complete structures of a novel series of cysteinyl-SPM (cys-SPM) were recently elucidated, and they proved to stimulate tissue regeneration in planaria and resolve acute inflammation in mice. Their functions in mammalian tissue repair are of interest. Here, the authors screened nine structurally distinct cys-SPM and found that PCTR1 uniquely enhances human keratinocyte migration with efficacy similar to epidermal growth factor. In skin wounds of mice, PCTR1 accelerated closure. Wound infection increased PCTR1 that coincided with decreased bacterial burden. Addition of PCTR1 reduced wound bacteria levels and decreased inflammatory monocytes/macrophages, which was coupled with increased expression of genes involved in host defense and tissue repair. These results suggest that PCTR1 is a novel regulator of host defense and tissue repair, which could inform new approaches for therapeutic management of delayed tissue repair and infection.
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http://dx.doi.org/10.1016/j.ajpath.2021.02.015DOI Listing
March 2021

CTCF-silenced miR-137 contributes to EMT and radioresistance in esophageal squamous cell carcinoma.

Cancer Cell Int 2021 Mar 8;21(1):155. Epub 2021 Mar 8.

Department of Radiation Oncology, Xuzhou Cancer Hospital, No. 131, Huancheng Road, Gulou District, Xuzhou, 221005, Jiangsu, China.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system. MicroRNAs (miRNAs) have been reported to be implicated in cancer development. However, the role of miR-137 has not been fully revealed in ESCC.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were separately used to examine RNA level and protein level. 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assays and flow cytometry analyses were conducted to assess biological behaviors of ESCC cells. Additionally, the interaction between genes were analyzed via Chromatin Immunoprecipitation (ChIP) assay, RNA Binding Protein Immunoprecipitation (RIP) assay, RNA pull down assay and luciferase reporter assay.

Results: MiR-137 was down-regulated in ESCC cells. Upregulation of miR-137 hindered ESCC cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT). Besides, miR-137 enhanced the sensitivity of ESCC cells to irradiation. Moreover, CCCTC-binding factor (CTCF) inactivated miR-137 transcription in ESCC cells. Furthermore, we revealed enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and paxillin (PXN) as the downstream targets of miR-137. In turn, EZH2 was recruited by CTCF and induced methylation in miR-137 promoter.

Conclusion: CTCF/Suz12/EZH2 complex-silenced miR-137 facilitates ESCC progression and radioresistance by targeting EZH2 and PXN.
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http://dx.doi.org/10.1186/s12935-020-01740-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938596PMC
March 2021

Kommerell diverticulum, vascular ring, and aberrant left subclavian artery: LSCA translocation or Aortopexy.

J Pediatr Surg 2021 Feb 12. Epub 2021 Feb 12.

Department of Cardiovascular Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address:

Background/purpose: Kommerell diverticulum (KD) in children with right aortic arch and aberrant left subclavian artery can be treated surgically via left subclavian artery (LSCA) translocation or aortopexy. These procedures remain controversial. We compared the outcomes of both procedures.

Methods: This retrospective study included 48 patients who underwent LSCA translocation (n = 26) or aortopexy (n = 22). Lateral thoracotomy and sternotomy were performed in 38 and 10 patients with severe intracardiac malformations, respectively.

Results: The median age of the aortopexy group was 10 months, median follow-up was 14 months, and mean length of hospitalization was 11.41 ± 6.8 days. The median age of the LSCA translocation group was 12 months, median follow-up was 22 months, and mean length of hospitalization was 14.96 ± 7.74 days. Two patients (LSCA translocation group) required secondary intubations and none suffered from recurrent laryngeal nerve injury or complications related to LSCA translocation. Breathing and swallowing symptoms were relieved in all patients. No additional thoracotomies due to respiratory symptoms were required.

Conclusions: These two procedures relieve the pressure on the trachea and esophagus with similar short-term outcomes. The long-term outcomes are unknown. LSCA translocation may be the best strategy to prevent symptom recurrence and late complications in these patients.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.02.009DOI Listing
February 2021

LSD1-mediated stabilization of SEPT6 protein activates the TGF-β1 pathway and regulates non-small-cell lung cancer metastasis.

Cancer Gene Ther 2021 Mar 4. Epub 2021 Mar 4.

Department of Oncology, Quanzhou First Hospital Affiliated Fujian Medical University, Quanzhou, P.R. China.

Non-small cell lung cancer (NSCLC) is a prevalent cancer with unfavorable prognosis. Over the past decade accumulating studies have reported an involvement of lysine-specific histone demethylase 1 (LSD1) in NSCLC development. Here, we aimed to explore whether LSD1 affects the metastasis of NSCLC by mediating Septin 6 (SEPT6) through the TGF-β1 pathway. RT-qPCR was used to determine LSD1 and SEPT6 expression in NSCLC tissues and cells. Interactions between LSD1, SEPT6, and TGF-β1 were detected using lentivirus-mediated silencing of LSD1 and overexpression of SEPT6. The role of LSD1 and SEPT6 in mediating the biological behavior of NSCLC cells was determined using the EdU proliferation assay, Transwell assay, and flow cytometry. Thereafter, transplanted cell tumors into nude mice were used to explore the in vivo effects of LSD1 and SEPT6 on metastasis of NSCLC. LSD1 and SEPT6 were overexpressed in NSCLC tissue and cell samples. LSD1 could demethylate the promoter of the SEPT6 to positively regulate SEPT6 expression. LSD1 promoted proliferation, migration, and invasion, while suppressing the apoptosis of NSCLC cells by increasing SEPT6 expression. LSD1-mediated SEPT6 accelerated in vivo NSCLC metastasis through the TGF-β1/Smad pathway. Collectively, LSD1 demethylates SEPT6 promoter to upregulate SEPT6, which activates TGF-β1 pathway, thereby promoting metastasis of NSCLC.
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http://dx.doi.org/10.1038/s41417-021-00297-6DOI Listing
March 2021

The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta-analysis.

J Obstet Gynaecol Res 2021 Mar 1. Epub 2021 Mar 1.

Reproductive Medicine Center, Lanzhou University Second Hospital, Lanzhou City, P.R. China.

Purpose: Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients. However, previous studies have found that the effect of metformin on the level of homocysteine were not consistent in PCOS patients. The aim of this review was to analyze the effect of metformin on homocysteine levels in patients with PCOS patients.

Methods: The Cochrane Library, Pubmed, and Web of Science were searched according to predefined search terms. There is no restriction for publication time and language.

Results: Eleven studies were included and the data were extracted. The homocysteine level in PCOS patients was significantly increased after taking metformin (mean difference [MD] -1.33; 95% confidence interval [CI] -2.16 to -0.49, p = 0.002). Subgroup analysis showed that the level of homocysteine was generally increased in PCOS patients with body mass index (BMI) ≥25 after taking metformin alone (MD -1.82; 95% CI -2.56 to -1.07, p < 0.00001). There was no significant change in homocysteine level in PCOS patients with BMI <25 (MD 0.69; 95% CI -0.41 to 1.79, p = 0.22). Subgroup analysis showed that there was no significant difference when taking metformin >3 months or taking metformin ≤3 months (p = 0.84). Taking metformin ≥1700 mg/days significantly increased homocysteine levels in PCOS patients (MD -2.05; 95% CI -2.40 to -1.70, p < 0.00001). When taking metformin <1700 mg/days, there was no significant difference in homocysteine level in PCOS patients (MD 0.15; 95% CI -1.06 to 1.37, p = 0.80). The difference between the two subgroups was significant (p = 0.0006). There was no significant difference in vitamin B12 level before and after metformin treatment (MD 24.70; 95% CI -22.54 to 71.93, p = 0.31). There was a decrease in serum folic acid level after metformin administration (MD 1.03; 95% CI 0.80 to 1.26, p < 0.00001).

Conclusion: Taking metformin alone increased homocysteine levels and decreased folic acid levels in nonpregnant PCOS patients. And, it was suggested that the dosage of metformin should be less than 1700 mg/days. The supplement of folic acid and B vitamins during metformin administration may be essential in nonpregnant PCOS patients. We should pay much attention to the potential effect of metformin in PCOS patients.
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http://dx.doi.org/10.1111/jog.14725DOI Listing
March 2021

Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes.

Philos Trans A Math Phys Eng Sci 2021 Apr 1;379(2195):20190542. Epub 2021 Mar 1.

School of Engineering, Newcastle University, Newcastle upon Tyne, UK.

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius-Clapeyron (CC) rate (6-7% K), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.
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http://dx.doi.org/10.1098/rsta.2019.0542DOI Listing
April 2021

The changes of retinal nerve fibre layer and ganglion cell layer with different severity of thyroid eye disease.

Eye (Lond) 2021 Feb 26. Epub 2021 Feb 26.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Objectives: To evaluate the changes of retinal nerve fibre layer (RNFL) and ganglion cell layer/inner plexiform layer (GCL/IPL) with the severity of thyroid eye disease (TED).

Methods: One hundred and forty-five eyes of 75 patients with TED and 70 eyes of 35 healthy controls were included. The eyes with TED were divided into mild group (35 eyes), moderate-to-severe group (42 eyes) and DON group (68 eyes). The thickness of RNFL and GCL/IPL were measured by optic coherence tomography (OCT). Clinical activity score (CAS), best corrected visual acuity (BCVA), intraocular pressure (IOP), proptosis and mean deviation (MD) by Humphrey perimetry were assessed.

Results: The CAS had significant difference between the three groups (p < 0.001). The proptosis and IOP were significantly higher in DON group and moderate-to-severe group than mild group (p < 0.05). The MD and BCVA were significantly worse in DON group compared with mild group and moderate-to-severe group (p < 0.001). The mean GCL/IPL thickness was thinnest in DON group (p < 0.001). The mean RNFL thickness had significant difference between moderate-to-severe group and DON group (p = 0.036). The mean GCL/IPL thickness had a significant correlation with MD (r = 0.449, p < 0.001) and VA (r = -0.388, p < 0.001), whereas the mean RNFL thickness had no significant correlation with MD (p = 0.082) or VA (p = 0.226).

Conclusions: Subclinical optic neuropathy might progress in the patients with moderate-to-severe TED. OCT measurements of GCL/IPL and RNFL are useful to detect the early changes of optic nerve. The thinning of GCL/IPL might be a strong suggestion for closer vision follow-up and earlier decompression surgery.
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http://dx.doi.org/10.1038/s41433-021-01453-wDOI Listing
February 2021

Experiences of healthcare providers during the coronavirus pandemic and its impact on them: protocol for a mixed-methods systematic review.

BMJ Open 2021 02 26;11(2):e043686. Epub 2021 Feb 26.

Health Science Center, Xi'an Jiaotong University, Xi'an, China.

Introduction: Frontline healthcare providers are redeployed to areas outside their clinical expertise and assigned high-loading workload to address the surge of patients with each coronavirus outbreak. Their importance in crisis is not in doubt. However, they experienced considerable physical distress and psychological stressors, even leading to psychological illness and infection in this environment. There is an urgent need to accurately, comprehensively and objectively understand their experiences, perceptions and current situation of burnout, post-traumatic stress disorder (PTSD), anxiety, depression, insomnia and coronavirus infection. Therefore, this protocol is to conduct a mixed-methods systematic review to summarise the evidence on the experiences of healthcare providers and impacts of the coronavirus on their psychological status and infection during the pandemics.

Methods: Published studies on experience, perspective, impact, burnout, PTSD, anxiety, depression, insomnia, and infection of healthcare providers with SARS, Middle East respiratory syndrome and COVID-19, and written in English and Chinese will be accepted. Databases (MEDLINE, EMBASE, CENTRAL, Web of Science, PubMed, Psychology Information, WanFang and SinoMed) from inception until 30 July 2020 will be searched. Two reviewers will select, screen, extract data and assess the risk of bias independently. Risk of bias of results will be using the Mixed-Methods Appraisal Tool. Using a convergent integrated approach on qualitative/quantitative studies, we will synthesise qualitative and quantitative data separately. The incidence and number of cases about burnout, PTSD, anxiety, depression, insomnia and coronavirus infection among medical staff will be extracted. Then we will transform quantitative data to synthesise narrative findings. This protocol will be reported per the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines.

Ethics And Dissemination: Ethical assessment is not required due to the nature of the proposed systematic review. Findings of our research will be disseminated at conferences related to this field and through publication in peer-reviewed journals.

Prospero Registration Number: CRD42020198506.
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http://dx.doi.org/10.1136/bmjopen-2020-043686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918807PMC
February 2021

Organic Solvent-Free Preparation of Chitosan Nanofibers with High Specific Surface Charge and Their Application in Biomaterials.

ACS Appl Mater Interfaces 2021 Mar 24;13(10):12347-12358. Epub 2021 Feb 24.

School of Food Science and Engineering, South China University of Technology, Guangzhou 510644, China.

The application of chitosan nanofibers in biological tissue-engineering materials has attracted wide attention. A novel and organic solvent-free method was developed for the fabrication of rootlike chitosan nanofibers (CSNFs) with diameters of 40-250 nm. This method includes three-step mechanical processing of swelling-beating-centrifugation or swelling-beating-homogenization. The obtained nanofibers showed high yields (>95%) and positive specific surface charges (up to +375 μeq/g) and could be uniformly dispersed in the aqueous phase. The unique fiber shape and the good length-to-diameter ratio of CSNFs endowed chitosan nanofiber paper (CSNFP) products with excellent mechanical properties, and the wet tensile strength of the CSNFPs was nearly five times higher than common chitosan films. In addition, the calvaria-derived preosteoblastic cells exhibited a higher adherence efficiency and proliferation on CSNFP than on chitosan films. The chitosan nanofiber scaffold products also benefited the attachment of preosteoblastic cells and allowed them to grow in three dimensions. This method has significant industrial potential for the industrialization of chitosan nanofibers, which may have broad applications in various biomaterials.
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http://dx.doi.org/10.1021/acsami.0c21796DOI Listing
March 2021

Subchondral Trabecular Microstructure and Articular Cartilage Damage Variations Between Osteoarthritis and Osteoporotic Osteoarthritis: A Cross-sectional Cohort Study.

Front Med (Lausanne) 2021 2;8:617200. Epub 2021 Feb 2.

Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Osteoporotic osteoarthritis (OP-OA) is a specific type of OA. In this study, we aimed to assess the subchondral plate and rod microstructural differences between OA and OP-OA patients by using an individual trabeculae segmentation (ITS) system and to analyze the relationships between subchondral microstructures and cartilage damage in OA and OP-OA patients. Overall, 31 femoral heads were included in this study, which included 11 samples with OA and 13 samples with OP-OA; the normal control (NC) group contained 7 healthy femoral heads. ITS was performed to segment the subchondral trabecular bone into plate and rod trabeculae based on microcomputed tomography (micro-CT) images. We compared the plate and rod trabeculae of the subchondral trabecular bone between OA and OP-OA patients. The Osteoarthritis Research Society International (OARSI) score was employed to evaluate cartilage damage based on histological observations. Pearson's correlation coefficient and linear regression analysis were applied to analyze the relationships between subchondral microstructures and articular cartilage damage. Results showed that several microstructural parameters, including bone volume fraction (BV/TV), plate bone volume fraction (pBV/TV), rod bone volume fraction (rBV/TV), plate trabecular number (pTb.N), rod trabecular number (rTb.N), junction density between rod and plate (R-P Junc.D), and junction density between plate and plate (P-P Junc.D), were significantly decreased in patients with OP-OA compared with those in patients with OA ( < 0.05). Histological observations indicated that cartilage damage was more serious in patients with OP-OA than that in patients with OA ( < 0.05). Moreover, BV/TV, pBV/TV, pTb.N, and pTb.Th were significantly related to the OARSI score in both OA and OP-OA patients. These results indicated that there were differences in the subchondral rod and plate trabeculae between OA and OP-OA patients. Subchondral decreased plate trabeculae (pBV/TV, pTb.N, and pTb.Th) might account for cartilage damage in the progression of OP-OA. This study provided new insights to research OA when it is combined with OP.
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http://dx.doi.org/10.3389/fmed.2021.617200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884461PMC
February 2021

Concentration, composition, and exposure contributions of fine particulate matter on subway concourses in China.

Environ Pollut 2021 Apr 2;275:116627. Epub 2021 Feb 2.

Department of Building Science, School of Architecture, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Indoor Air Quality Evaluation and Control, Tsinghua University, Beijing, 100084, China. Electronic address:

Concentrations of airborne metal-rich particles are typically higher on subway platforms and in subway tunnels than in ambient air. The subway concourse is an area of direct air exchange with both platforms and the outside environment, but few researchers have measured the concentrations and composition of fine particles on subway concourses. We characterized the concentrations and composition of fine particles on six subway concourses in Nanjing, China in both summer and winter. We used a respiration rate-adjusted microenvironment exposure model to estimate the contribution of a 6-h work period to daily mean exposure to fine particulate matter of subway workers and compared the estimate with those for general indoor and outdoor workers. We found that particle concentrations were typically higher on the station concourses than in ambient air. The most abundant elements composing the particles were Fe, S, Ca, Si, and K in both subway concourses and reference ambient air, but their contents varied greatly between indoor and outdoor air. The indoor/outdoor ratios of Fe, Cu, and Mn were highest, and subway workers were disproportionately exposed to these three metals. The mean daily exposure dose to Fe was 44.8 μg for subway workers, approximately five times the exposure dose of indoor and outdoor workers. Daily exposure doses of Cu, Mn, V, Sr, As, Co, Sn, and Cr were also higher for subway workers. The quality of indoor air at subway stations is therefore of occupational health concern and strategies should be formulated to reduce worker exposure.
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http://dx.doi.org/10.1016/j.envpol.2021.116627DOI Listing
April 2021

Early changes of NLRP3 inflammasome activation after hypoxic-ischemic brain injury in neonatal rats.

Int J Clin Exp Pathol 2021 1;14(2):209-220. Epub 2021 Feb 1.

Children's Neurorehabilitation Laboratory, Shenyang Children's Hospital Shenyang, China.

The pathogenesis of neonatal hypoxic-ischemic (HI) brain injury may involve activation of the NOD-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome and its downstream effectors, caspase-1 and interleukin (IL)-1β. The start time of therapy is associated with adverse neurodevelopmental outcome following HI injury. We performed this study investigating early dynamic changes in NLRP3, caspase-1, and IL-1β expression during the first 24 h following HI brain injury in an animal model, in order to optimize selection of treatment time after injury. Rats were randomized to an HI group (n=40) and sham group (n=40). Rats in the HI group were subjected to right common carotid artery ligation and then exposed to hypoxia (8% O) for 2 h, and divided into 5 subgroups with 8 cases in each group at 5 postoperative time points (0, 4, 8, 12, 24 h). Brain injury during the first 24 h after surgery/hypoxia was evaluated by cranial ultrasonography. RT-PCR, western blot, and immunohistochemistry were applied to determine protein and mRNA expressions. In the HI group, ultrasonography revealed accelerated right vertebrobasilar artery flow at 4 h, enhanced brain parenchyma echogenicity at 24 h, and blood stealing from the vertebrobasilar artery at 24 h. In the HI group, immunohistochemistry demonstrated elevated expressions of NLRP3 and IL-1β at 4, 8, 12, and 24 h and enhanced expression of caspase-1 at 8 and 12 h (all < 0.01). Western blot and RT-PCR revealed that, compared with the sham group, the HI group exhibited elevated expression of NLRP3 at 4, 8, and 24 h, caspase-1 at 12 h, and IL-1β at 8 h (all < 0.05). In summary, the present results suggested that activation of NLRP3/caspase-1/IL-1β signaling occurs within 4 h of HI brain injury in the neonatal rat.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868790PMC
February 2021

MOFs-Derived Fe-N Codoped Carbon Nanoparticles as O-Evolving Reactor and ROS Generator for CDT/PDT/PTT Synergistic Treatment of Tumors.

Bioconjug Chem 2021 Feb 5;32(2):318-327. Epub 2021 Feb 5.

Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy; Tianjin's Clinical Research Center for Cancer,Tianjin 300060, P.R. China.

Metal-organic frameworks (MOFs) derivatives had been widely explored in electronic and environmental fields, but rarely evaluated in the biomedical applications. Herein, Fe-N codoped carbon (FeNC) nanoparticles were synthesized and characterized via facile pyrolysis of precursor ZIF-8 (Fe/Zn) nanoparticles, and their potential applications in tumor therapy were assessed in this investigation both in vitro and in vivo. After PAA (sodium polyacrylate) modification, the FeNC@PAA nanoparticles were able to initiate a Fe-based Fenton-like reaction to generate ·OH and O for chemodynamic therapy (CDT) and O evolution. Meanwhile, the porphyrin-like metal center in the FeNC@PAA nanoparticles could be used as a photosensitizer for photodynamic therapy (PDT) of tumors, which could be enhanced by O generated in CDT. Furthermore, the FeNC@PAA nanoparticles were also found to be effective in photothermal therapy (PTT) with a photothermal conversion efficiency of 29.15%, owing to a high absorbance in the near-infrared region (NIR). In conclusion, the synthesized FeNC@PAA nanoparticles exhibited promising applications in O evolution and CDT/PDT/PTT synergistic treatment of tumors.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00694DOI Listing
February 2021

Safe treatment of congenital left atrial appendage aneurysm using lateral thoracotomy on a 3-year-old patient.

Cardiol Young 2021 Jan 29;31(1):144-147. Epub 2020 Oct 29.

Pediatric Cardiac Center, Beijing Children's Hospital & Capital Medical University, National Center for Children's Health, Beijing, China.

Limited literatures report the management of congenital left atrial appendage aneurysm (LAAA) which is extremely rare. Chest X-ray firstly showed an enlarged left cardiac silhouette for a 3-year-old patient with pneumonia. Echocardiography and magnetic resonance imaging confirmed a large cyst attached to the left atrium. Aneurysmectomy was performed through lateral thoracotomy using step-by-step method and under the guidance of transoesophageal echocardiography. We aim to show the safety and efficacy of this approach applied to children associated with congenital LAAA.
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http://dx.doi.org/10.1017/S1047951120003248DOI Listing
January 2021

Practical Experience of Endoscope Reprocessing and Working-Platform Disinfection in COVID-19 Patients: A Report from Guangdong China during the Pandemic.

Gastroenterol Res Pract 2020 31;2020:9869742. Epub 2020 Dec 31.

Department of Gastroenterology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000 Guangdong, China.

Background: No consensus exists regarding which procedures should be performed to disinfect endoscopes and working platforms after COVID-19 patients have undergone endoscopy.

Methods: We analyzed the disinfection quality of endoscopes and working platforms after 11 COVID-19 patients had undergone endoscopy.

Conclusions: For endoscopic preprocessing at the bedside, a key disinfection step is using a multienzyme stock solution. The nucleic acid tests for endoscopists, washers, endoscopes, and working platforms were all negative. Based on our experience with the 11 COVID-19 patients who had undergone endoscopy, we provide an endoscopic reprocessing method for the bedside endoscopic diagnosis and treatment of COVID-19 patients for reference.
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http://dx.doi.org/10.1155/2020/9869742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790553PMC
December 2020

Effects of site, cerebral perfusion and degree of cerebral artery stenosis on cognitive function.

Neuroreport 2021 02;32(3):252-258

Department of Neurology, The second affiliated hospital of Chongqing Medical University, Chongqing, China.

Objective: To investigate the effects of site, cerebral perfusion and degree of cerebral artery stenosis (CAS) on cognitive function.

Methods: A total of 57 patients with CAS and 53 controls from January 2019 to December 2019 were included. The former group was further divided into different subgroups according to the site, cerebral perfusion and degree of CAS. A series of neuropsychological tests were performed to evaluate the cognitive domains (such as memory, executive function, psychomotor speed, etc.). Rank sum test, t test, Chi-square test and analysis of variance were used for data analysis. Spearman correlation analysis was used to examine the relationship between the site, cerebral perfusion and degree of CAS and all tests' scores.

Results: For patients with CAS who have decreased cerebral perfusion, their global cognitive function, memory, psychomotor speed, executive function and frontal lobe function were significantly impaired (all P < 0.05). There was a significant decrease in global cognitive function, psychomotor speed, memory, executive function and frontal lobe function in patients with anterior circulation stenosis (all P < 0.05). Moderate and severe CAS impaired subjects' global cognitive function, memory, psychomotor speed, executive function and frontal lobe function (all P < 0.05). There was a correlation between the site, cerebral perfusion, the degree of CAS and cognitive function.

Conclusion: Global cognitive function, memory, psychomotor speed, frontal lobe function and executive function are impaired in patients with CAS, especially in those with anterior circulatory stenosis, moderate to severe stenosis and low cerebral perfusion.See Video Abstract, http://links.lww.com/WNR/A613.
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http://dx.doi.org/10.1097/WNR.0000000000001588DOI Listing
February 2021

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice.

J Bone Miner Res 2021 Jan 19. Epub 2021 Jan 19.

Department of Pathology, Yale University School of Medicine, New Haven,, CT, USA.

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1 mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1 mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1 mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1 mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4254DOI Listing
January 2021

FLNC and MYLK2 Gene Mutations in a Chinese Family with Different Phenotypes of Cardiomyopathy.

Int Heart J 2021 Jan 16;62(1):127-134. Epub 2021 Jan 16.

Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences.

Mutations in the sarcomeric protein filamin C (FLNC) gene have been linked to hypertrophic cardiomyopathy (HCM), as they have been determined to increase the risk of ventricular arrhythmia and sudden death. Thus, in this study, we identified a novel missense mutation of FLNC in a Chinese family with HCM, and, interestingly, a second novel truncating mutation of MYLK2 was discobered in one family member with different phenotype.We performed whole-exome sequencing in a Chinese family with HCM of unknown cause. To determine and confirm the function of a novel mutation of FLNC, we introduced the mutant and wild-type gene into AC16 cells (human cardiomyocytes): we then used western blotting to analyze the expression of FLNC in subcellular fractions, and confocal microscope to observe the subcellular distribution of the protein.As per our findings, we were able to identify a novel missense single nucleotide variant (FLNC c.G5935A [p.A1979T]) in the family, which segregates with the disease. FLNC expression levels were observed to be equivalent in both wild-type and p.A1979T cardiomyocytes. However, the expression of the mutant protein has resulted in cytoplasmic protein aggregations, in contrast to wild-type FLNC, which was distributed in the cytoplasm and did not form aggregates. Unexpectedly, a second truncating mutation, NM_033118:exon8:c.G1138T:p.E380X of the MYLK2 gene, was identified in the mother of the proband with dilated cardiomyopathy, which was not found in other subjects.We then identified the FLNC A1979T mutation as a novel pathogenic variant associated with HCM in a Chinese family as well as a second causal mutation in a family member with a distinct phenotype. The possibility that there is more than one causal mutation in cardiomyopathy warrants clinical attention, especially for patients with atypical clinical features.
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http://dx.doi.org/10.1536/ihj.20-351DOI Listing
January 2021

A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis.

Microbiome 2021 01 12;9(1):12. Epub 2021 Jan 12.

Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, Guangdong Province, China.

Background: Proteolysis regulation allows gut microbes to respond rapidly to dynamic intestinal environments by fast degradation of misfolded proteins and activation of regulatory proteins. However, alterations of gut microbial proteolytic signatures under complex disease status such as inflammatory bowel disease (IBD, including Crohn's disease (CD) and ulcerative colitis (UC)), have not been investigated. Metaproteomics holds the potential to investigate gut microbial proteolysis because semi-tryptic peptides mainly derive from endogenous proteolysis.

Results: We have developed a semi-tryptic peptide centric metaproteomic mining approach to obtain a snapshot of human gut microbial proteolysis signatures. This approach employed a comprehensive meta-database, two-step multiengine database search, and datasets with high-resolution fragmentation spectra to increase the confidence of semi-tryptic peptide identification. The approach was validated by discovering altered proteolysis signatures of Escherichia coli heat shock response. Utilizing two published large-scale metaproteomics datasets containing 623 metaproteomes from 447 fecal and 176 mucosal luminal interface (MLI) samples from IBD patients and healthy individuals, we obtain potential signatures of altered gut microbial proteolysis at taxonomic, functional, and cleavage site motif levels. The functional alterations mainly involved microbial carbohydrate transport and metabolism, oxidative stress, cell motility, protein synthesis, and maturation. Altered microbial proteolysis signatures of CD and UC mainly occurred in terminal ileum and descending colon, respectively. Microbial proteolysis patterns exhibited low correlations with β-diversity and moderate correlations with microbial protease and chaperones levels, respectively. Human protease inhibitors and immunoglobulins were mainly negatively associated with microbial proteolysis patterns, probably because of the inhibitory effects of these host factors on gut microbial proteolysis events.

Conclusions: This semi-tryptic peptide centric mining strategy offers a label-free approach to discover signatures of in vivo gut microbial proteolysis events if experimental conditions are well controlled. It can also capture in vitro proteolysis signatures to facilitate the evaluation and optimization of experimental conditions. Our findings highlight the complex and diverse proteolytic events of gut microbiome, providing a unique layer of information beyond taxonomic and proteomic abundance. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00967-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805185PMC
January 2021