Publications by authors named "Fei Xiao"

509 Publications

miR-30a-5p targets Becn1 to ameliorate high-glucose-induced glomerular podocyte injury in immortalized rat podocyte cell line.

Am J Transl Res 2021 15;13(3):1516-1525. Epub 2021 Mar 15.

Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, China.

Objective: Diabetic nephropathy (DN) is a serious kidney-based complication of diabetes, wherein podocyte injury is deemed crucial in the development of early stage. Various miRNAs, as report goes, is involved in the pathogenesis of varieties of kidney diseases including DN. In this study, we found a target relationship between miR-30a-5p and Becn1, of which there are few studies about the role in podocyte injury. We therefore used immortalized rat podocyte cell line to explore the role and molecular mechanism of miR-30a-5p targeting Becn1 gene in high-glucose-induced glomerular podocyte injury.

Methods: The mRNA and protein expressions of miR-30a-5p and Becn1 were detected respectively by quantitative reverse transcriptase PCR and western blotting. The proliferation, apoptosis, and the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were detected by MTT assay, flow cytometry, and enzyme-linked immuno sorbent assay, respectively. Intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also determined.

Results: Compared with normal group, miR-30a-5p in model groups were down-regulated, while Becn1 expression was significantly up-regulated, with slower proliferation, higher apoptosis rate, lower SOD level, and significantly higher ROS, MDA, IL-6, and TNF-α levels (all P<0.05). Overexpression of miR-30a-5p or Becn1 knock-out could lower Becn1 expression, apoptosis rate, promote proliferation, with relatively higher SOD level and lower ROS, MDA, Il-6, and TNF-α levels of model cells (all P<0.05).

Conclusion: Up-regulation of miR-30a-5p can suppress the expression of Becn1 to increase the growth and inhibit the apoptosis of immortalized rat podocyte cell line, therefore ameliorating podocyte injury induced by high glucose in vitro.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014343PMC
March 2021

Discovery of plasma biomarkers with data-independent acquisition mass spectrometry and antibody microarray for diagnosis and risk stratification of pulmonary embolism.

J Thromb Haemost 2021 Apr 7. Epub 2021 Apr 7.

Peking University, Fifth School of Clinical Medicine, Beijing, 100730, China.

Background: Pulmonary embolism (PE) is a leading cause of cardiovascular mortality worldwide. Rapid and accurate diagnosis and risk stratification are crucial for timely treatment options, especially in high-risk PE.

Objectives: The study aims to profile the comprehensive changes of plasma proteomes in PE patients and identify the potential biomarkers for both diagnosis and risk stratification.

Patients/methods: Based on the data-independent acquisition mass spectrometry and antibody array proteomic technology, we screened the plasma samples (13 and 32 proteomes, respectively) in two independent studies consisting of high-risk PE patients, non-high-risk PE patients, and healthy controls. Some significantly differentially expressed proteins were quantified by enzyme-linked immunosorbent assay in a new study group with 50 PE patients and 26 healthy controls.

Results: We identified 207 and 70 differentially expressed proteins in PE and high-risk PE. These proteins were involved in multiple thrombosis-associated biological processes including blood coagulation, inflammation, injury, repair, and chemokine-mediated cellular response. It was verified that five proteins including SAA1, S100A8, TNC, GSN and HRG had significant change in PE and/or in high-risk PE. The Receiver Operating Characteristic curve analysis based on binary Logistic regression showed that the area under the curve (AUC) of SAA1, S100A8, and TNC in PE diagnosis were 0.882, 0.788, and 0.795, and AUC of S100A8 and TNC in high-risk PE diagnosis were 0.773 and 0.720.

Conclusion: As predictors of inflammation or injury repair, SAA1, S100A8, and TNC are potential plasma biomarkers for the diagnosis and risk stratification of PE.
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http://dx.doi.org/10.1111/jth.15324DOI Listing
April 2021

Recent Advances in Electrocatalysts for Proton Exchange Membrane Fuel Cells and Alkaline Membrane Fuel Cells.

Adv Mater 2021 Mar 21:e2006292. Epub 2021 Mar 21.

Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

The rapid progress of proton exchange membrane fuel cells (PEMFCs) and alkaline exchange membrane fuel cells (AMFCs) has boosted the hydrogen economy concept via diverse energy applications in the past decades. For a holistic understanding of the development status of PEMFCs and AMFCs, recent advancements in electrocatalyst design and catalyst layer optimization, along with cell performance in terms of activity and durability in PEMFCs and AMFCs, are summarized here. The activity, stability, and fuel cell performance of different types of electrocatalysts for both oxygen reduction reaction and hydrogen oxidation reaction are discussed and compared. Research directions on the further development of active, stable, and low-cost electrocatalysts to meet the ultimate commercialization of PEMFCs and AMFCs are also discussed.
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http://dx.doi.org/10.1002/adma.202006292DOI Listing
March 2021

Multicenter Investigation of the Initial Hemodialysis Vascular Access and Its Related Factors in Hangzhou of China.

Biomed Res Int 2021 17;2021:6628139. Epub 2021 Feb 17.

Department of Nephrology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Objective: To investigate the initial hemodialysis vascular access in Hangzhou and provide evidence for improving the use of autologous arteriovenous fistula by identifying factors associated with the choice of initial vascular access.

Methods: We retrospectively studied the initial hemodialysis vascular access of 257 patients in five hemodialysis units in Hangzhou of China during a 21-month period (January 2018 to September 2019). A logistic regression was used to identify the risk factors of failing to use an arteriovenous fistula at the initiation of hemodialysis.

Results: (1) 257 participants with mean age 67.65 ± 13.43 years old were reviewed, including 165 males (64.2%) and 92 females (35.8%). The etiologies of end-stage renal disease included diabetic nephropathy (37.35%), chronic glomerulonephritis (31.13%), hypertensive nephropathy (14.01%), and other diseases (17.51%). Only 51 patients (19.84%) received arteriovenous fistula, whereas the remaining 206 patients (80.16%) initiated dialysis with a central venous catheter. (2) Logistic regression analysis revealed that the independent risk factors for central venous catheter at the initial hemodialysis were age >70 years old (OR = 4.827, < 0.01 versus ≤70 years old), chronic glomerulonephritis as the primary etiology (OR = 2.565, < 0.05 versus nonchronic glomerulonephritis) and eGFR <8.5 mL/min/1.73m (OR = 2.283, < 0.05 versus eGFR ≥8.5 mL/min/1.73m).

Conclusion: The proportion of patients using arteriovenous fistula as the initial hemodialysis vascular access in Hangzhou was still low. The choice of vascular access for the first hemodialysis was related to age, eGFR, and the primary etiology of end-stage renal disease. Increasing the proportion of planned vascular access and arteriovenous fistula at the initiation of hemodialysis is still our current goal.
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http://dx.doi.org/10.1155/2021/6628139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904347PMC
February 2021

Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2.

Front Med (Lausanne) 2021 15;8:585358. Epub 2021 Feb 15.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.
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http://dx.doi.org/10.3389/fmed.2021.585358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917136PMC
February 2021

Intra-host variation and evolutionary dynamics of SARS-CoV-2 populations in COVID-19 patients.

Genome Med 2021 02 22;13(1):30. Epub 2021 Feb 22.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China.

Background: Since early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown.

Methods: Using high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19 patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT).

Results: The 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks.

Conclusions: Our findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.
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http://dx.doi.org/10.1186/s13073-021-00847-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898256PMC
February 2021

Preparation, stability and commutability of candidate reference materials for lactate dehydrogenase (LDH).

Clin Biochem 2021 May 20;91:45-51. Epub 2021 Feb 20.

The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, PR China; Clinical Biobank, Beijing Hospital, National Center of Gerontology, Beijing 100730, PR China. Electronic address:

Background: Lactate dehydrogenase (LDH) is a key enzyme that functions as a marker of cell damage. Its activity can be measured by a variety of laboratory methods. To eliminate inter-method bias and enhance equivalence among different measurement procedures, LDH detection needs to be standardized.

Methods: Optimized sequences coding for lactate dehydrogenase subunit A (LDH-A) and subunit B (LDH-B) were synthesized and cloned into the pRSFDuet vector, and then the constructed 6His-LDHA-pRSFDuet, 6His-LDHB-pRSFDuet, and 6His-LDHA-LDHB-pRSFDuet plasmids were transformed into Escherichia coli BL21 (DE3) for expression. The enzyme activity and specific activity of recombinant LDHs were detected. Electrophoresis of LDH isoenzymes was performed. The stability of recombinant LDHs and serum LDH was evaluated. Commutability of recombinant LDH-B was studied by the IFCC reference method and six routine methods.

Results: Three plasmids were constructed and three highly concentrated recombinant LDH isoenzymes were obtained. The specific activities of LDH-A, LDH-AB, and LDH-B were 18.08 U/mg, 21.74 U/mg, and 14.18 U/mg, respectively. There was a desirable linear correlation between the activities of recombinant LDH isoenzymes and their protein concentrations. Electrophoresis of LDH isoenzymes showed that the recombinant LDH-B corresponded to LDH1 and it demonstrated good stability at 4 °C and 25 °C for 5 weeks. LDH-B formulations in saline-bovine serum albumin solution and human serum matrix were commutable for six routine methods.

Conclusion: Human recombinant LDH-B has great potential to become an improved and less expensive standard or reference material in external quality assessment for clinical LDH measurement.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.02.002DOI Listing
May 2021

Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14 monocytes.

iScience 2021 Mar 12;24(3):102187. Epub 2021 Feb 12.

Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.

Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Immunoglobulin-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14 monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 Å resolution reveals three remarkable changes on the amphipathic side of the four-stranded β-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14 monocytes triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19.
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http://dx.doi.org/10.1016/j.isci.2021.102187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879101PMC
March 2021

Network-Based Target Prioritization and Drug Candidate Identification for Multiple Sclerosis: From Analyzing "Omics Data" to Druggability Simulations.

ACS Chem Neurosci 2021 Mar 10;12(5):917-929. Epub 2021 Feb 10.

Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system. While the drugs currently available for MS provide symptomatic benefit, there is no curative treatment. The emergence of large-scale multiomics data and network theory provide new opportunities for drug discovery in MS, as these are promising strategies for developing novel drugs. In this study, we proposed a computational framework that combined biomolecular network modeling and structural dynamics analysis to facilitate the discovery of new drugs with potential activity in MS. First, we developed a new shortest path-based algorithm that prioritized differentially expressed genes using a newly topological and functional exploration of protein-protein interaction network. Then, pathway enrichment analysis and an assessment of target druggability suggested that TNF-α-induced protein 3 (), which is involved in NF-κ B signaling, could be a potential therapeutic target for MS. Finally, druggability simulations and mutation enrichment analysis of the TNFAIP3 dimer presented two druggable sites. Follow-up pharmacophore model-based virtual screening of the two sites yielded 30 hit compounds with low energy scores. In summary, this novel method based on analyzing "omics data" and performing druggability simulations, is a systematic approach that unravels disease mechanisms and links them to the chemical space to develop treatments and can be applied to other complex diseases.
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http://dx.doi.org/10.1021/acschemneuro.1c00011DOI Listing
March 2021

Acute kidney injury instigates malignant renal cell carcinoma via CXCR2 in mice with inactivated Trp53 and Pten in proximal tubular kidney epithelial cells.

Cancer Res 2021 Feb 8. Epub 2021 Feb 8.

Department of Cancer Biology, Metastasis Research Center, The University of Texas MD Anderson Cancer Center

Renal cell carcinoma (RCC) is one of the most common urologic malignancies with the highest mortality rates worldwide. However, relevant mouse models that recapitulated the genetic alterations in found in RCC have been lacking. In this study, we crossed Trp53 and Pten conditional knockout mice with Ggt1-Cre mice to generate a Ggt1-Cre; Trp53LoxP/LoxP; PtenLoxP/LoxP; YFPLoxP/LoxP (GPPY) mouse model, which resulted in the formation of dysplastic lesions involving kidney tubular epithelial cells (TEC) with only ~25% of mice developing RCC at an advanced age. Combining CRISPR/Cas9-mediated Vhl knockout in these mice increased the frequency of dysplasia but failed to increase the incidence of RCC. Assessments of whether ischemic injury of TECs in the GPPY kidney without Vhl knockout influences the emergence of RCC revealed that advanced RCC predominantly emerged in the contralateral, non-injured kidney with 100% penetrance at a younger age but rarely in the injured kidney due to severely damaged ischemic TEC. Injured TEC released CXCL1 into the microenvironment that traveled systemically to activate fibroblasts and recruit neutrophils to enable emergence of RCC in the contralateral kidney. Fibroblasts responded to CXCL1 via CXCR2 and recruited tumor-associated neutrophils, which in turn mediated tumor-promoting inflammation and angiogenesis. Treatment with anti-CXCR2 antibodies abolished the emergence of malignant RCC. Collectively, these results demonstrate a defining functional role of systemic inflammation and microenvironment in the emergence of malignant cancer from pre-established dysplastic precursor lesions.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2930DOI Listing
February 2021

Protein kinase PpCIPK1 modulates plant salt tolerance in Physcomitrella patens.

Plant Mol Biol 2021 Apr 4;105(6):685-696. Epub 2021 Feb 4.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, People's Republic of China.

Key Message: This work demonstrates that PpCIPK1, a putative protein kinase, participates in regulating plant salt tolerance in moss Physcomitrella patens. Calcineurin B-Like protein (CBL)-interacting protein kinases (CIPKs) have been reported to be involved in multiple signaling networks and function in plant growth and stress responses, however, their biological functions in non-seed plants have not been well characterized. In this study, we report that PpCIPK1, a putative protein kinase, participates in regulating plant salt tolerance in moss Physcomitrella patens (P. patens). Phylogenetic analysis revealed that PpCIPK1 shared high similarity with its homologs in higher plants. PpCIPK1 transcription level was induced upon salt stress in P. patens. Using homologous recombination, we constructed PpCIPK1 knockout mutant lines (PpCIPK1 KO). Salt sensitivity analysis showed that independent PpCIPK1 KO plants exhibited severe growth inhibition and developmental deficiency of gametophytes under salt stress condition compared to that of wild-type P. patens (WT). Consistently, ionic homeostasis was disrupted in plants due to PpCIPK1 deletion, and high level of HO was accumulated in PpCIPK1 KO than that in WT. Furthermore, PpCIPK1 functions in regulating photosynthetic activity in response to salt stress. Interestingly, we observed that PpCIPK1 could completely rescue the salt-sensitive phenotype of sos2-1 to WT level in Arabidopsis, indicating that AtSOS2 and PpCIPK1 are functionally conserved. In conclusion, our work provides evidence that PpCIPK1 participates in salt tolerance regulation in P. patens.
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http://dx.doi.org/10.1007/s11103-021-01120-4DOI Listing
April 2021

MYB30 and ETHYLENE INSENSITIVE3 antagonistically modulate root hair growth in Arabidopsis.

Plant J 2021 Feb 2. Epub 2021 Feb 2.

Key Laboratory of Bio-resource and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.

Root hair (RH) is essential for plant nutrient acquisition and the plant-environment communication. Here we report that transcription factors MYB30 and ETHYLENE INSENSITIVE3 (EIN3) modulate RH growth/elongation in Arabidopsis in an antagonistic way. The MYB30 loss-of-function mutant displays enhanced RH length, whereas the RH elongation in MYB30-overexpressing plants is highly repressed. MYB30 physically interacts with EIN3, a master transcription factor in ethylene signaling. MYB30 directly binds the promoter region of ROOT HAIR DEFECTIVE SIX-LIKE4 (RSL4) and represses its transcription. RSL4 loss-of-function suppresses the enhanced RH growth in myb30 mutant plants. Ethylene enhances MYB30-EIN3 complex formation, and reduces the association between MYB30 and RSL4 promotor via the action of EIN3. MYB30 and EIN3 antagonistically regulate the expression of RSL4 and a subset of core RH genes in a genome-wide way. Taken together, our work revealed a novel transcriptional network that modulates RH growth in plants.
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http://dx.doi.org/10.1111/tpj.15180DOI Listing
February 2021

Nogo‑66 promotes β‑amyloid protein secretion via NgR/ROCK‑dependent BACE1 activation.

Mol Med Rep 2021 Mar 26;23(3). Epub 2021 Jan 26.

Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.

The generation of β‑amyloid protein (Aβ) is considered a key step in the pathogenesis of Alzheimer's disease (AD) and the regulation of its production is an important therapeutic strategy. It was hypothesized in the present study that Nogo‑A may be involved in AD and may regulate the generation of Aβ. Nogo‑A is known to act as a major inhibitor of neuron regeneration in the adult central nervous system. A recent study indicated that Nogo‑A is associated with AD; however, the underlying effect and molecular mechanisms remain largely elusive. In the present study, the potential effects of Nogo‑A on AD were investigated. ELISA was used to detect the levels of Aβ, enzymatic activity detection kits were used to determine the activity of secretase enzymes in amyloid precursor protein (APP) metabolism, and western blot analysis was used to detect the expression levels of proteins associated with the APP processing and Nogo‑A/Nogo‑66 receptor (NgR) signaling pathways. The results revealed that Nogo‑66, the major inhibitory region of Nogo‑A, promoted neuronal Aβ secretion by increasing the activity of β‑secretase 1 via the NgR/Rho‑associated coiled‑coil containing kinases pathway in a dose‑dependent manner. The present data suggested that Nogo‑A may facilitate the onset and development of AD by promoting Aβ secretion, providing information on a potential novel target for AD therapy.
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http://dx.doi.org/10.3892/mmr.2021.11827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809900PMC
March 2021

The utility of simultaneous CT-guided localization for multiple pulmonary nodules using microcoil before video-assisted thoracic surgery.

BMC Pulm Med 2021 Jan 25;21(1):39. Epub 2021 Jan 25.

Department of Radiology, China-Japan Friendship Hospital, No. 2 Yinghua East Street, Chaoyang District, Beijing, 100029, China.

Background: To evaluate the feasibility and safety of microcoil in simultaneous localization for multiple pulmonary nodules before video-assisted thoracic surgery (VATS).

Methods: Twenty-eight consecutive patients (26 two-nodule, 2 three-nodule; 58 nodules in total; Group A) underwent simultaneous CT-guided localization of multiple pulmonary nodules before VATS using microcoil. Successful targeting, localization, and VATS were defined as implantation of microcoil at the target site on CT image which was obtained immediately after the marking procedure, visualization of nodule location, and complete resection of the target nodule with adequate margin, respectively. Meanwhile, the clinical characteristics, localization procedure-related variables of the nodules and procedure-related complications in group A were also assessed and compared with those in a control group (221 single-localization procedures in 221 patients; Group B).

Results: Similar rates of successful targeting, localization and VATS were observed in group A and B (96.6% vs. 98.2%; 91.4% vs. 91.0%; 100% vs. 99.1%). Although the rate of overall complications (including localized pneumothorax and intrapulmonary hemorrhage) was a bit higher in group A than that in group B (32.8% vs. 30.8%, p = 0.771), only minor complications were observed in the subjects of the two groups with no need for further treatment. In addition, the duration of simultaneous localization procedures was significantly longer than that of single localization (24 ± 7.5 vs.13 ± 6 min, p < 0.001).

Conclusions: CT-guided simultaneous microcoil localization for multiple pulmonary nodules before VATS was clinically feasible and safe with acceptable increase in the procedure time. Compared with localization for a single pulmonary nodule, simultaneous microcoil localizations for multiple nodules were prone to pneumothorax and hemorrhage. However, no statistically significant differences were observed between the two groups.
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http://dx.doi.org/10.1186/s12890-021-01393-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831238PMC
January 2021

Intermedin facilitates hepatocellular carcinoma cell survival and invasion via ERK1/2-EGR1/DDIT3 signaling cascade.

Sci Rep 2021 Jan 12;11(1):488. Epub 2021 Jan 12.

Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, No. 1, Ke Yuan 4th Road, Gao Peng Street, Chengdu, 610041, Sichuan, People's Republic of China.

As one of the most malignant cancer types, hepatocellular carcinoma (HCC) is highly invasive and capable of metastasizing to distant organs. Intermedin (IMD), an endogenous peptide belonging to the calcitonin family, has been suggested playing important roles in cancer cell survival and invasion, including in HCC. However, how IMD affects the behavior of HCC cells and the underlying mechanisms have not been fully elucidated. Here, we show that IMD maintains an important homeostatic state by activating the ERK1/2-EGR1 (early growth response 1) signaling cascade, through which HCC cells acquire a highly invasive ability via significantly enhanced filopodia formation. The inhibition of IMD blocks the phosphorylation of ERK1/2, resulting in EGR1 downregulation and endoplasmic reticulum stress (ER) stress, which is evidenced by the upregulation of ER stress marker DDIT3 (DNA damage-inducible transcript 3). The high level of DDIT3 induces HCC cells into an ER-stress related apoptotic pathway. Along with our previous finding that IMD plays critical roles in the vascular remodeling process that improves tumor blood perfusion, IMD may facilitate the acquisition of increased invasive abilities and a survival benefit by HCC cells, and it is easier for HCC cells to obtain blood supply via the vascular remodeling activities of IMD. According to these results, blockade of IMD activity may have therapeutic potential in the treatment of HCC.
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http://dx.doi.org/10.1038/s41598-020-80066-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803743PMC
January 2021

A semi-tryptic peptide centric metaproteomic mining approach and its potential utility in capturing signatures of gut microbial proteolysis.

Microbiome 2021 01 12;9(1):12. Epub 2021 Jan 12.

Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, Guangdong Province, China.

Background: Proteolysis regulation allows gut microbes to respond rapidly to dynamic intestinal environments by fast degradation of misfolded proteins and activation of regulatory proteins. However, alterations of gut microbial proteolytic signatures under complex disease status such as inflammatory bowel disease (IBD, including Crohn's disease (CD) and ulcerative colitis (UC)), have not been investigated. Metaproteomics holds the potential to investigate gut microbial proteolysis because semi-tryptic peptides mainly derive from endogenous proteolysis.

Results: We have developed a semi-tryptic peptide centric metaproteomic mining approach to obtain a snapshot of human gut microbial proteolysis signatures. This approach employed a comprehensive meta-database, two-step multiengine database search, and datasets with high-resolution fragmentation spectra to increase the confidence of semi-tryptic peptide identification. The approach was validated by discovering altered proteolysis signatures of Escherichia coli heat shock response. Utilizing two published large-scale metaproteomics datasets containing 623 metaproteomes from 447 fecal and 176 mucosal luminal interface (MLI) samples from IBD patients and healthy individuals, we obtain potential signatures of altered gut microbial proteolysis at taxonomic, functional, and cleavage site motif levels. The functional alterations mainly involved microbial carbohydrate transport and metabolism, oxidative stress, cell motility, protein synthesis, and maturation. Altered microbial proteolysis signatures of CD and UC mainly occurred in terminal ileum and descending colon, respectively. Microbial proteolysis patterns exhibited low correlations with β-diversity and moderate correlations with microbial protease and chaperones levels, respectively. Human protease inhibitors and immunoglobulins were mainly negatively associated with microbial proteolysis patterns, probably because of the inhibitory effects of these host factors on gut microbial proteolysis events.

Conclusions: This semi-tryptic peptide centric mining strategy offers a label-free approach to discover signatures of in vivo gut microbial proteolysis events if experimental conditions are well controlled. It can also capture in vitro proteolysis signatures to facilitate the evaluation and optimization of experimental conditions. Our findings highlight the complex and diverse proteolytic events of gut microbiome, providing a unique layer of information beyond taxonomic and proteomic abundance. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00967-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805185PMC
January 2021

Overexpression of LMP-1 Decreases Apoptosis in Human Nucleus Pulposus Cells via Suppressing the NF-B Signaling Pathway.

Oxid Med Cell Longev 2020 13;2020:8189706. Epub 2020 Dec 13.

Department of Emergency, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, Zhengzhou City, Henan 450052, China.

Intervertebral disc degeneration (IDD) is a prevalent disease characterized by low back pain. Increasing extracellular matrix (ECM) synthesis and decreasing nucleus pulposus cell (NPC) apoptosis are promising strategies to recover degenerated NP. LIM mineralization protein- (LMP-) 1 has anti-inflammatory potential and is a promising gene target for the treatment of NP degeneration. In this study, we measured the expression of LMP-1 in the NP of patients. Then, we constructed LMP-1-overexpressing NPCs using lentiviral vectors and investigated the effects of LMP-1 on cell proliferation, apoptosis, and ECM synthesis in NPCs. The results showed that LMP-1 was highly expressed in the NP of patients. LMP-1 overexpression significantly increased proliferation and decreased apoptosis in NPCs. The expression of collagen II and sulfated glycosaminoglycan (sGAG) in NPCs was also upregulated after LMP-1 was overexpressed. Moreover, we demonstrated that LMP-1 decreased apoptosis of NPCs by inhibiting NF-B signaling activation. These findings suggest that LMP-1 plays an essential role in mediating apoptosis in NPCs by regulating NF-B signaling and can be used as a gene target for the treatment of IDD.
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http://dx.doi.org/10.1155/2020/8189706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752285PMC
December 2020

Reply to: routine use of norepinephrine infusion in caesarean delivery.

Eur J Anaesthesiol 2021 02;38(2):196

From the Department of Anaesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, China.

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http://dx.doi.org/10.1097/EJA.0000000000001325DOI Listing
February 2021

SCN1A IVS5N+5 G>A Polymorphism and Risk of Febrile Seizure and Epilepsy: A Systematic Review and Meta-Analysis.

Front Neurol 2020 17;11:581539. Epub 2020 Dec 17.

Department of Paediatrics, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China.

Previous studies had investigated the association between polymorphism of IVS5N+5 G>A in and the risk of febrile seizure and epilepsy. However, the results were inconsistent. We aimed to conduct a systematic review and meta-analysis to evaluate the association between IVS5N+5 G>A polymorphism and risk of febrile seizures and epilepsy. We searched Embase, Medline, Scopus, and CNKI for studies on the association between IVS5N+5 G>A polymorphism and risk of febrile seizures and epilepsy up to 19 February 2020. We pooled odds ratios (ORs) and 95% confidence intervals (CIs) by different genetic models. To explore the source of heterogeneity, we performed the subgroup analysis by ethnicity and source of control. We included a total of 12 studies in the meta-analysis. We found a significant negative association between G allele IVS5N+5 G>A polymorphism, febrile seizures [G vs. A: OR (95% CI): 0.690 (0.530-0.897); GG vs. AA: 0.503 (0.279-0.908); AG vs. AA: 0.581 (0.460-0.733); GG + AG vs. AA: 0.543 (0.436-0.677); AA + GG vs. AG: 1.309 (1.061-1.615)], and epilepsy [G vs. A: 0.822 (0.750-0.902); GG vs. AA: 0.655 (0.515-0.832); AG vs. AA: 0.780 (0.705-0.862); GG vs. AG + AA: 0.769 (0.625-0.947); GG + AG vs. AA: 0.743 (0.663-0.833); AA + GG vs. AG: 1.093 (1.001-1.193)]. The subgroup analysis shows the association varied by type of disease, ethnicity, and source of control. The present meta-analysis suggests that G allele in IVS5N+5 G>A polymorphism is a protective factor of febrile seizures and epilepsy. It is possible to determine the vulnerability of each individual to develop febrile seizures or epilepsy genotype by these genetic variants. Future studies with better study designs are needed to confirm the results. This study was registered in the International Prospective register of systematic reviews (PROSPERO, CRD42020163318).
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http://dx.doi.org/10.3389/fneur.2020.581539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773848PMC
December 2020

Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis of high-throughput data.

Biosci Rep 2020 12;40(12)

Department of Orthopedic Surgery, Xinhua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine (SJTUSM), Shanghai, China.

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases. The present study aimed to identify hub genes involved in the pathogenesis and further explore the potential treatment targets of RA and OA.

Methods: The gene expression profile of GSE12021 was downloaded from Gene Expression Omnibus (GEO). Total 31 samples (12 RA, 10 OA and 9 NC samples) were used. The differentially expressed genes (DEGs) in RA versus NC, OA versus NC and RA versus OA groups were screened using limma package. We also verified the DEGs in GSE55235 and GSE100786. Functional annotation and protein-protein interaction (PPI) network construction of OA- and RA-specific DEGs were performed. Finally, the candidate small molecules as potential drugs to treat RA and OA were predicted in CMap database.

Results: 165 up-regulated and 163 down-regulated DEGs between RA and NC samples, 73 up-regulated and 293 down-regulated DEGs between OA and NC samples, 92 up-regulated and 98 down-regulated DEGs between RA and OA samples were identified. Immune response and TNF signaling pathway were significantly enriched pathways for RA- and OA-specific DEGs, respectively. The hub genes were mainly associated with 'Primary immunodeficiency' (RA vs. NC group), 'Ribosome' (OA vs. NC group), and 'Chemokine signaling pathway' (RA vs. OA group). Arecoline and Cefamandole were the most promising small molecule to reverse the RA and OA gene expression.

Conclusion: Our findings suggest new insights into the underlying pathogenesis of RA and OA, which may improve the diagnosis and treatment of these intractable chronic diseases.
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http://dx.doi.org/10.1042/BSR20193823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744737PMC
December 2020

Inhibition of Intermedin (Adrenomedullin 2) Suppresses the Growth of Glioblastoma and Increases the Antitumor Activity of Temozolomide.

Mol Cancer Ther 2021 02 9;20(2):284-295. Epub 2020 Dec 9.

Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan, China.

Glioblastoma multiforme (GBM; grade IV glioma) is the most malignant type of primary brain tumor and is characterized by rapid proliferation and invasive growth. Intermedin (IMD) is an endogenous peptide belonging to the calcitonin gene-related peptide family and has been reported to play an important role in cell survival and invasiveness in several types of cancers. In this study, we found that the expression level of IMD was positively related to the malignancy grade of gliomas. The highest expression of IMD was found in GBM, indicating that IMD may play an important role in glioma malignancy. IMD increased the invasive ability of glioma cells by promoting filopodia formation, which is dependent on ERK1/2 activation. IMD-induced ERK1/2 phosphorylation also promoted GBM cell proliferation. In addition, IMD enhanced mitochondrial function and hypoxia-induced responses in GBM cells. Treatment with anti-IMD monoclonal antibodies not only inhibited tumor growth in both ectopic and orthotopic models of GBM but also significantly enhanced the antitumor activity of temozolomide. Our study may provide novel insights into the mechanism of GBM cell invasion and proliferation and provide an effective strategy to improve the therapeutic effect of GBM treatments.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0619DOI Listing
February 2021

Predictive value of radiological features on spread through air space in stage cIA lung adenocarcinoma.

J Thorac Dis 2020 Nov;12(11):6494-6504

Department of General Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China.

Background: Spread through air space (STAS) is a risk factor for disease recurrence in patients with stage IA lung adenocarcinoma (LUAD) who undergo limited resection. Preoperative prediction of STAS could help intraoperative surgical decision-making in small LUAD patients. The aim of the study was to evaluate the predictive value of radiological features on STAS in stage cIA LUAD.

Methods: A case-control study was designed through retrospective analysis of the radiological features of patients who underwent curative surgery for LUAD with a clinical tumor size ≤3 cm. Univariable and multivariable analyses were used to identify the independent risk factors for STAS. The predicted probability of STAS was calculated by a specific formula. Receiver operating characteristic (ROC) curves were used to determine a cut-off value with appropriate specificity while maintaining high sensitivity for STAS positivity.

Results: STAS was frequently observed in acinar predominant (P<0.001), micropapillary predominant (P<0.001) and solid predominant (P<0.001) tumors and was significantly associated with larger pT size (P<0.001), presence of micropapillary component (P<0.001), lymphovascular invasion (LVI) (P<0.001), visceral pleura invasion (VPI) (P<0.001), both N1 and N2 lymph node metastasis (P<0.001) and ALK rearrangement (P<0.001). STAS-positivity was significantly associated with the presence of cavitation (P=0.047), lobulation (P=0.009), air bronchogram (P<0.001), and vascular convergence (P=0.016) and was also associated with greater maximum tumor diameter (P<0.001), maximum solid component diameter (P<0.001), maximum tumor area (P<0.001), consolidation/tumor ratio (CTR) (P<0.001), tumor disappearance ratio (TDR) (P<0.001) and computed tomography (CT) value (P<0.001). Multivariable analysis showed that STAS was associated with air bronchogram (P=0.042), maximum tumor diameter (P=0.015), maximum solid component diameter (P=0.022) and CTR (P<0.001). The ROC curve showed that the area under the curve (AUC) was 0.726 in the model for predicting STAS, with a sensitivity and specificity of 95.2% and 36.8%, respectively.

Conclusions: STAS-positive LUAD was associated with air bronchogram, maximum tumor diameter, maximum solid component diameter and CTR. These radiological features could predict STAS with excellent sensitivity but inferior specificity.
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http://dx.doi.org/10.21037/jtd-20-1820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711360PMC
November 2020

An improved deep learning model for predicting daily PM2.5 concentration.

Sci Rep 2020 12 2;10(1):20988. Epub 2020 Dec 2.

State Key Laboratory of Information Engineering in Surveying, Mapping and Remote Sensing, Wuhan University, 129 Luoyu Road, Wuhan, 430079, China.

Over the past few decades, air pollution has caused serious damage to public health. Therefore, making accurate predictions of PM2.5 is a crucial task. Due to the transportation of air pollutants among areas, the PM2.5 concentration is strongly spatiotemporal correlated. However, the distribution of air pollution monitoring sites is not even making the spatiotemporal correlation between the central site and surrounding sites vary with different density of sites, and this was neglected by previous methods. To this end, this study proposes a weighted long short-term memory neural network extended model (WLSTME), which addressed the issue that how to consider the effect of the density of sites and wind conditions on the spatiotemporal correlation of air pollution concentration. First, a number of nearest surrounding sites were chosen as the neighbor sites to the central site, and their distance, as well as their air pollution concentration and wind condition, were input to multilayer perception (MLP) to generate weighted historical PM2.5 time series data. Second, historical PM2.5 concentration of the central site and weighted PM2.5 series data of neighbor sites were input into a long short-term memory (LSTM) to address spatiotemporal dependency simultaneously and extract spatiotemporal features. Finally, another MLP was utilized to integrate spatiotemporal features extracted above with the meteorological data of the central site to generate the forecasts future PM2.5 concentration of the central site. Daily PM2.5 concentration and meteorological data on Beijing-Tianjin-Hebei from 2015 to 2017 were collected to train models and to evaluate its performance. Experimental results with three existing methods showed that the proposed WLSTME model has the lowest RMSE (40.67) and MAE (26.10) and the highest p (0.59). Further experiments showed that in all seasons and regions, WLSTME performed the best. This finding confirms that WLSTME can significantly improve PM2.5 prediction accuracy.
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http://dx.doi.org/10.1038/s41598-020-77757-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710732PMC
December 2020

Evaluating the Effects of Different Sleep Supplement Modes in Attenuating Metabolic Consequences of Night Shift Work Using Rat Model.

Nat Sci Sleep 2020 20;12:1053-1065. Epub 2020 Nov 20.

Department of Endocrinology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China.

Purpose: To study the effects of chronic-simulated night shift work using the rat model and examines if a particular sleep supplement mode could be better in alleviating the effects.

Methods: The male Wistar rats were randomly divided into the control (CTL: 8 rats) and night shift work (NW: 24 rats) groups of rats. Based on the sleep supplement strategy, the NW group was further segregated into three subgroups (8 rats each); late sleep supplement group (LSS), early sleep supplement group (ESS), and intermittent sleep supplement group (ISS). Sleep deprivation was achieved using the standard small-platform-over water method. Parameters such as animal body weight and food intake were measured daily. The intraperitoneal glucose tolerance test, fasting plasma insulin concentration, insulin resistance index and insulin sensitivity were measured twice, in the 4th and 8th weeks of the study. Plasma corticosterone concentration and pathological changes in islets (insulitis) were measured at the end of the 8th week.

Results: In NW group, night work resulted in a gain of body weight and albeit lower than that of the CTL group. NW rats also had higher food intake, showed impaired glucose metabolism and higher plasma corticosterone concentration. The sleep supplement experiments suggested that compared to the other modes, intermittent sleep supplement had significantly low changes in the body weight, glucose metabolism and the islet cells.

Conclusion: Similar to previous studies, we also found that night shift work adversely impacts the body weight and glucose metabolism in rats. However, upon evaluating different sleep supplement strategies, we found the intermittent sleep supplement strategy to be most effective.
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http://dx.doi.org/10.2147/NSS.S271318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685379PMC
November 2020

Single Crystal CdSe X-ray Detectors with Ultra-High Sensitivity and Low Detection Limit.

ACS Appl Mater Interfaces 2020 Dec 26;12(50):56126-56134. Epub 2020 Nov 26.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, China.

CdSe single crystals (SCs), with a relatively high atomic number, large X-ray absorption coefficients, and high carrier mobility, are expected to provide high-performance detection for X-ray. However, the difficulty of growing high-quality CdSe SC has severely limited its application in X-ray detection. In this work, we develop an unconstrained physical gas phase method and in situ annealing process to grow high-quality CdSe SCs under unconstrained conditions. Using this method, CdSe SCs exhibit natural exposure planes, ultrahigh resistivity of 5.43 × 10 to 1.29 × 10 Ω cm and high product of 1.3 × 10 to 1.5 × 10 cm V. It is also observed that CdSe SC X-ray detectors exhibit a record sensitivity of 2.08 × 10 μC Gy cm and a low detection limit of 85 nGy s, which are both desired in medical diagnostics. Moreover, those devices with different crystal directions provide anisotropic X-ray detection performance. Our findings pave a new avenue to exploit high-performance CdSe SC X-ray detectors.
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http://dx.doi.org/10.1021/acsami.0c13567DOI Listing
December 2020

ACOT11 promotes cell proliferation, migration and invasion in lung adenocarcinoma.

Transl Lung Cancer Res 2020 Oct;9(5):1885-1903

Department of Thoracic Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.

Background: Lung cancer is one of the most common cancers in the word. However, the underlying mechanism remains largely unknown. encodes enzymes hydrolyzing the fatty acyl-CoA esters into free fatty acids and CoA. Besides from its role in fatty acid metabolism, the other aspects regarding its function in the progression of lung cancer have not been revealed.

Methods: We first explored the clinical profile of in tumor samples. Next, we combined gene knockdown and and microarray gene profiling analysis to decipher the unknown regulatory role of in lung cancer carcinoma. Furthermore, we explored the potential molecular mechanisms of with immunoprecipitation.

Results: We found high expression of in tumor samples. High expression of showed significantly poor prognosis in lung squamous carcinoma (LUSC) patients. Knocking down of inhibited the cell proliferation, migration as well as invasion and . It also promoted the cell apoptosis and cell cycle arrest via multiple signaling pathways. Additionally, could bind with , which was proved to be an oncogene in lung cancer and speculated to be a potential target of

Conclusions: The results revealed that regulates proliferation, migration and invasion of lung cancer carcinoma via multiple signaling pathways, indicating its potential value in molecular therapy.
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http://dx.doi.org/10.21037/tlcr-19-509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653140PMC
October 2020

Efficacy and safety of dexmedetomidine in patients receiving mechanical ventilation: Evidence from randomized controlled trials.

Pharmacol Res Perspect 2020 12;8(6):e00658

Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

At present, the efficacy and safety of dexmedetomidine in patients receiving mechanical ventilation (MV) is still controversial. Therefore, the purpose of this research was to assess the efficacy and safety of dexmedetomidine in MV patients by reviewing the results of randomized controlled trials (RCT). RCTs evaluating the efficacy of dexmedetomidine in the treatment of MV patients were obtained by searching relevant online databases, including PubMed, EMbase, Web of Science, the Cochrane Library, Medline, OVID, and ClinicalTrials.gov. Literature meeting the inclusion criteria were selected and evaluated by two researchers independently. Risk ratio (RR)/standardized mean difference (SMD) and 95% confidence interval (CI) were used to express the differences between groups. Seven RCTs were included in our study, with 986 participants in the dexmedetomidine group and 862 participants in the control group. Summary analysis results displayed no reduction in 30-day mortality (RR = 0.77, 95% CI: 0.59 to 1.02), delirium (RR = 0.77, 95% CI: 0.57 to 1.03), and adverse events (RR = 1.06, 95% CI: 0.22 to 5.08) in the dexmedetomidine group compared with the control group. As the length of stay in the intensive care unit (ICU) were presented as median and interquartile range (IQR)/standard deviation (SD), descriptive analysis of the results were performed. Generally, for 99.65% (953/986) of patients, dexmedetomidine was not better than the control group in reducing ICU length of stay. Our results demonstrate that for patients requiring MV, dexmedetomidine was not superior to the control group. However, analysis of more RCTs is required to confirm this conclusion.
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http://dx.doi.org/10.1002/prp2.658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658106PMC
December 2020

Dose dependent reduction in median effective concentration (EC) of ropivacaine with adjuvant dexmedetomidine in labor epidural analgesia: An up-down sequential allocation study.

J Clin Anesth 2021 Feb 1;68:110115. Epub 2020 Nov 1.

Department of Anesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing Maternity and Child Care Hospital, Jiaxing City, China. Electronic address:

Study Objective: Adjuvant dexmedetomidine can be used to reduce the required concentration of ropivacaine for labor epidural analgesia. However, the potency of dexmedetomidine has not been fully studied. The purpose of this study was to determine the median effective concentration (EC) of ropivacaine with adjuvant dexmedetomidine.

Design: Prospective, double-blind, up-down sequential allocation study.

Setting: Academic medical center specializing in the care of women and children.

Patients: One hundred and fifty healthy, term parturients requesting labor epidural analgesia were randomly assigned to 1 of 5 different concentrations of dexmedetomidine: 0 μg/ml, 0.3 μg/ml, 0.4 μg/ml, 0.5 μg/ml, or 0.6 μg/ml.

Interventions: The study solution for the first patient in each group included the randomly assigned concentration of dexmedetomidine in 0.1% ropivacaine. Subsequent patients in each randomization group received the assigned concentration of dexmedetomidine in a new concentration of ropivacaine as determined by the up-down allocation methodology. Effective analgesia was defined as pain on the visual analogue scale of<3 at30 min after administration of local anesthetic. The up-down sequential allocation method and probit regression were used to calculate the EC of epidural ropivacaine.

Measurements: The primary outcome was pain 30 min after administration of local anesthetic via epidural catheter. Exploratory outcomes included side effects, neonatal outcomes, and obstetric outcomes.

Main Results: The EC values for ropivacaine in dexmedetomidine 0.4 μg/ml, 0.5 μg/ml, and 0.6 μg/ml (0.044% [95% CI 0.036% to 0.045%], 0.035% [95% CI 0.031% to 0.041%], and 0.039% [95% CI 0.034% to 0.045%], respectively) were lower compared to ropivacaine in dexmedetomidine 0 μg/ml and 0.3 μg/ml (0.086% [95% CI 0.081% to 0.092%], and, 0.069% [95% CI 0.056% to 0.076%], respectively). Differences between EC values for ropivacaine in dexmedetomidine 0.4 μg/ml, 0.5 μg/ml, and 0.6 μg/ml were not statistically significant. Results of our exploratory analyses did not reveal differences in side effects, neonatal outcomes, or obstetric outcomes.

Conclusions: In this study, the lowest concentration of dexmedetomidine in ropivacaine with the greatest clinical effect was 0.4 μg/ml, which is important because there may be no additional analgesic benefit of dexmedetomidine greater than 0.4 μg/ml.
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http://dx.doi.org/10.1016/j.jclinane.2020.110115DOI Listing
February 2021

Advanced Electrocatalysts with Single-Metal-Atom Active Sites.

Chem Rev 2020 Nov 2;120(21):12217-12314. Epub 2020 Nov 2.

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.

Electrocatalysts with single metal atoms as active sites have received increasing attention owing to their high atomic utilization efficiency and exotic catalytic activity and selectivity. This review aims to provide a comprehensive summary on the recent development of such single-atom electrocatalysts (SAECs) for various energy-conversion reactions. The discussion starts with an introduction of the different types of SAECs, followed by an overview of the synthetic methodologies to control the atomic dispersion of metal sites and atomically resolved characterization using state-of-the-art microscopic and spectroscopic techniques. In recognition of the extensive applications of SAECs, the electrocatalytic studies are dissected in terms of various important electrochemical reactions, including hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO2RR), and nitrogen reduction reaction (NRR). Examples of SAECs are deliberated in each case in terms of their catalytic performance, structure-property relationships, and catalytic enhancement mechanisms. A perspective is provided at the end of each section about remaining challenges and opportunities for the development of SAECs for the targeted reaction.
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http://dx.doi.org/10.1021/acs.chemrev.0c00594DOI Listing
November 2020

Effects of COPD on in-hospital outcomes of transcatheter aortic valve implantation: Results from the National Inpatient Sample database.

Clin Cardiol 2020 Dec 22;43(12):1524-1533. Epub 2020 Oct 22.

Department of Cardiovascular Surgery, Guangdong Provincial People's Hospital, Guangdong, China.

Background: Comorbid chronic obstructive pulmonary disease (COPD) increases morbidity and mortality among aortic valve replacement patients undergoing conventional surgery. The impact of COPD in patients undergoing less invasive transcatheter aortic valve insertion (TAVI) is unclear.

Hypothesis: This study evaluates the in-hospital outcomes of TAVI in patients with and without COPD.

Methods: This population-based, retrospective study of 8466 TAVI patients (29.87% with COPD) evaluates the effects of COPD on short-term clinical outcomes (in-hospital mortality, length of hospital stay, and postoperative complications) using data from the National Inpatient Sample database from 2011 to 2014. Logistic regression analysis was used to determine factors associated with in-hospital mortality and postoperative complications. Linear regression analysis was used to identify factors associated with length of hospital stay.

Results: COPD is significantly associated with increased risk of respiratory complications and pneumonia after TAVI (aOR = 1.43, 95% CI: 1.24-1.64; P < .001) but not in-hospital mortality, length of hospital stay, or non-respiratory postoperative complications as compared to non-COPD patients. Concomitant COPD is significantly associated with increased risk of respiratory complications or pneumonia after TAVI but may still be the best treatment option for some patients.

Conclusions: Patients with comorbid COPD who receive TAVI have greater risk of developing postoperative respiratory complications and pneumonia. Vigilance for specific respiratory complications is highly warranted when treating this subgroup. Treatment decisions must be individualized.
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http://dx.doi.org/10.1002/clc.23475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724217PMC
December 2020