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High-throughput screening of natural compounds and inhibition of a major therapeutic target HsGSK-3β for Alzheimer's disease using computational approaches.

J Genet Eng Biotechnol 2021 May 4;19(1):61. Epub 2021 May 4.

Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Waknaghat, Solan, H.P., 173234, India.

Background: Alzheimer's disease is a leading neurodegenerative disease worldwide and is the 6th leading cause of death in the USA. AD is a very complex disease and the drugs available in the market cannot fully cure it. The glycogen synthase kinase 3 beta plays a major role in the hyperphosphorylation of tau protein which forms the neurofibrillary tangles which is a major hallmark of AD. Read More

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Progress in tumour-targeted drug delivery based on cell-penetrating peptides.

J Drug Target 2021 May 4:1-15. Epub 2021 May 4.

Key Laboratory of Chemical Biology, Department of Pharmaceutics, School of Pharmaceutical Sciences, Ministry of Education, Shandong University, Jinan, China.

Since the discovery of cell-penetrating peptides (CPP) in the 1980s, they have played a unique role in various fields owing to their excellent and unique cell membrane penetration function. In particular, in the treatment of tumours, CPPS have been used to deliver several types of 'cargos' to cancer cells. To address the insufficient targeting ability, non-selectivity, and blood instability, activatable cell-penetrating peptides, which can achieve targeted drug delivery in tumour treatment, enhance curative effects, and reduce toxicity have been developed. Read More

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Pyroptosis in stroke-new insights into disease mechanisms and therapeutic strategies.

J Physiol Biochem 2021 May 4. Epub 2021 May 4.

State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, 210009, China.

Stroke is a common disease with high mortality and disability worldwide. Different forms of cell deaths, including apoptosis and necrosis, occur in ischemic or hemorrhagic brain tissue, among which pyroptosis, a newly discovered inflammation-related programmed cell death, is generally divided into two main pathways, the canonical inflammasome pathway and the non-canonical inflammasome pathway. Caspase-mediated pyroptosis requires the assembly of inflammasomes such as NLRP3, which leads to the release of inflammatory cytokines IL-1β and IL-18 through the pores formed in the plasma membrane by GSDMD followed by neuroinflammation. Read More

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Detection of low-frequency DNA variants by targeted sequencing of the Watson and Crick strands.

Nat Biotechnol 2021 May 3. Epub 2021 May 3.

Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Identification and quantification of low-frequency mutations remain challenging despite improvements in the baseline error rate of next-generation sequencing technologies. Here, we describe a method, termed SaferSeqS, that addresses these challenges by (1) efficiently introducing identical molecular barcodes in the Watson and Crick strands of template molecules and (2) enriching target sequences with strand-specific PCR. The method achieves high sensitivity and specificity and detects variants at frequencies below 1 in 100,000 DNA template molecules with a background mutation rate of <5 × 10 mutants per base pair (bp). Read More

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Antioxidant Properties of Galanin and Its N-Terminal Fragments in in vitro and in vivo Oxidative Stress Modeling.

Biochemistry (Mosc) 2021 Apr;86(4):496-505

National Medical Research Center for Cardiology, Ministry of Health of the Russian Federation, Moscow, 121552, Russia.

Antioxidant properties of rat galanin GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2 (Gal), N-terminal fragment of galanin (2-15 aa) WTLNSAGYLLGPHA (G1), and its modified analogue WTLNSAGYLLGPβAH (G2) were studied in vivo in the rat model of regional myocardial ischemia and reperfusion and in vitro in the process of Cu2+-induced free radical oxidation of human blood plasma low-density lipoproteins. Intravenous administration of G1, G2, and Gal to rats after ischemia induction reduced the infarction size and activities of the necrosis markers, creatine kinase-MB and lactate dehydrogenase, in blood plasma at the end of reperfusion. G1, G2, and Gal reduced formation of the spin adducts of hydroxyl radicals in the interstitium of the area at risk during reperfusion, moreover, G2 and Gal also reduced formation of the secondary products of lipid peroxidation in the reperfused myocardium. Read More

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Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome.

Stroke 2021 May 4:STROKEAHA120033547. Epub 2021 May 4.

Department of Neurological Surgery (S.L.M., A.K.C., T.K., S.B., B.C., K.C.M.-B., R.V.).

Background And Purpose: Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapidly in the rodent brain following focal ischemia. Read More

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miR-936 is Increased in Schizophrenia and Inhibits Neural Development and AMPA Receptor-Mediated Synaptic Transmission.

Schizophr Bull 2021 May 3. Epub 2021 May 3.

Section on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MD.

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression and play important roles in the development and function of synapses. miR-936 is a primate-specific miRNA increased in the dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia. The significance of miR-936 increase to schizophrenia is unknown. Read More

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The effect of prenatal temperature and PM exposure on birthweight: Weekly windows of exposure throughout the pregnancy.

Environ Int 2021 Apr 30;155:106588. Epub 2021 Apr 30.

Icahn School of Medicine at Mount Sinai, Department of Environmental Medicine and Public Health, New York, NY, USA.

Background: Birthweight is a strong predictor of normal growth, healthy development, and survival. Several studies have found associations between temperature, fine particulate matter (PM), and birth weight. However, the relevant timing of exposures varies between studies and is yet unclear. Read More

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Natural and synthetic antimicrobials reduce adherence of enteroaggregative and enterohemorrhagic Escherichia coli to epithelial cells.

PLoS One 2021 3;16(5):e0251096. Epub 2021 May 3.

Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Ciudad Universitaria, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.

Adherence of bacteria to the human intestinal mucosa can facilitate their internalization and the development of pathological processes. Escherichia coli O104:H4 is considered a hybrid strain (enteroaggregative hemorrhagic E. coli [EAHEC]), sharing virulence factors found in enterohemorrhagic (EHEC), and enteroaggregative (EAEC) E. Read More

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Preventing postnatal depression: a causal mediation analysis of a 20-year preconception cohort.

Philos Trans R Soc Lond B Biol Sci 2021 Jun 3;376(1827):20200028. Epub 2021 May 3.

Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria 3052, Australia.

Postnatal depression (PND) is common and predicts a range of adverse maternal and offspring outcomes. PND rates are highest among women with persistent mental health problems before pregnancy, and antenatal healthcare provides ideal opportunity to intervene. We examined antenatal perceived social support as a potential intervention target in preventing PND symptoms among women with prior mental health problems. Read More

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The role of muscular traction in the occurrence of skeletal relapse after advancement bilateral sagittal split osteotomy (BSSO): a systematic review.

Orthod Craniofac Res 2021 May 3. Epub 2021 May 3.

Department of Oral and Maxillofacial Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Purpose: The aim of this systematic review was 1) to determine the role of muscular traction in the occurrence of skeletal relapse after advancement BSSO, and 2) to investigate the effect of advancement BSSO on the perimandibular muscles.

Methods: This systematic review reports in accordance with the recommendations proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Electronic database searches were performed in the databases MEDLINE, Embase and Cochrane Library. Read More

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Generative Adversarial Networks Improve the Reproducibility and Discriminative Power of Radiomic Features.

Radiol Artif Intell 2020 May 27;2(3):e190035. Epub 2020 May 27.

Service of Radiology, Department of Diagnostics, Geneva University Hospital, Rue Gabrielle Perret-Gentil 4, 1211 Geneva 14, Switzerland (S.M., J.H., S.P.M., X.M.); Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland (S.M., J.H., M.G.P., S.P.M., D.V.D.V., X.M.); and Institute of Bioengineering/Center for Neuroprosthetics, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (S.M., M.G.P., D.V.D.V.).

Purpose: To assess the contribution of a generative adversarial network (GAN) to improve intermanufacturer reproducibility of radiomic features (RFs).

Materials And Methods: The authors retrospectively developed a cycle-GAN to translate texture information from chest radiographs acquired using one manufacturer (Siemens) to chest radiographs acquired using another (Philips), producing fake chest radiographs with different textures. The authors prospectively evaluated the ability of this texture-translation cycle-GAN to reduce the intermanufacturer variability of RFs extracted from the lung parenchyma. Read More

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Accelerated vaccine rollout is imperative to mitigate highly transmissible COVID-19 variants.

EClinicalMedicine 2021 May 25;35:100865. Epub 2021 Apr 25.

Center for Infectious Disease Modeling and Analysis (CIDMA), Yale School of Public Health, New Haven, CT, USA.

Background: More contagious variants of SARS-CoV-2 have emerged around the world, sparking concerns about impending surge in cases and severe outcomes. Despite the development of effective vaccines, rollout has been slow. We evaluated the impact of accelerated vaccine distribution on curbing the disease burden of novel SARS-CoV-2 variants. Read More

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The Antibacterial Effects of Supermolecular Nano-Carriers by Combination of Silver and Photodynamic Therapy.

Front Chem 2021 15;9:666408. Epub 2021 Apr 15.

The Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, The First Affiliated Hospital of Guangzhou Medical University and the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

The over-use of antibiotics has promoted multidrug resistance and decreased the efficacy of antibiotic therapy. Thus, it is still in great need to develop efficient treatment strategies to combat the bacteria infection. The antimicrobial photodynamic therapy (aPDT) and silver nanoparticles have been emerged as effective antibacterial methods. Read More

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Eltrombopag Dose Adjustment During Infection-Induced Thrombocytosis in a Patient With Chronic Idiopathic Thrombocytopenic Purpura.

Cureus 2021 Mar 29;13(3):e14166. Epub 2021 Mar 29.

Hematology and Oncology, Hamad General Hospital, Doha, QAT.

Idiopathic thrombocytopenic purpura (ITP) is an immune disorder in which antibodies attack platelets, leading to platelet destruction and increased bleeding risk. Standard treatment is to maintain a platelet count sufficient to mitigate the bleeding risk. First-line therapies include steroids and IV immunoglobulins, and second-line therapy includes thrombopoietin receptor agonists like eltrombopag in combination with other medications (e. Read More

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Leadless Left Ventricular Endocardial Pacing and Left Bundle Branch Area Pacing for Cardiac Resynchronisation Therapy.

Arrhythm Electrophysiol Rev 2021 Apr;10(1):45-50

School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

Cardiac resynchronisation therapy is an important intervention to reduce mortality and morbidity, but even in carefully selected patients approximately 30% fail to improve. This has led to alternative pacing approaches to improve patient outcomes. Left ventricular (LV) endocardial pacing allows pacing at site-specific locations that enable the operator to avoid myocardial scar and target areas of latest activation. Read More

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Predicting Tumor Cell Response to Synergistic Drug Combinations Using a Novel Simplified Deep Learning Model.

AMIA Annu Symp Proc 2020 25;2020:1364-1372. Epub 2021 Jan 25.

Institute for Informatics (I2), Washington University School of Medicine.

Drug combinations targeting multiple targets/pathways are believed to be able to reduce drug resistance. Computational models are essential for novel drug combination discovery. In this study, we proposed a new simplified deep learning model, for drug combination prediction. Read More

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January 2021

Leaving no one behind: a methodology for setting health inequality reduction targets for Sustainable Development Goal 3.

Rev Panam Salud Publica 2021 28;45:e63. Epub 2021 Apr 28.

Pan American Health Organization Washington, D.C. United States of America Pan American Health Organization, Washington, D.C., United States of America.

Objectives: To present a methodology for the simultaneous setting of quantitative targets that reflect both an improvement in the national average of an indicator for Sustainable Development Goal 3 (SDG3), as well as a reduction in its geographic inequality.

Methods: A five-step algorithm was developed: (a) calculate the national average annual percent change (AAPC) for an SDG3 indicator; (b) normatively define geographic strata from the subnational distribution of the indicator in a baseline year; (c) apply a proportional progressivity criterion to the AAPC to project the stratum-specific indicator value for the target year; (d) set the national target as the weighted average of the indicator in the subnational territorial units for the target year; and (e) set the inequality reduction targets by calculating the absolute and relative gaps between the bottom and top strata for the target year.

Results: The algorithm was applied to SDG indicator 3. Read More

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Elevated microRNA-21 Is a Brake of Inflammation Involved in the Development of Nasal Polyps.

Front Immunol 2021 15;12:530488. Epub 2021 Apr 15.

Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: CRSwNP is an inflammatory disease but the mechanism is not yet fully understood. MiR-21, a member of miRNAs, has been reported to play roles in mediating inflammation. However, the expression of miR-21 and its role in patients with CRSwNP remain elusive. Read More

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Digital Detectives: Websleuthing Reduces Eyewitness Identification Accuracy in Police Lineups.

Front Psychol 2021 15;12:640513. Epub 2021 Apr 15.

School of Computing & Communications, The Open University, Milton Keynes, United Kingdom.

Eyewitnesses to crimes sometimes search for a culprit on social media before viewing a police lineup, but it is not known whether this affects subsequent lineup identification accuracy. The present online study was conducted to address this. Two hundred and eighty-five participants viewed a mock crime video, and after a 15-20 min delay either (i) viewed a mock social media site including the culprit, (ii) viewed a mock social media site including a lookalike, or (iii) completed a filler task. Read More

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The Clinical and Angiographic Outcomes of Postdilation after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

J Interv Cardiol 2021 9;2021:6699812. Epub 2021 Apr 9.

Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.

Objective: The effect of postdilation in patients with acute coronary syndrome is still controversial. This meta-analysis aims to analyze the clinical and angiographic outcomes of postdilation after percutaneous coronary intervention in patients with acute coronary syndrome.

Methods: PubMed, Embase, the Cochrane Library, Web of Science, CNKI, and Wangfang databases were searched from inception to August 30, 2020. Read More

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Hepatitis E virus: Whole genome sequencing as a new tool for understanding HEV epidemiology and phenotypes.

J Clin Virol 2021 Jan 27;139:104738. Epub 2021 Jan 27.

MRC-University of Glasgow Centre for Virus Research, Glasgow, UK; Microbiology Department, Laboratoire National de Sante, Dudelange, Luxembourg. Electronic address:

Hepatitis E Virus (HEV) is emerging as a public health concern across Europe and tools for complete genome data to aid epidemiological and virulence analysis are needed. The high sequence heterogeneity observed amongst HEV genotypes has restricted most analyses to subgenomic regions using PCR-based methods, which can be unreliable due to poor primer homology. We designed a panel of custom-designed RNA probes complementary to all published HEV full genome NCBI sequences. Read More

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January 2021

Artesunate restores the levels of inhibitory synapse proteins and reduces amyloid-β and C-terminal fragments (CTFs) of the amyloid precursor protein in an AD-mouse model.

Mol Cell Neurosci 2021 Apr 29:103624. Epub 2021 Apr 29.

Institute of Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany. Electronic address:

Alzheimer's disease (AD) is the most frequent form of dementia, characterized histopathologically by the formation of amyloid plaques and neurofibrillary tangles in the brain. Amyloid β-peptide (Aβ) is a major component of amyloid plaques and is released together with carboxy-terminal fragments (CTFs) from the amyloid precursor protein (APP) through proteolytic cleavage, thought to contribute to synapse dysfunction and loss along the progression of AD. Artemisinins, primarily antimalarial drugs, reduce neuroinflammation and improve cognitive capabilities in mouse models of AD. Read More

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Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: A mathematical modelling analysis.

Vaccine 2021 Apr 8. Epub 2021 Apr 8.

MRC Centre for Global Infectious Disease Analysis, and the Abdul Latif Jameel Institute for Disease and Emergency Analytics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, United Kingdom. Electronic address:

The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extend a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. Read More

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Targeting a highly conserved domain in bacterial histidine kinases to generate inhibitors with broad spectrum activity.

Curr Opin Microbiol 2021 Apr 28;61:107-114. Epub 2021 Apr 28.

Department of Medicinal Chemistry, University of Minnesota, 2308 Harvard Street SE, Minneapolis, MN 55454, United States; Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN 55455, United States; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 321 Church St SE, Minneapolis, MN 55454, United States; Department of Pharmacology, University of Minnesota, 321 Church St SE, Minneapolis, MN 55454, United States. Electronic address:

With the rise in antimicrobial resistance and the dearth of effective strategies to combat this threat, the development of novel therapies is of utmost importance. Targeting of bacterial signaling through their the two-component systems (TCSs) may be a viable strategy. TCSs are comprisesd of a sensory histidine kinase (HK), of which a bacterium can have up to 160 distinct proteins, and a cognate response regulator (RR). Read More

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Plasma membrane targeted photodynamic O economizer for hypoxic tumor therapy.

Biomaterials 2021 Apr 26;273:120854. Epub 2021 Apr 26.

Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, PR China. Electronic address:

The development of photodynamic therapy (PDT) is severely limited by short half-life of singlet oxygen (O) and the hypoxic microenvironment. In this work, a plasma membrane targeted photodynamic O economizer (designated as P-POE) is developed to improve the subcellular delivery of photosensitizers and alleviate the tumor hypoxia for enhanced PDT effect. After self-assembly into nanomicelles, P-POE has a relatively high stability and a favorable photochemical performance, which are conducive to boosting the O production. Read More

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A comprehensive strategy to clarify the pharmacodynamic constituents and mechanism of Wu-tou Decoction based on the constituents migrating to blood and their in vivo process under pathological state.

J Ethnopharmacol 2021 Apr 28:114172. Epub 2021 Apr 28.

State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Provincal Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China; University of Science and Technology of China, 230026, Hefei, China. Electronic address:

Ethnopharmacological Relevance: As a traditional Chinese medicine (TCM) formula, Wu-tou decoction has been used for treating rheumatoid arthritis (RA) for more than a thousand years. Identifying pharmacodynamic constituents (PCs) of WTD and exploring their in vivo process are very meaningful for promoting the modernization of TCM. However, the pathological state might change this process. Read More

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Hyaluronic acid- Graphene Quantum Dot Nanocomposite: Potential Target Drug Delivery and Cancer Cell Imaging.

Biotechnol Appl Biochem 2021 May 1. Epub 2021 May 1.

Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Nowadays, the use of nanoparticle-based drug delivery systems has received much more attention. In this regard, here, Graphene quantum dots (GQD) were used as drug carriers as well as imaging agents for cancer cells. In order to optimize the dose of the drug and reduce its side effects for healthy cells, Hyaluronic acid was decorated on the surface of GQD to target cancer cells. Read More

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Testing the Effects of Disease-Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial.

ACR Open Rheumatol 2021 May 1. Epub 2021 May 1.

Columbia University, Vagelos College of Physicians & Surgeons, New York, New York.

Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18-Fluorodeoxyglucose [ F-FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Read More

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[Effect of electroacupuncture at Zusanli (ST36) and Zhongwan (CV12) on intestinal nutritional feeding intolerance in patients with severe acute pancreatitis].

Zhen Ci Yan Jiu 2021 Apr;46(4):312-7

Department of Emergency, Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, Hebei Province, China.

Objective: To observe the effect of electroacupuncture (EA) of Zusanli(ST36) and Zhongwan (CV12) on intestinal nutritional feeding intolerance in patients with severe acute pancreatitis (SAP).

Methods: A total of 68 SAP patients (hospitalized from January of 2018 to December of 2019 in Cangzhou Hospital of Integrated Medicine) were randomly divided into control and EA groups (=34 cases in each group). All patients of the two groups received the same early enteral nutrition treatment through nasojejunal tube. Read More

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