Publications by authors named "Hui Qi"

228 Publications

Linoleate Isomerase Complex Contributes to Metabolism and Remission of DSS-Induced Colitis in Mice of ZS2058.

J Agric Food Chem 2021 Jul 19;69(29):8160-8171. Epub 2021 Jul 19.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

A linoleate isomerase complex including myosin-cross-reactive antigen, short-chain dehydrogenase/oxidoreductase, and acetoacetate decarboxylase has been confirmed as the pivotal factor for conjugated linoleic acid (CLA) production in . However, its role in the metabolism and health-associated benefits of remain unclear. In the current study, the mild type, knockout, and complemented mutants of the linoleate isomerase complex of ZS2058 were used to investigate those putative effects. The metabonomic results showed that a linoleate isomerase complex could significantly influence the glycol-metabolism, lipid metabolism, and antioxidant compounds. Especially, with the stress of linoleic acid, linoleate isomerase complex knockout mutants induced the increase of several antioxidant compounds, such as glutamic acid, glycine, l-cysteine, glycerol, and l-sorbosone. Moreover, the linoleate isomerase complex played a pivotal role in ameliorating DSS-induced colitis. The knockout mutants showed effects similar to those in the DSS group, whereas complementation of the corresponding gene in the knockout mutants could restore the anti-inflammatory activity, wherein the integrity of a mucus layer was repaired, the level of pro-inflammatory cytokines decreased, and the amount of anti-inflammatory cytokines increased significantly. All the results indicated that the linoleate isomerase complex plays a key role in CLA production and metabolism as well as the health-associated benefits of ZS2058. These results are conducive to promote clinical trials and product development of probiotics for colitis.
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http://dx.doi.org/10.1021/acs.jafc.1c02944DOI Listing
July 2021

Epigenetic Regulation by Suv4-20h1 in Cardiopulmonary Progenitor Cells is Required to Prevent Pulmonary Hypertension and COPD.

Circulation 2021 Jul 12. Epub 2021 Jul 12.

Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, Bad Nauheim, Germany; Member, German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.

The etiology of life-threatening cardiopulmonary diseases such as Pulmonary Hypertension (PH) and Chronic Obstructive Pulmonary Disease (COPD) originates from a complex interplay of environmental factors and genetic predispositions, which is not fully understood. Likewise, little is known about developmental abnormalities or epigenetic dysregulations that might predispose for PH or COPD in adult individuals. To identify pathology-associated epigenetic alteration in diseased lung tissues, we screened a cohort of human PH and COPD patients for changes of histone modifications by immunofluorescence staining. To analyze the function of H4K20me2/3 in lung pathogenesis, we developed a series of Suv4-20h1 knockout mouse lines targeting cardiopulmonary progenitor cells (CPPs) and different heart and lung cell types, followed by hemodynamic studies and morphometric assessment of tissue samples. Molecular, cellular and biochemical techniques were applied to analyze the function of Suv4-20h1-dependent epigenetic processes in cardiopulmonary progenitor cells and their derivatives. We discovered a strong reduction of the histone modifications H4K20me2/3 in human COPD but not PH patients, which depend on the activity of the H4K20 di-methyltransferase SUV4-20H1. Loss of Suv4-20h1 in CPPs caused a COPD-like/PH phenotype in mice including formation of perivascular tertiary lymphoid tissue and goblet cell hyperplasia, hyper-proliferation of smooth muscle cells/myofibroblasts, impaired alveolarization and maturation defects of the microvasculature leading to massive right ventricular dilatation and premature death. Mechanistically, SUV4-20H1 binds directly to the 5'-upstream regulatory element of superoxide dismutase 3 () gene to repress its expression. Increased levels of the extracellular SOD3 enzyme in mutants increases hydrogen peroxide (H2O2) concentrations, causing vascular defects and impairing alveolarization. Our findings reveal a pivotal role of the histone modifier SUV4-20H1 in cardiopulmonary co-development and uncover developmental origins of cardiopulmonary diseases. We assume that the study will facilitate the understanding of pathogenic events causing PH and COPD, and aid the development of epigenetic drugs for treatment of cardiopulmonary diseases.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051680DOI Listing
July 2021

Dynamic anti-plane behavior of rare earth giant magnetostrictive medium with a circular cavity defect in semi-space.

Authors:
Zhiwei Liu Hui Qi

Sci Rep 2021 Jun 29;11(1):13442. Epub 2021 Jun 29.

College of Aerospace and Civil Engineering, Harbin Engineering University, Harbin, China.

An analytical solution to the anti-plane dynamics problem of semi-space rare earth giant magnetostrictive media with circular cavity defects near the horizontal boundary under the action of SH wave is studied. Based on the Helmholtz theorem and the theory of complex function, the elastic-magnetic dynamic equation of magnetostrictive medium is established, and the semi-space incident wave field is written. In addition, based on the theory of complex function and the method of wave function expansion, the expression of the wave function of the scattered displacement field and the corresponding magnetic potential of the scattered wave under the condition of no stress and magnetic insulation of the horizontal boundary are obtained. Then, based on the conditions of free boundary stress, continuous magnetic induction intensity and continuous magnetic potential around the circular cavity, the infinite linear algebraic equations are established. Finally, the analytical expressions of dynamic stress concentration factor and magnetic field intensity concentration factor around circular cavity in semi-space rare earth giant magnetostrictive medium are obtained. Numerical examples show that the analysis results depend on the following parameters: permeability, dimensional-piezomagnetic coefficient, frequency of the incident wave, incident angle, distance between the circular cavity and horizontal boundary. These results have certain reference value for the study of non-destructive testing and failure analysis of rare earth giant magnetostrictive materials.
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http://dx.doi.org/10.1038/s41598-021-92841-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241854PMC
June 2021

Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial.

Front Pharmacol 2021 9;12:635517. Epub 2021 Jun 9.

Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Early-onset neonatal sepsis (EONS), a bacterial infection that occurs within 72 h after birth, is associated with high likelihood of neonatal mortality. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has been brought back into empirical EONS treatment in recent years. In the preliminary work, we established a population pharmacokinetics (PPK) model for latamoxef in Chinese neonates. Moreover, in order to better guide clinical treatment, we conducted dose simulation and found that ascending administration frequency could improve the target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval (70% fT > MIC). Accordingly, this study is aimed to compare the 70% fT > MIC, efficacy and safety between conventional regimen and PPK model regimen for rational use of latamoxef in EONS treatment. A single-blind, multicenter randomized controlled trial (RCT) for latamoxef will be conducted in Chinese EONS patients. Neonates (≤3 days of age, expected number = 114) admitted to the hospital with the diagnosis of EONS and fulfilling inclusion and exclusion criteria will be randomized (ratio of 1:1) to either a conventional regimen (30 mg/kg q12h) or model regimen (20 mg/kg q8h) latamoxef treatment group for at least 3 days. Primary outcome measure will be 70% fT > MIC and secondary outcome indicators will be the latamoxef treatment failure, duration of antibiotic therapy, changes of white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT), blood culture results during administration and incidence of adverse event (AE)s. Assessments will be made at baseline, initial stage of latamoxef treatment (18-72 h) and before the end of latamoxef treatment. Ethical approval of our clinical trial has been granted by the ethics committee of the Beijing Children's Hospital (ID: 2020-13-1). Written informed consent will be obtained from the parents of the participants. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR 2000040064).It is hoped that our study will provide a clinical basis for the rational clinical use of latamoxef in EONS treatment.
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http://dx.doi.org/10.3389/fphar.2021.635517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220210PMC
June 2021

A 71-year-old female with an intrasellar mass.

Brain Pathol 2021 Jun 21:e12960. Epub 2021 Jun 21.

Department of Neurosurgery, Peking University Shenzhen Hospital, Shenzhen, P.R. China.

Magnetic resonance imaging revealed an intrasellar and suprasellar tumor with significant homogeneous contrast enchancement (Figure A). Under microscopy showed the dilated cavernous spaces of irregular size and shape, which are embedded in the loose collagenous matrix and adipose tissue, lined by normal flattened endothelial cells. These spaces are mostly empty and some cavities are filled with proteinaceous material (Figure B). This mass is immunohistoreactive for CD34 (Figure C) and D2-40 (Figure D).
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http://dx.doi.org/10.1111/bpa.12960DOI Listing
June 2021

Nitrogen-carbon materials base on pyrolytic graphene hydrogel for oxygen reduction.

J Colloid Interface Sci 2021 Jun 8;602:274-281. Epub 2021 Jun 8.

Lab of Advanced Nano-structures & Transfer Processes, Department of Chemical Engineering, Tianjin University, Tianjin 300354, China; Chemistry and Chemical Engineering Guangdong Laboratory, Shantou 515031 China. Electronic address:

Hypothesis: Oxygen reduction reaction (ORR) has played a significant role in the utilization of energy nowadays. Nitrogen-doped carbon materials are seen as promising catalysts for ORR, so it is of great significance in studying the functions of different nitrogen moieties.

Experiments: The graphene hydrogel-based nitrogen-arbon materials (GH N-C) were fabricated by first obtaining a gel through hydrothermal treatment using graphene oxide (GO) as precursor, and then calcined in an ammonia atmosphere at different temperatures to form N-doped graphitized materials with divers nitrogen configuration.

Findings: GH N-C materials with tunable nitrogen configuration were synthesized by a two-step method base on graphene hydrogel. Benefiting from the 3D hydrogel structure, rich defects and optimized chemical properties, GH N-C-900 prepared by NH pyrolysis at 900 °C exhibits an excellent electrocatalytic performance toward ORR, with the onset potential of 0.947 ± 0.013 V versus RHE, half-wave potential of 0.830 ± 0.010 V versus RHE, electron transfer number of 3.61-3.99, along as methanol tolerance and superior long-term stability. Comprehensive studies have shown that there is a positive correlation between the total amount of pyrrolic-N and quaternary-N and the catalytic performance of ORR.
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http://dx.doi.org/10.1016/j.jcis.2021.06.036DOI Listing
June 2021

Generation of neoantigen-specific T cells for adoptive cell transfer for treating head and neck squamous cell carcinoma.

Oncoimmunology 2021 May 25;10(1):1929726. Epub 2021 May 25.

Cytotherapy Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen Guangdong, China.

Adoptive cell therapy using TCR-engineered T cells (TCR-T cells) represents a promising strategy for treating relapsed and metastatic cancers. We previously established methods to identify neoantigen-specific TCRs based on patients' PBMCs. However, in clinical practice isolation of PBMCs from advanced-stage cancer patients proves to be difficult. In this study, we substituted blood-derived T cells for tumor-infiltrating lymphocytes (TILs) and used an HLA-matched cell line of antigen-presenting cells (APCs) to replace autologous dendritic cells. Somatic mutations were determined in head and neck squamous cell carcinoma resected from two patients. HLA-A*02:01-restricted neoantigen libraries were constructed and transferred into HLA-matched APCs for stimulation of patient TILs. TCRs were isolated from reactive TIL cultures and functionality was tested using TCR- T cells and . To exemplify the screening approach, we identified the targeted neoantigen leading to recognition of the minigene construct that stimulated the strongest TIL response. Neoantigen peptides were used to load MHC-tetramers for T cell isolation and a TCR was identified targeting the KIAA1429 mutation. TCR-T cells were activated, exhibited cytotoxicity, and secreted cytokines in a dose-dependent manner, and only when stimulated with the mutant peptide. Furthermore, comparable to a neoantigen-specific TCR that was isolated from the patient's PBMCs, KIAA1429-specific TCR T cells destroyed human tumors in mice. The established protocol provides the required flexibility to methods striving to identify neoantigen-specific TCRs. By using an MHC-matched APC cell line and neoantigen-encoding minigene libraries, autologous TILs can be stimulated and screened when patient PBMCs and/or tumor material are not available anymore. Abbreviations: Head and neck squamous cell carcinoma (HNSCC); adoptive T cell therapy (ACT); T cell receptor (TCR); tumor-infiltrating lymphocytes (TIL); cytotoxic T lymphocyte (CTL); peripheral blood mononuclear cell (PBMC); dendritic cell (DC); antigen-presenting cells (APC).
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http://dx.doi.org/10.1080/2162402X.2021.1929726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158031PMC
May 2021

Nuclear Factor Erythroid 2-Related Factor 2-Histone Deacetylase 2 Pathway in the Pathogenesis of Refractory Sudden Sensorineural Hearing Loss and Glucocorticoid Resistance.

ORL J Otorhinolaryngol Relat Spec 2021 4;83(4):227-233. Epub 2021 Jun 4.

Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Introduction: A significant number of sensorineural hearing loss (SSNHL) patients had no noticeable hearing improvement after glucocorticoid (GC) treatment. In the present study, we examined expression of the nuclear factor erythroid 2-related factor 2 (NRF2) and histone deacetylase 2 (HDAC2) in peripheral blood mononuclear cells (PBMCs) of refractory SSNHL patients to study the role of NRF2-HDAC2 pathway in GC insensitivity hearing improvement after GC treatment, which is usually referred to as refractory SSNHL or GC insensitivity.

Materials And Methods: Forty-four refractory SSNHL patients were treated by intratympanic GC infusion. Hearing was tested in all patients before and after treatment by pure tone hearing test. NRF2/HDAC2 mRNA and protein levels were examined in PBMCs of refractory SSNHL patients before and after treatment. PBMCs from healthy volunteers were used as normal controls.

Results: According to the hearing improvement after treatment, patients were assigned into 2 groups: the intratympanic GC sensitive (IGCS) group (hearing recovery ≥15 dB HL) and the intratympanic GC insensitive (IGCI) group (hearing recovery <15 dB HL). Before treatment, the NRF2 mRNA level was lower in all patients than the normal control group. After treatment, NRF2 and HDAC2 mRNA and protein levels were increased in the IGCS group, while no significant change was observed in the IGCI group.

Conclusion: Low response of NRF2/HDAC2 proteins is associated with GC insensitivity in SSNHL. We speculate that the NRF2-HDAC2 pathway affects GC sensitivity in SSNHL patients.
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http://dx.doi.org/10.1159/000515205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315675PMC
June 2021

Macular hole with inner limiting membrane peeling off spontaneously in Terson syndrome: A case report.

Medicine (Baltimore) 2021 Jun;100(22):e25960

Eye Center of the second hospital, Jilin University, ChangChun, Jilin Province, China.

Introduction: Terson's syndrome with inner limiting membrane (ILM) peeled off spontaneously is rarely seen, and the mechanism of it is not clear. Here we report a case of Terson Syndrome with a rare finding: the ILM peeled off spontaneously associated with macular hole (MH).

Patient Concerns: A 36-year-old female patient was admitted to our hospital with decreased visual acuity in the right eye lasting for 1 month. She just had surgery for subarachnoid hemorrhage that occurred 1 month before due to the rupture of the intracranial aneurysm.

Diagnosis: Terson syndrome was diagnosed according to her medical history and examination. A partial posterior vitreous detachment (PVD) and dense vitreous hemorrhage (VH) was confirmed in the right eye by performing ophthalmic B-scan ultrasonography examination. Head computed tomography showed the subarachnoid hemorrhage after aneurysmal rupture.

Interventions: The patient underwent pars plana vitrectomy in her right eye to remove the VH. After removal of the VH, a full-thickness macular hole was noted with the ILM peeled off spontaneously. So we conducted gas tamponade, and face-down positioning after pas plana vitrectomy.

Outcomes: At two weeks follow-up, her best corrected visual acuity was 0.15 in the right eye. Spectral domain optical coherence tomography showed that the MH was closed completely, while the thickness of the nasal retina of the foveal was thicker than that on the temporal side.

Lessons: ILM peeled off spontaneously associated with MH is a rarely seen complication of Terson Syndrome. Due to the large-scale of the ILM peeling off, final visual acuity may be poor in patients, even though successful macular hole closure after the operation.
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http://dx.doi.org/10.1097/MD.0000000000025960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183829PMC
June 2021

Bimetallic ZIF-Derived Co/N-Codoped Porous Carbon Supported Ruthenium Catalysts for Highly Efficient Hydrogen Evolution Reaction.

Nanomaterials (Basel) 2021 May 6;11(5). Epub 2021 May 6.

Lab of Advanced Nano-Structure and Transfer Process, Department of Chemical Engineering, Tianjin University, Tianjin 300354, China.

Exploring the economical, powerful, and durable electrocatalysts for hydrogen evolution reaction (HER) is highly required for practical application. Herein, nanoclusters-decorated ruthenium, cobalt nanoparticles, and nitrogen codoped porous carbon ([email protected]) are prepared with bimetallic zeolite imidazole frameworks (ZnCo-ZIF) as the precursor. Thus, the prepared [email protected] catalyst with a low Ru loading of 3.13 wt% exhibits impressive HER catalytic behavior in 1 M KOH, with an overpotential of only 30 mV at the current density of 10 mA cm, Tafel slope as low as 32.1 mV dec, and superior stability for long-time running with a commercial 20 wt% Pt/C. The excellent electrocatalytic properties are primarily by virtue of the highly specific surface area and porosity of carbon support, uniformly dispersed Ru active species, and rapid reaction kinetics of the interaction between Ru and O.
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http://dx.doi.org/10.3390/nano11051228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148513PMC
May 2021

The correlation between cytokine levels in the aqueous humor and the prognostic value of anti-vascular endothelial growth factor therapy for treating macular edema resulting from retinal vein occlusion.

Graefes Arch Clin Exp Ophthalmol 2021 Jun 1. Epub 2021 Jun 1.

Department of Ophthalmology, The Second Hospital of Jilin University, Nanguan District, Changchun, Jilin, 130041, China.

Purpose: To determine the correlation between aqueous humor cytokine levels and the prognostic value of anti-vascular endothelial growth factor (VEGF) therapy for treating macular edema resulting from retinal vein occlusion (RVO-ME).

Methods: This prospective study included 47 RVO-ME and 32 senile cataract cases. Aqueous humor collection was performed in patients with RVO-ME before intravitreal injection of ranibizumab and in patients before cataract surgery. VEGF, monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-8, IL-6, basic fibroblast growth factor (b-FGF), and tumor necrosis factor-α (TNF-α) levels were measured in the aqueous humor. Central retinal thickness (CRT) was measured before ranibizumab treatment and during each follow-up visit. The recovery rate following ranibizumab treatment was calculated as (CRT-CRT)/CRT, in which CRT was the CRT measured before treatment and CRT was measured 1 week after treatment. The recurrence time of RVO-ME was recorded.

Results: VEGF, MCP-1, IL-8, and IL-6 levels in the aqueous humor of patients with RVO-ME were significantly higher compared with control and were positively correlated with the CRT. Ranibizumab significantly reduced CRT, and VEGF levels positively correlated with the recovery rate. The mean recurrence time of RVO-ME was 43.5 days. IL-6 levels negatively correlated with the recurrence time of ME.

Conclusion: VEGF, MCP-1, IL-8, and IL-6 levels were significantly increased in patients with RVO-ME and were positively correlated with ME. Higher VEGF levels were indicative of CRT recovery, and higher IL-6 levels were indicative of ME recurrence after ranibizumab treatment.
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http://dx.doi.org/10.1007/s00417-021-05211-2DOI Listing
June 2021

Development and Preliminary Application of Multiplex Loop-Mediated Isothermal Amplification Coupled With Lateral Flow Biosensor for Detection of .

Front Cell Infect Microbiol 2021 27;11:666492. Epub 2021 Apr 27.

Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.

The aim of this study was to develop a simple and reliable method to detect (MTBC) and verify its clinical application preliminarily. A loop-mediated isothermal amplification method coupled with lateral flow biosensor (LAMP-LFB) assay, was developed and evaluated for detection of MTBC. Two sets of primers, which targeted IS and IS sequences of MTBC, were designed for establishment of multiplex LAMP-LFB assay. The amplicons were labelled with biotin and fluorescein isothiocyanate (FITC) by adding FITC labelled primer and biotin-14-dATP and biotin-14-dCTP and could be visualized using LFB. The optimal reaction conditions of multiplex LAMP-LFB assay confirmed were 66°C for 50 min. The analytical sensitivity of multiplex LAMP-LFB is 10 fg of genomic templates using pure culture, and no cross-reactivity with other common bacteria and non-tuberculous mycobacteria strains was obtained. A total of 143 clinical samples collected from 100 TB patients (62 definite TB cases and 38 probable TB cases) and 43 non-TB patients were used for evaluating the feasibility of multiplex LAMP-LFB assay. The multiplex LAMP-LFB (82.0%, 82/100) showed higher sensitivity than culture (47.0%, 47/100, P < 0.001) and Xpert MTB/RIF (54.0%, 54/100, P < 0.001). Importantly, the multiplex LAMP-LFB assay detected additional 28 probable TB cases, which increased the percentage of definite TB cases from 62.0% (62/100) to 90.0% (90/100). The specificity of multiplex LAMP-LFB assay in patients without TB was 97.7% (42/43). Therefore, multiplex LAMP-LFB assay is a simple, reliable, and sensitive method for MTBC detection, especially in probable TB cases and resource limited settings.
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http://dx.doi.org/10.3389/fcimb.2021.666492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110928PMC
July 2021

Correction: High performance blue quantum dot light-emitting diodes by attaching diffraction wrinkle patterns.

Nanoscale 2021 May;13(20):9446

Key Laboratory for Special Functional Materials of Ministry of Education, National & Local Joint Engineering Research Centre for High-efficiency Display and Lighting Technology, School of Materials and Engineering, Collaborative Innovation Centre of Nano Functional Materials and Applications, Henan University, Kaifeng 475004, China.

Correction for 'High performance blue quantum light-emitting diodes by attaching diffraction wrinkle patterns' by Hui Qi et al., Nanoscale, 2021, DOI: 10.1039/D1NR00082A.
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http://dx.doi.org/10.1039/d1nr90102hDOI Listing
May 2021

Population pharmacokinetics-pharmacodynamics of ceftazidime in neonates and young infants: Dosing optimization for neonatal sepsis.

Eur J Pharm Sci 2021 Aug 2;163:105868. Epub 2021 May 2.

Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan 250014, China. Electronic address:

Ceftazidime is a third-generation cephalosporin with high activity against many pathogens. But the ambiguity and diversity of the dosing regimens in neonates and young infants impair access to effective treatment. Thus, we conducted a population pharmacokinetic study of ceftazidime in this vulnerable population and recommended a model-based dosage regimen to optimize sepsis therapy. Totally 146 neonates and young infants (gestational age (GA): 36-43.4 weeks, postnatal age (PNA): 1-81 days, current weight (CW): 900-4500 g) were enrolled based on inclusion and exclusion criteria. Ceftazidime bloods samples (203) were obtained using the opportunistic sampling strategy and determined by the high-performance liquid chromatography. The population pharmacokinetic-pharmacodynamic analysis was conducted by nonlinear mixed effects model (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic data. Covariate analysis showed the significance of GA, PNA, and CW on developmental pharmacokinetics. Monte Carlo simulation was performed based on above covariates and minimum inhibitory concentration (MIC). In the newborns with PNA ≤ 3 days (MIC=8 mg/L), the dose regimen was 25 mg/kg twice daily (BID). For the newborns with PNA > 3 days (MIC=16 mg/L), the optimal dose was 30 mg/kg three times daily (TID) for those with GA ≤ 37 weeks and 40 mg/kg TID for those with GA > 37 weeks. Overall, on the basis of the developmental population pharmacokinetic-pharmacodynamic analysis covering the whole range of neonates and young infants, the evidence-based ceftazidime dosage regimens were proposed to optimize neonatal early-onset and late-onset sepsis therapy.
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http://dx.doi.org/10.1016/j.ejps.2021.105868DOI Listing
August 2021

Large-Scale Preparation of Highly Stable Recombinant Human Acidic Fibroblast Growth Factor in BL21(DE3) plysS Strain.

Front Bioeng Biotechnol 2021 13;9:641505. Epub 2021 Apr 13.

Wenzhou Medical University, Chashan University Park, Wenzhou, China.

In this study, the optimum human gene encoding haFGF was cloned in pET3c and transferred to BL21(DE3) plysS. To enhance the yield of fermentation and the expression level of the target protein, the fermentation parameters, including temperature, pH, dissolved oxygen, glucose concentration, ammonium chloride concentration, induction time, and inducer (IPTG) concentration, were optimized. The optimized fermentation parameters were used in large-scale fermentation (30 L). Ion-exchange and heparin-affinity column chromatography techniques were used for separation and purification of rhaFGF protein. HPLC, isoelectric focusing electrophoresis, and mass spectrometry were used to detect the purity, isoelectric point, and molecular weight and peptide map of rhaFGF protein, respectively. Mitogenic activity of rhaFGF protein was detected in NIH-3T3 cells and a full-thickness injury wound diabetic rat model. The production and expression level of rhaFGF in the 30-L scale fermentation reached 80.4 ± 2.7 g/L culture and 37.8% ± 1.8%, respectively. The RP-HPLC and SDS-PAGE purity of the final rhaFGF product almost reached 100%, and the final pure protein yield was 158.6 ± 6.8 mg/L culture. Finally, the cell and animal experiments showed that rhaFGF retained a potent mitogenic activity. The large-scale process of rhaFGF production reported herein is relatively stable and time-saving, and thus, it can be used as an efficient and economic strategy for the synthesis of rhaFGF at the industrial level.
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http://dx.doi.org/10.3389/fbioe.2021.641505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072344PMC
April 2021

High performance blue quantum light-emitting diodes by attaching diffraction wrinkle patterns.

Nanoscale 2021 May;13(18):8498-8505

Key Laboratory for Special Functional Materials of Ministry of Education, National & Local Joint Engineering Research Centre for High-efficiency Display and Lighting Technology, School of Materials and Engineering, Collaborative Innovation Centre of Nano Functional Materials and Applications, Henan University, Kaifeng 475004, China.

Highly efficient blue quantum-dot light-emitting diodes (QLEDs) are still challenging to use in displays and solid-state lighting. Enhancing light outcoupling is one of the most effective methods to improve the performance of blue QLEDs. Here, a strategy for a spectrally independent boost in light outcoupling of blue QLEDs is demonstrated by quasi-periodic wrinkles, which are successfully used as a diffraction grating for extracting trapped light at the substrate/air interface. The quasi-periodic wrinkles can be adjusted from nano-scale to micron-scale under the condition of a constant aspect ratio, and the optimized wrinkle device shows a maximum luminance of 11 769 cd m-2 and a peak EQE of 15.41%. The enhancement of EQE is 49.5% higher compared to that of the reference device. Furthermore, simulation and calculation also indicate that external micron-scattering wrinkle patterns are an attractive option for boosting the performances of blue QLEDs.
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http://dx.doi.org/10.1039/d1nr00082aDOI Listing
May 2021

Research progress on the molecular mechanisms of hepatic metastasis in lung cancer: a narrative review.

Ann Palliat Med 2021 Apr 24;10(4):4806-4822. Epub 2021 Mar 24.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.

The liver is one of the most common sites of metastatic spread of lung cancer, and the process of metastasis is regulated by many factors. A number of genes, including multiple tumor suppressor 1 (mts1), p120 catenin, and CT45A1, increase the possibility of hepatic metastasis in lung cancer, whereas Tip30/CC3, CUL5, and SOCS3 expression in lung tumors inhibit tumor metastasis. microRNAs (miRNAs), such as miRNA-126, miRNA-338, and miRNA-218, can affect the metastasis of lung cancer cells to the liver. The D114-Notch signaling pathway can inhibit liver metastasis in small cell lung cancer. Serum tumor markers cytokeratin 19 fragment antigen 21-1 and neuron-specific enolase (NSE) are closely related to the risk of hepatic metastasis in lung cancer. Based on previously published literature, we found that the metastasis and invasion of lung cancer to the liver are determined by molecular factors. Therefore, the selective identification and intervention of these erroneous signals can predict early lung cancer metastasis to the liver. In this review article, we describe the mechanisms and influencing factors (genes, signal pathways, chemicals, proteins, miRNAs) of hepatic metastasis in lung cancer. We hope to provide a summary of the evidence for the mechanisms by which related genes or proteins affect the malignancy of liver metastasis from lung cancer so that doctors and researchers can improve treatment options.
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http://dx.doi.org/10.21037/apm-20-1675DOI Listing
April 2021

TMAO Aggregates Neurological Damage Following Ischemic Stroke by Promoting Reactive Astrocytosis and Glial Scar Formation the Smurf2/ALK5 Axis.

Front Cell Neurosci 2021 18;15:569424. Epub 2021 Mar 18.

Department of Neurosurgery, Peking University Shenzhen Hospital, Shenzhen, China.

Ischemic stroke has been reported to cause significant changes to memory, thinking, and behavior. Intriguingly, recently reported studies have indicated the association of Trimethylamine N-oxide (TMAO) with the acute phase of ischemic stroke. However, the comprehensive underlying mechanism remained unknown. The objective of the present study was to investigate the association between TMAO and recovery of neurological function after ischemic stroke. For this purpose, a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established and treated with TMAO or/and sh-ALK5, followed by the neurological function evaluation. Behaviors of rats were observed through staircase and cylinder tests. Moreover, the expression of Smurf2 and ALK5 was detected by immunohistochemistry while expression of GFAP, Neurocan, and Phosphacan in brain tissues was determined by immunofluorescence. Thereafter, gain- and loss-of-function assays in astrocytes, the proliferation, viability, and migration were evaluated by the EdU, CCK-8, and Transwell assays. Besides, Smurf2 mRNA expression was determined by the RT-qPCR, whereas, Smurf2, ALK5, GFAP, Neurocan, and Phosphacan expression was evaluated by the Western blotting. Finally, the interaction of Smurf2 with ALK5 and ALK5 ubiquitination was assessed by the co-immunoprecipitation. Notably, our results showed that TMAO promoted the proliferation of reactive astrocyte and formation of glial scar in MCAO/R rats. However, this effect was abolished by the Smurf2 overexpression or ALK5 silencing. We further found that TMAO upregulated the ALK5 expression by inhibiting the ubiquitination role of Smurf2. Overexpression of ALK5 reversed the inhibitory effect of Smurf2 on astrocyte proliferation, migration, and viability. Collectively, our work identifies the evolutionarily TMAO/Smurf2/ALK5 signaling as a major genetic factor in the control of reactive astrocyte proliferation and glial scar formation in ischemic stroke, thus laying a theoretical foundation for the identification of ischemic stroke.
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http://dx.doi.org/10.3389/fncel.2021.569424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012716PMC
March 2021

Aberrant methylation modifications reflect specific drug responses in small cell lung cancer.

Genomics 2021 May 8;113(3):1114-1126. Epub 2021 Mar 8.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No 507 Zhengmin Road, Shanghai 200433, China. Electronic address:

In the study, Methylated DNA immunoprecipitation sequencing, RNA sequencing, and whole-exome sequencing were employed to clinical small cell lung cancer (SCLC) patients. Then, we verified the therapeutic predictive effects of differentially methylated genes (DMGs) in 62 SCLC cell lines. Of 4552 DMGs between chemo-sensitive and chemo-insensitive group, coding genes constituted the largest percentage (85.08%), followed by lncRNAs (10.52%) and miRNAs (3.56%). Both two groups demonstrated two methylation peaks near transcription start site and transcription end site. Two lncRNA-miRNA-mRNA networks suggested the extensive genome connection between chemotherapy efficacy-related non-coding RNAs (ncRNAs) and mRNAs. Combing miRNAs and lncRNAs could effectively predict chemotherapy response in SCLC. In addition, we also verified the predictive values of mutated genes in SCLC cell lines. This study was the first to evaluate multiple drugs efficacy-related ncRNAs and mRNAs which were modified by methylation in SCLC. DMGs identified in our research might serve as promising therapeutic targets to reverse drugs-insensitivity by complex lncRNA-miRNA-mRNA mechanisms in SCLC.
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http://dx.doi.org/10.1016/j.ygeno.2020.12.045DOI Listing
May 2021

Hypoglycemic Efficacy of Rh-aFGF Variants in Treatment of Diabetes in ZDF Rats.

Front Cell Dev Biol 2021 18;9:609383. Epub 2021 Feb 18.

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Acidic fibroblast growth factor (aFGF) is a promising regulator of glucose with no adverse effects of hypoglycemia. Previous researches revealed that aFGF mediated adipose tissue remodeling and insulin sensitivity. These findings supported rh-aFGF would be used as a new candidate for the treatment of insulin resistance and type 2 diabetes. In this study, we aimed to investigate the hypoglycemic efficacy of recombinant human acidic fibroblast growth factor 135 (rh-aFGF) with low mitogenic in type 2 diabetic ZDF rats. ZDF rats were treated with rh-aFGF at a daily dosage of 0.25 and 0.50 mg/kg by tail intravenous injection for 5 weeks. The blood glucose levels, oral glucose tolerance test, insulin tolerance test, HOMA-IR for insulin resistance, serum biochemical parameters, and the histopathological changes of adipose tissue, liver and other organs were detected at designed time point. The glucose uptake activity and anti-insulin resistance effect of rh-aFGF were also detected in HepG2 cells. Results revealed that rh-aFGF exhibited a better hypoglycemic effect compared with vehicle group and without the adverse effect of hypoglycemia in ZDF rats. Compared with vehicle group, rh-aFGF significantly improved the situation of hyperglycemia and insulin resistance. Rh-aFGF decreased ALT, AST, GSP, and FFA levels noticeably compared with vehicle control group ( < 0.01 or < 0.001). After 5 weeks of treatment, high-dosage rh-aFGF could remodel adipose tissue, and has no influence on other organs. H&E staining showed that rh-aFGF reduced the size of adipocytes. In addition, rh-aFGF may improve insulin resistance partly by increasing the protein expression of p-IRS-1 (human Ser 307). As a hypoglycemic drug for long-term treatment, rh-aFGF would be a potentially safe candidate for the therapy of type 2 diabetes.
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http://dx.doi.org/10.3389/fcell.2021.609383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930327PMC
February 2021

Extracellular vesicles from GPNMB-modified bone marrow mesenchymal stem cells attenuate bone loss in an ovariectomized rat model.

Life Sci 2021 May 11;272:119208. Epub 2021 Feb 11.

Beijing Research Institute of Traumatology and Orthopaedics, The Beijing Jishuitan Hospital, Beijing 100035, China. Electronic address:

Aims: The efficacy of anti-osteoporotic treatments is still limited. Our study aimed to investigate the effect of extracellular vesicles (EVs) derived from bone marrow-derived MSCs (BMSCs) overexpressing glycoprotein non-melanoma clone B (GPNMB) on osteoporosis (OP).

Main Methods: Lentiviral vector for GPNMB overexpression or its negative control was generated and transfected into BMSCs. EVs enriched with GPNMB (GPNMB-EVs) were extracted from GPNMB-modified BMSC-conditioned medium and then identified. Cellular uptake and proliferation were analyzed using the Dil-labeled assay and CCK-8 assay, respectively. Cytochemical staining, western blot, and RT-qPCR analysis were performed to assess the effect of GPNMB-EVs on osteogenic differentiation of BMSCs in vitro. Dickkopf-1 (DKK1) as the inhibitor was applied to explore the Wnt/β-catenin signaling pathway involved in the GPNMB-EV-induced osteogenic differentiation. In vivo experiments were conducted using an ovariectomized (OVX) rat model of postmenopausal osteoporosis, and then assessed the effect of GPNMB-EVs by micro-CT, and histological and immunohistochemical assays.

Key Findings: GPNMB-EVs were taken up by BMSCs, and they noticeably promoted the proliferation of BMSCs. Additionally, GPNMB-EVs activated the Wnt/β-catenin signaling to stimulate osteogenesis in BMSCs. In vivo examination showed that GPNMB-EVs remarkably improved trabecular bone regeneration and alleviated the osteoporotic phenotype in the OVX-induced rat model of OP.

Significance: EVs derived from GPNMB-modified BMSCs significantly stimulated the proliferation and osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling and attenuated the bone loss in the OVX-induced rat model of OP. Our findings suggest the promising potential of GPNMB-EVs as cell-free therapy for the treatment of OP.
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http://dx.doi.org/10.1016/j.lfs.2021.119208DOI Listing
May 2021

Mycobacterium tuberculosis infection up-regulates MFN2 expression to promote NLRP3 inflammasome formation.

J Biol Chem 2020 12;295(51):17684-17697

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address:

Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (MTB), is one of the leading causes of death worldwide, especially in children. However, the mechanisms by which MTB infects its cellular host, activates an immune response, and triggers inflammation remain unknown. Mitochondria play important roles in the initiation and activation of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) inflammasome, where mitochondria-associated endoplasmic reticulum membranes (MAMs) may serve as the platform for inflammasome assembly and activation. Additionally, mitofusin 2 (MFN2) is implicated in the formation of MAMs, but, the roles of mitochondria and MFN2 in MTB infection have not been elucidated. Using mircroarry profiling of TB patients and in vitro MTB stimulation of macrophages, we observed an up-regulation of MFN2 in the peripheral blood mononuclear cells of active TB patients. Furthermore, we found that MTB stimulation by MTB-specific antigen ESAT-6 or lysate of MTB promoted MFN2 interaction with NLRP3 inflammasomes, resulting in the assembly and activation of the inflammasome and, subsequently, IL-1β secretion. These findings suggest that MFN2 and mitochondria play important role in the pathogen-host interaction during MTB infection.
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http://dx.doi.org/10.1074/jbc.RA120.014077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762945PMC
December 2020

Graphene oxide and self-avoiding molecular recognition systems-assisted recombinase polymerase amplification coupled with lateral flow bioassay for nucleic acid detection.

Mikrochim Acta 2020 Nov 19;187(12):667. Epub 2020 Nov 19.

Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Disease, Beijing Pediatric Research Institute, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, 10045, People's Republic of China.

A new nucleic acid detection technique, termed Nano-SAMRS-RPA, is reported which employed carbon nanomaterial (graphene oxide, GO) and self-avoiding molecular recognition systems (SAMRS) to improve the specificity of recombinase polymerase amplification (RPA). In the presence of GO and SAMRS primers, the assay artifacts, including primer-dimers, nonspecific products, off-target hybrids, and non-canonical folds, are completely suppressed and eliminated, which makes the creation of RPA-based methods faster by simplifying the primer design and eliminating the need for primer optimization and complex probe. Moreover, a lateral flow bioassay (LFB) was also devised for simply and rapidly indicating the Nano-SAMRS-RPA results. Particularly, the new detection system only requires a single-labeled primer, eliminating the false-positive result from hybridization (the labeled probe and reverse primer) and the use of real-time instrument, more complex enzymatic solutions, and probes. As a result, GO, SAMRS primers, and LFB convert RPA from a technique suited only for the research laboratory into one that has a practical value in clinical settings, field environments, and at points-of-care testing. Human papillomaviruses (HPV) genotypes 16 and 18 were applied as model analytes to test the assay's availability. The initial data indicated that Nano-SAMRS-RPA could detect down to 10 copies per reaction, and the sensitivity (14/14 samples collected from HPV16 and HPV 18 patients) and specificity (75/75 samples collected from non-HPV patients) for clinical sample detection were 100%. The proof-of-concept technique can be reconfigured to detect various nucleic acid sequences by redesigning the specific RPA primers.Graphical abstract.
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http://dx.doi.org/10.1007/s00604-020-04637-5DOI Listing
November 2020

Promotion of the water oxidation activity of iridium oxide by a nitrogen coordination strategy.

Chem Commun (Camb) 2020 Nov;56(94):14909-14912

Institute of Physical Chemistry, College of Chemistry, Jilin University, Changchun 130021, P. R. China.

The water oxidation reaction is the pivotal half-reaction for photo-/electro-catalytic water splitting. Fabrication of high-efficiency and robust water oxidation is essential to realize wide-scale artificial photosynthesis. Here, we report an efficient strategy to improve the water oxidation activity of iridium oxide by a nitrogen-coordination method. Due to the coordination effect, the iridium oxide can be well dispersed to generate ultra-small nanoparticles and the intrinsic activity can be improved for the water oxidation reaction. This study suggests that high-performance water oxidation catalysts can be constructed based on a nitrogen-coordination strategy.
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http://dx.doi.org/10.1039/d0cc06748bDOI Listing
November 2020

Aluminium nanoparticle modelling coupled with molecular dynamic simulation method to compare the effect of annealing rates on diethyl ether coating and oxidation behaviours.

J Mol Graph Model 2020 11 7;100:107667. Epub 2020 Jul 7.

College of Aerospace and Civil Engineering, Harbin Engineering University, Nangang District, Harbin City, Heilongjiang Province, China.

This study was conducted to examine the influence of annealing rates on coating and oxidation performances of Aluminium (Al) nanoparticle (ANP) by molecular dynamic (MD) simulations. Four levels of cooling rates were utilized on melted ANP to obtain annealed ANP models with different microstructures. Then those nanoparticles were placed into pure diethyl ether or oxygen gas environments to perform coating and oxidation simulations respectively. It was revealed that there was a relatively optimal annealing condition for ANP models to recover the initial microstructure of themselves as much as possible. The ether coating behaviour of annealed ANP model under this condition was better than other models. In contrast, the oxidation of all different models was almost the same. So, the factor of the annealing rate had little effect on the oxidation results. Along with the growth of the oxide layer, the core of ANP still kept its annealed microstructure.
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http://dx.doi.org/10.1016/j.jmgm.2020.107667DOI Listing
November 2020

A flexible and physically transient electrochemical sensor for real-time wireless nitric oxide monitoring.

Nat Commun 2020 06 25;11(1):3207. Epub 2020 Jun 25.

School of Materials Science and Engineering, The Key Laboratory of Advanced Materials of Ministry of Education, State Key Laboratory of New Ceramics and Fine Processing, Center for Flexible Electronics Technology, Tsinghua University, Beijing, 100084, China.

Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01-100 μM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.
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http://dx.doi.org/10.1038/s41467-020-17008-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316789PMC
June 2020

[Bone remodeling after total hip arthroplasty with anatomic medullary locking prosthesis and its long-term effectiveness].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Jun;34(6):689-695

Department of Orthopedics, First Affiliated Hospital, Soochow University, Suzhou Jiangsu, 215006, P.R.China.

Objective: To investigate the femoral bone remodeling and long-term effectiveness of total hip arthroplasty (THA) with anatomic medullary locking (AML) prosthesis.

Methods: The clinical data of 24 cases (26 hips) who were treated with THA with AML prosthesis between November 1997 and January 2003 were retrospectively analyzed. There were 12 males and 12 females with an age of 32-69 years (mean, 53.7 years). There were 5 cases (5 hips) of avascular necrosis of the femoral head, 6 cases (7 hips) of secondary osteoarthritis of the hip dysplasia, 6 cases (6 hips) of femoral neck fracture, 2 cases (2 hips) of primary osteoarthritis, 3 cases (3 hips) of revision surgery, 1 case (2 hips) of ankylosing spondylitis, 1 case (1 hip) of femoral head fracture. The patients were followed up at immediate, 6 weeks, 3 months, 6 months, 1 year, and then every year after operation for imaging evaluation (X-ray film was taken immediately after operation to evaluate the femoral isthmus compression, Engh standard was used to evaluate the biological fixation of the femoral shaft prosthesis, and Brooker method was used to evaluate the occurrence of heterotopic ossification); bone reconstruction evaluation [reconstruction of prosthesis and bone interface (type of bone reaction, Gruen zone, incidence, and occurrence time were recorded), reconstruction of bone around prosthesis (proximal femur stress shielding bone absorption was evaluated according to Engh and Bobyn methods, and bone mineral density change rate was measured)]; clinical efficacy evaluation [Harris score for efficacy, visual analogue scale (VAS) score for thigh pain].

Results: All patients were followed up 15 years and 2 months to 20 years and 4 months, with a median of 16 years and 6 months. At immediate after operation, 24 hips (92.3%) had good femoral isthums compression, 24 hips (92.3%) had good bone ingrowth. Heterotopic ossification occurred in 2 patients with degree 1, 2 patients with degree 2, and 1 patient with degree 3 at 3-6 months after operation. Hyperplastic bone reactions were more common in Gruen 2, 3, 4, 5, 6, 10, 11, and 12 zones, mainly occurring at 6-20 months after operation, with the incidence of 3.8%-69.2%, with the highest incidence of spot welding. All absorptive bone reactions were osteolysis, which was common in Gruen 1 and 7 zones, and mainly occurred at 8 years after operation, with an incidence of 42.3%. No clear line (area) or enlarged sign of medullary cavity was observed. Twenty-one hips (80.8%) had 1 degree stress shieding, and 5 hips (19.2%) had 2 degree stress shieding. It mainly occurred at 10-24 months after operation in Gruen 1 and 7 zones. Dual energy X-ray absorptiometry showed that bone mineral density mainly decreased in Gruen 1, 2, 6, and 7 zones, mainly increased in Gruen 3, 4, and 5 zones. Bone mineral density loss progressed slowly after 2 years of operation, and it was stable in 5-8 years, but decreased rapidly in 8-9 years, and stabilized after 10 years. The Harris score increased from 51.1±6.2 before operation to 88.3±5.1 at last follow-up ( =-21.774, =0.000). Mild thigh pain occurred in only 2 cases (7.7%) with the VAS score of 2. No aseptic loosening or revision of femoral prosthesis occurred during the follow-up.

Conclusion: The application of AML prosthesis in THA has a good bone remodeling and a good long-term effectiveness.
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http://dx.doi.org/10.7507/1002-1892.201910033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171526PMC
June 2020

Validation of a Double-Sandwich Enzyme-Linked Immunoassay for Pharmacokinetic Study of an rh-aFGF Hydrogel in Rat Skin and Serum.

Front Pharmacol 2020 19;11:700. Epub 2020 May 19.

The Department of Dermatology of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

In this study, we validated a double-sandwich enzyme-linked immunosorbent assay (ELISA) to investigate the pharmacokinetics of a recombinant human acidic fibroblast growth factor (rh-aFGF) hydrogel in rat skin and serum. A total of 130 Sprague-Dawley rats were divided into a control group, rh-aFGF hydrogel group, and a positive-control group (commercial rh-aFGF-Ai). We first determined the dilution ratio of skin homogenate and then validated the quantitative range, specificity, precision, and accuracy of our double-sandwich ELISA method, as well as the stability of our rh-aFGF hydrogel. For our pharmacokinetic study, skin and serum samples were collected at 0.5, 1, 2, 4, 6, and 10 h after rh-aFGF administration, and the concentration of rh-aFGF was measured by ELISA. The results showed that a 10-fold dilution of the skin tissue homogenate circumvented non-specific interference with endogenous proteins. The quantitative scope of the rh-aFGF calibration curve ranged from 62.5 to 4,000 pg/mL. The precision and accuracy of rh-aFGF quality-control samples were below 20%. Furthermore, bFGF, FGF21, KGF-2, and insulin did not interfere with the detection of aFGF, confirming that our method was specific. Rh-aFGF was stable under normal storage conditions. The maximum concentration (C) and time to peak (T) of the rh-aFGF hydrogel were 909.2 pg/cm and 0.5 h, respectively. The relative bioavailability (F) of the rh-aFGF hydrogel was 120% compared with that of rh-aFGF-Ai. The serum concentration of rh-aFGF was too low to be detected. Taken together, the pharmacokinetics of this rh-aFGF hydrogel provide further support for clinical research on rh-aFGF, and our double-sandwich ELISA method may be useful for pharmacokinetic studies of other protein-based drugs.
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http://dx.doi.org/10.3389/fphar.2020.00700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248203PMC
May 2020

IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters.

Respir Res 2020 May 24;21(1):123. Epub 2020 May 24.

Department of Pediatrics, the First Affiliated Hospital of Xiamen University, Xiamen, 361003, China.

Background: Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated.

Methods: To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM.

Results: We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure.

Conclusions: Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.
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http://dx.doi.org/10.1186/s12931-020-01368-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245756PMC
May 2020
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