Publications by authors named "Qi Liang"

248 Publications

The health effects of wearing facemasks on cardiopulmonary system of healthy young adults: A double-blinded, randomized crossover trial.

Int J Hyg Environ Health 2021 Jul 12;236:113806. Epub 2021 Jul 12.

Key Joint Laboratory of Environmental Simulation and Pollution Control, International Joint Laboratory for Regional Pollution Control (IJRC), Ministry of Education, College of Environmental Sciences and Engineering, Beijing, 100871, China. Electronic address:

Background: Facemask had increasingly been utilized as a personal protective measure to reduce exposure to ambient particulate matter (PM) during heavily-polluted days and routine life. However, evidence on the potential effects on cardiovascular system by wearing particulate-filtering facemask was limited.

Methods: We conducted a double-blinded randomized crossover trial (RCT) to evaluate the effects of wearing N95 facemasks on the molecular responses of cardiopulmonary system among 52 healthy college students in Beijing, China. We measured cardiopulmonary health indicators and collected biological samples before and after (up to 5 h at multiple time points) a 2-h walk to examine the changes in lung function, biomarkers of respiratory and systemic oxidative stress/inflammation. We applied linear mixed-effect models to evaluate the effect of the facemask-intervention on the health of cardio-pulmonary system.

Results: In the trial wearing real facemasks, FEV increased by 2.05% (95% CI: 0.27%-3.87%), 2.80% (95% CI: 1.00%-4.63%), and 2.87% (95% CI: 1.07%-4.70%) at V1 (30-min), V2 (3-h), and V3 (5-h) after the 2-h walk outsides, respectively. Compared with participants wearing the sham mask, the percentage change of nitrate in EBC was lower among those wearing the real mask. After the 2-h exposure, urinary MDA levels increased compared to the baseline in both trials. Real trial was lower than sham trial for 6 cytokines (i.e., IL-6, IL-10, IL-13, IL-17A, IFN-γ and TNF-α) in serum at 5-h post-exposure. Wearing facemasks on polluted days produced better improvement, however, on cleaner days, the improvement was weaker.

Conclusions: Short-term use of N95 facemasks appeared to effectively reduce the levels of lung function declines, the respiratory oxidative stress, and the systemic inflammation/oxidative stress which may be induced by short-term exposure to PM. Wearing facemasks on polluted days (PM > 75 μg/m) presented larger beneficial effects on the cardiopulmonary health than in clean days (PM < 75 μg/m).
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http://dx.doi.org/10.1016/j.ijheh.2021.113806DOI Listing
July 2021

Few-unit-cell MFI zeolite synthesized using a simple di-quaternary ammonium structure-directing agent.

Angew Chem Int Ed Engl 2021 Jun 29. Epub 2021 Jun 29.

University of Minnesota Twin Cities: University of Minnesota, Department of Chemical Engineering and Materials Sciences, UNITED STATES.

Synthesis of a pentasil-type zeolite with ultra-small few-unit-cell crystalline domains, which we call FDP (few-unit-cell crystalline domain pentasil), is reported. FDP is made using bis-1,5(tributyl ammonium) pentamethylene cations as structure directing agent (SDA). This di-quaternary ammonium SDA combines (i) butyl ammonium, in place of the commonly used, for MFI synthesis, propyl ammonium, and (ii) a five-carbon nitrogen-connecting chain, in place of the six-carbon connecting chain SDAs that are known to fit well within the MFI pores. Although each modification, singularly implemented, is known to hinder nucleation and growth rates of MFI, they have not been, hitherto, combined to synergistically act on MFI morphology. X-ray diffraction analysis and electron microscopy imaging of FDP indicate ca. 10 nm crystalline domains organized in hierarchical micro-/meso-porous aggregates exhibiting mesoscopic order with an aggregate particle size that can be up to ca. 4 μm. The synthesis of FDP is attributed to conflicting crystal shaping trends attributed to distinct moieties being incorporated in a single SDA. Specifically, the pentamethylene moiety is known to favor early crystal growth along the b-axis, while the butyl moieties are known to hinder growth along the b-axis. We attribute the obtained ultrasmall crystalline domains to the conflicting trends of the frustrated SDA. It is demonstrated that Al and Sn can be incorporated into the FDP zeolite framework to produce active and selective methanol-to-hydrocarbon and glucose isomerization catalysts, respectively.
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http://dx.doi.org/10.1002/anie.202104574DOI Listing
June 2021

A Domain-Guided Noise-Optimization-Based Inversion Method for Facial Image Manipulation.

IEEE Trans Image Process 2021 9;30:6198-6211. Epub 2021 Jul 9.

A style-based architecture (StyleGAN2) yields outstanding results in data-driven unconditional generative image modeling. This work proposes a Domain-guided Noise-optimization-based Inversion (DNI) method to perform facial image manipulation. It works based on an inverse code that includes: 1) a novel domain-guided encoder called Image2latent to project the image to StyleGAN2 latent space, which can reconstruct an input image with high-quality and maintain its semantic meaning well; 2) a noise optimization mechanism in which a set of noise vectors are used to capture the high-frequency details such as image edges, further improving image reconstruction quality; and 3) a mask for seamless image fusion and local style migration. We further propose a novel semantic alignment evaluation pipeline. It evaluates the semantic alignment with an inverse code by using different attribute boundaries. Extensive qualitative and quantitative comparisons show that DNI can capture rich semantic information and achieve a satisfactory image reconstruction. It can realize a variety of facial image manipulation tasks and outperform state of the art.
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http://dx.doi.org/10.1109/TIP.2021.3089905DOI Listing
July 2021

Antenna-Coupled Titanium Microbolometers: Application for Precise Control of Radiation Patterns in Terahertz Time-Domain Systems.

Sensors (Basel) 2021 May 18;21(10). Epub 2021 May 18.

Center for Physical Sciences and Technology (FTMC), Department of Optoelectronics, Saulėtekio Ave. 3, LT-10257 Vilnius, Lithuania.

An ability of lensless titanium-based antenna coupled microbolometers (Ti-μbolometers) operating at room temperature to monitor precisely radiation patterns in terahertz time-domain spectroscopy (THz-TDS) systems are demonstrated. To provide comprehensive picture, two different THz-TDS systems and Ti-μbolometers coupled with three different antennas-narrowband dipole antennas for 0.3 THz, 0.7 THz and a log-periodic antenna for wideband detection-were selected for experiments. Radiation patterns, spatial beam profiles and explicit beam evolution along the propagation axis are investigated; polarization-sensitive properties under various THz emitter power ranges are revealed. It was found that the studied Ti-μbolometers are convenient lensless sensors suitable to discriminate and control THz radiation pattern features in various wideband THz-TDS systems.
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http://dx.doi.org/10.3390/s21103510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158144PMC
May 2021

Mechanism and Kinetics of Acetone Conversion to Isobutene over Isolated Hf Sites Grafted to Silicalite-1 and SiO.

J Am Chem Soc 2021 Jun 27;143(22):8352-8366. Epub 2021 May 27.

Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

Isolated hafnium (Hf) sites were prepared on Silicalite-1 and SiO and investigated for acetone conversion to isobutene. Characterization by IR, H MAS NMR, and UV-vis spectroscopy suggests that Hf atoms are bonded to the support via three O atoms and have one hydroxyl group, i.e, (≡SiO)Hf-OH. In the case of Hf/Silicalite-1, Hf-OH groups hydrogen bond with adjacent Si-OH to form (≡SiO)Hf-OH···HO-Si≡ complexes. The turnover frequency for isobutene formation from acetone is 4.5 times faster over Hf/Silicalite-1 than Hf/SiO. Lewis acidic Hf sites promote the aldol condensation of acetone to produce mesityl oxide (MO), which is the precursor to isobutene. For Hf/SiO, both Hf sites and Si-OH groups are responsible for the decomposition of MO to isobutene and acetic acid, whereas for Hf/Silicalite-1, the (≡SiO)Hf-OH···HO-Si≡ complex is the active site. Measured reaction kinetics show that the rate of isobutene formation over Hf/SiO and Hf/Silicalite-1 is nearly second order in acetone partial pressure, suggesting that the rate-limiting step involves formation of the C-C bond between two acetone molecules. The rate expression for isobutene formation predicts a second order dependence in acetone partial pressure at low partial pressures and a decrease in order with increasing acetone partial pressure, in good agreement with experimental observation. The apparent activation energy for isobutene formation from acetone over Hf/SiO is 116.3 kJ/mol, while that for Hf/Silicalite-1 is 79.5 kJ/mol. The lower activation energy for Hf/Silicalite-1 is attributed to enhanced adsorption of acetone and formation of a C-C bond favored by the H-bonding interaction between Hf-OH and an adjacent Si-OH group.
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http://dx.doi.org/10.1021/jacs.1c01315DOI Listing
June 2021

Identification of selective ligands targeting two GPCRs by receptor-affinity chromatography coupled with high-throughput sequencing techniques.

Bioorg Chem 2021 Jul 12;112:104986. Epub 2021 May 12.

College of Life Sciences, Northwest University, Xi'an 710069, China. Electronic address:

The rapid growth of demands for drug discovery has necessitated the ongoing pursuit of new methods for specific ligands screening and identification. This work combined receptor-affinity chromatography (RAC) with high-throughput sequencing techniques to rapidly screen and identify the specific ligands. By this method, immobilized angiotensin II type I receptor (ATR) and endothelin receptor A (ETR) based on RAC were utilized for lead screening from a DNA-encoded library. The specific ligands of ATR (ligand A, A) and ETR (ligand B, B) were synthesized after decoding by high-throughput sequencing techniques. The dissociation rate constants (k) of ligand A, A to ATR and B, B to ETR were 9.65 × 10, 31.1 × 10 and 0.66, 1.22 s by peak profiling assay. The association constant (K) to the receptors of four ligands was 5.4 × 10, 3.3 × 10 and 1.6 × 10, 2.2 × 10 by injection amount dependent method. The kinetic and thermodynamic parameters of the four specific ligands are similar to those of the positive drugs. This indicates that they are promising to drug candidates. The druggability of the four ligands through pharmacokinetic investigation by HPLC-MS/MS presented desired pharmacokinetic behavior including the fast absorption, the relatively slow elimination. These results, taking together, indicated that the RAC combined with high-throughput sequencing techniques can screen and identify the specific ligands according to various proteins, thus creating a general strategy for rapid discovery of promising drug candidates.
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http://dx.doi.org/10.1016/j.bioorg.2021.104986DOI Listing
July 2021

The Amorphous Quercetin/ Hydroxypropylmethylcellulose Acetate Succinate Solid Dispersions Prepared by Co-Precipitation Method to Enhance Quercetin Dissolution.

J Pharm Sci 2021 May 15. Epub 2021 May 15.

School of Pharmacy, Guilin Medical University, Guilin 541004, PR China. Electronic address:

HPMCAS-HF, HPMCAS-MF and HPMCAS-LF were used as carriers to prepare the amorphous solid dispersions (ASDs) of quercetin (Que) by co-precipitation. The Que ASD based on PVP K30 was prepared by solvent evaporation method. The ability of polymer to inhibit Que crystallization was evaluated. The study found the order of the ability of polymer to inhibit Que nucleation to be: HF > MF > LF > K30, and that to maintain Que supersaturation to be: HF > K30 > MF > LF. The prepared solid dispersions were characterized by IR, DSC and PXRD. Although HF was the most effective crystallization inhibitor, the release of the Que/HF ASD was poor and assigned to the carrier-controlled dissolution for the strong interactions between Que and HF. The Que/MF ASD exhibited better dissolution behavior compared to the Que/K30 ASD. The dissolution behavior of the Que ASD depended on the polymer-Que interactions and the ability of crystallization inhibition of the polymer.
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http://dx.doi.org/10.1016/j.xphs.2021.05.004DOI Listing
May 2021

Investigation of EDTA concentration on the size of carbonated flowerlike hydroxyapatite microspheres.

R Soc Open Sci 2021 Mar 10;8(3):202148. Epub 2021 Mar 10.

School of Transportation and Civil Engineering, Shandong Jiaotong University, Ji'nan 250357, People's Republic of China.

Ethylenediamine tetraacetic acid (EDTA) is considered an effective crystal growth modifier for template-assisted hydrothermal synthesis of hydroxyapatite (HA) materials. In this work, flowerlike-carbonated HA (CHA) microspheres were synthesized using EDTA via a one-step hydrothermal route. The phase, functional groups, morphology and particle size distribution of the products were examined by X-ray diffraction, Fourier transform infrared spectrometer, field emission scanning electron microscopy as well as laser diffraction particle size analysis. Results show that the morphology of the products can be well controlled by adjusting the EDTA concentration. With an increase of the EDTA concentration, the particle size of flowerlike microspheres decreased from tens of microns down to a few microns. The underlying mechanism for the morphological transition of CHA microspheres with different concentrations of EDTA under hydrothermal conditions is proposed. This work provides a simple way to controllably fabricate CHA microspheres with various sizes using the same synthesis system for biomedical applications, such as cell carriers and drug delivery.
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http://dx.doi.org/10.1098/rsos.202148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074982PMC
March 2021

3D food printing: Applications of plant-based materials in extrusion-based food printing.

Crit Rev Food Sci Nutr 2021 Apr 15:1-15. Epub 2021 Apr 15.

College of Food Science, Shenyang Agricultural University, Shenyang, China.

As an emerging digital production technology, 3D food printing intends to meet the demand for customized food design, personalized nutrition, simplification of the food supply chain system, and greater food material diversity. Most 3D food printing studies focus on the development of materials for extrusion-based food printing. Plant-based foods are essential for a healthy diet, and they are growing in popularity as their positive effects on human health gain wider recognition. The number of original studies on plant-based printable materials has increased significantly in the past few years. Currently, there is an absence of a comprehensive systematic review on the applications of plant-based materials in extrusion-based food printing. Thus, this review aims to provide a more intuitive overview and guidance for future research on 3D printing of plant-based materials. The requirements, classifications, and binding mechanisms of extrusion-based food printing materials are first summarized. Additionally, notable recent achievements and emerging trends involving the use of plant-based materials in extrusion-based food printing are reviewed across three categories, namely, hot-melt (e.g., chocolate), hydrogel, and soft (e.g., cereal- and fruit/vegetable-based) materials. Finally, the challenges facing 3D food printing technology as well as its future prospects are discussed.
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http://dx.doi.org/10.1080/10408398.2021.1911929DOI Listing
April 2021

Inhibitory Smads suppress pancreatic stellate cell activation through negative feedback in chronic pancreatitis.

Ann Transl Med 2021 Mar;9(5):384

Institute of Pancreas, Southeast University, Nanjing, China.

Background: Activation of pancreatic stellate cells (PSCs) is a key cause of chronic pancreatitis (CP), while inhibition of transforming growth factor-β (TGF-β) signaling renders PSCs inactive. Inhibitory Smads (I-Smads) impede TGF-β intracellular signaling and may provide a way to alleviate CP. Thus, we aimed to investigate the molecular mechanism of I-Smads in CP animals and freshly-isolated PSCs.

Methods: Sixteen male C57BL/6 mice were randomly divided into two groups; a control group (treated with saline) and a CP group (treated with caerulein) for 6 weeks. Masson's staining was performed to identify fibrosis, and immunohistochemistry (IHC) was performed to measure the levels of Smad6 between the two groups. An improved method derived from internal digestion was used to isolate PSCs from male Sprague Dawley rats. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining were used to measure the messenger ribonucleic acid (mRNA) and protein levels of alpha-smooth muscle actin (α-SMA). Plasmids of I-Smads or SB431542 were transfected into freshly-isolated PSCs, and relative mRNA levels of marker genes were quantified by qRT-PCR. The two-tailed Student's t-test was performed to assess significance.

Results: The Smad6 protein level was significantly higher in the pancreas tissue of CP mice compared to the control group. A large number of PSCs were isolated from rat pancreas using an improved isolating method and were confirmed by quiescent and active PSC markers including cluster differentiation antigen 133 (CD133), perilipin 2 (Plin2), α-SMA, Desmin, and collagen 1 (Col1). The mRNA levels of both Smad6 and Smad7 were down-regulated during freshly-isolated PSC activation. Over-expression of both Smad6 and Smad7 in freshly-isolated PSC reduced the mRNA level of α-SMA, glial fibrillary acidic protein (GFAP), Desmin, Col1, Col3, and fibronectin 1 (Fn1) significantly. SB431542 reduced the mRNA level of α-SMA, Col1, Col3, and Fn1 significantly in freshly-isolated PSCs.

Conclusions: This study demonstrated that CP promoted the expression of I-Smads, which suppressed the activation of freshly-isolated PSCs via a negative feedback loop.
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http://dx.doi.org/10.21037/atm-20-4282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033383PMC
March 2021

Selective Discovery of GPCR Ligands within DNA-Encoded Chemical Libraries Derived from Natural Products: A Case Study on Antagonists of Angiotensin II Type I Receptor.

J Med Chem 2021 04 30;64(7):4196-4205. Epub 2021 Mar 30.

College of Life Sciences, Northwest University, Xi'an 710069, China.

Natural products have failed to meet the urgent need for drug discovery in recent decades due to limited resources, necessitating new strategies for re-establishing the key role of natural products in hit screening. This work introduced DNA-encoding techniques into the synthesis of phenolic acid-focused libraries containing 32 000 diverse compounds. Online selection of the library using immobilized angiotensin II type I receptor (ATR) resulted in seven phenolic acid derivatives. The half-maximal concentration (IC) of hit 1 for the right shift of the [I]-Sar1-AngII competition curve was 19.6 nM. Pharmacological examination of renovascular hypertensive rats demonstrated that hit 1 significantly lowered the blood pressure of the animals without changing their heart rates. These results were used to create a general strategy for rapid and unbiased discovery of hits derived from natural products with high throughput and efficiency.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00123DOI Listing
April 2021

Immune persistence induced by three doses of 60 μg hepatitis B vaccine in non-responders following standard primary vaccination in Chinese adults.

Hum Vaccin Immunother 2021 Mar 18:1-6. Epub 2021 Mar 18.

School of Public Health, Nanjing Medical University, Nanjing, China.

This study consisted of two rounds of cross-sectional observations designed to evaluate the persistence of immune protection induced high antigen content hepatitis B (HB) vaccine at 60 μg/1.0 ml formulations administered at a three-dose schedule (Days 0, 28, and 56) in non-responders to routine HB vaccination. In the original phase 3 study, we enrolled 1091 healthy participants (16-60 years old) seronegative for antibody against HB surface antigen (anti-HBs) after primary vaccination. Participants were randomized (2:2:1) to receive three booster doses of HB vaccine containing 60 μg, 30 μg, or 10 μg of antigen per dose 28 days apart. In the group receiving the 60 μg HB vaccine, 428 participants' serum samples were available at pre-vaccination and 28 days after each vaccine dose and were included in immunogenicity analysis. With two written informed consents, we collected blood samples from 276 (67.2%) participants in 2014 and 239 (58.2%) in 2019, who had completed the full course of revaccination and reached the seropositive (anti-HBs≥10 mIU/ml) standard in the 60 μg vaccine group of the original phase 3 study. The HBV seropositive rate was found to decrease from 96.0% in 28 days after receiving the third dose of 60 μg HB vaccine, to 48.2% in 2014, and to 40.6% in 2019, with anti-HBs GMC of seropositive individuals was 584.0 mIU/ml, 142.4 mIU/ml, and 169.1 mIU/ml, respectively. Analysis of 181 vaccinees who had serologic test results available both in 2014 and in 2019, and results revealed a dynamic trend in anti-HBs titer similar to that for the whole immune persistence cohort. Of paramount importance, the serologic test results found that 24.9% (45/181) participants had higher anti-HBs concentrations in 2019 than in 2014, this could be interpreted as natural boosters, secondary to HBV exposure without infection because protected. In conclusion, protective antibody persists about 11 years after immunization of Chinese non-responders with 3 doses of 60 μg HB vaccine. Booster doses of vaccine do not seem necessary to ensure long-term protection.
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http://dx.doi.org/10.1080/21645515.2021.1877079DOI Listing
March 2021

Long-Term Outcomes of Percutaneous Coronary Intervention for Patients With In-Stent Chronic Total Occlusion Versus De Novo Chronic Total Occlusion.

Angiology 2021 Mar 4:3319721998575. Epub 2021 Mar 4.

Department of Cardiology, First Affiliated Hospital of 162798Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Limited data are available on long-term outcomes and health status in the treatment of in-stent coronary chronic total occlusion (IS-CTO) and de novo coronary chronic total occlusion (de novo CTO). This study compared the long-term clinical outcomes and health status of percutaneous coronary intervention (PCI) for patients with IS-CTO versus patients with de novo CTO in the drug-eluting stent era. We screened 483 consecutive patients with 1 CTO lesion, including 81 patients with IS-CTO and 402 patients with de novo CTO. Propensity score matching was used to balance baseline characteristics between the 2 groups. The clinical end point was major adverse cardiac events (MACE). The success rates of CTO lesion revascularization were similar in both groups. In the propensity score-matched patients, after a median follow-up of 36 months, MACE was observed in 32.8% of patients with IS-CTO versus 13.5% of the patients with de novo CTO ( < .001), mainly driven by target-vessel revascularization (21.9% vs 6.7%; < .01). Moreover, patients with IS-CTO had significantly worse Seattle Angina Questionnaire anginal stability scores than the patients with de novo CTO. In conclusion, patients with IS-CTO after PCI had a worse clinical outcome, mainly MACE, and a poorer anginal stability in the long term than patients with de novo CTO.
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http://dx.doi.org/10.1177/0003319721998575DOI Listing
March 2021

Clinical mid-term outcomes of the Chinese-made CL-V bileaflet mechanical heart valve in Chinese patients.

J Thorac Dis 2021 Jan;13(1):10-17

The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.

Background: The CL-V full-carbon bileaflet mechanical heart valve is a novel Chinese-made prosthetic valve. This study evaluated the mid-term outcomes of the CL-V bileaflet mechanical heart valve after implantation in Chinese patients.

Methods: This study retrospectively enrolled a total of 38 consecutive patients who underwent elective mechanical heart valve replacement (MHVR) with two different valve types from April 2004 and May 2010, including 18 patients with the CL-V bileaflet mechanical heart valve (44.4% male, mean age 47.4±6.2 years, mean body weight 64.7±11.9 kg) and 20 patients with the St. Jude mechanical heart valve (45.0% male, mean age 49.7±7.6 years, mean body weight 66.1±11.1 kg). All patients underwent follow-up clinical evaluations in the outpatient department at all-time points.

Results: No complications occurred during the mean 61.3 months follow-up time (range, 47-102 months). The cardiothoracic ratios (52.7%±4.5% 50.1%±4.0%), left atrium diameter (46.5±7.6 44.8±9.3 mm), left ventricular diastolic diameter (47.6±4.9 48.2±8.5 mm) and left ventricular ejection fraction (65.4%±8.7% 64.5%±8.0%) were not significantly different between the two groups (P>0.05). Transthoracic Doppler echocardiography showed that the hemodynamic indexes were not significantly different between the two groups at 1 year and 3 years (P>0.05). Furthermore, no significant differences were found between the two groups in hemocompatibility indexes at both 6 months and 3 years postoperatively (P>0.05).

Conclusions: The mid-term follow-up results of the CL-V bileaflet mechanical heart valve were similar to those of the St. Jude Medical heart valve, which showed stable hemodynamics and good blood compatibility. Chinese-made CL-V bileaflet mechanical heart valves can be a substitute for St. Jude Medical heart valves, and can be widely used in cardiac surgery.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2000034158.
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http://dx.doi.org/10.21037/jtd-20-2644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867806PMC
January 2021

Recent advances of dual FGFR inhibitors as a novel therapy for cancer.

Eur J Med Chem 2021 Mar 23;214:113205. Epub 2021 Jan 23.

Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, China. Electronic address:

Fibroblast growth factor receptor (FGFR) includes four highly conserved transmembrane receptor tyrosine kinases (FGFR1-4). FGF and FGFR regulate many biological processes, such as angiogenesis, wound healing and tissue regeneration. The abnormal expression of FGFR is related to the tumorigenesis, tumor progression and drug resistance of anti-tumor treatments in many types of tumors. Nowadays there are many anti-cancer drugs targeting FGFR. However, traditional single-target anti-tumor drugs are easy to acquire drug resistance. The therapeutic effect can be enhanced by simultaneously inhibiting FGFR and another target (such as VEGFR, EGFR, PI3K, CSF-1R, etc.). We know drug combination can bring problems such as drug interactions. Therefore, the development of FGFR dual target inhibitors is an important direction. In this paper, we reviewed the research on dual FGFR inhibitors in recent years and made brief comments on them.
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http://dx.doi.org/10.1016/j.ejmech.2021.113205DOI Listing
March 2021

Halo-tagged protein immobilization: Effect of halide linkers on peak profile and drug-protein interaction.

J Chromatogr A 2021 Mar 28;1640:461946. Epub 2021 Jan 28.

College of Life Sciences, Northwest University, Xi'an 710069, China. Electronic address:

In previous work, we have established a one-step method to immobilize halo-tagged proteins onto microspheres through the covalent bond formed between the halo-tag and the halide linkers on the support surface. We observe extremely tailed peaks of most of drugs on the immobilized proteins, which is reasoned by the nonspecific interaction between the linkers and the drugs. To prove this, the current work designed five different halide linkers for the immobilization of beta-adrenoceptor (β-AR). We applied the immobilized receptor to systematically realize the effects of these halide linkers on drug-receptor interaction by analyzing peak profiles of five drugs. The retention times and the half-widths of the drugs appeared to be negatively correlated to the atom numbers of the linkers in the range of 6-13 atoms. Subsequent increase of linker atoms resulted in reduced retention times and wider peaks of the drugs. Applying identical linker length, we observed clear reduced retention times and half-widths of the five drugs than the linker in the absence of oxygen atom. Such improvement was dominated by the number of oxygen atoms. These indicated that linker S-4 (2-(2-(2-(2-chloroethoxy) ethoxy) ethoxy) acetic acid) was optimal to eliminate the unwanted non-specific interactions. In comparison with the columns prepared by linker S-1 (6-chlorocaproic acid) and histidine tagged β-AR, the drugs on the linker S-4 column gave greater dissociation rate constants (e.g. 60.3±0.3 s for salbutamol), which is closer to the data in literatures. Taking together, we concluded that optimization of the linker structure plays particular role in reducing the non-specific interaction between the immobilized protein and the drugs, thereby making the determination of drug-protein interaction more reliable.
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http://dx.doi.org/10.1016/j.chroma.2021.461946DOI Listing
March 2021

Grey matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

J Sleep Res 2021 Feb 8:e13298. Epub 2021 Feb 8.

Department of Central Laboratory, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, China.

Brain structural abnormalities in idiopathic restless legs syndrome have long been debated. Voxel-based morphometry is an objective structural magnetic resonance imaging technique to investigate regional grey matter volume or density differences between groups. In the last decade, voxel-based morphometry studies have exhibited inconsistent and conflicting findings regarding the presence and localization of brain grey matter alterations in restless legs syndrome. We therefore conducted a coordinate-based meta-analysis to quantitatively examine whether there were consistent grey matter findings in restless legs syndrome using the latest algorithms, seed-based d mapping with permutation of subject images. We included 12 voxel-based morphometry studies (13 datasets, 375 patients and 385 healthy controls). Our coordinate-based meta-analysis did not identify evidence of consistent grey matter alterations in restless legs syndrome. Grey matter alterations via voxel-based morphometry analysis are not therefore recommended to be used as a reliable surrogate neuroimaging marker for restless legs syndrome. This lack of consistency may be attributed to differences in sample size, genetics, gender distribution and age at onset, clinical heterogeneity (clinical course, anatomical distribution of symptoms, disease severity, disease duration, abnormal sensory profiles and comorbidity), and variations in imaging acquisition, data processing and statistical strategies. Longitudinal studies with multimodal neuroimaging techniques are needed to determine whether structural changes are dynamic and secondary to functional abnormalities.
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http://dx.doi.org/10.1111/jsr.13298DOI Listing
February 2021

Circular RNAs in body fluids as cancer biomarkers: the new frontier of liquid biopsies.

Mol Cancer 2021 01 11;20(1):13. Epub 2021 Jan 11.

Department of Biostatistics, Centre for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, People's Republic of China.

Cancer is a leading cause of death worldwide, particularly because of its high mortality rate in patients who are diagnosed at late stages. Conventional biomarkers originating from blood are widely used for cancer diagnosis, but their low sensitivity and specificity limit their widespread application in cancer screening among the general population. Currently, emerging studies are exploiting novel, highly-accurate biomarkers in human body fluids that are obtainable through minimally invasive techniques, which is defined as liquid biopsy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs generated mainly by pre-mRNA splicing. Following the rapid development of high-throughput transcriptome analysis techniques, numerous circRNAs have been recognized to exist stably and at high levels in body fluids, including plasma, serum, exosomes, and urine. CircRNA expression patterns exhibit distinctly differences between patients with cancer and healthy controls, suggesting that circRNAs in body fluids potentially represent novel biomarkers for monitoring cancer development and progression. In this study, we summarized the expression of circRNAs in body fluids in a pan-cancer dataset and characterized their clinical applications in liquid biopsy for cancer diagnosis and prognosis. In addition, a user-friendly web interface was developed to visualize each circRNA in fluids ( https://mulongdu.shinyapps.io/circrnas_in_fluids/ ).
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http://dx.doi.org/10.1186/s12943-020-01298-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798340PMC
January 2021

Acupuncture for Cancer Pain - An Adjuvant Therapy for Cancer Pain Relief.

Am J Chin Med 2020 9;48(8):1769-1786. Epub 2020 Dec 9.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P. R. China.

As current pain management methods cannot effectively control pain among cancer patients, acupuncture has developed as an adjuvant therapy for cancer pain relief. However, the efficacy of acupuncture in treating cancer pain remains controversial. Here, we briefly introduced the development of pain management, analgesic mechanisms, and acupuncture methods. Meanwhile, a comprehensive overview of acupuncture programs was provided in terms of different cancer types, sources, and degrees. Interestingly, acupuncture can treat both tumor-induced pain and therapy-induced pain well among cancer patients. We preliminarily summarized frequently-used acupoints for different types of cancer pain and found that needle retention time was mostly 30 min, and treatment cycle was two weeks. Additionally, clinicians consistently selected Ashi acupoint or bilateral Zusanli acupoint and combined multiple acupuncture methods for different degrees of cancer pain.
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http://dx.doi.org/10.1142/S0192415X20500883DOI Listing
May 2021

Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What's Known and What's to Know.

Front Physiol 2020 28;11:570276. Epub 2020 Oct 28.

Department of Endocrinology, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.

The clinical significance of diabetes arising in the setting of pancreatic disease (also known as diabetes of the exocrine pancreas, DEP) has drawn more attention in recent years. However, significant improvements still need to be made in the recognition, diagnosis and treatment of the disorder, and in the knowledge of the pathological mechanisms. The clinical course of DEP is different from type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). DEP develops in patients with previous existing exocrine pancreatic disorders which damage both exocrine and endocrine parts of pancreas, and lead to pancreas exocrine insufficiency (PEI) and malnutrition. Therefore, damage in various exocrine and endocrine cell types participating in glucose metabolism regulation likely contribute to the development of DEP. Due to the limited amount of clinical and experimental studies, the pathological mechanism of DEP is poorly defined. In fact, it still not entirely clear whether DEP represents a distinct pathologic entity or is a form of T2DM arising when β cell failure is accelerated by pancreatic disease. In this review, we include findings from related studies in T1DM and T2DM to highlight potential pathological mechanisms involved in initiation and progression of DEP, and to provide directions for future research studies.
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http://dx.doi.org/10.3389/fphys.2020.570276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673428PMC
October 2020

Electrochemical Tandem Fluoroalkylation-Cyclization of Vinyl Azides: Access to Trifluoroethylated and Difluoroethylated N-Heterocycles.

J Org Chem 2020 12 23;85(23):15708-15716. Epub 2020 Nov 23.

Key Lab of Science and Technology of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.

A transition-metal- and oxidant-free electrochemical strategy for radical fluoroalkylation of vinyl azides was developed. The reaction was carried out under mild conditions by using inexpensive and bench-stable RSONa (R = CF, CFH) as fluorination reagents. Depending on the starting material, both the electrochemical radical cyclization and dearomatization products could be obtained. This method provides a green and safe approach to synthesize fluorinated nitrogen heterocycles.
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http://dx.doi.org/10.1021/acs.joc.0c02213DOI Listing
December 2020

First-Principles Exploration of Hazardous Gas Molecule Adsorption on Pure and Modified AlN Nanoclusters.

Nanomaterials (Basel) 2020 Oct 29;10(11). Epub 2020 Oct 29.

Key Laboratory of Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education) & School of Software, Shandong University, Jinan 250061, China.

In this work, we use the first-principles method to study in details the characteristics of the adsorption of hazardous NO, NO, CO, CO and SO gas molecules by pure and heteroatom (Ti, Si, Mn) modified AlN nanoclusters. It is found that the pure AlN cluster is not sensitive to CO. When NO, NO, CO, CO and SO are adsorbed on AlN cluster'stop.b, edge.a, edge.a, edge.a andedge.a sites respectively, the obtained configuration is the most stable for each gas. Ti, Si and Mn atoms prefer to stay on the top sites of AlN cluster when these heteroatoms are used to modify the pure clusters. The adsorption characteristics of above hazardous gas molecules on these hetero-atom modified nanoclusters are also revealed. It is found that when Ti-AlN cluster adsorbs CO and SO, the energy gap decreases sharply and the change rate of gap is 62% and 50%, respectively. The Ti-modified AlN improves the adsorption sensitivity of the cluster to CO and SO. This theoretical work is proposed to predict and understand the basic adsorption characteristics of AlN-based nanoclusters for hazardous gases, which will help and guide researchers to design better nanomaterials for gas adsorption or detection.
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http://dx.doi.org/10.3390/nano10112156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692222PMC
October 2020

Volume changes of subcortical structures in patients with post-hepatitis B cirrhosis: A magnetic resonance imaging study.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Sept 28;45(9):1109-1114

Department of Radiology, Third Xiangya Hospital, Central South University, Changsha 410013, China.

Objectives: To investigate volume changes of subcortical structures in patients with post-hepatitis B cirrhosis.

Methods: Thirty patients with post-hepatitis B cirrhosis (the cirrhosis group) and 24 age- and sex-matched healthy controls (the control group) were enrolled in this prospective study. All subjects underwent neuropsychological tests, blood biochemical determinations, and cerebral MRI. Volumes of 18 selected subcortical structures were automatically segmented and analyzed by the FreeSurfer. In the cirrhosis group, the relationships between abnormal subcortical volumes and clinical index or neurocognitive performance were investigated. The relationships between globus pallidus volumes and pallidal hyperintensity were also examined.

Results: Compared with the healthy controls, patients with post-hepatitis B cirrhosis displayed smaller bilateral putamen, amygdala, and nucleus accumbens volumes and larger bilateral globus pallidus volumes (<0.001 or =0.001). In the cirrhosis group, the volumes of left putamen and amygdala were negatively correlated with the number connection test-A (NCT-A)(left putamen =-0.410, =0.034; left amygdala =-0.439, =0.022), and the volumes of bilateral globus pallidus were positively correlated with pallidal index (PI) (left globus pallidus =0.889, <0.001; right globus pallidus =0.900, <0.001).

Conclusions: Abnormalities of subcortical volumes appear bilaterally symmetrical in patients with post-hepatitis B cirrhosis. Atrophy of left putamen and amygdala might contribute to poor neurocognitive performance, and the manganese deposition might contribute to the increased globus pallidus volumes in patients with post-hepatitis B cirrhosis.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190338DOI Listing
October 2020

Higher anxiety rating does not mean poor speech performance: dissociation of the neural mechanisms of anticipation and delivery of public speaking.

Brain Imaging Behav 2020 Oct 9. Epub 2020 Oct 9.

Faculty of Education, East China Normal University, Shanghai, China.

Public speaking anxiety refers to feelings of nervousness when anticipating or delivering a speech. However, the relationship between anxiety in the anticipation phase and speech delivery phase is unclear. In this study, we used functional near-infrared spectroscopy to record participants' brain activities when they were anticipating or performing public speaking tasks in an immersive virtual reality environment. Neuroimaging results showed that participants' subjective ratings of public anxiety in the anticipation phase but not the delivery phase were correlated with activities in the dorsolateral prefrontal cortex, the inferior frontal gyrus, and the precentral and postcentral gyrus. In contrast, their speaking performance could be predicted by activities in the temporal gyrus and the right postcentral gyrus in the delivery phase. This suggests a dissociation in the neural mechanisms between anxiety in preparation and execution of a speech. The conventional anxiety questionnaire is a good predictor of anticipatory anxiety, but cannot predict speaking performance. Using virtual reality to establish a situational test could be a better approach to assess in vivo public speaking performance.
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http://dx.doi.org/10.1007/s11682-020-00387-3DOI Listing
October 2020

Highly multiplexed quantifications of 299 somatic mutations in colorectal cancer patients by automated MALDI-TOF mass spectrometry.

BMC Med Genomics 2020 10 2;13(1):143. Epub 2020 Oct 2.

School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Background: Detection of somatic mutations in tumor tissues helps to understand tumor biology and guide treatment selection. Methods such as quantitative PCR can analyze a few mutations with high efficiency, while next generation sequencing (NGS) based methods can analyze hundreds to thousands of mutations. However, there is a lack of cost-effective method for quantitatively analyzing tens to a few hundred mutations of potential biological and clinical significance.

Methods: Through a comprehensive database and literature review we selected 299 mutations associated with colorectal cancer. We then designed a highly multiplexed assay panel (8-wells covering 299 mutations in 109 genes) based on an automated MADLI-TOF mass spectrometry (MS) platform. The multiplex panel was tested with a total of 319 freshly frozen tissues and 92 FFPE samples from 229 colorectal cancer patients, with 13 samples also analyzed by a targeted NGS method covering 532 genes.

Results: Multiplex somatic mutation panel based on MALDI-TOF MS detected and quantified at least one somatic mutation in 142 patients, with KRAS, TP53 and APC being the most frequently mutated genes. Extensive validation by both capillary sequencing and targeted NGS demonstrated high accuracy of the multiplex MS assay. Out of 35 mutations tested with plasmid constructs, sensitivities of 5 and 10% mutant allele frequency were achieved for 19 and 16 mutations, respectively.

Conclusions: Automated MALDI-TOF MS offers an efficient and cost-effective platform for highly multiplexed quantitation of 299 somatic mutations, which may be useful in studying the biological and clinical significance of somatic mutations with large numbers of cancer tissues.
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http://dx.doi.org/10.1186/s12920-020-00804-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532609PMC
October 2020

An Antibody Targeting ICOS Increases Intratumoral Cytotoxic to Regulatory T-cell Ratio and Induces Tumor Regression.

Cancer Immunol Res 2020 12 30;8(12):1568-1582. Epub 2020 Sep 30.

Kymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.

The immunosuppressive tumor microenvironment constitutes a significant hurdle to immune checkpoint inhibitor responses. Both soluble factors and specialized immune cells, such as regulatory T cells (Treg), are key components of active intratumoral immunosuppression. Inducible costimulatory receptor (ICOS) can be highly expressed in the tumor microenvironment, especially on immunosuppressive Treg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we performed immune profiling of samples from tumor-bearing mice and patients with cancer to demonstrate differential expression of ICOS in immune T-cell subsets in different tissues. ICOS expression was higher on intratumoral Treg than on effector CD8 T cells. In addition, by immunizing an knockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that bound ICOS from different species. We showed that KY1044 induced sustained depletion of ICOS T cells but was also associated with increased secretion of proinflammatory cytokines from ICOS effector T cells (T). In syngeneic mouse tumor models, KY1044 depleted ICOS Treg and increased the intratumoral T:Treg ratio, resulting in increased secretion of IFNγ and TNFα by T cells. KY1044 demonstrated monotherapy antitumor efficacy and improved anti-PD-L1 efficacy. In summary, we demonstrated that using KY1044, one can exploit the differential expression of ICOS on T-cell subtypes to improve the intratumoral immune contexture and restore an antitumor immune response.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0034DOI Listing
December 2020

Pickering Emulsion-Based Microreactors for Size-Selective Interfacial Enzymatic Catalysis.

Front Bioeng Biotechnol 2020 21;8:950. Epub 2020 Aug 21.

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

In this study, we have developed a mild and effective method to prepare a metal-organic framework (MOF)-based microcapsule by the self-assembly of pre-synthesized zeolite imidazolate framework-8 (ZIF-8) nanoparticles at the oil-water interface combined with deposition of a dense ZIF-8 coating outside the capsule. By introducing the enzyme lipase B (CalB) directly into the stabilizer ZIF-8 or the water phase of Pickering emulsion during the preparation process, we achieved that the enzyme was immobilized within the shell ([email protected]@cap) or in the cavity ([email protected]) of the microcapsules, respectively. The resulting CalB-loaded microcapsules were robust and had a core-shell structure proved by scanning electron microscopy. Meanwhile, Fourier transform infrared spectroscopy was conducted to confirm the encapsulation of enzymes in the microcapsules and their position in the microcapsules was confirmed by fluorescence microscopy. Furthermore, through the comparison of transesterification reactions between a pair of small substrates and a pair of larger ones, the two types of CalB-loaded microcapsules showed great catalytic activity, stability and size selectivity, and the catalytic activity of [email protected]@cap was slightly higher than that of [email protected] Importantly, due to the large size of the microcapsules, the catalyst could be separated from the reaction system by sedimentation, thereby reducing the energy consumption for separation. These kinds of multifunctional MOF-enzyme composites may open up new opportunities for the biocatalysis and microreactor.
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http://dx.doi.org/10.3389/fbioe.2020.00950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471251PMC
August 2020

Fullerene rotational dynamics generate disordered configurations that suppress thermal conductivity in superatomic crystals.

Nanoscale Horiz 2020 Nov 10;5(11):1524-1529. Epub 2020 Sep 10.

Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, School of Energy and Power Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.

The thermal conductivity of fullerene-based superatomic crystals (SACs) is investigated using molecular dynamics simulations. The temperature-dependent predictions agree with the trends of previous measurements. The thermal conductivity behavior emerges as a result of the C molecule rotational dynamics and orientation, which are quantified using the root mean square displacements of the carbon atoms and the relative orientations of the Cs. At low temperatures, the Cs exhibit small rotations around equilibrium positions (i.e., librations). When the librating Cs are orientationally-ordered, as in the [C] and [CoSe(PEt)][C] SACs, thermal conductivity decreases with increasing temperature, as is typical for a crystal. When the librating Cs are orientationally-disordered, however, as in the [CoTe(PEt)][C] SAC, thermal conductivity is lower and temperature independent, as is typical for an amorphous solid. At higher temperatures, where the Cs in all three SACs freely-rotate and are thus dynamically disordered, thermal conductivity is temperature independent. The abrupt changes driven by the C dynamics suggest that fullerene-based SACs can be designed to be thermal conductivity switches based on a variety of external stimuli.
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http://dx.doi.org/10.1039/d0nh00358aDOI Listing
November 2020

Combination of 3.0T magnetic resonance imaging T mapping with texture analysis for evaluating the degeneration of lumbar facet joints.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Jul;45(7):827-833

Department of Radiology, Third Xiangya Hospital, Central South University, Changsha 410013.

Objectives: Quantitative magnetic resonance imaging has been successfully applied to assess the status of cartilage biochemical components. This study aimed to investigate the performance of 3.0T magnetic resonance imaging T mapping combined with texture analysis for evaluating the early degeneration of lumbar facet joints.

Methods: A total of 38 patients (20 in the asymptomatic group and 18 in the symptomatic group) were enrolled. All patients underwent 3.0T magnetic resonance imaging conventional sequences, water excitation three-dimensional spoiled gradient echo sequence (3D-WATSc), and T mapping scans. The bilateral L and L/S lumbar facet joints were morphological graded using the Weishaupt criteria, T values, and texture parameters derived from T mapping of cartilage. The Kruskal-Wallis test was used to compare the differences of parameters among different groups. Multivariate logistic regression analysis was used to obtain the independent predictive factors for evaluating the early degeneration of lumbar facet joints. Receiver operating characteristic (ROC) curve was performed and the area under curve (AUC) was calculated. Spearman correlation analysis was used to evaluate the correlation of the independent predictors of cartilage T value and texture parameters with the subjects' Japanese Orthopedic Association (JOA) score or Visual Analogue Scale (VAS) score.

Results: A total of 148 facet joints were selected, including 70 in Weishaupt 0 (normal) group, 58 in Weishaupt 1 group, and 20 in Weishaupt 2-3 group. T value, entropy, and contrast increased significantly as the exacerbation of facet joint degeneration (all <0.05), while the inverse difference moment, energy, and correlation decreased (all <0.05). Entropy among different groups was significantly different (all <0.05), and the differences of T value, contrast, inverse difference moment, and energy between Weishaupt 0 and Weishaupt 1 groups, or Weishaupt 0 and Weishaupt 2-3 groups were statistically significant (all <0.05). Multivariate logistic regression analysis suggested that T value and inverse difference moment were the independent predictors for evaluating early degeneration of facet joints. The combination of T value with inverse difference moment achieved the best performance in distinguishing Weishaupt 0 from Weishaupt 1 (AUC=0.85), with sensitivity and specificity at 92.7% and 76.5%, respectively. In the symptom group, the cartilage T value combined inverse difference moment was positively correlated with JOA score (=0.475, <0.05) and VAS score (=0.452, <0.05).

Conclusions: 3.0T magnetic resonance imaging T mapping combined with texture analysis is helpful to quantitatively evaluate the early degeneration of lumbar facet joints, in which the T value and inverse difference moment show an indicative significance..
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190640DOI Listing
July 2020

The effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines.

BMC Infect Dis 2020 Aug 31;20(1):641. Epub 2020 Aug 31.

Jiangsu Provincial Center for Disease Control and Prevention, NO. 172 Jiangsu Rd., Gulou District, Nanjing, 210009, Jiangsu Province, China.

Background: Maternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines.

Methods: There were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (< 1:8) and maternal antibody positive (≥1:8), and the second one included maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fold increases (GMIs) and seroconversion rates of poliovirus type-specific neutralizing antibodies after vaccination among participants with different maternal poliovirus antibody levels.

Results: The GMTs and GMIs of three types of poliovirus antibodies after vaccination in maternal antibody negative participants were significantly higher than those in maternal antibody positive participants. The seroconversion rates of type II and type III poliovirus antibodies in maternal antibody positive participants were significantly lower than those in maternal antibody negative participants. Among participants with maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32, the GMTs and GMIs of three types of poliovirus antibodies after vaccination showed a tendency to decline with the increasing of maternal antibody levels. The seroconversion rates of three types of poliovirus antibodies in participants with maternal antibody titer ≥1:32 were significantly lower than those in participants with maternal antibody titer < 1:8 and 1:8 ~ < 1:32.

Conclusions: Maternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect.

Trial Registration: ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.
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http://dx.doi.org/10.1186/s12879-020-05348-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460787PMC
August 2020
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