Publications by authors named "Guanghui Xu"

116 Publications

A case of meningoencephalocele in the nasal cavity 6 years after skull base fracture.

Neurol Sci 2021 Sep 23. Epub 2021 Sep 23.

Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Xianglin Road, Luzhou, 646000, Sichuan, China.

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http://dx.doi.org/10.1007/s10072-021-05604-5DOI Listing
September 2021

Size effects of polystyrene microplastics on the accumulation and toxicity of (semi-)metals in earthworms.

Environ Pollut 2021 Sep 16;291:118194. Epub 2021 Sep 16.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, 130102, China. Electronic address:

Microplastics (MPs) are plastic fragments less than 5 mm, which may have adverse impacts on organisms. In this study, we investigated the impacts and mechanisms of polystyrene MPs (10 μm and 100 μm) and nanoplastics (NPs, 100 nm) with different concentrations (10 mg/kg and 100 mg/kg) in soil on the uptake of metal Cd and semi-metal As in earthworms, Eisenia fetida. MPs facilitated the accumulation of (semi-)metals via damaging the integrity of earthworm intestine, and earthworms accumulated more (semi-)metals in MP treatment groups than NP treatment groups, especially in group of 100 mg/kg of 10 μm MP with concentrations of 1.13 mg/kg and 32.7 mg/kg of Cd and As, respectively. Higher genotoxicity to earthworms was observed for MPs than NPs. Antioxidant enzymes activity and their mRNA gene relative expression levels indicated that MPs with high concentration induced severer damage to earthworms, thus resulting in the increased accumulation of (semi-)metals by earthworms. In addition, proteomic and metabolomic analysis revealed that MPs (100 ppm of 10 μm) disturbed the earthworm immune and metabolic systems, resulting in the highest accumulation of (semi-)metals in earthworms. This study clarifies the influence mechanisms of MPs with different sizes and levels on the accumulation of (semi-)metals by terrestrial invertebrates.
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http://dx.doi.org/10.1016/j.envpol.2021.118194DOI Listing
September 2021

Polystyrene microplastics impact the occurrence of antibiotic resistance genes in earthworms by size-dependent toxic effects.

Authors:
Guanghui Xu Yong Yu

J Hazard Mater 2021 08 20;416:125847. Epub 2021 Apr 20.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China. Electronic address:

Microplastics (MPs) and antibiotic resistance genes (ARGs) are two classes of emerging and prevalent contaminants in terrestrial environments. To date, effects of MPs on the occurrence of ARGs in terrestrial invertebrates remain uncertain. Here we exposed earthworms to a soil amended with polystyrene MPs at two environmentally relevant concentrations to elucidate the occurrence and mechanisms of ARGs in earthworms impacted by MPs with different sizes. Nano-size and 10 mg/kg of 100 µm MPs slightly affected the occurrence of ARGs in earthworms. Highest abundance of ARGs was found in the presence of 10 mg/kg of 10 µm MPs, whereas 100 mg/kg of 10 µm MPs significantly changed the profile of ARGs. Metagenomics sequencing and toxicity tests indicated that MPs caused toxicity and influenced the abundance of microbial community in earthworms, resulting in the changes of ARGs. Results of proteomics and metabolomics demonstrated that 100 mg/kg of 10 µm MPs changed the microenvironment of earthworm gut, built a new homeostatic process, and thus increased the abundance of key bacterial that carried a variety of ARGs. This study highlights the size-dependent toxic effects of MPs and their impacts on the transfer of ARGs in terrestrial environments.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125847DOI Listing
August 2021

Berberine administrated with different routes attenuates inhaled LPS-induced acute respiratory distress syndrome through TLR4/NF-κB and JAK2/STAT3 inhibition.

Eur J Pharmacol 2021 Oct 17;908:174349. Epub 2021 Jul 17.

Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China.

Accumulating evidence showed that berberine possessed the anti-inflammatory action in various diseases caused by inflammation. However, it was still unclear whether both inhalation and injection with berberine produced pulmonary protective role in acute respiratory distress syndrome (ARDS). This study was aimed to evaluate the effects of both administration routes including inhalation and injection with berberine in ARDS induced by lipopolysaccharide (LPS) inhalation. Histopathological examination and weight of lung were evaluated. Phosphorylation of NF-κB, JAK2 and STAT3 were measured to assess the activity of inflammation related signaling pathways. Proinflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the bronchoalveolar lavage fluid (BALF) and serum were also detected. The results showed that LPS caused the lung injury, while both administration routes with berberine attenuated the injury and improved the pulmonary morphology. In addition, the primary TLR4/NF-κB and secondary JAK2/STAT3 signaling pathways which were activated by LPS in lung were totally inhibited by berberine administration. Moreover, proinflammatory cytokines in both BALF and serum were decreased by berberine. Considering that molecular docking simulation indicated that berberine could bind with TLR4, the present suggested that the inhibition of the inflammation related TLR4/NF-κB and JAK2/STAT3 signaling pathways might be involved in the pulmonary protective effect of berberine in LPS-induced ARDS.
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http://dx.doi.org/10.1016/j.ejphar.2021.174349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285933PMC
October 2021

Clinicopathological and prognostic values of PD-L1 expression in oesophageal squamous cell carcinoma: a meta-analysis of 31 studies with 5368 patients.

Postgrad Med J 2021 Jul 12. Epub 2021 Jul 12.

Digestive Diseases Center, Wuxi Mingci Hospital, Wuxi, Jiangsu, People's Republic of China

Several immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1)/programmed death 1 have successfully improved the prognosis of oesophageal squamous cell carcinoma (ESCC) with approval in certain countries. However, whether the expression of PD-L1 is associated with the degree of benefit is unclear yet and a unified standard of antibody and cut-off value of PD-L1 detection is also lacking. The current meta-analysis then aimed to explore the association between PD-L1 expression and clinicopathological features as well as prognosis in ESCC.A systematic search on PubMed, Embase, Cochrane Library and Web of Science databases was performed up to 30 March 2021. The correlation between PD-L1 expression and clinicopathological features, as well as prognosis in ESCC, was estimated with the random-effects model.A total of 5368 patients from 31 retrospective studies were enrolled. The overexpression of PD-L1 was significantly associated with lymph node metastasis (OR 1.342, 95% CI 0.995 to 1.809, p=0.050) and distant metastasis (OR 1.516, 95% CI 1.001 to 2.294, p=0.050). The pooled HR showed that PD-L1 overexpression was significantly correlated with poor overall survival (OS) of patients with ESCC (HR 1.306, 95% CI 1.108 to 1.539, p<0.010) but not disease-free survival (DFS) (HR 1.180, 95% CI 0.937 to 1.487, p=0.160). Heterogeneity decreased significantly in subgroup analyses. The overexpression of PD-L1 was associated with poor DFS at the cut-off point of ≥1% (HR 1.642, 95% CI 1.367 to 1.973, p<0.010; I=0%) and worse OS at the cut-off point of ≥10% (HR 1.575, 95% CI 1.175 to 2.111, p<0.010; I=0%).The overexpression of PD-L1 was correlated with lymph node and distant metastasis as well as poor survival of ESCC.
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http://dx.doi.org/10.1136/postgradmedj-2021-140029DOI Listing
July 2021

Freeze-thaw cycles promote vertical migration of metal oxide nanoparticles in soils.

Sci Total Environ 2021 Nov 6;795:148894. Epub 2021 Jul 6.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China. Electronic address:

Understanding the migration of engineered nanoparticles (ENPs) in soil is of great significance for evaluating the potential risks of ENPs to ecosystem. So far, their migration under freeze-thaw cycles (FTCs) has not been investigated. This study explored the impacts of FTCs on the migration of three commonly used ENPs, copper oxide (CuO-NPs), cerium oxide (CeO-NPs), and zinc oxide (ZnO-NPs), in three types of soil. After 32 FTC cycles, the highest migration rate of ENPs was found in black soil due to its higher clay particle content. CeO-NPs with low surface charge exhibited the highest mobility among three ENPs, which migrated to 9-11 cm layer with the concentration of 42.1 mg/kg in the black soil column. ZnO-NPs were less influenced by FTCs as they were adsorbed onto sand grains due to electrostatic interaction, which migrated to 3-5 cm layer with the concentration of 25.2 mg/kg in the black soil. Higher moisture contents (50% and 100%) resulted in increased migration depth of the ENPs in all soils. Lower freezing temperature (-25 °C) caused fragmentation of large soil particles and produced more clay colloids. FTCs promoted the movement of moisture, which penetrated the soil and thus facilitated the movement of ENPs by increasing the contents and movement of clay colloids. This work reveals the migration behavior of ENPs in soils in freeze-thaw period and provides insights into the fate and environmental risk of nanomaterial at middle and high latitudes.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148894DOI Listing
November 2021

Influences and mechanisms of nanoparticles on pentachloronitrobenzene accumulation by earthworms.

Environ Sci Pollut Res Int 2021 Oct 13;28(37):51471-51479. Epub 2021 May 13.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, 130102, China.

Pesticides and nanoparticles may coexist in soil; however, influences of nanoparticles on accumulation of pesticides in terrestrial organisms are still unclear. This study aims to investigate the influences and mechanisms of metal oxide nanoparticles (nano ZnO and nano CuO) on accumulation of pentachloronitrobenzene (PCNB) in earthworms and their combined toxicity. The earthworms were cultivated in the soil spiked with nanoparticles (10, 50, 250 mg/kg) and PCNB (100 μg/kg) for 21 days. The concentrations of PCNB in earthworms in binary exposure treatments (PCNB + ZnO and PCNB + CuO) reached 2.47 and 3.13 times of that in individual PCNB exposure treatment, indicating that nanoparticles facilitated the accumulation of PCNB in earthworms. The contents of reactive oxygen species (ROS) in earthworms in treatments PCNB + ZnO 250 and PCNB + CuO 250 reached 379 and 316 fluorescence intensity/mg Protein, respectively, which were significantly higher than that in control group (183 fluorescence intensity/mg protein), indicating that nanoparticles would cause oxidative stress to earthworms. Earthworm coelomocytes were extracted from healthy earthworms and cultivated in culture media in cytotoxicity tests. Changes of intracellular ROS contents and cell viability suggested that PCNB and nanoparticles caused serious oxidative damage to earthworm coelomocytes, thus leading to the damage of cell membrane and cell death. In in vivo tests, changes of biomarkers (ROS and malondialdehyde) demonstrated that these pollutants injured the earthworms. Increased accumulation of PCNB in binary exposure treatments was due to the damage of body cavity caused by nanoparticles. This study provides a novel hypothesis for nanoparticles facilitating organic pollutants entering terrestrial organisms and determines whether nanoparticles would bring about greater environmental risks of other pollutants.
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http://dx.doi.org/10.1007/s11356-021-14368-6DOI Listing
October 2021

Effects of polystyrene microplastics on uptake and toxicity of phenanthrene in soybean.

Sci Total Environ 2021 Aug 10;783:147016. Epub 2021 Apr 10.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China. Electronic address:

Microplastics (MPs) can influence the availability of contaminants in the soil and have adverse effects on plants. Up to now, the effects of MPs on the uptake of organic pollutants by leguminous plants are still unclear. In this study, we explored the impacts and mechanisms of polystyrene MPs of different sizes on the uptake of phenanthrene (Phe) by soybean seedlings. The results showed that MPs decreased the uptake of Phe in soybean roots and leaves. Micron-size MPs showed a higher inhibition of Phe uptake in roots than nano-size MPs (4.83 mg/kg) at the beginning with concentrations of 1.89 mg/kg, 3.40 mg/kg, and 0.72 mg/kg in groups 1 μm, 10 μm, and 100 μm MPs/Phe, respectively. The combined toxicity of micron-size MPs and Phe to soybean plants was higher than that of nano-size MPs and Phe, and 100 μm MPs and Phe co-contaminant show the highest toxicity to soybean. The activities of antioxidative enzymes and their gene expression showed that micron-size MPs induced higher genotoxic and oxidative damage to soybean roots than nano-size MPs, which decreased the activity of roots, thus leading to the lower uptake of Phe by soybean roots and leaves. This study highlights that the combined exposure to MPs and Phe causes harmful effects on soybean plants and MPs inhibit the uptake of organic pollutants by higher plants.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147016DOI Listing
August 2021

Hyperamylasemia of Abnormally Elevated Serum Amylase: Macroamylasemia in a Healthy Individual.

Clin Lab 2021 Apr;67(4)

Background: Serum amylase is secreted by salivary glands and pancreas and is used for the diagnosis of pancreatic and parotid diseases. A number of factors can elevate the level of serum amylase including pancreatic diseases, salivary disease, gastrointestinal diseases, liver diseases, gynecologic disease, cholecystitis, peritonitis, renal failure, and drug induced.

Methods: We reported a case with abnormally elevated serum amylase, namely hyperamylasemia. Abdominal B-ultrasound, abdominal magnetic resonance imaging (MRI), parotid computed tomography (CT), gastroscopy, and colonoscopy were used to screen the causes of hyperamylasemia. Common serum tumor markers and serum biochemistry were detected to exclude some common causes. The amylase-creatinine clearance ratio (ACCR) was calculated for the patient.

Results: The average value of serum amylase were 881 U/L, which was significantly higher than reference value (10 - 220 U/L). According to ACCR value, the patient was diagnosed with macroamylasemia after the exclusion of some possible causes for elevating serum amylase.

Conclusions: When renal function is normal, serum amylase continues to increase and urine amylase is normal or decreased, macroamylasemia should be considered after the exclusion of pancreatic and parotid diseases. Macroamylasemia can not only be associated with autoimmune diseases, malignant tumors and other diseases, but also can be found in healthy population.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200827DOI Listing
April 2021

Dual-ligand supramolecular nanofibers inspired by the renin-angiotensin system for the targeting and synergistic therapy of myocardial infarction.

Theranostics 2021 27;11(8):3725-3741. Epub 2021 Jan 27.

Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Department of Cardiology and Laboratory of Heart Center, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.

The compensatory activation of the renin-angiotensin system (RAS) after myocardial infarction (MI) plays a crucial role in the pathogenesis of heart failure. Most existing studies on this subject focus on mono- or dual-therapy of blocking the RAS, which exhibit limited efficacy and often causes serious adverse reactions. Few studies have been conducted on targeted therapy based on the activated RAS post-MI. Thus, the development of multiple-functional nanomedicine with concurrent targeting ability and synergistic therapeutic effect against RAS may show great promise in improving cardiac function post-MI. We utilized a cooperative self-assembly strategy constructing supramolecular nanofibers- telmisartan-doped co-assembly nanofibers ( ) to counter-regulate RAS through targeted delivery and combined therapy. were prepared through serial steps of solvent exchange, heating incubation, gelation, centrifugation, and lyophilization, in which the telmisartan was doped in the self-assembly process of to obtain the co-assembly nanofibers wherein they act as both therapeutic agents and target-guide agents. exhibited the desired binding affinity to the two different receptors, AT1R and MasR. Through the dual ligand-receptor interactions to mediate the coincident downstream pathways, not only displayed favorably targeted properties to hypoxic cardiomyocytes, but also exerted synergistic therapeutic effects in apoptosis reduction, inflammatory response alleviation, and fibrosis inhibition and , significantly protecting cardiac function and mitigating post-MI adverse outcomes. A dual-ligand nanoplatform was successfully developed to achieve targeted and synergistic therapy against cardiac deterioration post-MI. We envision that the integration of multiple therapeutic agents through supramolecular self-assembly would offer new insight for the systematic and targeted treatment of cardiovascular diseases.
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http://dx.doi.org/10.7150/thno.53644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914367PMC
July 2021

Metal oxide nanoparticles facilitate the accumulation of bifenthrin in earthworms by causing damage to body cavity.

Environ Pollut 2020 Aug 19;263(Pt A):114629. Epub 2020 Apr 19.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, 130102, China. Electronic address:

In this study, we explored the influence of two metal oxide nanoparticles, nano CuO and nano ZnO (10, 50, 250 mg/kg), on accumulation of bifenthrin (100 μg/kg) in earthworms (Eisenia fetida) and its mechanism. The concentrations of bifenthrin in earthworms from binary exposure groups (bifenthrin + CuO and bifenthrin + ZnO) reached up to 23.2 and 28.9 μg/g, which were 2.65 and 3.32 times of that in bifenthrin exposure group without nanoparticles, respectively, indicating that nanoparticles facilitated the uptake of bifenthrin in earthworms. The contents of biomarkers (ROS, SOD, and MDA) in earthworms indicated that nanoparticles and bifenthrin caused damage to earthworms. Ex vivo test was utilized to investigate the toxic effects of the pollutants to cell membrane of earthworm coelomocytes and mechanism of increased bifenthrin accumulation. In ex vivo test, cell viability in binary exposure groups declined up to 30% and 21% compared to the control group after 24 h incubation, suggesting that coelomocyte membrane was injured by the pollutants. We conclude that nanoparticles damage the body cavity of earthworms, and thus lead to more accumulation of bifenthrin in earthworms. Our findings provide insights into the interactive accumulation and toxicity of nanoparticles and pesticides to soil organisms.
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http://dx.doi.org/10.1016/j.envpol.2020.114629DOI Listing
August 2020

Reduction of Autophagosome Overload Attenuates Neuronal Cell Death After Traumatic Brain Injury.

Neuroscience 2021 04 16;460:107-119. Epub 2021 Feb 16.

Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, China; Sichuan Clinical Research Center for Neurosurgery, China; Neurological Diseases and Brain Functions Laboratory, Clinical Medical Research Center of Southwest Medical University, China; Academician (Expert) Workstation of Sichuan Province, China. Electronic address:

Previous studies have shown that alterations in autophagy-related proteins exist extensively after traumatic brain injury (TBI). However, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, a controlled cortical impact was used to establish a model of moderate TBI in rats. We found that a significant increase in protein levels of LC3-II and SQSTM1 in the injured cortex group. However, there were no significant differences in protein levels of VPS34, Beclin-1, and phosphor-ULK1, which are the promoters of autophagy. Lysosome dysfunction after TBI might lead to autophagosome accumulation. In addition, the highly specific autophagy inhibitor SAR405 administration reduced TBI-induced apoptosis-related protein cleaved caspase-3 and cleaved caspase-9 levels in the ipsilateral cortex, as well as brain edema and neurological defects accessed by mNSS. Furthermore, chloroquine treatment reversed the beneficial effects of SAR405 by increasing the accumulation of autophagosomes. Finally, our data showed that autophagy inhibition by VPS34 gene knockout method attenuated cell death after TBI. Our findings indicate that impaired autophagosome degradation is involved in the pathological reaction after TBI, and the inhibition of autophagy contributes to attenuate neuronal cell death and functional defects.
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http://dx.doi.org/10.1016/j.neuroscience.2021.02.007DOI Listing
April 2021

A Spatial-Temporal Approach Based on Antenna Array for GNSS Anti-Spoofing.

Sensors (Basel) 2021 Jan 30;21(3). Epub 2021 Jan 30.

School of Instrumentation Science and Engineering, Harbin Institute of Technology, Harbin 150001, China.

The presence of spoofing signals poses a significant threat to global navigation satellite system (GNSS)-based positioning applications, as it could cause a malfunction of the positioning service. Therefore, the main objective of this paper is to present a spatial-temporal technique that enables GNSS receivers to reliably detect and suppress spoofing. The technique, which is based on antenna array, can be divided into two consecutive stages. In the first stage, an improved eigen space spectrum is constructed for direction of arrival (DOA) estimation. To this end, a signal preprocessing scheme is provided to solve the signal model mismatch in the DOA estimation for navigation signals. In the second stage, we design an optimization problem for power estimation with the estimated DOA as support information. After that, the spoofing detection is achieved by combining power comparison and cross-correlation monitoring. Finally, we enhance the genuine signals by beamforming while the subspace oblique projection is used to suppress spoofing. The proposed technique does not depend on external hardware and can be readily implemented on raw digital baseband signal before the despreading of GNSS receivers. Crucially, the low-power spoofing attack and multipath can be distinguished and mitigated by this technique. The estimated DOA and power are both beneficial for subsequent spoofing localization. The simulation results demonstrate the effectiveness of our method.
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http://dx.doi.org/10.3390/s21030929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866517PMC
January 2021

β-Blockers for traumatic brain injury: A systematic review and meta-analysis.

J Trauma Acute Care Surg 2021 06;90(6):1077-1085

From the Department of Neurosurgery (H.D., Z.L.), Chongqing Yubei District People's Hospital; Department of Neurosurgery (L. Liao), Nan'an District People's Hospital of Chongqing, Chongqing; Department of Neurosurgery (Q.W.), People's Hospital of Hejiang City; Department of Neurosurgery (L. Liao, G.X., X.L., L. Liu), and Department of Neurology (X.Z.), Affiliated Hospital of Southwest Medical University; Neurosurgery Clinical Medical Research Center of Sichuan Province (L. Liu); Academician (Expert) Workstation of Sichuan Province (L. Liu); and Neurological Diseases and Brain Function Laboratory (L. Liu), Luzhou, China.

Background: Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).β Adrenergic receptor blockers (β-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of β-blockers on outcomes in patients with TBI.

Methods: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of β-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of β-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes.

Results: Fifteen studies with 12,721 patients were included. Exposure to β-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30-0.51; I2 = 66.3%; p < 0.001). β-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09-2.80; I2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55-1.50; I2 = 25.9%; p = 0.702).

Conclusion: This meta-analysis demonstrated that administration of β-blockers after TBI was safe and effective. Administration of β-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of β-blockers in the management of TBI.

Level Of Evidence: Systematic review and meta-analysis, level III.
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http://dx.doi.org/10.1097/TA.0000000000003094DOI Listing
June 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

Impacts of polyethylene microplastics on bioavailability and toxicity of metals in soil.

Sci Total Environ 2021 Mar 10;760:144037. Epub 2020 Dec 10.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China. Electronic address:

In this study, we investigated the bioavailability and toxicity of metals (Cu and Ni) in the soil containing polyethylene microplastics (PE-MPs). The bioavailability of the metals determined by the five-step chemical sequential extraction method increased with the addition of MPs (0.1%, 1%, 10%) in the soil, which was confirmed by the adsorption-desorption characteristics. To further examine the bioavailability and toxicity of metals, earthworms (Eisenia fetida) were exposed to soil containing Cu (100 mg/kg) or Ni (40 mg/kg) with different amounts (0.01%, 0.05%, and 0.1%) of PE-MPs for 21 days. The highest concentrations of Cu and Ni in earthworms reached to 73.3 and 36.3 mg/kg, respectively. Moreover, metal concentrations in earthworms increased with MP contents in the soil, which was consistent with the bioavailability measured by the sequential extraction method. Furthermore, changes in biomarkers including peroxidase (POD), catalase (CAT) and superoxide dismutase (SOD) activity, malondialdehyde (MDA) contents, and related gene expression levels in earthworms suggested that the pollutants caused toxicity to earthworms. Overall, MPs increased the bioavailability of metals in the soil and the toxic effects to earthworms. These findings provide insights regarding the impacts of MPs on the bioavailability of metals and the combined toxic effects of these two kinds of pollutants on terrestrial animals.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144037DOI Listing
March 2021

YAP accelerates vascular senescence via blocking autophagic flux and activating mTOR.

J Cell Mol Med 2021 01 12;25(1):170-183. Epub 2020 Dec 12.

Key Laboratory of Construction and Detection of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Yes-associated protein (YAP), a major effector of the Hippo signalling pathway, is widely implicated in vascular pathophysiology processes. Here, we identify a new role of YAP in the regulation of vascular senescence. The inhibition or deficiency and overexpression of YAP were performed in human umbilical vein endothelial cells (HUVECs) and isolated vascular tissues. Cellular and vascular senescence was assessed by analysis of the senescence-associated β-galactosidase (SA-β-gal) and expression of senescence markers P16, P21, P53, TERT and TRF1. We found that YAP was highly expressed in old vascular tissues, inhibition and knockdown of YAP decreased senescence, while overexpression of YAP increased the senescence in both HUVECs and vascular tissues. In addition, autophagic flux blockage and mTOR pathway activation were observed during YAP-induced HUVECs and vascular senescence, which could be relieved by the inhibition and knockdown of YAP. Moreover, YAP-promoted cellular and vascular senescence could be relieved by mTOR inhibition. Collectively, our findings indicate that YAP may serve as a potential therapeutic target for ageing-associated cardiovascular disease.
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http://dx.doi.org/10.1111/jcmm.15902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810949PMC
January 2021

Size effects of microplastics on accumulation and elimination of phenanthrene in earthworms.

J Hazard Mater 2021 02 15;403:123966. Epub 2020 Sep 15.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, PR China. Electronic address:

Microplastics (MPs) are a class of emerging contaminants with diverse sizes. They influence the behavior of pollutants in the environment and cause harmful effects on organisms. To date, the size effects of MPs on the accumulation of organic pollutants by terrestrial invertebrates remain unclear. Here, we study the impacts and mechanisms of polystyrene MPs on the accumulation and elimination of phenanthrene in earthworms. Results showed that larger-size MPs (10 and 100 µm) facilitated the accumulation of phenanthrene by earthworms in the first week, whereas 100 nm MPs inhibited the elimination of phenanthrene in earthworms afterwards. Higher genotoxicity to earthworms was observed for co-exposure of micron-size MPs and phenanthrene, and 10 µm MPs were detected at the highest concentration and caused the most serious DNA damage to earthworm coelomocytes. Biomarkers and their mRNA gene expression levels suggested that larger-size MPs caused severer damage to earthworms, thus leading to increased accumulation of phenanthrene by earthworms at the beginning. Moreover, high-throughput 16S rRNA gene sequencing indicated that nano-size MPs significantly inhibited phenanthrene-degrading bacteria in earthworms, resulting in the highest residual concentration of phenanthrene. This study highlights the size effects of MPs and their impacts on the accumulation of organic pollutants by terrestrial organisms.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123966DOI Listing
February 2021

Challenges Faced by Multidrug-Resistant Tuberculosis Patients in Three Financially Affluent Chinese Cities.

Risk Manag Healthc Policy 2020 2;13:2387-2394. Epub 2020 Nov 2.

Department of Pulmonary Medicine & Tuberculosis, The Third People's Hospital of Shenzhen, Shenzhen, People's Republic of China.

Purpose: The aim of this study was to analyze socioeconomic burdens and other difficulties that multidrug-resistant tuberculosis (MDR-TB) patients in cities are facing, to identify major obstacles and which groups of patients are most affected.

Methods: Face-to-face and phone-call interviews were conducted in early 2018 to follow-up with patients newly diagnosed with MDR-TB in 2017 in three tuberculosis hospitals in three financially affluent Chinese cities. Demographic data and information on their medical care, insurance coverage, and medical expenses were collected and analyzed.

Results: A total of 144 newly diagnosed MDR-TB cases were reviewed during the study period, excluding 38 who were lost to follow-up and 29 patients who refused to participate, 77 patients were enrolled in this study. A total of 61 (79%) of these patients were hospitalized after MDR-TB diagnosis with an average hospital stay of 14 days, of them 57 (74%) were sputum positive on diagnosis. The proportion of patients who failed community care were 48% married, 56% in white collar employment and 43% in temp jobs/unemployed. In terms of insurance coverage, the proportion of patients who failed community care were 23% with no insurance and/or New Rural Co-operative Medical Care Scheme (NRCMS) and 45% with Urban Employee Basic Medical Insurance (UEBMI)/Urban Residents Basic Medical Insurance (URBMI) and commercial insurance. Difficulties patients encountered were, financial pressure (33%), psychological stress (26%), adverse drug reactions (23%), repulsive reaction to injections (17%). Fourty-eight percent of the patients spent over ¥2000 (USD300) per month on TB treatment.

Conclusion: Despite insurance coverage, financial hardship remains the number one difficulty MDR-TB patients encountered in relatively financially affluent cities. Among them, the married working class were found to be the most financially sensitive group and have the highest tendency to fail community care. It is of utmost urgency to enhance the current medical policy to improve treatment adherence.
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http://dx.doi.org/10.2147/RMHP.S275400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648070PMC
November 2020

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia.

Future Oncol 2021 Mar 2;17(9):1069-1081. Epub 2020 Nov 2.

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases & Digestive Diseases of Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, PR China.

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.
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http://dx.doi.org/10.2217/fon-2020-0703DOI Listing
March 2021

Long Noncoding RNA CDKN2B-AS1 Facilitates Lung Cancer Development Through Regulating miR-378b/NR2C2.

Onco Targets Ther 2020 20;13:10641-10649. Epub 2020 Oct 20.

Department of Thoracic Oncology, Henan Chest Hospital, Zhengzhou, Henan, People's Republic of China.

Aim: Long noncoding RNA (lncRNA) have proved to be important regulators in various diseases. CDKN2B-AS1 was a newly identified tumor-related lncRNA, and previous studies have reported its function in laryngeal squamous cancer and osteosarcoma. However, the function and mechanism of lncRNA CDKN2B-AS1 in lung cancer are still unknown.

Methods: Cell proliferation, invasion, migration and apoptosis were detected via CCK-8, transwell assay and Western blot. Bioinformatics analysis was used to predict the potential target of CDKN2B-AS1. A rescue experiment was performed to identify the relationship between CDKN2B-AS1 and miR-378b.

Results: The expression of lncRNA CDKN2B-AS1 was significantly upregulated in lung cancer tissues and cell lines. Overexpression of CDKN2B-AS1 promoted cell proliferation, invasion and reduced cell apoptosis. Knockdown of CDKN2B-AS1 inhibited cell proliferation, invasion and increased cell apoptosis. Bioinformatics analysis predicted that miR-378b was the direct target. We also provided evidence that NR2C2 was the target of miR-378b. The expression of NR2C2 was significantly upregulated in lung cancer tissues and cell lines. The rescue experiment further confirmed the relationship between CDKN2B-AS1 and miR-378b. Overexpression of miR-378b completely reversed the function of CDKN2B-AS1.

Conclusion: Taken together, our results comprehensively analyzed the function of CDKN2B-AS1 in lung cancer and provided a possible mechanism that CDKN2B-AS1 facilitates lung cancer development by regulating miR-378b and NR2C2. Thus, our study offers a potential therapeutic target for treating lung cancer.
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http://dx.doi.org/10.2147/OTT.S261973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585785PMC
October 2020

Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress induced GRP78 expression in thyroid carcinoma.

Cell Biosci 2020 1;10:115. Epub 2020 Oct 1.

Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038 Shanxi China.

Background: Thyroid cancer (TC) is the most common type of endocrine malignancy and its incidence is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), and these are regarded as the most malignant types of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 in TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC.

Results: GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data with regard to si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13, which were highly relevant to ATC cells. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that is suppressed by GRP78 depletion.

Conclusions: GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP78 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.
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http://dx.doi.org/10.1186/s13578-020-00478-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528585PMC
October 2020

Exosomal Circ-MEMO1 Promotes the Progression and Aerobic Glycolysis of Non-small Cell Lung Cancer Through Targeting MiR-101-3p/KRAS Axis.

Front Genet 2020 28;11:962. Epub 2020 Aug 28.

Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Circular RNA mediator of cell motility 1 (circ-MEMO1) was identified as an oncogene in non-small cell lung cancer (NSCLC). Nevertheless, the working mechanism behind circ-MEMO1-mediated progression of NSCLC is barely known. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ-MEMO1, microRNA-101-3p (miR-101-3p), and KRAS proto-oncogene, GTPase (KRAS). Cell proliferation and aerobic glycolysis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and glycolysis detection kits. Flow cytometry was used to evaluate cell cycle progression and apoptosis of NSCLC cells. Western blot assay was used to measure the protein expression of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), KRAS, CD9, CD81, tumor susceptibility 101 (TSG101), and Golgi matrix protein 130 kDa (GM130). The target relationship between miR-101-3p and circ-MEMO1 or KRAS was predicted by StarBase software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay. tumor growth assay was conducted to assess the effect of circ-MEMO1 . Exosomes were isolated using the ExoQuick precipitation kit. Circ-MEMO1 was up-regulated in NSCLC, and high expression of circ-MEMO1 predicted poor prognosis in NSCLC patients. Circ-MEMO1 accelerated the proliferation, cell cycle progression, and glycolytic metabolism and inhibited the apoptosis of NSCLC cells. Circ-MEMO1 negatively regulated the expression of miR-101-3p through direct interaction, and si-circ-MEMO1-induced biological effects were attenuated by the introduction of anti-miR-101-3p. MiR-101-3p directly interacted with the 3' untranslated region (3' UTR) of KRAS messenger RNA (mRNA), and KRAS level was regulated by circ-MEMO1/miR-101-3p axis. Circ-MEMO1 silencing suppressed the NSCLC tumor growth . ROC curve analysis revealed that high expression of serum exosomal circ-MEMO1 (exo-circ-MEMO1) might be a valuable diagnostic marker for NSCLC. Circ-MEMO1 facilitated the progression and glycolysis of NSCLC through regulating miR-101-3p/KRAS axis.
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http://dx.doi.org/10.3389/fgene.2020.00962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483554PMC
August 2020

Analysis of the Incompletely Hoisted Vertebrae in the Anterior Controllable Antedisplacement and Fusion Surgery: Causes and Prevention.

Clin Spine Surg 2021 05;34(4):125-131

Department of Statistics, Second Military Medical University, Shanghai, China.

Purpose: Anterior controllable antedisplacement and fusion (ACAF) has been reported to be a safe and effective technique. However, incompletely hoisted vertebrae (IV) were found in the postoperative images. This study aims to analyze the causes and prevention of IV.

Methods: The ACAF-treated case series subjects were retrospectively reviewed. The vertebrae were separated into the IV group and completely hoisted vertebrae (CV) group according to the gap between the vertebrae and plate. The radiographic data, degree of cervical lordosis, bone mineral density, number of hoisted vertebrae, operative time, blood loss, and Japanese Orthopaedic Association score were compared between the patients with IV and the patients without IV.

Results: A total of 248 vertebrae were hoisted in the enrolled patients. Intervertebral disc height in the IV group was 3.7±0.4 mm, which is significantly lower than that in the CV group. The anterior or posterior overhanging lip, osteoporosis, and oblique osteotomy troughs and hinges existing after osteotomy were found to be impingements preventing the hoisting of the vertebrae. There were no differences in the age, sex, degree of cervical lordosis, number of hoisted vertebrae, and neurological improvement rate between the groups of patients with and without IV.

Conclusions: Lower intervertebral space height and impingements preventing hoisting were found to be possible causes of IV in ACAF. Measures to prevent the problem should be carried out.
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http://dx.doi.org/10.1097/BSD.0000000000001037DOI Listing
May 2021

Industrial environmental efficiency and its influencing factors in China: analysis based on the Super-SBM model and spatial panel data.

Environ Sci Pollut Res Int 2020 Dec 6;27(35):44267-44278. Epub 2020 Aug 6.

Department of Economic Management, Guangxi Financial Vocational College, Nanning, 530007, China.

The industry sector is not only an important driving force for economic growth but also the largest sector of resource consumption and pollution emission. In this study, we first constructed a super-slack-based measure (Super-SBM) model including the resource consumption and undesirable outputs, and estimated the industrial environmental efficiency (IEE) in China from 2007 to 2016. Afterwards, based on the spatial autocorrelation test and the spatial Durbin model, the spatio-temporal evolution and the influencing factors of IEE were analyzed. The empirical results are obtained as follows: the average IEE from 2007 to 2016 was 0.5176. IEE in the east of China was the highest, whereas it was the lowest in the west. The spatial autocorrelation test showed that the regions with similar levels of IEE in China had significant spatial agglomeration, whereas the local spatial distribution of IEE was unbalanced. The high-high IEE agglomeration areas were located in Liaoning, Jilin, and Inner Mongolia. The low-low IEE agglomeration areas were concentrated in Gansu, Ningxia, and Sichuan. Finally, according to the spatial Durbin panel model and spillover effect decomposition, GDP, FDI, human capital, environmental governance investment, research and development investment, and urbanization have a positive impact on IEE. The industrial and energy consumption structures have a negative impact on IEE. Therefore, the central government should focus on balancing IEE of different provinces and regions, increasing investment in industrial pollution treatment, and encouraging FDI to improve IEE.
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http://dx.doi.org/10.1007/s11356-020-10235-yDOI Listing
December 2020

miR-486 is involved in the pathogenesis of acute myeloid leukemia by regulating JAK-STAT signaling.

Naunyn Schmiedebergs Arch Pharmacol 2021 01 29;394(1):177-187. Epub 2020 May 29.

Department of Oncology, The First People's Hospital of Lianyungang, No. 6 Zhenhua Earth Road, Lianyungang City, 222061, Jiangsu Province, People's Republic of China.

Acute myeloid leukemia (AML) is a widely prevalent disease worldwide and poses a large threat to public health. Previous studies have shown that AML is associated with cytogenetic heterogeneity, complex subtypes, and different therapeutic approaches. In this study, we found that miR-486 was upregulated in AML using both The Cancer Genome Atlas (TCGA) database and patient tissues. After knockdown of miR-486 by short hairpin RNA (shRNA), we discovered that miR-486 was required for cell proliferation. Through miRNA profile analysis and a dual-luciferase reporter assay, suppressor of cytokine signaling 2 (SOCS2) was identified as a direct target of miR-486. Therefore, by silencing SOCS2, a negative regulator of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, miR-486 enhanced JAK-STAT3 activity and promoted cell proliferation. The miR-486-SOCS2-STAT3 proliferation axis is therefore involved in the pathogenesis of AML, providing a novel molecular mechanism and diagnostic and therapeutic clues for AML.
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http://dx.doi.org/10.1007/s00210-020-01892-4DOI Listing
January 2021

Edible Oils Attenuate Button Battery-Induced Injury in Porcine Esophageal Segments.

Front Pediatr 2020 13;8:97. Epub 2020 Mar 13.

Department of Emergency, Xijing Hospital, Air Force Medical University, Xi'an, China.

The objective of the study is to test whether the use of edible oil might be an early treatment strategy for reducing button battery-induced esophageal injury. A button battery was inserted into esophageal segments collected from pigs. The esophageal segments were randomly allotted to one of the following six treatments: (1) untreated (nothing injected), (2) lemon juice, (3) orange juice, (4) colza oil, (5) peanut oil, and (6) olive oil. Every hour, the battery discharge and the pH value were measured in the esophageal tissue. After treatment for 6 h, the residual voltage of the battery was measured and the esophageal tissue was processed with H&E staining. In esophageal segments of the untreated group, a large area of the mucous membrane was severely eroded. Partial erosion was observed in esophageal tissues treated with either lemon juice or orange juice. Furthermore, the esophageal tissues were basically intact, had little damage when treated with oils. The highest extra-esophageal discharge voltage was recorded in the untreated group, a medium amount of discharge voltage was recorded in the lemon juice and orange juice groups, and the lowest discharge voltage was recorded in all the edible oils groups. Edible oils immersed the battery, reduced the surrounding electrolysis, and thus attenuated battery discharge. As a result, treatment with edible oils attenuated the pH alkalization and tissue damage in button battery injury of pig esophageal segments. These results indicate that edible oils might be used in the treatment of button battery ingestion.
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http://dx.doi.org/10.3389/fped.2020.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082351PMC
March 2020

Necessity of prophylactic splenic hilum lymph node clearance for middle and upper third gastric cancer: a network meta-analysis.

BMC Cancer 2020 Feb 24;20(1):149. Epub 2020 Feb 24.

Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 West Changle Road, Xi'an, 710032, Shaanxi, China.

Background: It remains controversial whether prophylactic No.10 lymph node clearance is necessary for gastric cancer. Thus, the present study aims to investigate the impact of prophylactic No.10 lymph node clearance on the perioperative complications and prognosis of upper and middle third gastric cancer.

Methods: A network meta-analysis to identify both direct and indirect evidence with respect to the comparison of gastrectomy alone (G-A), gastrectomy combination with splenectomy (G + S) and gastrectomy combination with spleen-preserving splenic hilar dissection (G + SPSHD) was conducted. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published before September 2018. Perioperative complications and overall survival were analyzed. Hazard ratios (HR) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods.

Results: Ten retrospective studies involving 2565 patients were included. In the direct comparison analyses, G-A showed comparable 5-year overall survival rate (HR: 1.1, 95%CI: 0.97-1.3) but lower total complication rate (OR: 0.37, 95%CI: 0.17-0.77) compared with G + S. Similarly, the 5-year overall survival rate between G + SPSHD and G + S was comparable (HR: 1.1, 95%CI: 0.92-1.4), while the total complication rate of G + SPSHD was lower than that of G + S (OR: 0.50, 95%CI: 0.28-0.88). In the indirect comparison analyses, both the 5-year overall survival rate (HR: 1.0, 95%CI: 0.78-1.3) and total complication rate (OR: 0.75, 95%CI: 0.29-1.9) were comparable between G-A and G + SPSHD.

Conclusions: Prophylactic No.10 lymph node clearance was not recommended for treatment of upper and middle third gastric cancer.
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http://dx.doi.org/10.1186/s12885-020-6619-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041100PMC
February 2020

Stem-like cells of various origins showed therapeutic effect to improve the recovery of spinal cord injury.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):627-638

Department of Orthopedics, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

We aimed to evaluate the therapeutic effects of exosomes, which were collected from human neuroepithelial stem cells (HNESCs) treated by miR-29b mimics, on the treatment of spinal cord injury (SCI). Computational analysis, real-time PCR, Western blot analysis and TUNEL assay, a BBB score system, the Nissl staining and IHC assay were conducted to explore the molecular signalling pathway underlying the function of exosomes in SCI. Exosomes isolated from cells treated with HNESC exhibited the strongest inhibitory effect on cell apoptosis while exhibiting the highest level of miR-29b expression and the lowest levels of PTEN and caspase-3 expression. Moreover, PTEN and caspase-3 were identified as the direct target genes of miR-29b. The exosomes isolated from the groups of HNESC and HNESC + miR-29b mimics exhibited therapeutic effects by restoring the BBB score and apoptosis index of post-SCI neuron cells to those of normal neuron cells, with the exosomes collected from the group of HNESC + miR-29b mimics showing the strongest effect. We suggested that the exosomes derived from the group of HNESC + miR-29b mimics exerted therapeutic effects on SCI by down-regulating the expression of PTEN/caspase-3 and subsequently suppressing the apoptosis of neuron cells.
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http://dx.doi.org/10.1080/21691401.2020.1725031DOI Listing
December 2020

The therapeutic effect of bone marrow-derived mesenchymal stem cells on osteoarthritis is improved by the activation of the KDM6A/SOX9 signaling pathway caused by exposure to hypoxia.

J Cell Physiol 2020 10 5;235(10):7173-7182. Epub 2020 Feb 5.

Department of Orthopedics, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

Abnormal expression of KDM6A and SOX9 is a key factor in the pathogenesis of osteoarthritis (OA). Cellular treatments of OA with articular cartilage chondrocytes (ACCs) and bone marrow mesenchymal stem cells (BMSCs) are promising, but their underlying mechanisms remain to be explored. The pellet size, weight and sulfated glycosaminoglycan/DNA content of ACCs were measured to evaluate the effect of BMSCs on the chondrogenic differentiation of SCCs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the proliferation of ACCs cultured along or cocultured with BMSCs. Quantitative polymerase chain reaction (qPCR) was performed to evaluate the messenger RNA expression of KDM6A, SOX9, type2 collagen, and Aggrecan in ACCs and OA rats. Western blot and immunohistochemistry were performed to analyze the expression of KDM6A and SOX9 proteins. Bisulfite sequencing PCR was performed to assess the DNA methylation level of the SOX9 promoter. Flow cytometry was used to evaluate the apoptotic status of ACCs. The chondrogenic differentiation of ACCs was significantly enhanced by coculturing with BMSCs, especially under a hypoxic condition. The expression of KDM6A, SOX9, type2 collagen, and Aggrecan was remarkably elevated in ACCs cocultured with BMSCs. Also, the DNA methylation of SOX9 promoter was decreased in ACCs cocultured with BMSCs, along with notably reduced apoptosis. Moreover, ACCs cocultured with BMSCs could repair cartilage lesions and prevent the abnormal expression of KDM6A, SOX9, type2 collagen, and Aggrecan in OA rats. In this study, we cocultured ACCs with BMSCs and used them to treat OA rats. Our findings presented a mechanistic basis for explaining the therapeutic effect of BMSCs on OA treatment.
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http://dx.doi.org/10.1002/jcp.29615DOI Listing
October 2020
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