Publications by authors named "Qin Qin"

382 Publications

Novel nanoliposomes alleviate contrast-induced acute kidney injury in New Zealand rabbits by mediating inflammatory response.

Ann Transl Med 2021 Aug;9(15):1250

Department of Cardiology, Tianjin Chest Hospital, Tianjin, China.

Background: The purpose of the research was to investigate the preventive effect of nanoliposomes on contrast-induced nephropathy (CIN) in New Zealand rabbits and to provide a theoretical basis for clinically effective prevention and treatment of CIN and the development of new contrast agents.

Methods: A total of 48 New Zealand rabbits were divided into four groups randomly, there were 12 rabbits in eacj group: (I) control group; (II) contrast group; (III) hydration prevention group; and (IV) nanoliposome group. The changes of serum creatinine (SCr) and blood urea nitrogen (BUN) were messured before and after injection of iopromide. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory and oxidative stress indexes, including neutrophil gelatinase-associated lipoprotein (NGAL), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA). Twenty-four hours after injection of the contrast medium, the rabbits were killed and the pathological changes were observed under an electron microscope.

Results: There were statistical significances in sCr and BUN values among the four groups at both 8 hours and 24 hours after injection of the contrast medium. Serum NGAL and TNF-α levels were also significantly different among the four groups (P<0.05) 24 hours after injection of the contrast medium. The incidence rate of CIN in each group was statistically significant. Nanoliposomes had obvious advantages over hydration prevention in NGAL and TNF-α levels.

Conclusions: Nanoliposomes can prevent the occurrence of CIN and reduce the damage of contrast agent to the kidney by reducing inflammatory reaction.
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http://dx.doi.org/10.21037/atm-21-3201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421945PMC
August 2021

EPA and DHA confer protection against DON-induced endoplasmic reticulum stress and iron imbalance in IPEC-1 cells.

Br J Nutr 2021 Sep 14:1-29. Epub 2021 Sep 14.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, China 430023.

This study assessed the molecular mechanism of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) protection against IPEC-1 cell damage induced by deoxynivalenol (DON). The cells were divided into six groups, including the CON group, the EPA group, the DHA group, the DON group, the EPA+DON group, and the DHA+DON group. RNA sequencing was used to investigate the potential mechanism, and qRT-PCR was employed to verify the expression of selected genes. Changes in ultrastructure were used to estimate pathological changes and endoplasmic reticulum (ER) injury in IPEC-1 cells. Transferrin receptor 1 (TFR1) was tested by ELISA. Fe2+ and malondialdehyde (MDA) contents were estimated by spectrophotometry, and reactive oxygen species (ROS) was assayed by fluorospectrophotometry. RNA sequencing analysis showed that EPA and DHA had a significant effect on the expression of genes involved in ER stress and iron balance during DON-induced cell injury. The results showed that DON increased ER damage, the content of MDA and ROS, the ratio of X-box binding protein 1s (XBP-1s)/X-box binding protein 1u (XBP-1u), the concentration of Fe2+, and the activity of TFR1. However, the results also showed that EPA and DHA decreased the ratio of XBP-1s/XBP-1u to relieve DON-induced ER damage of IPEC-1 cells. Moreover, EPA and DHA (especially DHA) reversed the factors related to iron balance. It can be concluded that EPA and DHA reversed IPEC-1 cell damage induced by DON. DHA has the potential to protect IPEC-1 cells from DON-induced iron imbalance by inhibiting ER stress.
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http://dx.doi.org/10.1017/S0007114521003688DOI Listing
September 2021

Diagnostic and prognostic predictive values of circulating sTREM-1 in sepsis: A meta-analysis.

Infect Genet Evol 2021 Sep 7:105074. Epub 2021 Sep 7.

Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

Background: With the increasing studies regarding the diagnostic value of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in sepsis in recent years, it is essential to make an updated meta-analysis to explore the sepsis differentiation value of circulating sTREM-1 from systemic inflammatory response syndrome (SIRS). Recently, no meta-analysis was made to explore the prognostic predictive value of circulating sTREM-1 in sepsis. Thus, the present aimed to make meta-analyses to explore the diagnostic and prognostic predictive values of circulating sTREM-1 in sepsis.

Methods: Articles published before March 2021 were searched in databases: PubMed, Web of Science, EMBASE, Medline and Google Scholar. After a summary of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR), the receive-operating characteristics (SROC) curve were performed to summarize true positive (TP) and false positive (FP) rates. Q test and I were used to explore heterogeneity between studies.

Results: Circulating sTREM-1 showed a high sensitivity (0.85 (95% confidence interval (CI): 0.76-0.91)) and moderate specificity (0.79 (95% CI: 0.70-0.86)) to differentiate sepsis from SIRS. The study showed a high sensitivity (0.80 (95% CI: 0.66-0.89)) and moderate specificity (0.75 (95% CI: 0.69-0.81)) to predict 28-day mortality in sepsis.

Conclusion: In conclusion, the present study suggested that circulating sTREM-1 showed diagnostic and prognostic predictive values in sepsis.
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http://dx.doi.org/10.1016/j.meegid.2021.105074DOI Listing
September 2021

Quantitative evaluation of the joint disease prevention and control policy in China using the difference-in-difference method.

Authors:
Qin Qin Youhai Sun

Int J Health Plann Manage 2021 Aug 30. Epub 2021 Aug 30.

Law School, Tianjin University, Tianjin, China.

Emergent infectious diseases represent a real threat to global health, but their harmful effects can be reduced by implementing appropriate response policies. According to the panel data of 10 provinces in Northern China from 2009 to 2018, the disease prevention and control policy jointly implemented in the Beijing-Tianjin-Hebei region in 2013 was regarded as a 'quasi-natural experiment'. However, this policy has not yet been sufficiently evaluated. In this paper, we used the difference-in-difference method to quantitatively evaluate the net effects of applying the joint prevention and control policy against regional key notifiable infectious diseases. The results revealed that the joint disease prevention and control policy had a significant limiting effect and a time lag on the incidence rate of key infectious diseases. In conclusion, this policy is beneficial to the effective prevention and control of infectious diseases, which provides supporting evidence to interpret and improve the joint disease prevention and control mechanisms.
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http://dx.doi.org/10.1002/hpm.3312DOI Listing
August 2021

Novel Nanoliposomes Alleviate Contrast-Induced Nephropathy by Mediating Apoptosis Response in New Zealand Rabbits.

Front Mol Biosci 2021 6;8:681849. Epub 2021 Jul 6.

Department of Cardiology, Tianjin Chest Hospital, Tianjin, China.

The aim of this study was to test the preventive effects of nano liposomes against contrast-induced nephropathy (CIN) in New Zealand rabbits. Sixty New Zealand rabbits were randomly divided into four groups, with 15 rabbits in each group: control group, contrast group, hydration group and nano liposome group. Serum creatinine (Scr) and Blood Urea Nitrogen (BUN) were measured before and after injection of the contrast agent iopromide. Oxidative stress markers, such as superoxide dismutase (SOD) and malondialdehyde (MDA), and apoptosis markers, such as Bcl2-Associated X (Bax) and B-cell lymphoma-2 (Bcl-2), were measured by enzyme-linked immunosorbent assay (ELISA). Rabbits were killed 24 h after injection of the contrast medium and both kidneys were removed. Real-time Polymerase Chain Reaction (RT-PCR) and Western blot assays were performed in kidney tissue. Pathological changes were analyzed under the optical and electron microscope. Compared with the hydration group, the nano liposome group showed improved protection of renal function, with significantly different Scr and BUN levels, incidence of CIN, apoptosis index, RT-PCR and Western blot protein expression patterns. Under the optical and electron microscope, the renal injury in the nano liposome group was less than in the hydration group. However, based on SOD and MDA, there was no significant difference in oxidative stress when compared with the hydration group. Apoptosis is an important mechanism in CIN. Nano liposomes can prevent the occurrence of CIN by decreasing apoptosis, reducing damage to the kidney by the contrast agent.
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http://dx.doi.org/10.3389/fmolb.2021.681849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290201PMC
July 2021

Silencing of Sulfoquinovosyl Diacylglycerol Synthase 1 Impairs the Glycolipids Accumulation and Photosynthesis in Phosphate-deprived Rice.

J Exp Bot 2021 Jun 24. Epub 2021 Jun 24.

Institute of Eco-Environment and Plant Protection, Shanghai Academy of Agricultural Sciences, Shanghai, China.

Phosphate (Pi) starved crops utilize the phospholipids as a source for internal Pi supply by replacing the non-phosphorus glycolipids. In rice, sulfoquinovosyl diacylglycerol synthase 1 (OsSQD1) functions as a key enzyme to catalyse SQDG formation. In this study, differential expression of OsSQD1 in response to Pi, nitrogen (N), potassium (K) and iron (Fe)-deficiencies in different durations was measured. A electrophoretic mobility shift assay (EMSA) suggests that OsSQD1 is regulated by OsPHR2, an MYB domain-containing transcription factor. The analyses of different lipid species concentrations in a ossqd1-knockout mutant demonstrated that OsSQD1 silencing increased the phospholipid contents and altered the fatty acid composition under Pi-deficiency. Moreover, OsSQD1 silencing reduces glycolipid accumulation under -Pi condition. It also triggered the saturation of fatty acid in phospholipids and glycolipids treated with different Pi regimes. Relative amounts of transcripts related to phospholipid degradation and glycolipid synthesis was assessed to explore the mechanism by which OsSQD1 exerts an effect on lipid homeostasis under -P conditions. Furthermore, OsSQD1 silencing inhibited photosynthesis, especially under Pi-deficient conditions, by down-regulating glycolipids in rice shoots. The study reveals that OsSQD1 plays a key role in lipid homeostasis, especially the glycolipids accumulation under Pi-deficiency, which results in the inhibition of photosynthesis responding to Pi-deficiency.
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http://dx.doi.org/10.1093/jxb/erab300DOI Listing
June 2021

Ginsenoside Rg3 attenuates angiotensin II-induced myocardial hypertrophy through repressing NLRP3 inflammasome and oxidative stress via modulating SIRT1/NF-κB pathway.

Int Immunopharmacol 2021 Sep 18;98:107841. Epub 2021 Jun 18.

Department of Cardiology, Tianjin Chest Hospital, Tianjin, China. Electronic address:

Background: Ginsenoside Rg3 (Rg3), one of the most potent components extracted from the roots of the traditional Chinese herb Panax ginseng, has prominent roles in anti-tumor and anti-inflammation. However, the applications of Rg3 against myocardial hypertrophy are not fully revealed.

Methods: Transverse aortic constriction (TAC) was adopted to build the myocardial hypertrophy model in rats. The in vitro model of myocardial hypertrophy was induced by angiotensin II (Ang II) in the human cardiomyocyte cell line AC16 and HCM, which were then treated with different doses of Rg3. The levels of myocardial hypertrophy markers (ANP, BNP, and β-MHC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot (WB) was conducted to verify the expressions of myocardial fibrosis-associated proteins (MyHc, Collagen Ⅰ, and TGF-β1) and oxidative stress (OS) proteins (HO-1 and Nrf2). The markers of fibrosis, hypertrophy, NLRP3 inflammasome and OS in cardiomyocytes were evaluated by qRT-PCR, western blot (WB), enzyme-linked immunosorbent assay (ELISA), and cellular immunofluorescence, respectively. Furthermore, pharmacological intervention on sirtuin-1 (SIRT1) was performed to clarify the function of SIRT1 in Rg3-mediated effects.

Results: Rg3 dose-dependently attenuated the Ang II-induced myocardial hypertrophy and fibrosis. What's more, Rg3 markedly inhibited NLRP3-ASC-Caspase1 inflammasome and OS (reflected by SOD, MDA, HO-1, and Nrf2) in cardiomyocytes treated with Ang II. Mechanistically, Rg3 attenuated NF-κB activation and promoted SIRT1 expression. Inhibiting SIRT1 (by AGK2) mostly reversed Rg3-mediated effects against Ang II-induced myocardial hypertrophy and fibrosis. In the TAC rat model, administration of Rg3 mitigated myocardial hypertrophy and fibrosis through pressing overproduced inflammation and OS.

Conclusion: Rg3 prevents Ang II-induced myocardial hypertrophy via inactivating NLRP3 inflammasome and oxidative stress by modulating the SIRT1/NF-κB pathway.
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http://dx.doi.org/10.1016/j.intimp.2021.107841DOI Listing
September 2021

Engineering the permeability of Halomonas bluephagenesis enhanced its chassis properties.

Metab Eng 2021 09 5;67:53-66. Epub 2021 Jun 5.

School of Life Sciences, Tsinghua University, Beijing, 100084, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China; MOE Key Lab of Industrial Biocatalysis, Dept Chemical Engineering, Tsinghua University, Beijing, 100084, China. Electronic address:

Bacterial outer membrane (OM), an asymmetric lipid bilayer functioning as a self-protective barrier with reduced permeability for Gram-negative bacteria, yet wasting nutrients and energy to synthesize, has not been studied for its effect on bioproduction. Here we construct several OM-defected halophile Halomonas bluephagenesis strains to investigate the effects of OM on bioproduction. We achieve enhanced chassis properties of H. bluephagenesis based on positive cellular properties among several OM-defected strains. The OM-defected H. bluephagenesis WZY09 demonstrates better adaptation to lower salinity, increasing 28%, 30% and 12% on dry cell mass (DCM), poly(3-hydroxybutyrate) (PHB) accumulation and glucose to PHB conversion rate, respectively, including enlarged cell sizes and 21-folds reduced endotoxin. Interestingly, a poly(3-hydroxybutyrate-co-21mol%4-hydroxybutyrate) (P(3HB-co-21mol%4HB)) is produced by H. bluephagenesis WZY09 derivate WZY249, increasing 60% and 260% on polyhydroxyalkanoate (PHA) production and 4HB content, respectively. Furthermore, increased electroporation efficiency, more sensitive isopropyl β-D-1-thio-galactopyranoside (IPTG) induction, better oxygen uptake, enhanced antibiotics sensitivity and ectoine secretion due to better membrane permeability are observed if OM defected, demonstrating significant OM defection impacts for further metabolic engineering, synthetic biology studies and industrial applications.
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http://dx.doi.org/10.1016/j.ymben.2021.05.010DOI Listing
September 2021

[Quality Control Test of Transcranial MRI-guided Focused Ultrasound Treatment System before Surgery].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Jun;45(3):340-343

The First Medical Center of Chinese PLA General Hospital, Beijing, 100853.

Objective: To investigate the pre-treatment preventive maintenance and quality control procedure of MRI system and transcranial MRI-guided focused ultrasound (TcMRgFUS) treatment system by monitoring quality control of these two systems.

Methods: The general performance index and image quality control index of MRI system, as well as the quality assurance program of TcMRgFUS EXABLATE 4000 system were tested and recorded.

Results: The general performance index and image quality control index of MRI system met requirements.

Conclusions: Through system detection, the system performance could be monitored, ensuring the accuracy and safety of surgery.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.03.023DOI Listing
June 2021

Transcriptional regulation of the mannitol phosphotransferase system operon by the ferric uptake regulator (Fur) in Vibrio cholerae El Tor serogroup O1.

Res Microbiol 2021 Jun-Aug;172(4-5):103848. Epub 2021 Jun 2.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address:

The phosphoenolpyruvate (PEP): carbohydrate phosphotransferase system (PTS) allows bacteria to use various carbohydrates as energy resources including mannitol. The mannitol-specific PTS transporter in Vibrio cholerae is encoded by the mtlADR operon. Expression of the mtl operon has been shown to be strictly regulated by CRP, MtlS, and MtlR. In the present study, we investigated the regulation of mtlADR by the ferric uptake regulator (Fur). The results showed that Fur binds to the promoter-proximal DNA region of mtlADR to repress its transcription independent of iron, in mannitol-containing growth medium. The capacity for mannitol fermentation was significantly increased in Δfur relative to that of WT for normal and iron-replete growth media. The level of organic acids produced by Δfur was significantly enhanced relative to that produced by the WT strain in the normal and iron-replete media but not in an iron-starved medium. The results provided for a deeper understanding of the regulation of mtlADR in V. cholerae.
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http://dx.doi.org/10.1016/j.resmic.2021.103848DOI Listing
June 2021

Influence of elemental sulfur on cadmium bioavailability, microbial community in paddy soil and Cd accumulation in rice plants.

Sci Rep 2021 Jun 1;11(1):11468. Epub 2021 Jun 1.

ECO-Environment Protection Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai, 201403, China.

Cadmium (Cd) is highly toxic to living organisms and the contamination of Cd in paddy soil in China has received much attention. In the present study, by conducting pot experiment, the influence of S fertilizer (S) on rice growth, iron plaque formation, Cd accumulation in rice plants and bacterial community in rice rhizosphere soil was investigated. The biomass of rice plants was significantly increased by S addition (19.5-73.6%). The addition of S increased the formation of iron plaque by 24.3-45.8%, meanwhile the amount of Cd sequestered on iron plaque increased. In soil treated with 5 mg/kg Cd, addition of 0.2 g/kg S decreased the diffusive gradients in thin films (DGT) extractable Cd by 60.0%. The application of S significantly decreased the concentration of Cd in rice grain by 12.1% (0.1 g/kg) and 36.6% (0.2 g/kg) respectively. The addition of S significantly increased the ratio of Acidobacteria, Bacteroidetes in rice rhizosphere soil. Meanwhile, the ratio of Planctomycetes and Chloroflexi decreased. The results indicated that promoting Fe- and S-reducing and residue decomposition bacterial in the rhizosphere by S may be one biological reason for reducing Cd risk in the soil-rice system.
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http://dx.doi.org/10.1038/s41598-021-91003-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169911PMC
June 2021

Highly efficient desalination performance of carbon honeycomb based reverse osmosis membranes unveiled by molecular dynamics simulations.

Nanotechnology 2021 Jun 23;32(37). Epub 2021 Jun 23.

Physics Department, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabia.

Seawater desalination is vital to our modern civilization. Here, we report that the carbon honeycomb (CHC) has an outstanding water permeability and salt rejection in the seawater desalination, as revealed by molecular dynamics simulations. More than 92% of ions are rejected by CHC at applied pressures ranging from 50 to 250 MPa. CHC has a perfect salt rejection at pressures below 150 Mpa. On increasing the applied pressure up to 150 MPa, the salt rejection reduces only to 92%. Pressure, temperature and temperature gradient are noted to play a significant role in modulating the water flux. The water flux increases with pressure and temperature. With the introduction of a temperature gradient of 3.5 K nm, the seawater permeability increases by 33% as compared to room temperature. The water permeability of the CHC is greater than other carbon materials and osmosis membranes including graphene (8.7 times) and graphyne (2.1 times). It indicates the significant potential of the CHC for commercial application in water purification.
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http://dx.doi.org/10.1088/1361-6528/ac03d8DOI Listing
June 2021

Multi-Parametric Evaluation of Cerebral Hemodynamics in Neonatal Piglets Using Non-Contrast-Enhanced Magnetic Resonance Imaging Methods.

J Magn Reson Imaging 2021 Oct 6;54(4):1053-1065. Epub 2021 May 6.

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Disruption of brain oxygen delivery and consumption after hypoxic-ischemic injury contributes to neonatal mortality and neurological impairment. Measuring cerebral hemodynamic parameters, including cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO ), is clinically important.

Purpose: Phase-contrast (PC), velocity-selective arterial spin labeling (VSASL), and T -relaxation-under-phase-contrast (TRUPC) are magnetic resonance imaging (MRI) techniques that have shown promising results in assessing cerebral hemodynamics in humans. We aimed to test their feasibility in quantifying CBF, OEF, and CMRO in piglets.

Study Type: Prospective.

Animal Model: Ten neonatal piglets subacutely recovered from global hypoxia-ischemia (N = 2), excitotoxic brain injury (N = 6), or sham procedure (N = 2).

Field Strength/sequence: VSASL, TRUPC, and PC MRI acquired at 3.0 T.

Assessment: Regional CBF was measured by VSASL. Global CBF was quantified by both PC and VSASL. TRUPC assessed OEF at the superior sagittal sinus (SSS) and internal cerebral veins (ICVs). CMRO was calculated from global CBF and SSS-derived OEF. End-tidal carbon dioxide (EtCO ) levels of the piglets were also measured. Brain damage was assessed in tissue sections postmortem by counting damaged neurons.

Statistical Tests: Spearman correlations were performed to evaluate associations among CBF (by PC or VSASL), OEF, CMRO , EtCO , and the pathological neuron counts. Paired t-test was used to compare OEF at SSS with OEF at ICV.

Results: Global CBF was 32.1 ± 14.9 mL/100 g/minute and 30.9 ± 8.3 mL/100 g/minute for PC and VSASL, respectively, showing a significant correlation (r = 0.82, P < 0.05). OEF was 54.9 ± 8.8% at SSS and 46.1 ± 5.6% at ICV, showing a significant difference (P < 0.05). Global CMRO was 79.1 ± 26.2 μmol/100 g/minute and 77.2 ± 12.2 μmol/100 g/minute using PC and VSASL-derived CBF, respectively. EtCO correlated positively with PC-based CBF (r = 0.81, P < 0.05) but negatively with OEF at SSS (r = -0.84, P < 0.05). Relative CBF of subcortical brain regions and OEF at ICV did not significantly correlate, respectively, with the ratios of degenerating-to-total neurons (P = 0.30, P = 0.10).

Data Conclusion: Non-contrast MRI can quantify cerebral hemodynamic parameters in normal and brain-injured neonatal piglets.

Level Of Evidence: 1 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440374PMC
October 2021

Three-dimensional whole-brain mapping of cerebral blood volume and venous cerebral blood volume using Fourier transform-based velocity-selective pulse trains.

Magn Reson Med 2021 09 6;86(3):1420-1433. Epub 2021 May 6.

The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Purpose: To develop 3D MRI methods for cerebral blood volume (CBV) and venous cerebral blood volume (vCBV) estimation with whole-brain coverage using Fourier transform-based velocity-selective (FT-VS) pulse trains.

Methods: For CBV measurement, FT-VS saturation pulse trains were used to suppress static tissue, whereas CSF contamination was corrected voxel-by-voxel using a multi-readout acquisition and a fast CSF T scan. The vCBV mapping was achieved by inserting an arterial-nulling module that included a FT-VS inversion pulse train. Using these methods, CBV and vCBV maps were obtained on 6 healthy volunteers at 3 T.

Results: The mean CBV and vCBV values in gray matter and white matter in different areas of the brain showed high correlation (r = 0.95 and P < .0001). The averaged CBV and vCBV values of the whole brain were 5.4 ± 0.6 mL/100 g and 2.5 ± 0.3 mL/100 g in gray matter, and 2.6 ± 0.5 mL/100 g and 1.5 ± 0.2 mL/100 g in white matter, respectively, comparable to the literature.

Conclusion: The feasibility of FT-VS-based CBV and vCBV estimation was demonstrated for 3D acquisition with large spatial coverage.
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http://dx.doi.org/10.1002/mrm.28815DOI Listing
September 2021

Magnetic resonance angiography and perfusion mapping by arterial spin labeling using Fourier transform-based velocity-selective pulse trains: Examination on a commercial perfusion phantom.

Magn Reson Med 2021 09 2;86(3):1360-1368. Epub 2021 May 2.

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, USA.

Purpose: Benchmarking of flow and perfusion MR techniques on standardized phantoms can facilitate the use of advanced angiography and perfusion-mapping techniques across multiple sites, field strength, and vendors. Here, MRA and perfusion mapping by arterial spin labeling (ASL) using Fourier transform (FT)-based velocity-selective saturation and inversion pulse trains were evaluated on a commercial perfusion phantom.

Methods: The FT velocity-selective saturation-based MRA and FT velocity-selective inversion-based ASL perfusion imaging were compared with time-of-flight and pseudo-continuous ASL at 3 T on the perfusion phantom at two controlled flow rates, 175 mL/min and 350 mL/min. Velocity-selective MRA (VSMRA) and velocity-selective ASL (VSASL) were each performed with three velocity-encoding directions: foot-head, left-right, and oblique 45°. The contrast-to-noise ratio for MRA scans and perfusion-weighted signal, as well as labeling efficiency for ASL methods, were quantified.

Results: On this phantom with feeding tubes having only vertical and transverse flow directions, VSMRA and VSASL exhibited the dependence of velocity-encoding directions. The foot-head-encoded VSMRA and VSASL generated similar signal contrasts as time of flight and pseudo-continuous ASL for the two flow rates, respectively. The oblique 45°-encoded VSMRA yielded more uniform contrast-to-noise ratio across slices than foot-head and left-right-encoded VSMRA scans. The oblique 45°-encoded VSASL elevated labeling efficiency from 0.22-0.68 to 0.82-0.90 through more uniform labeling of the entire feeding tubes.

Conclusion: Both FT velocity-selective saturation-based VSMRA and FT velocity-selective inversion-based VSASL were characterized on a commercial perfusion phantom. Careful selection of velocity-encoding directions along the major vessels is recommended for their applications in various organs.
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http://dx.doi.org/10.1002/mrm.28805DOI Listing
September 2021

Brevilin A inhibits NLRP3 inflammasome activation in vivo and in vitro by acting on the upstream of NLRP3-induced ASC oligomerization.

Mol Immunol 2021 07 20;135:116-126. Epub 2021 Apr 20.

School of Pharmacy, Dali University, Dali, 671000, China; Department of Liver Diseases, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. Electronic address:

Brevilin A (BA), is a natural biologically active ingredient derived from Centipeda minima with several reports of anti-cancer, while its anti-inflammatory activity is rarely reported. Current studies have found the dysregulated activation of NLRP3 inflammasome cause a variety of inflammatory diseases. Targeting the NLRP3 inflammasome contributes to the treatment of NLRP3-induced diseases. Here, we found that BA significantly attenuates the activation of caspase-1 and the subsequent secretion of the interleukin-1β (IL-1β) in mouse macrophages and human THP-1 cells, showing the inhibitory effect of BA on the NLRP3 inflammasome activation. Moreover, BA specifically inhibits NLRs inflammasomes activation triggered by multi-stimuli, but it has no effect on the AIM2 inflammasome activation, indicating that BA is a specific inhibitor of the NLRs inflammasomes. Research on the mechanism found BA inhibits NLRP3 inflammasome activation by blocking the upstream of ASC oligomerization. Importantly, in vivo experiments showed that BA markedly reduces the secretion of IL-1β to suppress NLRP3 inflammasome in the LPS-induced inflammation and MSU-challenged peritonitis model. In conclusion, our experiments show that BA is an effective NLRP3 inflammasome inhibitor and can be regarded as a drug candidate for NLRP3 inflammasome-driven diseases.
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http://dx.doi.org/10.1016/j.molimm.2021.03.025DOI Listing
July 2021

In vitro and in vivo relaxation and anti-inflammation of natural flavonoids from Elaeagnus pungens leaf via L-type calcium channel and targeting MAPK signal pathway.

J Ethnopharmacol 2021 Jul 6;275:114071. Epub 2021 Apr 6.

School of Pharmaceutical Science, South-Central University for Nationalities, Wuhan, 430074, PR China. Electronic address:

Ethnopharmacological Relevance: In traditional Chinese medicine (TCM), the leaf of Elaeagnus pungens Thunb. (Family Elaeagnaceae) is a herb documented as an antiasthmatic remedy to treat the severe asthma, bronchitis and other respiratory diseases in the early material medica "Bencao Gangmu" (Ming dynasty, about 442 years ago).

Aim Of The Study: This work is purposed to investigate the pharmacological effects and mechanism of total flavonoids from Elaeagnus pungens leaves (FLA) on asthma in vivo and vitro.

Materials And Methods: Female BALB/c mice were sensitized by intraperitoneal injection of OVA with aluminum hydroxide and intranasal challenged with OVA. After treatment with FLA (10, 20 mg/kg p.o.), the behaviors of mice were observed by score evaluation. Enumeration of total cells and OVA-specific IgE assay in the blood were measured as well as enumeration of total cells and cytokines assay in the BALF. Furthermore, histopathological analysis was performed by HE staining. The in vitro relaxing action on muscle force of FLA (0.0316-10.0 mg/ml) was evaluated using isometric tension in tracheal rings, and VDLCC currents were recorded to explore the relaxation mechanism in the isolated tracheal rings and mouse ASM cells, respectively. In vitro anti-inflammatory actions were assessed with LPS-stimulated RAW 264.7 macrophages. The production of inflammatory mediators and MAPK signaling pathway was estimated using ELISA and Western blotting analysis, respectively.

Results: The high dose of flavones from E. pungens leaf (20 mg/kg) can significantly improve the symptom of asthma breakout and relieve the lung swelling. FLA treatment decreased eosinophils and leukocytes numbers in blood and BLAF with a dosedependent manner. Furthermore, the inhibiting effect of FLA on the level of Ig E and inflammatory-related cytokines including TNF-α, IL-5 showed dose-independent. FLA relaxed high K + -induced contraction in a dose-dependent manner. The maximal relaxation produced by FLA was 99.7% (IC 50 = 0.46 mg/ml). The whole-cell VDLCC currents were abolished by FLA (3.16 mg/ml) and FLA significantly decreased the maximal amplitude of VDLCCs. No cytotoxic effect of FLA was observed in RAW264.7 cells under the tested concentrations (1-300 μg/mL). The increased IL-6 and NO by the stimulation of LPS in RAW264.7 cells were significantly inhibited by FLA in the dosedependent manner. Treatment with LPS in the presence of FLA, LPS-induced phosphorylation of ERK1/2 and JNK was inhibited in the macrophages.

Conclusion: FLA from Elaeagnus pungens leaf can alleviate the inflammation symptom via reducing the eosinophils and leukocytes numbers as well as the production of pro-inflammatory cytokines. This anti-inflammatory effect is related to the modulation of the MAPK signaling pathway. FLA can relax the precontracted TRs by blocking the VDLCCs, which interrupts extracellular Ca 2+ influx and inhibit the rise of [Ca 2+ ]i. It strongly suggests that these flavonoids components are the substances basis of Elaeagnus pungens leaves for allergic action, bronchospasm and inflammation in asthma.
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http://dx.doi.org/10.1016/j.jep.2021.114071DOI Listing
July 2021

Calibration of T oximetry MRI for subjects with sickle cell disease.

Magn Reson Med 2021 08 14;86(2):1019-1028. Epub 2021 Mar 14.

Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA.

Purpose: Cerebral T oximetry is a non-invasive imaging method to measure blood T and cerebral venous oxygenation. Measured T values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T oximetry calibration relationships in clinically meaningful ways. Previous in vitro works by two independent groups established potentially competing calibration models.

Methods: This study analyzed pooled datasets from these two studies to establish a unified and more robust sickle-specific calibration to serve as a reference standard in the field.

Results: Even though the combined calibration did not demonstrate statistical superiority compared to previous models, the calibration was unbiased compared to blood-gas co-oximetry and yielded limits of agreement of (-10.1%, 11.6%) in non-transfused subjects with sickle cell disease. In transfused patients, this study proposed a simple correction method based on individual hemoglobin S percentage that demonstrated reduced bias in saturation measurement compared to previous uncorrected sickle calibrations.

Conclusion: The combined calibration is based on a larger range of hematocrit, providing greater confidence in the hematocrit-dependent model parameters, and yielded unbiased estimates to blood-gas co-oximetry measurements from both sites. Additionally, this work also demonstrated the need to correct for transfusion in T oximetry measurements for hyper-transfused sickle cell disease patients and proposes a correction method based on patient-specific hemoglobin S concentration.
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http://dx.doi.org/10.1002/mrm.28757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076101PMC
August 2021

SNORA23 inhibits HCC tumorigenesis by impairing the 2'-O-ribose methylation level of 28S rRNA.

Cancer Biol Med 2021 Mar 12. Epub 2021 Mar 12.

Department of Laboratory Diagnostics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Objective: The dysregulation of ribosome biogenesis is associated with the progression of numerous tumors, including hepatocellular carcinoma (HCC). Small nucleolar RNAs (snoRNAs) regulate ribosome biogenesis by guiding the modification of ribosomal RNAs (rRNAs). However, the underlying mechanism of this process in HCC remains elusive.

Methods: RNA immunoprecipitation and sequencing were used to analyze RNAs targeted by ribosome proteins. The biological functions of SNORA23 were examined in HCC cells and a xenograft mouse model. To elucidate the underlying mechanisms, the 2'-O-ribose methylation level of rRNAs was evaluated by qPCR, and the key proteins in the PI3K/Akt/mTOR pathway were detected using Western blot.

Results: Twelve snoRNAs were found to co-exist in 4 cancer cell lines using RPS6 pull-down assays. SNORA23 was downregulated in HCC and correlated with the poor prognoses of HCC patients. SNORA23 inhibited the proliferation, migration, and invasion of HCC cells both and . We also found that SNORA23 regulated ribosome biogenesis by impairing 2'-O-ribose methylation of cytidine of 28S rRNA. Furthermore, SNORA23, which is regulated by the PI3K/Akt/mTOR signaling pathway, significantly inhibited the phosphorylation of 4E binding protein 1. SNORA23 and rapamycin blocked the PI3K/AKT/mTOR signaling pathway and impaired HCC growth .

Conclusions: SNORA23 exhibited antitumor effects in HCC and together with rapamycin, provided a promising therapeutic strategy for HCC treatment.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0343DOI Listing
March 2021

Noncontrast assessment of blood-brain barrier permeability to water: Shorter acquisition, test-retest reproducibility, and comparison with contrast-based method.

Magn Reson Med 2021 07 8;86(1):143-156. Epub 2021 Feb 8.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Purpose: Assessment of the blood-brain barrier (BBB) permeability without the need for contrast agent is desirable, and the ability to measure the permeability to small molecules such as water may further increase the sensitivity in detecting diseases. This study proposed a time-efficient, noncontrast method to measure BBB permeability to water, evaluated its test-retest reproducibility, and compared it with a contrast agent-based method.

Methods: A single-delay water extraction with phase-contrast arterial spin tagging (WEPCAST) method was devised in which spatial profile of the signal along the superior sagittal sinus was used to estimate bolus arrival time, and the WEPCAST signal at the corresponding location was used to compute water extraction fraction, which was combined with global cerebral blood flow to estimate BBB permeability surface area product to water. The reliability of WEPCAST sequence was examined in terms of intrasession, intersession, and inter-vendor (Philips [Ingenia, Best, the Netherlands] and Siemens [Prisma, Erlangen, Germany]) reproducibility. Finally, we compared this new technique to a contrast agent-based method.

Results: Single-delay WEPCAST reduced the scan duration from approximately 20 min to 5 min. Extract fraction values estimated from single-delay WEPCAST showed good consistency with the multi-delay method (R = 0.82, P = .004). Group-averaged permeability surface area product values were found to be 137.5 ± 9.3 mL/100 g/min. Intrasession, intersession, and inter-vendor coefficient of variation of the permeability surface area product values were 6.6 ± 4.5%, 6.9 ± 3.7%, and 8.9 ± 3.0%, respectively. Finally, permeability surface area product obtained from WEPCAST MRI showed a significant correlation with that from the contrast-based method (R = .73, P = .02).

Conclusion: Single-delay WEPCAST MRI can measure BBB permeability to water within 5 min with an intrasession, intersession, and inter-vendor test-retest reproducibility of 6% to 9%. This method may provide a useful marker of BBB breakdown in clinical studies.
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http://dx.doi.org/10.1002/mrm.28687DOI Listing
July 2021

Fractional anisotropy from diffusion tensor imaging correlates with acute astrocyte and myelin swelling in neonatal swine models of excitotoxic and hypoxic-ischemic brain injury.

J Comp Neurol 2021 Jul 15;529(10):2750-2770. Epub 2021 Feb 15.

Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.

The specific cytopathology that causes abnormal fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI) after neonatal hypoxia-ischemia (HI) is not completely understood. The panoply of cell types in the brain might contribute differentially to changes in DTI metrics. Because glia are the predominant cell type in brain, we hypothesized that changes in FA and MD would signify perturbations in glial microstructure. Using a 3-Tesla clinical scanner, we conducted in vivo DTI MRI in nine neonatal piglets at 20-96 h after excitotoxic brain injury from striatal quinolinic acid injection or global HI. FA and MD from putamen, caudate, and internal capsule in toto were correlated with astrocyte swelling, neuronal excitotoxicity, and white matter injury. Low FA correlated with more swollen astrocytes immunophenotyped by aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), and glutamate transporter-1 (GLT-1). Low FA was also related to the loss of neurons with perineuronal GLT-1+ astrocyte decorations, large myelin swellings, lower myelin density, and oligodendrocyte cell death identified by 2',3'-cyclic nucleotide 3'-phosphodiesterase, bridging integrator-1, and nuclear morphology. MD correlated with degenerating oligodendrocytes and depletion of normal GFAP+ astrocytes but not with astrocyte or myelin swelling. We conclude that FA is associated with cytotoxic edema in astrocytes and oligodendrocyte processes as well as myelin injury at the cellular level. MD can detect glial cell death and loss, but it may not discern subtle pathology in swollen astrocytes, oligodendrocytes, or myelin. This study provides a cytopathologic basis for interpreting DTI in the neonatal brain after HI.
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http://dx.doi.org/10.1002/cne.25121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113130PMC
July 2021

Protein Adsorption at Nanorough Titanium Oxide Surfaces: The Importance of Surface Statistical Parameters beyond Surface Roughness.

Nanomaterials (Basel) 2021 Feb 1;11(2). Epub 2021 Feb 1.

Technical and Macromolecular Chemistry, Paderborn University, Warburger Str. 100, 33098 Paderborn, Germany.

The nanoscale surface topography of biomaterials can have strong effects on protein adsorption. While there are numerous surface statistical parameters for the characterization of nanorough surfaces, none of them alone provides a complete description of surface morphology. Herein, a selection of nanorough titanium oxide surfaces has been fabricated with root-mean-square roughness () values below 2.7 nm but very different surface morphologies. The adsorption of the proteins myoglobin (MGB), bovine serum albumin (BSA), and thyroglobulin (TGL) at these surfaces was investigated in situ by ellipsometry to assess the importance of six of the most common surface statistical parameters. For BSA adsorption, both protein film thickness and time constant of adsorption were found to scale linearly with s. For TGL, however, the same adsorption characteristics depend linearly on the surface skewness (), which we attribute to the rather extreme size of this protein. Finally, a mixed behavior is observed for MGB adsorption, showing different linear correlations with and . These results demonstrate the importance of a thorough morphological characterization of the surfaces employed in protein adsorption and possibly also cell adhesion studies.
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http://dx.doi.org/10.3390/nano11020357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912717PMC
February 2021

Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications.

Sci Rep 2021 01 28;11(1):2519. Epub 2021 Jan 28.

Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA.

Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb's ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer.
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http://dx.doi.org/10.1038/s41598-021-81620-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844014PMC
January 2021

Long-Term Survival in Nonsurgical Esophageal Cancer Patients Who Received Consolidation Chemotherapy Compared With Patients Who Received Concurrent Chemoradiotherapy Alone: A Systematic Review and Meta-Analysis.

Front Oncol 2020 7;10:604657. Epub 2021 Jan 7.

Department of Radiation Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China.

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for nonsurgical esophageal cancer (EC). However, esophageal cancer patients receiving CCRT alone are still unsatisfactory in terms of local control and overall survival (OS) benefit. Clinicians generally add consolidation chemotherapy (CCT) after CCRT. It remains controversial whether CCT following CCRT is beneficial for esophageal cancer. We, therefore, undertook a meta-analysis to assess the need for CCT in inoperable esophageal cancer.

Materials And Methods: We combed PubMed, Embase, Cochrane Library, Web of Science, and CNKI for relevant published articles up to July 2020 that compared CCRT plus CCT to CCRT alone for patients with nonsurgical EC. Our primary endpoint was OS and progression-free survival (PFS), and the secondary endpoint was treatment toxicity. We analyzed the hazard ratio (HR) to estimate the time-to-event data and the odds ratio (OR) to compare the treatment-related effect. To assess heterogeneity, we performed the I test and examined publication bias using funnel plots analysis.

Results: The 11 retrospective studies involved 2008 patients. Of these 2008 patients, 1018 received CCRT plus CCT, and 990 received CCRT. Compared to CCRT alone, CCT after CCRT did not improve disease control rate (DCR) (OR 1.66; 95% CI 0.53-5.15, p=0.384) and objective response rate (ORR) (OR 1.44; 95% CI 0.62-3.35, p=0.393). However, OS (HR 0.72; 95% CI 0.59-0.86, p < 0.001) and PFS (HR 0.61; 95% CI 0.44-0.84, p=0.003) did increase. Our results show that CCT plus CCRT had a clear survival advantage over CCRT alone. The risk of treatment toxicity did not increase for EC patients who received CCT.

Conclusion: CCT after CCRT significantly increases OS and PFS in patients with nonsurgical EC and could provide them remarkable survival benefits. The results provide an evidence-based framework for the use of CCT after CCRT.
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http://dx.doi.org/10.3389/fonc.2020.604657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817852PMC
January 2021

No Longterm Severe Thyroid Dysfunction Seen In Patients With Preexisting Reduced Serum Tt3 Concentrations After A Single Large Dose Of Iodinated Contrast.

Endocr Pract 2020 Aug;26(8):840-845

From the Department of Cardiovascular Disease, Tianjin Chest Hospital, the Affiliated Hospital of Tianjin University and Nankai University, the Clinical College of Tianjin Medical University, Tianjin, China.

Objective: After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease.

Methods: This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention.

Results: There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative (P<.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative (P>.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative (P<.001).

Conclusion: The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery.

Abbreviations: FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization.
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http://dx.doi.org/10.4158/EP-2019-0600DOI Listing
August 2020

Psoralidin, a major component of Psoraleae Fructus, induces inflammasome activation and idiosyncratic liver injury.

Int Immunopharmacol 2021 Mar 7;92:107352. Epub 2021 Jan 7.

China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100039, China; Integrative Medical Center, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100039, China. Electronic address:

Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially fatal disease that is unpredictable and independent of the dose of the drug. Increasing evidence suggests that the majority of IDILI cases are immune-mediated, and the aberrant activation of inflammasome plays a vital role in progression. Psoraleae Fructus (PF), a tonic Chinese medicine, has been able to cause IDILI, but the precise mechanism of hepatotoxicity remains unclear. In this study, eight bioactive compounds involved in PF-induced inflammasome activation were investigated. The results demonstrated that psoralidin activated the inflammasomes followed by secreting caspase-1 and interleukin 1β (IL-1β) in a dose-dependent manner. Interestingly, MCC950, a potent inhibitor of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, could not entirely suppress the psoralidin-induced inflammasome activation. Moreover, psoralidin significantly induced IL-1β maturation and caspase-1 activation in NLRP3-knockout bone marrow-derived macrophages (BMDMs), suggesting that psoralidin not only activates the NLRP3 inflammasome but also activates other types of inflammasomes. The results also demonstrated that psoralidin activated the inflammasomes by promoting the C-terminal caspase recruitment domain (ASC) oligomerization, and the production of mitochondrial reactive oxygen species (mtROS) is a decisive factor in psoralidin-induced inflammasome activation. Importantly, in vivo data revealed that psoralidin induced hepatic inflammation, increased aminotransferase activity and increased the production of IL-1β and tumor necrosis factor(TNF-α) in a susceptible mouse model of lipopolysaccharide (LPS)-mediated IDILI. In summary, these results confirmed that psoralidin causes IDILI by inducing inflammasome activation. The study suggests that psoralidin is a possible risk factor and is responsible for PF-induced IDILI.
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http://dx.doi.org/10.1016/j.intimp.2020.107352DOI Listing
March 2021

Enzyme-Instructed Self-Assembly Enabled Monomer-Excimer Transition to Construct Higher Ordered Luminescent Supramolecular Assembly for Activity-based Bioimaging.

Angew Chem Int Ed Engl 2021 04 3;60(15):8121-8129. Epub 2021 Mar 3.

Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Diseases, Department of Cardiology and Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.

It is challenging to construct high-performing excimer-based luminescent analytic tools at low molecular concentrations. We report that enzyme-instructed self-assembly (EISA) enables the monomer-excimer transition of a coumarin dye (Cou) at low molecular concentrations, and the resulting higher ordered luminescent supramolecular assemblies (i.e., nanofibers) efficiently record the spatiotemporal details of alkaline phosphatase (ALP) activity in vitro and in vivo. Cou was conjugated to short self-assembly peptides with a hydrophilic ALP-responsive group. By ALP triggering, EISA actuated a nanoparticles-nanofibers transition at low peptide concentrations followed by monomer-excimer transition of Cou. Analysis of structure-property relationships revealed that the self-assembly motif was a prerequisite for peptides to induce the monomer-excimer transition of Cou. Luminescent supramolecular nanofibers of pYD (LSN-pYD) illuminated the intercellular bridge of cancer cells and distinguished cancer cells (tissues) from normal cells (tissues) efficiently and rapidly, promising potential use for the early diagnosis of cancer. This work extends the functions of EISA and provides a new application of supramolecular chemistry.
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http://dx.doi.org/10.1002/anie.202014278DOI Listing
April 2021

The Effects of Earthworms on Fungal Diversity and Community Structure in Farmland Soil With Returned Straw.

Front Microbiol 2020 17;11:594265. Epub 2020 Dec 17.

Eco-Environmental Protection Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai, China.

Background: To promote the decomposition of returned straw, reduce the incidence of soil-borne diseases caused by returned straw, and accelerate the conversion of straw carbon into soil carbon, we inoculated earthworms into fields with returned straw. The earthworms accelerated straw degradation and promoted carbon conversion. However, the impact of externally inoculated earthworms on the farmland soil ecosystem, especially the structure and the function of its microbial community, remains unclear.

Methods: We analyzed the effects of straw return and earthworms on the diversity of fungal populations and the community structure of dominant fungal taxa in soil by quantifying fungal population size and community composition PCR amplification of internal transcribed spacer genes and 18S rRNA gene sequencing.

Results: The results showed that earthworm inoculation significantly accelerated the degradation of rice straw and promoted the conversion of straw carbon to soil carbon. Both fungal abundance and α-diversity (Sobs and Shannon indices) were higher in the plots with surface straw but without earthworms than in those inoculated with earthworms and in the CK. Principal component analysis indicated that straw return increased the diversity and the abundance of the fungal community, whereas earthworms inhibited this expansion of the fungal community caused by straw return. Interestingly, the overall differences in fungal community composition were smallest in plots with straw return, while the dominant fungal community features in plots inoculated with earthworms were closer to those of the CK.

Conclusion: Generally, straw return stimulated unclassified_K_fungi, , and with strong cellulolytic ability. In contrast, the abundances of , unclassified_c_Sordariomycetes, unclassified_f_Lasiosphaeriaceae, and were higher in the plots inoculated with earthworms and in the CK. Furthermore, evolutionary analysis showed that the evolution of soil fungal communities tended to diverge after straw return, and the evolutionary directions of fungal species in the plots inoculated with earthworms were similar to those in the CK.
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http://dx.doi.org/10.3389/fmicb.2020.594265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773728PMC
December 2020

The Polymorphisms of Interleukin-12B Gene and Susceptibility to Inflammatory Bowel Diseases: A Meta-analysis and Trial Sequential Analysis.

Immunol Invest 2021 Jan 4:1-20. Epub 2021 Jan 4.

Department of Prevention and Health Care, Zhongshan Hospital, Xiamen University, Xiamen, China.

: Inflammatory bowel disease (IBD) is a heterogeneous complex disease referring to two chronic disorders: Crohn's disease (CD) and ulcerative colitis (UC). To clarify the relationship between IL-12B gene polymorphisms and susceptibility to CD and UC, a meta-analysis was conducted.: A comprehensive search of the PubMed, Web of Science, Embase and Cochrane databases was conducted up to Oct 2019. Studies evaluating the relationship between risk of IBD and variants of IL-12B (rs6887695, rs3212227 and rs10045431) were included. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Trial sequential analysis (TSA) was implemented to estimate the required information size (RIS) and evaluate the credibility of the meta-analysis results.: Seventeen studies containing 9827 patients with CD, 7583 patients with UC and 16044 controls were included. The results showed significant association between rs6887695 polymorphism and susceptibility to CD (allele model: OR = 1.17, 95% CI: 1.12-1.22) and UC (allele model: OR = 1.16, 95% CI: 1.09-1.23), and "C" allele carriers had a higher risk, with TSA conclusive. For rs10045431, no significant association with CD susceptibility was identified, while a significantly increased risk in UC was found (allele mode: OR = 1.16, 95% CI: 1.07-1.25), both results were conclusive according to TSA. No significant association between rs3212227 and CD or UC susceptibility was found, and TSA research warranted further investigation to certify the results. No significant heterogeneity was found.: IL-12B rs6887695 polymorphism was associated with increased risk of CD and UC, while IL-12B rs10045431 polymorphism might only be correlated with the risk of UC.: IBD: inflammatory bowel disease; CD: Crohn's disease; UC: ulcerative colitis; IL-12B: interleukin-12B; OR: odds ratio; CI: confidence interval; TSA: trial sequential analysis; RIS: required information size; DCs: dendritic cells; NK: nature killer; APCs: antigen-presenting cells; TNF: tumor necrosis factor; SNP: single nucleotide polymorphisms; HWE: Hardy-Weinberg equilibrium; NOS: Newcastle-Ottawa scale; RRR: relative risk reduction.
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http://dx.doi.org/10.1080/08820139.2020.1863981DOI Listing
January 2021

Effects of mobile learning for nursing students in clinical education: A meta-analysis.

Nurse Educ Today 2021 Feb 5;97:104706. Epub 2020 Dec 5.

School of Nursing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, PR China. Electronic address:

The objective of this meta-analysis was to assess the effects of mobile learning for nursing students in clinical nursing education. Five electronic databases including PubMed, CINAHL, EMBASE, the Cochrane library and Web of Science were searched for English language articles published on or before February 10, 2020. Two reviewers retrieved articles, evaluated quality and extracted data independently. Review Manager (RevMan) version 5.3 software was used to perform meta-analysis. A total of 9 studies including 580 nursing students receiving clinical nursing education met the inclusion criteria. The mobile learning intervention led to significant improvements in nursing students' skills (SMD = 1.22, 95% CI [0.29, 2.14], P = 0.009), knowledge (SMD = 0.43, 95% CI [0.11, 0.76], P = 0.009), satisfaction (SMD = 0.31, 95% CI [0.05, 0.56], P = 0.020), and confidence (SMD = 0.4, 95% CI [0.16, 0.63], P < 0.001) compared with the control group. Due to differences in experimental design among studies and limited data availability, we cautiously conclude that mobile learning has a beneficial effect on clinical nursing education for nursing students compared with conventional methods.
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http://dx.doi.org/10.1016/j.nedt.2020.104706DOI Listing
February 2021
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