Publications by authors named "Libo Zhao"

160 Publications

Model-Based Meta-Analysis in Psoriasis: A Quantitative Comparison of Biologics and Small Targeted Molecules.

Front Pharmacol 2021 1;12:586827. Epub 2021 Jul 1.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed. Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90). A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71-92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12-92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91-77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8-75.7%). What's more, the risankizumab provided the highest response of PASI90 at week 16 and week 24. This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.
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http://dx.doi.org/10.3389/fphar.2021.586827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281289PMC
July 2021

BoDV-1 infection induces neuroinflammation by activating the TLR4/MyD88/IRF5 signaling pathway, leading to learning and memory impairment in rats.

J Med Virol 2021 Jul 14. Epub 2021 Jul 14.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Borna disease virus (BoDV-1) can infect the hippocampus and limbic lobes of newborn rodents, causing cognitive deficits and abnormal behavior. Studies have found that neuroinflammation caused by viral infection in early life can affect brain development and impair learning and memory function, revealing the important role of neuroinflammation in cognitive impairment caused by viral infection. However, there is no research to explore the pathogenic mechanism of BoDV-1 in cognition from the direction of neuroinflammation. We established a BoDV-1 infection model in rats, and tested the learning and memory impairment by Morris water maze (MWM) experiment. RNAseq was introduced to detect changes in the gene expression profile of BoDV-1 infection, focusing on inflammation factors and related signaling pathways. BoDV-1 infection impairs the learning and memory of Sprague-Dawley rats in the MWM test and increases the expression of inflammatory cytokines in the hippocampus. RNAseq analysis found 986 differentially expressed genes (DEGs), of which 845 genes were upregulated and 141 genes were downregulated, and 28 genes were found to be enriched in the toll-like receptor (TLR) pathway. The expression of TLR4, MyD88, and IRF5 in the hippocampus was significantly changed in the BoDV-1 group. Our results indicate that BoDV-1 infection stimulates TLR4/MyD88/IRF5 pathway activation, causing the release of downstream inflammatory factors, which leads to neuroinflammation in rats. Neuroinflammation may play a significant role in learning and memory impairment caused by BoDV-1 infection.
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http://dx.doi.org/10.1002/jmv.27212DOI Listing
July 2021

A flexible electrostatic nanogenerator and self-powered capacitive sensor based on electrospun polystyrene mats and graphene oxide films.

Nanotechnology 2021 Jul 14;32(40). Epub 2021 Jul 14.

State Key Laboratory for Manufacturing Systems Engineering, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi'an Jiaotong University, Xi'an, Shannxi 710049, People's Republic of China.

Electrostatic nanogenerators or capacitive sensors that leverage electrostatic induction for power generation or sensing, has attracted significant interests due to their simple structure, ease of fabrication, and high device stability. However, in order for such devices to work, an additional power source or a post-charging process is necessary to activate the electrostatic effect. In this work, an electrostatic nanogenerator is fabricated using electrospun polystyrene (PS) mats and dip-coated graphene oxide (GO) films as the self-charged components. The electret performances of the PS mats and GO films are characterized via the electrostatic force microscopy phase shift and surface potential measurements. With a multilayer device structure that consists of top electrodes/GO films/spacer/electrospun PS mats/bottom electrodes, the resultant device acts as an electrostatic generator that operates in the noncontact mode. The nanogenerator can output a peak voltage of ca. 6.41 V and a peak current of ca. 6.57 nA at a rate of 1 Hz of mechanical compression, and with no attenuation of electrical outputs even after 50 000 cycles over a 13 h period. Furthermore, this as-prepared device is also capable of serving as a self-powered capacitive sensor for detection of tiny mechanical impacts and measurement of human finger bending. This results of this work provides a new avenue to easily fabricate electrostatic nanogenerators with high durability and self-powered capacitive sensors for the detection of small impacts.
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http://dx.doi.org/10.1088/1361-6528/ac1019DOI Listing
July 2021

A thin-film temperature sensor based on a flexible electrode and substrate.

Microsyst Nanoeng 2021 1;7:42. Epub 2021 Jun 1.

State Key Laboratory for Mechanical Manufacturing Systems Engineering, Xi'an Jiaotong University, 710049 Xi'an, China.

Accurate temperature measurements can efficiently solve numerous critical problems and provide key information. Herein, a flexible micro-three-dimensional sensor, with a combination of platinum and indium oxide to form thermocouples, is designed and fabricated by a microfabrication process to achieve in situ real-time temperature measurements. The stability and reliability of the sensor are greatly improved by optimizing the process parameters, structural design, and preparation methods. A novel micro-three-dimensional structure with better malleability is designed, which also takes advantage of the fast response of a two-dimensional thin film. The as-obtained flexible temperature sensor with excellent stability and reliability is expected to greatly contribute to the development of essential components in various emerging research fields, including bio-robot and healthcare systems. The model of the application sensor in a mask is further proposed and designed to realize the collection of health information, reducing the number of deaths caused by the lack of timely detection and treatment of patients.
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http://dx.doi.org/10.1038/s41378-021-00271-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166532PMC
June 2021

Effect of More Intensive LDL-C-Lowering Therapy on Long-term Cardiovascular Outcomes in Early-Phase Acute Coronary Syndrome: A Systematic Review and Meta-analysis.

Clin Ther 2021 Jun 3. Epub 2021 Jun 3.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address:

Purpose: The effect of more intensive LDL-C-lowering therapy (ILLT) on long-term cardiovascular outcomes during the early phase of acute coronary syndromes (ACSs) remains uncertain. We aimed to explore the influence of more intensive LDL-C-lowering therapyduring the early disease phase on long-term cardiovascular events among patients with ACSs.

Methods: Randomized controlled trials that focused on the effect of more ILLT during early-phase ACSs on long-term major adverse cardiac events (MACEs) were searched in electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases) from database inception until November 23, 2019. The end points included the incidence of MACEs, myocardial infarction, stroke, revascularization, heart failure, and death events. Study risk of bias was assessed using the Cochrane Collaboration tools. Fixed- or random-effects models and meta-regression were performed to evaluate the association between baseline/proportional reduction of LDL-C levels during early-phase disease and the risk of end points using risk ratios with 95% CIs.

Findings: A total of 53,199 participants were involved from 19 studies. The risk of MACEs decreased by 17% (95% CI, 0.76-0.90; P = 0.0012) for more intensive versus control therapy but varied by baseline and proportional reduction of LDL-C levels during early disease phase. The risk reduction of MACEs for more intensive versus control therapy among different subgroups was 26% (95% CI, 0.57-0.95; P = 0.06) with a baseline level >130 mg/dL, 23% (95% CI, 0.63-0.94; P = 0.02) with a baseline level of 100 to 130 mg/dL, and 10% (95% CI, 0.83-0.99; P = 0.07) with a baseline level <100 mg/dL. A significant difference of risk reduction for MACEs existed between patients treated with statin plus ezetimibe versus statin alone in the subgroup with a baseline level >130 mg/dL and proportional reduction >50%. Patients treated with more intensive therapy benefited from reduced risk of myocardial infarction, stroke, revascularization, and heart failure compared with control therapy.

Implications: More ILLT during early disease phase could significantly reduce the risk of long-term cardiovascular outcome in patients with ACSs. This benefit was most pronounced in patients with higher baseline and larger reduction of LDL-C levels in MACEs.
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http://dx.doi.org/10.1016/j.clinthera.2021.04.019DOI Listing
June 2021

Comprehensive analysis of the lysine acetylome and succinylome in the hippocampus of gut microbiota-dysbiosis mice.

J Adv Res 2021 05 7;30:27-38. Epub 2020 Dec 7.

Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.

Introduction: Major depressive disorder is caused by gene-environment interactions, and the host microbiome has been recognized as an important environmental factor. However, the underlying mechanisms of the host-microbiota interactions that lead to depression are complex and remain poorly understood.

Objectives: The present study aimed to explore the possible mechanisms underlying gut microbiota dysbiosis-induced depressive-like behaviors.

Methods: We used high-performance liquid chromatography-tandem mass spectrometry to analyze alterations in the hippocampal lysine acetylome and succinylome in male mice that had received gut microbiota from fecal samples of either patients with major depressive disorder or healthy controls. This was followed by bioinformatic analyses.

Results: A total of 315 acetylation sites on 223 proteins and 624 succinylation sites on 494 proteins were differentially expressed in the gut microbiota-dysbiosis mice. The significantly acetylated proteins were primarily associated with carbon metabolism disruption and gene transcription suppression, while the synaptic vesicle cycle and protein translation were the most significantly altered functions for succinylated proteins. Additionally, our findings suggest that gut microbiota dysbiosis disturbs mitochondria-mediated biological processes and the MAPK signaling pathway through crosstalk between acetylation and succinylation on relevant proteins.

Conclusions: This is the first study to demonstrate modifications in acetylation and succinylation in gut microbiota-dysbiosis mice. Our findings provide new avenues for exploring the pathogenesis of gut microbiota dysbiosis-related depression, and highlight potential targets for depression treatment.
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http://dx.doi.org/10.1016/j.jare.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132208PMC
May 2021

Integrated Pharmacological Analysis on the Mechanism of Fuyou Formula in Treating Precocious Puberty.

Front Pharmacol 2021 7;12:649732. Epub 2021 May 7.

Department of Pharmacy, National Center for Children Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Fu-you formula (FY), a Traditional Chinese Medicine (TCM) formula composed of 12 herbs, as an in-hospital preparation, has been used treat to precocious puberty (PP) for decades. However, the lack of phytochemical characterization and mechanism of FY remains the main limitation for its spreading. In this study, we analyze the components and mechanisms of FY in PP, based on the integrated pharmacology. Investigated main constituents, targets, pathways of FY by using an integrative pharmacology, and recognized main constituents by HPLC-MS/MS. Then, observed the levels of Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E) in danazol-induced PP in Sprague-Dawley (SD) rats. Lastly, retrospective study analyzed the clinical data of 575 patients who were diagnosed PP, treated by the FY, and followed-up in our hospital from 2014-2020. The result that total of 116 important candidate targets were selected based on pharmacological analysis. Selected the top 10 values key targets such as the estrogen receptor alpha (ESR1) and insulin-like growth factor 1 (IGF1), were localized and the related gene functions were determined. Gene functions were associated with biological regulation, a cellular process, or signaling pathway, such as the Estrogen signaling pathway, MAPK signaling pathway and PI3K-Akt signaling pathway. By recognizing the five compounds related to the ESR1 and IGF1, which are Quercetin, kaempferol, Luteolin, Apigenin, and Emodin. The results of the molecular docking study further showed that the flavonoids had a strong binding affinity for ESR1 and IGF1 after docking into the crystal structure. The results showed that the FY could effectively reduce E, LH, and FSH levels in SD rats. Furthermore, the results of the retrospective analysis of medical records showed that the FY could remarkably reduce E levels in girls with PP.
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http://dx.doi.org/10.3389/fphar.2021.649732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138182PMC
May 2021

Methotrexate Polyglutamates Analysis by Chromatography Methods in Biological Matrices: A Review.

Anal Sci 2021 May 21. Epub 2021 May 21.

Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University.

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http://dx.doi.org/10.2116/analsci.21R001DOI Listing
May 2021

Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment.

Transl Psychiatry 2021 05 20;11(1):303. Epub 2021 May 20.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, China.

Depression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. Moreover, we identified 15 serum metabolites responsible for discriminating R and NR group. Those differential metabolites were mainly involved in phospholipid metabolism. Significantly, the bacterial OTUs belonging to family Lachnospiraceae, Helicobacteraceae, and Muribaculaceae formed strong co-occurring relationships with serum metabolites, indicating alternations of gut microbiome and metabolites as potential mediators in efficiency of ESC treatment. Together, our study demonstrated that the alterations of microbial compositions and metabolic functions might be relevant to the different response to ESC, which shed new light in uncovering the mechanisms of differences in efficacy of antidepressants.
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http://dx.doi.org/10.1038/s41398-021-01428-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138009PMC
May 2021

The Natural History and Reperfusion Therapy Outcomes of Acute Ischemic Stroke due to Isolated M2 Occlusions.

Biomed Res Int 2021 27;2021:6626604. Epub 2021 Apr 27.

Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.

Objective: Currently, the standard treatment modality for patients with acute ischemic stroke (AIS) presenting with isolated M2 occlusions is not specific. We therefore assessed the difference in treatment outcomes for patients with isolated M2 occlusions.

Methods: We retrospectively analyzed consecutive patients with AIS presenting with isolated M2 occlusions from October 1, 2018, to June 30, 2020. Patients were divided into 3 groups based on the treatments they received: no reperfusion therapy (NRT), intravenous thrombolysis treatment (IVT), and endovascular intervention (EVT), which comprised IVT in conjunction with EVT or EVT alone. The primary outcomes were improvements in modified Rankin Scale (mRS) scores at 90 days and National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours after treatment compared with the baseline. The secondary efficacy outcome comprised a good outcome rate defined as a 90 - day mRS score ≤ 2, final infarct volume (FIV), 90-day mortality rate, and successful recanalization rate, which was defined as a modified thrombolysis in cerebral infarction score ≥ 2b. Safety outcomes included symptomatic intracerebral hemorrhage and procedure-related complications.

Results: Seventy patients were enrolled and divided into 3 groups: the NRT group ( = 25), IVT group ( = 27), and EVT group ( = 18). Twenty-four-hour posttreatment NIHSS scores were substantially decreased by EVT compared with NRT (adjusted -4.01, 95% confidence interval [CI] -6.60 to -1.43; = 0.003) or IVT (adjusted , -3.61 [95% CI, -6.45 to -0.77]; = 0.013). Compared with the outcomes observed after NRT, patients who received EVT were more likely to achieve lower 90-day mRS scores (adjusted , -1.42 [95% CI, -2.66 to -0.63]; = 0.007), higher good outcome rates (adjusted odds ratio, 8.73 [95% CI, 1.43-53.24]; = 0.019), and smaller FIVs (adjusted , -29.66 [95% CI, -59.73 to 0.42]; = 0.048). The recanalization rate of EVT was high (88.89%), and procedure-related complications were rare (5.56%).

Conclusions: For acute, isolated M2 occlusions, EVT could dramatically and rapidly improve neurological deficits with high safety and effectiveness. These changes were observed at 24 hours after treatment and were maintained over the long term.
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http://dx.doi.org/10.1155/2021/6626604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096556PMC
May 2021

Discontinuation Syndrome of Extended-Release Venlafaxine during the COVID-19 Epidemic.

Psychiatr Danub 2021 ;33(1):121-122

Chongqing Key Laboratory of Cerebrovascular Disease Research, Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.

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April 2021

Quality assessment of clinical guidelines on probiotics therapy in children with IBD using the AGREE II instrument.

J Clin Pharm Ther 2021 Aug 25;46(4):1155-1165. Epub 2021 Mar 25.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

What Is Known And Objective: The morbidity of inflammatory bowel disease (IBD) in children has significantly increased in recent years. The diagnosis and treatment of IBD in children are progressing rapidly. Probiotics have been extensively studied in a variety of gastrointestinal diseases. However, the effectiveness of probiotics for IBD is inconsistent. This study summarized the recommendations on using probiotics from high-quality guidelines, and the recommendations may assist clinicians in the treatment of paediatric IBD.

Methods: Guidelines were identified by searching PubMed, EMBASE, three Chinese literature databases and websites of relevant institutions. Guidelines that addressed the treatments of paediatric IBD in Chinese and English were included and evaluated with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument to assess methodological quality. The levels of recommendation were also evaluated, and finally, the recommendations of probiotics application in IBD were summarized.

Results And Discussion: A total of 14 guidelines that met inclusion criteria were identified and evaluated, and 12 of them were evidence-based (EB) guidelines, and the other two guidelines were developed by consensus. The mean percentages for the AGREE II domain scores were as follows: "Scope and purpose" 97.22%, "Clarity of presentation" 93.78%, "Applicability" 55.85%, "Editorial independence" 59.92%, "Stakeholder involvement" 74.34%, and "Rigor of development" 71.58%. Three guidelines received the Grade A-"Strongly recommended," the rest of the guidelines received a B grade-"Recommended with modifications" in the overall assessment.

What Is New And Conclusion: The overall quality of the guidelines on IBD management in children was high. Conversely, the fundamental recommendations on the application of probiotics in the treatment of IBD varied. For instance, the recommendations of probiotics on Crohn's disease (CD) were not available by any of the analysed guidelines, the recommendations of utilizing probiotics in treating ulcerative colitis (UC) were not uniform as several guidelines considered using VSL#3 or Escherichia coli Nissle 1917 for the treatment.
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http://dx.doi.org/10.1111/jcpt.13422DOI Listing
August 2021

Optimization of Busulfan Dosing Regimen in Pediatric Patients Using a Population Pharmacokinetic Model Incorporating GST Mutations.

Pharmgenomics Pers Med 2021 15;14:253-268. Epub 2021 Feb 15.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, Beijing, People's Republic of China.

Purpose: The aim of this study was to develop a novel busulfan dosing regimen, based on a population pharmacokinetic (PPK) model in Chinese children, and to achieve better area under the concentration-time curve (AUC) targeting.

Patients And Methods: We collected busulfan concentration-time samples from 69 children who received intravenous busulfan prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). A population pharmacokinetic model for busulfan was developed by nonlinear mixed effect modelling and was validated by an external dataset (n=14). A novel busulfan dosing regimen was developed through simulated patients, and has been verified on real patients. Limited sampling strategy (LSS) was established by Bayesian forecasting. Mean absolute prediction error (MAPE) and relative root mean Squared error (rRMSE) were calculated to evaluate predictive accuracy.

Results: A one-compartment model with first-order elimination best described the data. genotypes, body surface area (BSA) and aspartate aminotransferase (AST) were found to be significant covariates of Bu clearance, and BSA had significant impact of the volume of distribution. Moreover, two equations were obtained for recommended dose regimens: dose (mg)=34.14×BSA (m)+3.75 (for ), Dose (mg)=30.99×BSA (m)+3.21 (for ). We also presented a piecewise dosage based on BSA categories for each mutation. A two-point LSS, two hours and four hours after dosing, behaved well with acceptable prediction precision (rRMSE=1.026%, MAPE=6.55%).

Conclusion: We recommend a -BSA and BSA-based dosing (Q6 h) based on a PPK model for personalizing busulfan therapy in pediatric population. Additionally, an optimal LSS (C and C) provides convenience for therapeutic drug monitoring (TDM) in the future.
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http://dx.doi.org/10.2147/PGPM.S289834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894888PMC
February 2021

Preparation, Characterization, Pharmacokinetic, and Therapeutic Potential of Novel 6-Mercaptopurine-Loaded Oral Nanomedicines for Acute Lymphoblastic Leukemia.

Int J Nanomedicine 2021 12;16:1127-1141. Epub 2021 Feb 12.

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.

Background: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. It requires a long and rigorous course of chemotherapy treatments. 6-Mercaptopurine (6-MP) is one of the primary drugs used in chemotherapy. Unfortunately, its efficacy has been limited due to its insolubility, poor bioavailability and serious adverse effects. To overcome these drawbacks, we constructed 6-mercaptopurine (6-MP)-loaded nanomedicines (6-MPNs) with biodegradable poly(lactide-co-glycolide) (PLGA) to enhance the anticancer efficacy of 6-MP.

Methods: We prepared the 6-MPNs using a double-emulsion solvent evaporation method, characterizing them for the physicochemical properties. We then investigated the plasma, intestinal region and other organs in Sprague Dawley (SD) rats for pharmacokinetics. Additionally, we evaluated its anticancer efficacy in vitro on the human T leukemia cell line Jurkat and in vivo on the ALL model mice.

Results: The 6-MPNs were spherical in shape with uniform particle size and high encapsulation efficiency. The in vitro release profile showed that 6-MPNs exhibited a burst release that a sustained release phase then followed. The apoptosis assay demonstrated that 6-MPNs could improve the in vitro cytotoxicity in Jurkat cells. Pharmacokinetics profiles revealed that 6-MPNs had improved oral bioavailability. Tissue distribution experiments indicated that 6-MPNs increased the duodenum absorption of 6-MP, at the same time having a low accumulation of the toxic metabolites of 6-MP. The in vivo pharmacodynamics study revealed that 6-MPNs could prolong the survival time of the ALL model mice. The prepared 6-MPNs, therefore, have superior properties in terms of anticancer efficacy against ALL with reduced systemic toxicity.

Conclusion: Our nanomedicines provide a promising delivery strategy for 6-MP; they offer a simple preparation method and high significance for clinical translation.
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http://dx.doi.org/10.2147/IJN.S290466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886780PMC
March 2021

Population Pharmacokinetics and Dosage Optimization of Linezolid in Critically Ill Pediatric Patients.

Antimicrob Agents Chemother 2021 Feb 8. Epub 2021 Feb 8.

Pediatric intensive care unit, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China

Linezolid is an oxazolidinone antibiotic exhibiting efficacy against multidrug-resistant (MDR) Gram-positive-related infections. However, its population pharmacokinetic (PopPK) profile in Chinese critically ill children has not been characterized. Optimal dosing regimens should be established according to the PopPK/pharmacodynamic(PD) properties of linezolid in the specific population. This work aims to describe the pharmacokinetic (PK) properties of linezolid, assess the factors affecting interpatient variability, and establish an optimized regimen for children in pediatric intensive care unit (PICU). A single-center, prospective, open-labeled PK study was performed. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to measure the plasma levels during linezolid treatment. PopPK analysis was conducted using Phoenix NLME software. Sixty-three critically ill pediatric patients were included. The data showed good fit for a two-compartment model with linear elimination. Body weight and aspartate aminotransferase (AST) were the most significant covariates explaining variabilities in linezolid PK for the pediatric population. Therapeutic target was defined as the ratio of the area under drug plasma concentration-time curve over 24 h to minimum inhibitory concentration (AUC/MIC) of >80. Different dosing regimens were evaluated using Monte Carlo simulation to determine the optimal dosage strategy for linezolid. Although the probability of target attainment (PTA) was high (>96%) for 10 mg/kg every 8 h at MIC≤1 mg/L, it was lower than 70% at MIC>1 mg/L. Thus, the dosing regimen required adjustment. When the dosing regimen was adjusted to 15 mg/kg every 6 h, the PTA increased from 63.6% to 94.6% at MIC=2 mg/L, thereby indicating higher treatment success. Children with AST of >40 U/L had significant higher AUC than those with AST of ≤40 U/L (205.45 159.96). Therefore, dosage adjustment was required according to the AST levels. The PopPK characteristics of linezolid in critically ill children were evaluated, and an optimal dosage regimen was constructed based on developmental PopPK/PD model and simulation. (This study has been registered in the Chinese Clinical Trial Registry under no. ChiCTR1900021386.).
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http://dx.doi.org/10.1128/AAC.02504-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092909PMC
February 2021

Alteration of lipids and amino acids in plasma distinguish schizophrenia patients from controls: A targeted metabolomics study.

Psychiatry Clin Neurosci 2021 Apr 5;75(4):138-144. Epub 2021 Feb 5.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Schizophrenia (SCZ) is a serious psychiatric disorder. Metabolite disturbance is an important pathogenic factor in schizophrenic patients. In this study, we aim to identify plasma lipid and amino acid biomarkers for SCZ using targeted metabolomics.

Methods: Plasma from 76 SCZ patients and 50 matched controls were analyzed using the LC/MS-based multiple reaction monitoring (MRM) metabolomics approach. A total of 182 targeted metabolites, including 22 amino acids and 160 lipids or lipid-related metabolites were observed. We used binary logistic regression analysis to determine whether the lipid and amino acid biomarkers could discriminate SCZ patients from controls. The area under the curve (AUC) from receiver operation characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of the biomarkers panel.

Results: We identified 19 significantly differentially expressed metabolites between the SCZ patients and the controls (false discovery rate < 0.05), including one amino acid and 18 lipids or lipid-related metabolites. The binary logistic regression-selected panel showed good diagnostic performance in the drug-naïve group (AUC = 0.936) and all SCZ patients (AUC = 0.948), especially in the drug-treated group (AUC = 0.963).

Conclusions: Plasma lipids and amino acids showed significant dysregulation in SCZ, which could effectively discriminate SCZ patients from controls. The LC/MS/MS-based approach provides reliable data for the objective diagnosis of SCZ.
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http://dx.doi.org/10.1111/pcn.13194DOI Listing
April 2021

Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

Clin Infect Dis 2020 12;71(Suppl 4):S363-S371

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015.

Methods: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System.

Results: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions.

Conclusions: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.
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http://dx.doi.org/10.1093/cid/ciaa1536DOI Listing
December 2020

A Novel Micro-Displacement Sensor Based on Double Optical Fiber Probes Made through Photopolymer Materials.

Materials (Basel) 2020 Dec 1;13(23). Epub 2020 Dec 1.

State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

In this paper, a novel micro-displacement sensor with double optical fiber probes is proposed and designed, which can realize the highly sensitive sensing of longitudinal or lateral micro-displacements. The optical fiber probes are made through photopolymer formulation, and the effects of reaction time and optical power on the growth length of the probe are illustrated. The relationship between light intensity and longitudinal micro-displacement is a power function in the range of 0-100 μm at room temperature with a correlation coefficient of 98.92%. For lateral micro-displacement, the sensitivity is -2.9697 dBm/μm in the range of 0-6 μm with a linear fit of 99.61%. In addition, the linear correlation coefficient decreases as the initial longitudinal distance increases, and the function of these correlation coefficients is also linear with a linearity of 96.14%. This sensor has a simple manufacturing process, low cost, high sensitivity, and fast response speed. It is suitable for harsh environments such as strong electromagnetic interference and corrosivity, and has a broad application prospect in the field of micro-displacement sensing.
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http://dx.doi.org/10.3390/ma13235475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730009PMC
December 2020

[Cardiac functional alterations and its risk factors in elderly patients with obstructive sleep apnea syndrome free of cardiovascular disease].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Nov;40(11):1587-1592

Department of Pulmonary and Critical Care Medicine, General Hospital of PLA, Beijing 100853, China.

Objective: To evaluate the changes of cardiac structure and function and their risk factors in elderly patients with obstructive sleep apnea syndrome (OSA) without cardiovascular complications.

Methods: Eighty-two elderly OSA patients without cardiovascular disease admitted between January, 2015 and October, 2016 were enrolled in this study. According to their apnea-hypopnea index (AHI, calculated as the average number of episodes of apnoea and hypopnoea per hour of sleep), the patients were divided into mild OSA group (AHI < 15) and moderate to severe OSA group (AHI ≥ 15). The demographic data and the general clinical data were recorded and fasting blood samples were collected from the patients on the next morning following polysomnographic monitoring for blood cell analysis and biochemical examination. Echocardiography was performed within one week after overnight polysomnography, and the cardiac structure, cardiac function and biochemical indexes were compared between the two groups.

Results: Compared with those with mild OSA group, the patients with moderate to severe OSA had significantly higher hematocrit (0.22±0.08 0.17±0.04, =0.032) and serum creatinine level (70.94± 27.88 54.49±34.22 μmol/L, =0.022). The left ventricular ejection fraction, interventricular septal thickness, left ventricular posterior wall thickness, left atrial diameter and left ventricular end-diastolic diameter were all similar between the two groups. With a similar early diastolic mitral flow velocity (E) between the two groups, the patients with moderate to severe OSA had a significantly higher late diastolic mitral flow velocity (A) (70.35±6.87 64.09±8.31, =0.0001) and a significantly lower E/A ratio (0.98±0.06 1.08±0.05, =0.0001) than the patients with mild OSA. Multiple linear regression showed that the E/A ratio was negatively correlated with AHI (β =- 0.645, =0.0001).

Conclusions: Cardiac diastolic function impairment may occur in elderly patients with moderate or severe OSA who do not have hypertension or other cardiovascular diseases, and the severity of the impairment is positively correlated with AHI.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.11.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704368PMC
November 2020

Closed-Form Expressions on CMUTs With Layered Anisotropic Microplates Under Residual Stress and Pressure.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 May 26;68(5):1828-1843. Epub 2021 Apr 26.

Capacitive micromachined ultrasonic transducers (CMUTs) are promising in the emerging fields of personalized ultrasonic diagnostics, therapy, and noninvasive 3-D biometric. However, previous theories describing their mechanical behavior rarely consider multilayer and anisotropic material properties, resulting in limited application and significant analysis errors. This article proposes closed-form expressions for the static deflection, collapse voltage, and resonant frequency of circular-microplate-based CMUTs, which consider both the aforementioned properties as well as the effects of residual stress and hydrostatic pressure. These expressions are established by combining the classical laminated thin plate (CLTP) theory, Galerkin method, a partial expansion approach for electrostatic force, and an energy equivalent method. A parametric study based on finite-element method simulations shows that considering the material anisotropy can significantly improve analysis accuracy (~25 times higher than the theories neglecting the material anisotropy). These expressions maintain accuracy across almost the whole working voltage range (up to 96% of collapse voltages) and a wide dimension range (diameter-to-thickness ratios of 20-80 with gap-to-thickness ratios of ≤2). Furthermore, their utility in practical applications is well verified using numerical results based on more realistic boundary conditions and experimental results of CMUT chips. Finally, we demonstrate that the high accuracy of these expressions at thickness-comparable deflection results from the extended applicable deflection range of the CLTP theory when it is used for electrostatically actuated microplates.
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http://dx.doi.org/10.1109/TUFFC.2020.3037320DOI Listing
May 2021

[Correlation between severity of obstructive sleep apnea syndrome and red cell distribution width in elderly patients].

Nan Fang Yi Ke Da Xue Xue Bao 2020 May;40(5):703-707

Department of Respiratory Disease, Second Medical Center of General Hospital of PLA, Beijing 100853, China.

Objective: To investigate the correlation between the severity of obstructive sleep apnea syndrome (OSAS) and red cell distribution width (RDW) in elderly patients.

Methods: A cross-sectional study was conducted among 311 elderly patients diagnosed with OSAS in the snoring clinic between January, 2015 and October, 2016 and 120 healthy controls without OSAS from physical examination populations in the General Hospital of PLA. The subjects were divided into control group with apnea-hypopnea index (AHI) <5 (=120), mild OSAS group (AHI of 5.0-14.9; =90), moderate OSAS group (AHI of 15.0-29.9; =113) and severe OSAS group (AHI ≥ 30; =108). The clinical characteristics and the results of polysomnography, routine blood tests and biochemical tests of the subjects were collected. Multiple linear regression analysis was used to examine the correlation between OSAS severity and RDW.

Results: The levels of RDW and triglyceride were significantly higher in severe OSAS group than in the other groups ( < 0.01). The levels of fasting blood glucose and body mass index were significantly higher in severe and moderate OSAS groups than in mild OSAS group and control group ( < 0.05 or < 0.01). Multiple linear regression analysis showed that AHI was positively correlated with body mass index (β=0.111, =0.032) and RDW (β=0.106, =0.029). The area under ROC curve of RDW for predicting the severity of OSAS was 0.687 (=0.0001).

Conclusions: The RDW increases as OSAS worsens and may serve as a potential marker for evaluating the severity of OSAS.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.05.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277309PMC
May 2020

Novel high-performance piezoresistive shock accelerometer for ultra-high-g measurement utilizing self-support sensing beams.

Rev Sci Instrum 2020 Aug;91(8):085001

State Key Laboratory for Manufacturing Systems Engineering, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Collaborative Innovation Center of Suzhou Nano Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.

This study describes the design and implementation of a novel high-performance piezoresistive accelerometer for the measurement of shock acceleration of up to 100 000 g. The structure of the accelerometer sensing chip was implemented with piezoresistive self-support beams. The piezoresistors were made in piezoresistive sensing micro-beams, which were independent of support beams, to weaken the correlation between measuring sensitivity and resonant frequency. In this way, the measuring sensitivity of the proposed novel piezoresistive accelerometer could be increased without sacrificing resonant frequency. The optimization of structural dimensions of the sensing chip was conducted through finite element method simulations. The sensing chip was fabricated employing bulk-micromachining technology with a silicon-on-insulator wafer. The fabricated accelerometer was encapsulated in stainless shell and evaluated using the Hopkinson bar system. Results demonstrated the proposed accelerometer with the measuring sensitivity of 0.54 µV/g/V and the resonant frequency of 445 kHz.
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http://dx.doi.org/10.1063/5.0008451DOI Listing
August 2020

Simultaneous UPLC-MS/MS Determination of 6-mercaptopurine, 6-methylmercaptopurine and 6-thioguanine in Plasma: Application to the Pharmacokinetic Evaluation of Novel Dosage forms in Beagle Dogs.

Curr Pharm Des 2020 ;26(46):6013-6020

Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

Background: 6-Mercaptopurine (6-MP) is widely used to treat pediatric acute lymphoblastic leukemia (ALL). Mini-tablets of 5 mg per tablet were developed for precision individual therapy for children and individuals with poor thiopurine S-methyltransferase (TPMT) or nucleoside diphophate-linked moiety X-type motif 15 (NUDT15) metabolism. This study investigated the pharmacokinetic profiles of mini-tablets and conventional tablets with an improved ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method.

Methods: After giving 8 healthy beagle dogs 50 mg 6-MP in different dosage forms, plasma samples collected at different time points were analyzed for pharmacokinetic evaluation. The samples were precipitated by methanol with 0.05% formic acid and separated on a Waters Atlantis T3 column (2.1 × 150 mm, 3 μm particles) using 0.1% formic acid in water and methanol at a flow rate of 0.4 mL/min in 4 min.

Results: This method showed good linearity, accuracy, precision and stability with a detection range of 5.0-500.0 ng/mL for 6-MP, 6-methylmercaptopurine (6-MMP) and 6-thioguanine (6-TG). The main parameters, half-life of apparent terminal disposition, maximum observed plasma concentration, total AUC extrapolated to infinity, AUC since initiation of the experiment, mean residence time, distribution volume and clearance were 1.62 ± 0.87 hours, 90.58 ± 60.43 ng/mL, 151.20 ± 94.18 ng·h/mL, 292.06 ± 184.02 ng·h2/mL, 1.90 ± 0.92 hours, 864.08 ± 538.52 L, and 432.75 ± 360.64 L/h for conventional tablets and 1.70 ± 1.10 hours, 84.15 ± 39.50 ng/mL, 147.70 ± 51.80 ng·h/mL, 300.92 ± 124.48 ng·h2/mL, 2.07 ± 0.50 hours, 756.90 ± 324.00 L, and 340.75 ± 125.81 L/h for minitablets, respectively. Paired t-tests showed no significant difference in any of the evaluated pharmacokinetic parameters between the two types tablets (P > 0.05).

Conclusion: Two dosage forms showed the same pharmacokinetic characteristics. This developing, novel formulation will help to provide a more accurate and optimal dosing regimen of 6-MP for humans in the future.
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http://dx.doi.org/10.2174/1381612826999200820161343DOI Listing
April 2021

WRe26-InO probe-type thin film thermocouples applied to high temperature measurement.

Rev Sci Instrum 2020 Jul;91(7):074901

State Key Laboratory for Mechanical Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710048, China.

A novel probe-type thin film thermocouple has been fabricated successfully for high temperature measurement applications. WRe26 (tungsten-26% rhenium)-InO thermoelectric materials were used in the thermocouples to achieve high thermoelectric output and high temperature resistance. The films were deposited on a cylindrical substrate by magnetron sputtering technology. The annealing process of the thermocouples was studied to achieve optimal performance. The calibration results showed the thermoelectric output of WRe26-InO thin film thermocouples reached 93.7 mv at 700 °C, and its sensitivity was 165.5 µV/°C under the temperature of the cold junction, which was 133.8 °C. The thermocouples developed in this work have great potential for practical applications.
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http://dx.doi.org/10.1063/5.0008887DOI Listing
July 2020

Equivalent Circuit Model for a Large Array of Coupled Piezoelectric Micromachined Ultrasonic Transducers With High Emission Performance.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Mar 25;68(3):718-733. Epub 2021 Feb 25.

In this article, an analytical equivalent circuit model is established for the piezoelectric micromachined ultrasonic transducer (PMUT) cell and array with a combination of the annular and circular diaphragms used for structural optimization and complex array design. Based on this model, a comprehensive analysis is conducted on the acoustic-structural coupling of an annular and circular diaphragm-coupled PMUT (AC-PMUT) with a new excitation method. The model-derived results are in good agreement with the simulation and experimental results. Then, an optimized design has been presented to achieve high-output pressure and a good array working performance. In summary, a comparison of the array working performance is conducted between the arrays that consist of AC-PMUTs and traditional circular diaphragm PMUTs (C-PMUTs). The results indicate that the AC-PMUT array has a much lower crosstalk effect than that of the traditional C-PMUT array. By this means, the AC-PMUT array can fully use the high vibration amplitude achieved by each AC-PMUT cell to improve its output ability. As a result, the highest ultrasonic output pressure generated by the AC-PMUT array in its resonant condition can achieve an increase of 155%, compared with that generated by the C-PMUT array.
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http://dx.doi.org/10.1109/TUFFC.2020.3008179DOI Listing
March 2021

The first study in pediatric: Population pharmacokinetics of sirolimus and its application in Chinese children with immune cytopenia.

Int J Immunopathol Pharmacol 2020 Jan-Dec;34:2058738420934936

Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

The narrow therapeutic index and large inter-individual variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring (TDM) necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with immune cytopenia. The objective of this study was to characterize the PK of sirolimus in pediatric patients with immune cytopenia and to develop a population PK model in Chinese children and evaluate its utility for dose individualization. A total of 27 children with either acquired or congenital immune cytopenia aged 8.16 ± 3.60 years (range: 1-15 years) were included. TDM data for sirolimus were collected. The population PK model of sirolimus was described using the nonlinear mixed-effects modeling (Phoenix NLME 1.3 software) approach. Covariate analysis was applied to select candidate factors associated with PK parameters. The final model was validated using bootstrap (1000 runs) and visual predictive check (VPC) method. A one-compartment model with first-order absorption and elimination was developed. The outcome parameters were as follows: apparent clearance (CL/F) 5.63 L/h, apparent distribution volume (V/F) 144.16 L. Inter-individual variabilities for CL/F and V/F were 3.53% and 7.27%, respectively. The intra-individual variability of proportional error model was 22.45%. The covariate test found that body weight and total bilirubin were strongly associated with clearance; however, we did not find the relevance between the covariate and volume of distribution of sirolimus. Personalized dosage regimens were provided based on Bayesian method. The oral dose should be adjusted according to weight and total bilirubin. This is the first study to describe a population PK model of sirolimusin pediatric patients with immune cytopenia. Population pharmacokinetic (PPK) model-based dose individualization of sirolimus and the design of future clinical studies in children will be facilitated by the developed model in this study.
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http://dx.doi.org/10.1177/2058738420934936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388097PMC
June 2021

Vascular endothelial growth factor in major depressive disorder, schizophrenia, and bipolar disorder: A network meta-analysis.

Psychiatry Res 2020 10 20;292:113319. Epub 2020 Jul 20.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; College of Biomedical Engineering, Chongqing Medical University, Chongqing, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

The peripheral levels of vascular endothelial growth factor (VEGF) have been studied in major psychiatric diseases compared with healthy controls (HCs), but the results were inconsistent. Moreover, few studies have compared VEGF levels between these psychiatric diseases. The aim of the present study was to compare blood VEGF levels in major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder either in a manic episode, a depressive episode, or a euthymic state, and HC. We supposed that VEGF levels may be elevated in some of these diseases as a potential biomarker. In this study, forty-four studies with 6343 participants were included, and network meta-analysis was used to synthesize evidence from both direct and indirect comparisons. The main analysis showed that no significant differences were found between these groups. Subgroup analysis found that patients with MDD may have higher blood VEGF levels than patients with SCZ when the levels were measured through ELISA, and VEGF levels were increased in medication-treated MDD patients compared with HCs. Taken together, blood VEGF levels may be unaltered in these psychiatric disorders, while detection of VEGF in blood by ELISA may a feasible way to distinguish MDD and SCZ. Further replicated studies with larger samples are needed.
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http://dx.doi.org/10.1016/j.psychres.2020.113319DOI Listing
October 2020

Effect of Annealing on the Thermoelectricity Properties of the WRe26-InO Thin Film Thermocouples.

Micromachines (Basel) 2020 Jul 7;11(7). Epub 2020 Jul 7.

State Key Laboratory for Mechanical Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

WRe26-InO (WRe26 (tungsten-26% rhenium) and InO thermoelectric materials) thin film thermocouples (TFTCs) have been fabricated based on magnetron sputtering technology, which can be used in temperature measurement. Many annealing processes were studied to promote the sensitivity of WRe26-InO TFTCs. The optimal annealing process of the thermocouple under this kind of RF magnetron sputtering method was proposed after analyzing the properties of InO films and the thermoelectric voltage of TFTCs at different annealing processes. The calibration results showed that the WRe26-InO TFTCs achieved a thermoelectric voltage of 123.6 mV at a temperature difference of 612.9 K, with a sensitivity of up to 201.6 µV/K. Also, TFTC kept a stable thermoelectric voltage output at 973 K for 20 min and at 773 K for two hours. In general, the WRe26-InO TFTCs developed in this work have great potential for practical applications. In future work, we will focus on the thermoelectric stability of TFTCs at higher temperatures.
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http://dx.doi.org/10.3390/mi11070664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407526PMC
July 2020

Erratum: Author correction to 'Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer' [Acta Pharmaceutica Sinica B 2019; 9(5):1061-1077].

Acta Pharm Sin B 2020 06 26;10(6):1143-1144. Epub 2020 Mar 26.

Key Laboratory of Molecular Pharmaceutics, New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

[This corrects the article DOI: 10.1016/j.apsb.2019.03.006.].
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http://dx.doi.org/10.1016/j.apsb.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332668PMC
June 2020

Combination of Size-Exclusion Chromatography and Ultracentrifugation Improves the Proteomic Profiling of Plasma-Derived Small Extracellular Vesicles.

Biol Proced Online 2020 23;22:12. Epub 2020 Jun 23.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050 P. R. China.

Background: Circulating small extracellular vesicles (sEVs) and its associated proteins are of great interest in the early detection of many diseases. However, there is no gold standard for plasma sEVs isolation, especially for proteomic profiling which could be largely affected by contamination such as lipoproteins and plasma proteins. Previous studies suggested combinations of different sEVs isolation methods could improve the yield and purity of the isolated fractions. Nevertheless, there is no systematic evaluation of size-exclusion chromatography (SEC), ultracentrifugation (UC), and their combination in a proteomic perspective.

Results: Plasma samples were collected from healthy individuals, and sEVs were separated by one-step SEC, one-step UC, and combining SEC with UC, respectively. Here we exhibited that the purity of sEVs was improved by SEC in contrast to traditional UC. Furthermore, by conducting a SEC procedure followed by UC, we separated sEVs with the highest purity. In the proteomic analysis, 992 protein species were identified in the plasma sEVs isolated by our novel separation method, of which several proteins are sEVs-associated proteins but hitherto never been identified in the previous studies and database, much more than plasma sEVs isolated by UC (453) or SEC (682) alone. As compared to Vesiclepedia and Exocarta databases, plasma sEVs isolated by the new procedure kept 584 previously identified sEVs-associated proteins and 360 other proteins that have not been detected before. Detailed analysis suggested that more kinds of sEVs biomarkers, such as CD9, ALIX, and FLOT1, could be identified in plasma sEVs isolated by the novel isolation method as compared to one-step UC/SEC. Furthermore, the lower abundance ranks of common contaminants, such as lipoproteins and IgG chains, in the sEVs fractions obtained by our new method as compared to one-step UC/SEC also demonstrated the purity of sEVs had been improved.

Conclusions: Combining SEC with UC could significantly improve the performance of mass spectrometry-based proteomic profiling in analyzing plasma-derived sEVs.
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http://dx.doi.org/10.1186/s12575-020-00125-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313174PMC
June 2020
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