Publications by authors named "Zhang Lin"

4,599 Publications

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Linking peripheral CD8 single-cell transcriptomic characteristics of mood disorders underlying with the pathological mechanism.

Clin Transl Med 2021 Jul;11(7):e489

Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1002/ctm2.489DOI Listing
July 2021

Assessment of the reporting quality of randomised controlled trials of massage.

Chin Med 2021 Jul 28;16(1):64. Epub 2021 Jul 28.

Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, 307 Room, Jockey Club School of Chinese Medicine Building, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, HKSAR, China.

Objective: To assess the reporting quality of randomised controlled trials (RCTs) of massage, particularly whether necessary elements related to massage interventions were adequately reported.

Methods: A total of 8 electronic databases were systematically searched for massage RCTs published in English and Chinese from the date of their inception to June 22, 2020. Quality assessment was performed using three instruments, namely the CONSORT (Consolidated Standards of Reporting Trials) 2010 Checklist (37 items), the CONSORT Extension for NPT (Nonpharmacologic Treatments) 2017 checklist (18 items), and a self-designed massage-specific checklist (16 items) which included massage rationale, intervention and control group details. Descriptive statistics were additionally used to analyse the baseline characteristics of included trials.

Results: A total of 2,447 massage RCTs were identified, of which most (96.8%) were distributed in China. For the completeness of CONSORT, NPT Extension, and massage-specific checklists, the average reporting percentages were 50%, 10% and 45%, respectively. Of 68 assessed items in total (exclusion of 3 repeated items on intervention), 42 were poorly presented, including 18 CONSORT items, 15 NPT items, and 9 massage-specific items. Although the overall quality of reporting showed slightly improvement in articles published after 2010, the international (English) journals presented a higher score of the CONSORT and NPT items, while the Chinese journals were associated with the increased score of massage-specific items.

Conclusion: The quality of reporting of published massage RCTs is variable and in need of improvement. Reporting guideline "CONSORT extension for massage" should be developed.
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http://dx.doi.org/10.1186/s13020-021-00475-6DOI Listing
July 2021

Suppressing Syndecan-1 Shedding to Protect Against Renal Ischemia/Reperfusion Injury by Maintaining Polarity of Tubular Epithelial Cells.

Shock 2021 Jul 26. Epub 2021 Jul 26.

Department of Nephrology, Zhongshan Hospital, Fudan University; Shanghai Institute of Kidney Disease and Dialysis (SIKD), Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai Medical Center of Kidney Disease, Shanghai, P.R China Human Phenome Institute, Fudan University, 825 Zhangheng Road, Shanghai 201203, China.

Abstract: Syndecan-1 (SDC-1), a type of heparan sulfate proteoglycan on the surface of epithelial cells, is involved in maintaining cell morphology. Loss of cell polarity constitutes the early stage of ischemic acute kidney injury (AKI). This study investigated the role of SDC-1 shedding in ischemia/reperfusion (I/R)-induced AKI and the underlying mechanisms. Levels of the shed SDC-1 in the serum were measured with ELISA 12 h and 24 h after reperfusion in renal I/R model mice. Na+/K+-ATPase-α1 expression was evaluated using western blotting in vivo and immunofluorescence in hypoxia/reoxygenation (H/R) cysts. Renal tubular epithelial cell apoptosis was measured using TUNEL and flow cytometry in vitro. Furthermore, plasma syndecan-1(pSDC-1) levels were measured in patients at the time of anesthesia resuscitation after cardiac surgery. We found that shed SDC-1 levels increased and Na+/k+-ATPase-α1 expression decreased after H/R in the three-dimensional (3D) tubular model, and this state was exacerbated with extended period of hypoxia. After the inhibition of SDC-1 shedding by GM6001, SDC-1 and Na+/k+-ATPase-α1 expression was restored, while H/R-induced apoptosis was decreased. In vivo, SDC-1 shedding was induced by renal I/R and was accompanied with a loss of renal tubular epithelial cell polarity and increased apoptosis. GM6001 pretreatment protected against I/R injury by alleviating the disruption of cell polarity and apoptosis. pSDC-1 levels were significantly higher in AKI patients than in non-AKI patients. ROC curve showed that the accuracy of pSDC-1 for AKI prediction was 0.769. In conclusion, inhibition of I/R-induced SDC-1 shedding could contribute to renal protection by restoring the loss of cell polarity and alleviating apoptosis in tubular epithelial cells.
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http://dx.doi.org/10.1097/SHK.0000000000001838DOI Listing
July 2021

Species richness and endemism pattern of Fagaceae in Southwest China and their environmental interpretation.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2290-2300

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.

How to accurately model species macro-richness patterns and endemism centers is a key focus of biodiversity conservation efforts and a hot biogeographical topic. Southwest China is one of regions with high Fagaceae species richness, the species diversity patterns and driving mechanisms are unclear. In this study, the distribution pattern of species richness (SR), weighted endemism (WE), and corrected weighted endemism (CWE) indices were estimated based on 7258 occurrence points of 161 Fagaceae species in Southwest China using both occurrence-to grid method and species distribution model (SDM). We used the spatial autoregressive (SAR) model to analyze the relationship between diversity indices and environmental factors. Overall, the three SDM-simulated diversity indices were more continuous in values than that of the occurrence-to grid method, though the distributions of those indices obtained by the two methods were similar. The areas with high SR value were mainly distributed in the south edge of Yunnan, north Guangxi and southwest Guangxi (62-89 species). The maximum of WE concentrated in south Yunnan and west Guangxi (1.77-5.02). The highest CWE (0.07-0.17) was found in southeast Tibet, Qinling-Daba Mountains, southwest Guangxi, and southeast Yunnan. The SAR models showed significant effect of precipita-tion in the driest month, standard deviations of seasonal temperature, altitude range and soil organic carbon content on SR. The effects of precipitation in the driest month, standard deviations of seaso-nal temperature, potential evaporation and altitude range on the WE were significant. The precipitation in the driest month, standard deviations of seasonal temperature, historical temperature change, coefficient of variation of enhanced vegetation index and altitude variation had significant effects on the CWE. The of SAR model for SR, WE and CWE was 0.857, 0.733, 0.593, respectively, being higher than that of ordinary least squares (OLS) (=0.689, 0.425, 0.422). In conclusion, water availability, climate seasonality, habitat heterogeneity, historical climate change and soil condition were the most important factors limiting the distribution of SR and WE of Fagaceae in Southwest China. The SR and WE centers of Fagaceae were located in south and southeast Yunnan, southwest Guangxi, west Guangxi, Qinling-Daba Mountains, and southeast Tibet, where should be adequately protected.
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http://dx.doi.org/10.13287/j.1001-9332.202107.012DOI Listing
July 2021

Development of a dual-labeled, hydrolysis probe-based, real-time quantitative PCR assay for detection of both genotypes of duck circovirus-1 (DuCV-1) and DuCV-2.

Virus Genes 2021 Jul 26. Epub 2021 Jul 26.

China Animal Health and Epidemiology Center, Qingdao, Shandong, China.

In this study, we developed a real-time quantitative polymerase chain reaction (qPCR) assay based on a dual-labeled hydrolysis probe to simultaneously detect both duck circovirus (DuCV) 1 and DuCV-2. The reproducibility, sensitivity and specificity of the primer set and probe were evaluated using other duck pathogens. The detection limit was 20 copies per µL. The intra-assay coefficients of variation (CVs) were ≤ 0.73% and the inter-assay CVs were ≤ 1.89%. No cross-reaction occurred with other duck pathogens. In addition, the qPCR assay was successfully applied to the simultaneous detection of DuCV-1 and DuCV-2 in clinical field samples. Therefore, this assay will be useful for laboratory diagnosis and epidemiological field studies of DuCV.
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http://dx.doi.org/10.1007/s11262-021-01862-9DOI Listing
July 2021

N-methyladenosine demethylase ALKBH5 suppresses malignancy of esophageal cancer by regulating microRNA biogenesis and RAI1 expression.

Oncogene 2021 Jul 26. Epub 2021 Jul 26.

Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

N-Methyladenosine (mA) is the most prevalent epigenetic RNA modification and is vital in regulating malignancies. The roles of mA modifiers on noncoding RNAs have not been fully investigated in esophageal cancer. By screening all mA modifiers, ALKBH5 was the most potent member related to patient outcomes and suppressing esophageal cancer malignancy in cell and animal models. It demethylated pri-miR-194-2 and inhibited miR-194-2 biogenesis through an mA/DGCR8-dependent manner. RAI1, previously considered as a circadian clock transcriptional regulator, was the main target of miR-194-2. It enhanced transcription of Hippo pathway upstream genes by binding to their 3'UTR and suppressed YAP/TAZ nuclear translocation. The ALKBH5/miR-194-2/RAI1 axis was also validated in clinical samples. In addition, the increased malignancy by low ALKBH5 was abolished by the YAP inhibitor verteporfin. Our findings uncover a critical role of ALKBH5 in miRNAs biogenesis and provide novel insight for developing treatment strategies in esophageal cancer.
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http://dx.doi.org/10.1038/s41388-021-01966-4DOI Listing
July 2021

Electrochemical Oxidative C3 Acyloxylation of Imidazo[1,2-]pyridines with Hydrogen Evolution.

Org Lett 2021 Jul 23. Epub 2021 Jul 23.

National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, Jiangxi 330022, P. R. China.

The C3-functionalized imidazo[1,2-]pyridines are versatile nitrogen-fused heterocycles; however, the methods for the C3 acyloxylation of imidazo[1,2-]pyridines have never been reported. Herein we demonstrate the electrochemical oxidative C3 acyloxylation of imidazo[1,2-]pyridines for the first time. Notably, by using electricity, the electrochemical oxidative C3 acyloxylation of imidazo[1,2-]pyridines was carried out under mild conditions. Moreover, in addition to aromatic carboxylic acids, alkyl carboxylic acids were also competent substrates.
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http://dx.doi.org/10.1021/acs.orglett.1c02032DOI Listing
July 2021

Predictive value of cytoplasmic granulation patterns during in vitro fertilization in metaphase II oocytes: part II, donor oocyte cycles.

Fertil Steril 2021 Jul 19. Epub 2021 Jul 19.

The Center for Human Reproduction, New York, New York; The Foundation for Reproductive Medicine, New York, New York; Stem Cell Biology and Molecular Embryology Laboratory, Rockefeller University, New York, New York; Department of Obstetrics and Gynecology, Vienna University School of Medicine, Vienna, Austria.

Objective: To determine whether the ooplasm granulation patterns of donor oocytes, like those of oocytes from poor-prognosis patients, are predictive of in vitro fertilization (IVF) outcomes.

Design: Retrospective cohort study.

Setting: Academically affiliated private clinical infertility and research center.

Patient(s): 770 fresh and 381 vitrified-thawed metaphase II oocytes from young donors (aged 21.0-34.6 years) used for IVF during 2017-2020.

Intervention(s): Determination of granulation patterns in every oocyte during intracytoplasmic sperm injection as fine, central, uneven, dispersed, and peripheral (thawed only).

Main Outcome Measure(s): Fertilization, pregnancy, and live birth rates in fresh and thawed donor oocytes. Both overall and known-outcome analyses were performed for pregnancy and live birth.

Result(s): In fresh donor oocytes, 2 pronuclei rates trended down from 96.1% to 90.2%, 88.9%, and 69.7% from fine to central, uneven, and dispersed granulations; overall pregnancy rates trended down from 50.4% to 29.0%, 17.7%, and 6.9%, as well as live birth rates (43.4%, 21.6%, 12.5%, and 6.4%), from fine to uneven, central, and dispersed granulations. Known pregnancy and known-live birth analyses showed similar findings. Thawed donor oocytes demonstrated similar trends in differences in fertilization, pregnancy, and live birth analyses with relatively worse outcomes. Peripheral granulation, unique to vitrification and thawing, always demonstrated the worst IVF outcomes. Moreover, granulation patterns were relatively disassociated from embryo morphological grades in fresh and largely disassociated in thawed donor oocytes.

Conclusion(s): Predictive values of oocyte granulation patterns for fertilization, pregnancy, and live birth in IVF cycles are even more pronounced in young donors than results in older poor-prognosis patients, further supporting integration of oocyte granulation patterns into embryo selection.
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http://dx.doi.org/10.1016/j.fertnstert.2021.06.026DOI Listing
July 2021

Protein Binding and Population Pharmacokinetics of Dexmedetomidine after Prolonged Infusions in Adult Critically Ill Patients.

Clin Ther 2021 Jul 22. Epub 2021 Jul 22.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.

Purpose: Dexmedetomidine (DEX) is a highly selective α-adrenoceptor agonist with high protein binding of 94%. Critical illness may affect protein binding and the pharmacokinetic (PK) parameters of many drugs, including DEX. In critically ill patients receiving prolonged infusions of DEX, there is little information documenting the relationship between key pathophysiologic factors and DEX protein binding or PK parameters. The purpose of this study was to characterize the protein binding and PK profile of prolonged DEX infusion in critically ill patients.

Methods: Critically ill, adult intensive care unit patients at a university hospital in Hong Kong were studied. The association between the pathophysiologic changes of critical illness and protein binding was evaluated using a generalized estimating equation. A population pharmacokinetic model to establish the PK profile of DEX was developed, and key pathophysiologic covariate effects of severity of illness, organ dysfunction measures, and altered protein binding on DEX PK parameters in this critically ill population were evaluated.

Findings: A total of 22 critically ill patients and 1 healthy control were included. Mean protein binding of DEX in the critically ill patients was 90.4% (95% CI, 89.1-91.7), which was 4% lower than that in the healthy control. The PK data were adequately described by a 2-compartment model. The estimated population mean (relative standard error [RSE]) values of systemic clearance (CL), volume of distribution of the central compartment (V2), intercompartmental clearance (Q), and V in the peripheral compartment (V3) were 38.6 (11.7) L/h, 32.1 (46.1) L, 114.5 (58.3) L/h and 95.1 (30.6) L, respectively. The corresponding estimated interindividual variability expressed as CV% (RSE) was 52.4 (23.8) for CL, 172.9 (19.3) for V2, 123.7 (33.7) for Q, and 106 (39.9) for V3. No significant explanatory pathophysiologic covariates were identified.

Implications: Although a marginally significant reduction of protein binding in critically ill patients was demonstrated, the magnitude of the difference was unlikely to be of clinical significance. Higher alanine aminotransferase concentration was associated with decreased protein binding. No significant pathophysiologic covariates were associated with the observed PK parameters. The high interindividual variability of PK parameters supports the current practice of dose titration to ensure the desired clinical effects of DEX infusion in the intensive care unit setting.
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http://dx.doi.org/10.1016/j.clinthera.2021.06.004DOI Listing
July 2021

Polymer-Functionalized Upconversion Nanoparticles for Light/Imaging-Guided Drug Delivery.

Biomacromolecules 2021 Jul 25. Epub 2021 Jul 25.

Cluster for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales (UNSW Sydney), Sydney NSW 2052, Australia.

The strong upconversion luminescence (UCL) of upconversion nanoparticles (UCNPs) endows the nanoparticles with attractive features for combined imaging and drug delivery. UCNPs convert near-infrared (NIR) light into light of shorter wavelengths such as light in the ultraviolet (UV) and visible regions, which can be used for light-guided drug delivery. Although light-responsive drug delivery systems as such have been known for many years, their application in medicine is limited, as strong UV-light can be damaging to tissue; moreover, UV light will not penetrate deeply into the skin, an issue that UCNPs can now address. However, UCNPs, as obtained after synthesis, are usually hydrophobic and require further surface functionalization to be stable in plasma. Polymers can serve as versatile surface coatings, as they can provide good colloidal stability, prevent the formation of a protein corona, provide a matrix for drugs, and be stimuli-responsive. In this Review, we provide a brief overview of the most recent progress in the synthesis of UCNPs with different shapes/sizes. We will then discuss the purpose of polymer coating for drug delivery before summarizing the strategies to coat UCNPs with various polymers. We will introduce the different polymers that have so far been used to coat UCNPs with the purpose to create a drug delivery system, focusing in detail on light-responsive polymers. To expand the application of UCNPs to allow photothermal therapy or magnetic resonance imaging (MRI) or to simply enhance the loading capacity of drugs, UCNPs were often combined with other materials to generate multifunctional nanoparticles such as carbon-based NPs and nanoMOFs. We then conclude with a discussion on drug loading and release and summarize the current knowledge on the toxicity of these polymer-coated UCNPs.
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http://dx.doi.org/10.1021/acs.biomac.1c00669DOI Listing
July 2021

Overexpression of the Autoimmune Risk Variant LYP-620W Fails to Restrain Human CD4 T Cell Activation.

J Immunol 2021 Aug 23;207(3):849-859. Epub 2021 Jul 23.

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL; and

A missense mutation (R620W) of protein tyrosine phosphatase nonreceptor type 22 (), which encodes lymphoid-tyrosine phosphatase (LYP), confers genetic risk for multiple autoimmune diseases including type 1 diabetes. LYP has been putatively demonstrated to attenuate proximal T and BCR signaling. However, limited data exist regarding expression within primary T cell subsets and the impact of the type 1 diabetes risk variant on human T cell activity. In this study, we demonstrate endogenous is differentially expressed and dynamically controlled following activation. From control subjects homozygous for the nonrisk allele, we observed 2.1- ( < 0.05) and 3.6-fold ( < 0.001) more transcripts in resting CD4 memory and regulatory T cells (Tregs), respectively, over naive CD4 T cells, with expression peaking 24 h postactivation. When LYP was overexpressed in conventional CD4 T cells, TCR signaling and activation were blunted by LYP-620R ( < 0.001) but only modestly affected by the LYP-620W risk variant versus mock-transfected control, with similar results observed in Tregs. LYP overexpression only impacted proliferation following activation by APCs but not anti-CD3- and anti-CD28-coated microbeads, suggesting LYP modulation of pathways other than TCR. Notably, proliferation was significantly lower with LYP-620R than with LYP-620W overexpression in conventional CD4 T cells but was similar in Treg. These data indicate that the LYP-620W variant is hypomorphic in the context of human CD4 T cell activation and may have important implications for therapies seeking to restore immunological tolerance in autoimmune disorders.
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http://dx.doi.org/10.4049/jimmunol.2000708DOI Listing
August 2021

Simultaneous determination of first-line anti-tuberculosis drugs and one metabolite of isoniazid by liquid chromatography/tandem mass spectrometry in patients with human immunodeficiency virus-tuberculosis coinfection.

Heliyon 2021 Jul 9;7(7):e07532. Epub 2021 Jul 9.

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

The incidence rate of tuberculosis (TB) in patients with human immunodeficiency virus (HIV) infection is 26 times higher than that in other patients. Patients with both infections require long-term combination therapy, which increases therapy complexity and might lead to serious adverse reactions and drug-drug interactions. To optimize therapy for patients with HIV and TB coinfection, we developed an ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify four anti-tuberculosis drugs and one isoniazid (INH) metabolite. Blood samples (n = 32) from 16 patients with HIV and TB coinfection were collected. Plasma protein precipitation with acetonitrile was followed by a hydrazine reaction between INH and cinnamaldehyde (CA) to produce phenylhydrazone (CA-INH) and dilution with heptafluorobutyric acid. The separation was performed on an Acquity UHPLC HSS T3 1.8 μm column (2.1 × 100 mm, Waters) with a mobile phase consisting of 10 mmol/L ammonium formate (pH = 4) in water (solvent A) and 0.1 % formic acid in methanol (solvent B) in a gradient elution. The compounds were detected using a positive multiple reaction monitoring model. INH, acetyl-INH (AC-INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA) showed good linear relationships in their quantitative ranges, with lower limits of quantification of 48, 192, 200, 96, and 480 ng/mL, respectively. The inter- and intraday precision was within 15 %, and the accuracy was between 85 % and 115 %. The mean plasma concentrations of INH, AC-INH, RIF, EMB, and PZA in patients were 1990.23 (24-16 600), 863.06 (96-2880), 3507.05 (229-9800), 808.10 (149-2130), and 18 838.33 (240-34 800) ng/mL, respectively. The plasma concentrations detected in the 16 patients were lower than the targeted concentrations in HIV-negative TB patients. In summary, we developed a simple UHPLC-MS/MS method for simultaneous quantification of first-line TB drugs, and successfully applied it for therapeutic drug monitoring in patients with HIV and TB coinfection. This method will facilitate monitoring of TB drugs in the future.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282971PMC
July 2021

Personalized 0D-1D multiscale hemodynamic modeling and wave dynamics analysis of cerebral circulation for an elderly patient with dementia.

Int J Numer Method Biomed Eng 2021 Jul 22:e3510. Epub 2021 Jul 22.

Graduate School of Engineering, Chiba University, Chiba, Japan.

Senile dementia is associated with pronounced alterations in cerebral circulation. A fundamental understanding of intracranial hemodynamics and wave dynamics is essential for assessing dementia risk. Recent findings suggest that higher carotid artery wave intensity (WI) can predict future cognitive impairments in the elderly. However, wave power (WP) is more advantageous for assessing the risk of cognitive impairment and dementia because of its conservative form, which allows quantification of detailed WP distribution among the entire cerebrovascular network. Unfortunately, intracranial hemodynamics and wave dynamics in elderly patients with dementia remain poorly understood due to ethical issues and technical challenges. In this paper, we proposed a novel and easily achievable personalized methodology for the 0D-1D model of cerebral circulation using widely available clinical data on transcranial Doppler ultrasonography velocity, cerebral artery anatomy from magnetic resonance imaging, and brachial artery pressure. Using the proposed model, we simulated the cerebral blood flows and compared the wave dynamics between a healthy elderly subject and one living with dementia. Moreover, we performed a variance-based global sensitivity analysis to quantify the model-predicted WI and WP sensitivity to the uncertainties of model inputs. This provided more precise information for model personalization and further insights into the wave dynamics of cerebral circulation. In conclusion, the proposed personalized model framework provides a practical approach for patient-specific modeling and WI/WP analysis of cerebral circulation through noninvasive clinical data. The wave dynamics features of higher WI and lower WP in cerebral arteries may be an invaluable biomarker for assessing dementia risk. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/cnm.3510DOI Listing
July 2021

Retrospective analysis of 23 Chinese children with congenital hyperinsulinemia undergoing pancreatectomy.

Endokrynol Pol 2021 Jul 22. Epub 2021 Jul 22.

Genetics and Metabolism Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health.

Objectives: The clinical data of 23 cases of congenital hyperinsulinemia (CHI) treated by pancreatectomy were retrospectively analyzed, and the therapeutic effect and prognosis of pancreatectomy in the treatment of CHI were discussed.

Methods: A total of 23 Chinese children with CHI who had undergone pancreatectomy between February 2002 and March 2020 were selected as the study objects. The clinical data, the results of the 18Fluoro-L-3-4 dihydroxyphenylalanine positron emission tomography/computerized tomography (18F-DOPA PET/CT) scanning, and the diagnosis, treatment, and follow-up were analyzed retrospectively.

Results: Among the 23 cases, 14 patients were diagnosed with focal-type CHI via a 18F-DOPA PET/CT scan prior to the operation, with the lesions removed via partial pancreatectomy. After the operation, ten patients (71%) had normal blood glucose levels, while frequent feeding was required in four patients (29%) to control the hypoglycemia. Three cases were diagnosed as diffuse-type CHI via preoperative scanning, two of which were treated by subtotal pancreatectomy, with one returning to normal blood glucose levels, while a subcutaneous injection of octreotide was required in the other to prevent hypoglycemia. The other case was treated by near-total pancreatectomy, and the blood glucose level was normal following the operation. The remaining six cases were not diagnosed via the pancreatic scanning prior to the operation due to the limitation of certain conditions. Here, pancreatectomy was performed directly due to severe hypoglycemia.

Conclusions: 18F-DOPA PET/CT scanning was a reliable method for determining the histological type and localizing the lesion before the operation. Partial pancreatectomy for focal-type CHI had a high cure rate. In the children with diffuse-type CHI, the surgical methods were more complex and the therapeutic effect and the prognosis were also different.
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http://dx.doi.org/10.5603/EP.a2021.0066DOI Listing
July 2021

Synergistic chromium(VI) reduction and phenol oxidative degradation by FeS/Fe and persulfate.

Chemosphere 2021 Oct 26;281:130957. Epub 2021 May 26.

Department of Environmental Engineering, School of Metallurgy and Environment, Central South University, Lushan South Road 932, Changsha, Hunan, 410083, PR China; Chinese National Engineering Research Center for Control & Treatment of Heavy Metal Pollution, Changsha, 410083, PR China. Electronic address:

It is a challenge to simultaneously treat the combined pollutants of chromium(VI) (Cr(VI)) and organics (such as phenol) in wastewater. Here, a stable and efficient redox system based on FeS sulfidated zero valent iron (FeS/Fe) and persulfate (PS) was developed to synchronously remove Cr(VI) and phenol. 100% of phenol (10 mg/L) was oxidized in 10 min and Cr(VI) (20 mg/L) was completely reduced to Cr(III) in 90 min in the FeS/Fe+PS system with a pH range of 3.0-9.0, respectively. phenol was selectively oxidized without re-oxidizing Cr(III) in such system. The surface-bound Fe was the major reactive species to synchronously reduce Cr(VI) and oxidize phenol. The mechanisms were elucidated that the phenol degradation was accelerated by the generated Cr(III) complexing with its products, and that SO, whose production speed was accelerated by the PS activation to oxidize phenol and FeS, was conductive to corrode Fe to regenerate the surface-bound Fe for reducing Cr(VI) and oxidizing phenol. It is potential to develop a high-performance and large-scaled FeS/Fe-based redox platform to remediate the complex pollution of Cr(VI) and organics.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130957DOI Listing
October 2021

Occurrence of postharvest snow rot caused by on Asian ginseng in China.

Plant Dis 2021 Jul 20. Epub 2021 Jul 20.

Chinese Academy of Agricultural Sciences, 12661, Institute of Special Wild Economic Animal and Plant Science, Chinese Academy of Agricultural Sciences, Changchun, Jilin, China;

Asian ginseng () is a valuable medicinal plant that is commercially cultivated in China. A long postharvest storage period is required before ginseng is processed. From October 2019 to May 2020, snow rot was observed on the roots of 4- and 5-year-old fresh ginseng stored in three cold storage facilities located in Tonghua and Changbai cities in northeastern China, which are the most important regions for Asian ginseng production. We sampled 1,000 ginseng roots from the three cold storage facilities, and the average disease incidence was 21%. Initially, sparse hyphae and microsclerotia appeared on the root epidermis. Lesions gradually softened and the epidermis detached easily. Multiple infected sites slowly converged, resulting in the formation of a dense complex of multiple sclerotia and thick hyphae on the surface of the ginseng root as well as internal decay. The infection eventually spread to the adjacent ginseng roots (Fig. 1). Sixteen diseased ginseng roots were collected and then sclerotia were removed from the root surface, immersed in 1% NaClO for 2 min, rinsed three times with sterile water, and placed on potato dextrose agar (PDA) containing streptomycin (40 μg/mL) in Petri dishes. After a 3-day incubation at 20 °C in darkness, 22 suspected Sclerotinia isolates were obtained. Isolates SN1 and SN2 were randomly selected for identification. On PDA, fast-growing colonies produced white, sparse, powdery, and cotton-like aerial mycelia, and the reverse side showed the same color (Fig. 2). Small and white sclerotial primordia formed 3 days later and a ring of sclerotia was detected at the plate periphery. At 7 to 10 days after incubation, the mature sclerotia were black, spherical-to-subspherical, and elongated or fused to form irregular shapes. Each Petri dish produced 55-65 sclerotia, measuring 1.1 × 1.2 to 3.2 × 3.9 mm (n = 100). The sclerotia were firmly attached to the agar surface. The isolates were initially identified as sp. (Saito 1997). After sequencing the nuclear ribosomal internal transcribed spacer region (MW927134 and MW927135) and the β-tubulin gene (MW929179 and MW929180) (White et al. 1990; Glass and Donaldson 1995), BLAST searches revealed 100% homology with JX262268 and JX296007 of the published strain KGC-S0601, respectively. The pathogenicity of the two isolates was tested using detached ginseng roots. Briefly, healthy roots were washed, surface-disinfested with 75% alcohol, and rinsed with sterile water. Mycelial plugs (5 mm diameter) removed from the margin of actively growing colonies on PDA were placed on the ginseng roots. For each isolate, four roots were inoculated, with two plugs per root. Additionally, PDA plugs without mycelia were used as the negative control. The roots were placed in a fresh-keeping box at 20 °C in darkness and evaluated after 7 days. The pathogenicity test was repeated twice. The symptoms on the inoculated roots were the same as those observed on the roots during cold storage, whereas the control roots remained symptomless. The same fungus was reisolated consistently from all infected roots and its identity was confirmed by resequencing, thereby fulfilling Koch's postulates. To the best of our knowledge, this is the first report of causing postharvest snow rot on Asian ginseng in China. The occurrence of this disease threatens the postharvest storage of Asian ginseng. Hence, effective management strategies must be developed.
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http://dx.doi.org/10.1094/PDIS-04-21-0868-PDNDOI Listing
July 2021

The Impact of Policy and COVID-19 Prevention Strategies in China: A Qualitative Study.

Res Sq 2021 Jul 15. Epub 2021 Jul 15.

Background: Ongoing infection-control strategies have played an important role in preventing the spread of COVID-19 and mitigating its effects. However, limited studies have explored the influence of these strategies from the perspective of COVID-19 patients. This study aims to describe the impact of governmental COVID-19 policy and prevention strategies on COVID-19 patients in China.

Methods: Twenty-six people who had been treated for COVID-19 in a COVID-19-designated facility in Shanghai, China, were recruited using the purposive sampling method. These individuals participated in semi-structured interviews by phone from April to June 2020. A thematic content analysis approach was conducted. The consolidated criteria for reporting qualitative studies checklist was applied.

Results: Three categories of themes emerged from the thematic analysis. The first was "Consciously adhere to COVID-19-related infection-control strategies." Most of these patients followed the COVID-19 strategies throughout the stages of their illness. The second category was "Positive experiences of the COVID-19-related infection-control strategies." These patients shared their positive experiences of the governmental infection-control strategies to contain the virus; for example, they experienced a quick and adequate medical response, they were confident in the medical system, or they received help from community workers. The third category was "Negative experiences of the COVID-19-related infection-control strategies." These patients experienced psychological distress, stigma, privacy exposures, and inconveniences from the governmental strategies.

Conclusions: Our findings exemplify how patients with COVID-19 adhered to the infection-control strategies in China. It is urgent to develop a culturally sensitive intervention to eliminate the psychological distress and stigma of patients with COVID-19 and to protect their privacy during and after the pandemic.
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http://dx.doi.org/10.21203/rs.3.rs-710681/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288153PMC
July 2021

Effect of vision loss on plasticity of the head and neck proprioception.

Int J Ophthalmol 2021 18;14(7):1059-1065. Epub 2021 Jul 18.

Department of Orthopedics, Chinese PLA General Hospital, Beijing 100853, China.

Aim: To investigate whether head and neck proprioception and motor control could be compensatory enhanced by long-term vision loss or impairment.

Methods: Individuals who were blind, low vision or sighted were included in the study, which would undergo the head repositioning test (HRT). The constant error (CE), absolute error (AE), variable error (VE) and root mean square error (RMSE) of each subject were statistically analyzed. Data were analyzed using the SAS 9.4. Tukey-Kramer for one-way ANOVA was used for comparison of blind, low vision, and sighted subjects, as well as to compare subjects with balanced vision, strong vision in the left eye and strong vision in the right eye. Independent sample -test was used to compare subjects with congenital blindness and acquired blindness, as well as left and right hand dominance subjects.

Results: A total of 90 individuals (25 blind subjects, 31 low vision subjects, and 34 sighted subjects) were included in the study. Among the blind subjects, 14 cases had congenital blindness and 11 cases had acquired blindness. Among the blind and low vision subjects, 21 cases had balanced binocular vision, 17 cases had strong vision in the left eye and 18 cases had strong vision in the right eye. Among all subjects, 11 cases were left hand dominance, and 79 cases were right hand dominance. There were significant differences in AE, VE, and RMSE in head rotation between blind, low vision, and sighted subjects (<0.01), in AE, VE, and RMSE between blind and sighted (<0.01), and in VE and RMSE between low vision and sighted (<0.05). No significant difference between blind and low vision (>0.05). Significant differences in CE and AE of head right rotation and CE of general head rotation between congenital and acquired (<0.05). No significant differences between left and right hand dominance and in balance or not of binocular vision (>0.05).

Conclusion: Long-term vision loss or impairment does not lead to compensatory enhancement of head and neck proprioception and motor control. Acquired experience contributes to HRT performance in the blind and has long-lasting effects on plasticity in the development of proprioception and sensorimotor control.
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http://dx.doi.org/10.18240/ijo.2021.07.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243183PMC
July 2021

A tailored LNA clamping design principle: Efficient, economized, specific and ultrasensitive for the detection of point mutations.

Biotechnol J 2021 Jul 18:e2100233. Epub 2021 Jul 18.

School of Biomedical Engineering/Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, PR China.

In the development of personalized medicine, the ultrasensitive detection of point mutations that correlate with diseases is important to improve the efficacy of treatment and guide clinical medication. In this study, locked nucleic acid (LNA) was introduced as an amplification suppressor of a massive number of wild-type alleles in an amplification refractory mutation system (ARMS) to achieve the detection of low-abundance mutations with high specificity and sensitivity of at least 0.1%. By integrating the length of clamp, base type, number and position of LNA modifications, we have established a "shortest length with the fewest LNA bases" principle from which each LNA base would play a key role in the affinity and the ability of single base discrimination could be improve. Finally, based on this LNA design guideline, a series of the most important single point mutation sites of epidermal growth factor receptor (EGFR) was verified to achieve the optimal amplification state which as low as 0.1% mutation gene amplification was not affected under the wild gene amplification was completely inhibited, demonstrating that the proposed design principle has good applicability and versatility and is of great significance for the detection of circulating tumor DNA.
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http://dx.doi.org/10.1002/biot.202100233DOI Listing
July 2021

Nanoconfinement Effect for Signal Amplification in Electrochemical Analysis and Sensing.

Small 2021 Jul 18:e2101665. Epub 2021 Jul 18.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, P.R. China.

Owing to the urgent need for electrochemical analysis and sensing of trace target molecules in various fields such as medical diagnosis, agriculture and food safety, and environmental monitoring, signal amplification is key to promoting analysis and sensing performance. The nanoconfinement effect, derived from nanoconfined spaces and interfaces with sizes approaching those of target molecules, has witnessed rapid development for ultra-sensitive analyzing and sensing. In this review, the two main types of nanoconfinement systems - confined nanochannels and planes - are assessed and recent progress is highlighted. The merits of each nanoconfinement system, the nanoconfinement effect mechanisms, and applications for electrochemical analysis and sensing are summarized and discussed. This review aims to help deepen the understanding of nanoconfinement devices and their effects in order to develop new analysis and sensing applications for researchers in various fields.
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http://dx.doi.org/10.1002/smll.202101665DOI Listing
July 2021

Synthesis and Study of a New Type of Nonanionic Demulsifier for Chemical Flooding Emulsion Demulsification.

ACS Omega 2021 Jul 2;6(27):17709-17719. Epub 2021 Jul 2.

School of Petroleum Engineering, Northeast Petroleum University, Daqing 163318, China.

The application of chemical flooding improves the stability of the produced emulsion, which reduces the demulsification efficiency of conventional demulsifiers. To improve the demulsification effect, in this paper, a new multibranched nonanionic polyether demulsifier, FYJP, was prepared by grafting carboxylate based on a nonionic demulsifier. The FYJP demulsifier could generate an initiator through --butylphenol, triethylenetetramine, and methanol, which was polymerized with ethylene oxide (EO) and propylene oxide (PO) to produce a nonionic polyether demulsifier. Sodium chloroacetate was used to modify the polyether demulsifier to obtain a new type of nonanionic polyether demulsifier. The FYJP polyether demulsifier was characterized by the hydrophilic-lipophilic balance (HLB) value, relative solubility (RSN), and surface activity of the demulsifier, and the demulsification mechanism was analyzed by a microscopic demulsification process test, and the effect of demulsifier dosage on the demulsification effect was discussed. Meanwhile, a dehydration test was carried out. The experimental results showed that the highest dehydration rate of the demulsifier was 94.7% at 85 °C, 100 ppm demulsifier dosage, 50 mL of a W/O emulsion, and 120 min demulsification time. The abovementioned studies show that FYJP is an effective demulsifier for chemical flooding emulsions, and this work promises to provide a reference for future demulsifier research.
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http://dx.doi.org/10.1021/acsomega.1c02352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280667PMC
July 2021

The Role of High-Content Complex Dietary Fiber in Medical Nutrition Therapy for Gestational Diabetes Mellitus.

Front Pharmacol 2021 1;12:684898. Epub 2021 Jul 1.

Shanghai General Hospital Shanghai, Shanghai, China.

A controlled open clinical study was conducted to evaluate the role of Ricnoat, a high-content complex dietary fiber powder produced by Zhuhai Aimed Biotechnology Co. Ltd., in medical nutrition therapy (MNT) to treat gestational diabetes mellitus (GDM). The study aimed to investigate glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM, as well as evaluate the clinical safety of Ricnoat. A total of 120 patients with GDM who were admitted to three hospitals in Shanghai between January 2019 and January 2020 were enrolled. Ricnoat was used for intervention for patients in the experimental group. Using a χ test and -test, respectively, comparisons were conducted between the measurement data and countable data of the demographics and baseline disease characteristics of the experimental group and control group. Fasting blood glucose, 2-h postprandial blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein, maternal gestational weight gain, neonatal weight, serum creatinine, glutamate transaminase, and aspartate aminotransferase were lower in the experimental group than in the control group, whereas high-density lipoprotein was higher in the experimental group than in the control group. Ricnoat intervention resulted in satiety higher than the expected 80% and more common occurrence of type 4 (smooth and soft, like salami or a snake) and type 5 (a soft mass with clear edges) stools. Ricnoat intervention had a significant effect on glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM by enhancing maternal satiety and improving the stool features of pregnant women. It was also found to be safe for application during pregnancy.
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http://dx.doi.org/10.3389/fphar.2021.684898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281130PMC
July 2021

Method for Teaching Life-Saving Combat First-Aid Skills With live-actor Patients Using a Wearable Training Apparatus.

Mil Med 2021 Jul 17. Epub 2021 Jul 17.

State Key Laboratory of Trauma, Burn and Combined Injury, Department for Combat Casualty Care Training, Training Base for Army Health Care, Army Medical University, Chongqing 400038, China.

Introduction: Training combat personnel in combat first-aid skills has faced many challenges over time, such as the need to combine tactics with medicine and to overcome combat personnel's lack of medical background knowledge. Therefore, many simulation methods are currently being developed, each of which has its advantages and disadvantages. In this study, a combined simulation method involving live-actor patients using a wearable training apparatus was developed, and the effects of this method were observed.

Materials And Methods: Focusing on the major causes of preventable deaths among victims killed in action, wearable training apparatuses simulating massive hemorrhage, airway obstruction, and tension pneumothorax were designed and produced. Methods of simulating these three injury types using live-actor patients with these training apparatuses were developed, and medical teachers evaluated the simulation effects. The live-actor patients were incorporated into a tactical scenario to train and test nonmedical and medical students in year 3, respectively. High-fidelity simulator-based training and traditional training without simulation served as the control. A post-training survey using a 7-point Likert scale evaluated the trainees' feelings toward these training approaches.

Results: Three types of training apparatuses were developed to simulate three life-threatening injuries, and the simulation effects of the live-actor patients using these apparatuses were highly recognized by medical teachers. Both live-actor patients and high-fidelity simulator-based training improved performance significantly more than traditional training. However, the improvement due to training with live-actor patients was greater than that due to high-fidelity simulator-based training for nonmedical students, whereas there was no difference between these two simulation methods for medical students. A post-training survey revealed that all the trainees were confident in practicing first-aid skills after training, and they all agreed that live-actor patients could combine tactical situations with first aid better than high-fidelity simulators. The nonmedical students strongly agreed that live-actor patients were more helpful in the training of injury evaluation than high-fidelity simulators.

Conclusions: The method using wearable training apparatus-based live-actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.
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http://dx.doi.org/10.1093/milmed/usab286DOI Listing
July 2021

Characteristics and outcomes of over 300,000 COVID-19 individuals with history of cancer in the United States and Spain.

Cancer Epidemiol Biomarkers Prev 2021 Jul 16. Epub 2021 Jul 16.

Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USA.

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and COVID-19. Secondly, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza.

Methods: We conducted a cohort study using eight routinely-collected healthcare databases from Spain and the US, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: i) diagnosed with COVID-19, ii) hospitalized with COVID-19, and iii) hospitalized with influenza in 2017-2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes.

Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5-19% and 1-14% in the diagnosed cohort, respectively). Hematological malignancies were also frequent, with non-Hodgkin's lymphoma being among the 5 most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n=67,743) had a similar distribution of cancer subtypes, sex, age and comorbidities but lower occurrence of adverse events.

Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematological malignancies were frequent.

Impact: This study provides epidemiologic characteristics that can inform clinical care and etiological studies.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0266DOI Listing
July 2021

Photocatalytic degradation of sulfamonomethoxine by mesoporous phosphorus-doped titania under simulated solar light irradiation.

Chemosphere 2021 Jul 12;285:131553. Epub 2021 Jul 12.

College of Resources and Environmental Engineering, Key Laboratory of Karst Georesources and Environment, Ministry of Education, Guizhou University, Guiyang, Guizhou, China.

Photocatalytic degradation of sulfamonomethoxine (SMM) by mesoporous phosphorus-doped TiO (P-TiO) was studied under simulated solar light irradiation. The morphological structure and chemical composition of P-TiO were analyzed by XRD, SEM, HRTEM, BET, XPS and FTIR. Using the central composite design (CCD) of response surface methodology (RSM), the degradation of SMM was investigated with a range of antibiotic concentrations (4-8 mg L), catalyst dosages (400-900 mg L), P doping amounts (5-15 wt %) and irradiation time (90-150 min). The Ti-O-P bond formed during the calcination of TiO, thereby generating plate-like P-TiO, where P was uniformly distributed. Phosphorus doping can stabilize anatase TiO, which has a larger specific surface area and a lower average particle and pore size than bare TiO. The result obtained from the RSM model showed a significant correlation between the predicted values and the experimental results of SMM degradation (P < 0.05). Under the optimal experimental conditions (antibiotic concentration = 6 mg/L, catalyst dosage = 800 mg/L, P doping = 5 wt% and irradiation time = 90 min), the degradation rate of SMM was 99.51%, and the TOC was 50%. Toxicity showed a considerable reduction towards Vibrio-qinghaiensis sp.-Q67 after SMM photocatalytic degradation. Through free radical capture experiments, LC-MS detection and DFT calculations, the possible photocatalytic degradation mechanism of SMM using P-TiO as the catalyst was revealed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131553DOI Listing
July 2021

The Warming Climate Aggravates Atmospheric Nitrogen Pollution in Australia.

Research (Wash D C) 2021 7;2021:9804583. Epub 2021 Jun 7.

College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.

Australia is a warm country with well-developed agriculture and a highly urbanized population. How these specific features impact the nitrogen cycle, emissions, and consequently affect environmental and human health is not well understood. Here, we find that the ratio of reactive nitrogen ( ) losses to air over losses to water in Australia is 1.6 as compared to values less than 1.1 in the USA, the European Union, and China. Australian emissions to air increased by more than 70% between 1961 and 2013, from 1.2 Tg N yr to 2.1 Tg N yr. Previous emissions were substantially underestimated mainly due to neglecting the warming climate. The estimated health cost from atmospheric emissions in Australia is 4.6 billion US dollars per year. Emissions of to the environment are closely correlated with economic growth, and reduction of losses to air is a priority for sustainable development in Australia.
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http://dx.doi.org/10.34133/2021/9804583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254137PMC
June 2021

Efficacy and Safety of Anti-PD-1/ PD-L1 Monotherapy for Metastatic Breast Cancer: Clinical Evidence.

Front Pharmacol 2021 29;12:653521. Epub 2021 Jun 29.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Success has been reported in PD-1/PD-L1 blockade pembrolizumab, atezolizumab, or avelumab monotherapy in manifold malignancies including metastatic breast cancer. Due to lack of large-scale study, here we present interim analyses to evaluate the safety and efficacy of these promising strategies in patients with advanced breast cancer. Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 monotherapy agents before July 1, 2020, were included. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab, land avelumab. Statistics was analyzed by R software and IBM SPSS Statistics 22. Global analysis showed that for this monotherapy, the complete response was 1.26%, partial response was 7.65%, objective response rate (ORR) was 9.85%, and disease control rate (DCR) was 18.33%. 1-year overall survival rate and 6-month progression-free survival rate were 43.34 and 17.24%. Overall incidence of adverse events (AEs) was 64.18% in any grade and 12.94% in severe grade, while the incidence of immune-related AEs (irAEs) was approximately 14.75%: the most common treatment-related AEs of any grade that occurred in at least 5% of patients were arthralgia and asthenia; the most common severe treatment-related AEs occurred in at least 1% of patients were anemia and autoimmune hepatitis; the most common irAEs were hypothyroidism. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06 and 0.31%, respectively. Additionally, by comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, an implicated correspondence between efficacy and the expression of PD-L1 biomarker was found: the PR was 9.93 vs 2.69%; the ORR was 10.62 vs. 3.07%; the DCR was 17.95 vs. 4.71%. Anti-PD-1/PD-L1 monotherapy showed a manageable safety profile and had a promising and durable anti-tumor efficacy in metastatic breast cancer patients. Higher PD-L1 expression may be closely correlated to a better clinical efficacy.
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http://dx.doi.org/10.3389/fphar.2021.653521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276035PMC
June 2021

Haplotype-resolved genome assembly provides insights into evolutionary history of the tea plant Camellia sinensis.

Nat Genet 2021 Jul 15. Epub 2021 Jul 15.

Department of Plant Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Tea is an important global beverage crop and is largely clonally propagated. Despite previous studies on the species, its genetic and evolutionary history deserves further research. Here, we present a haplotype-resolved assembly of an Oolong tea cultivar, Tieguanyin. Analysis of allele-specific expression suggests a potential mechanism in response to mutation load during long-term clonal propagation. Population genomic analysis using 190 Camellia accessions uncovered independent evolutionary histories and parallel domestication in two widely cultivated varieties, var. sinensis and var. assamica. It also revealed extensive intra- and interspecific introgressions contributing to genetic diversity in modern cultivars. Strong signatures of selection were associated with biosynthetic and metabolic pathways that contribute to flavor characteristics as well as genes likely involved in the Green Revolution in the tea industry. Our results offer genetic and molecular insights into the evolutionary history of Camellia sinensis and provide genomic resources to further facilitate gene editing to enhance desirable traits in tea crops.
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http://dx.doi.org/10.1038/s41588-021-00895-yDOI Listing
July 2021

Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom.

Int J Obes (Lond) 2021 Jul 15. Epub 2021 Jul 15.

Data Science to Patient Value Program, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Background: A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity.

Methods: We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status.

Results: We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity.

Conclusion: We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies.
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http://dx.doi.org/10.1038/s41366-021-00893-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281807PMC
July 2021

Acupuncture methods for functional constipation: protocol for a systematic review and network meta-analysis.

Ann Palliat Med 2021 Jul 6. Epub 2021 Jul 6.

Graduate School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders, with the most significant negative impact on health-related quality of life. Despite that multiple systematic reviews and clinical trials have suggested that acupuncture could be effective for FC treatment, the comparative effectiveness among various acupuncture approaches has remained unknown. This protocol proposed a plan to assess and rank the effectiveness and safety of different acupuncture methods for patients with FC.

Methods: We will search 8 bibliographic databases from their inception to 30 June 2021, including the Cochrane Central Register of Controlled Trials, MEDLINE (via PubMed), EMBASE, Allied and Complementary Medicine Database, the Chinese Biomedical Literature Database (CBM), Wanfang Database, VIP Database, and China National Knowledge Infrastructure (CNKI). Randomized controlled trials (RCT) examining acupuncture methods for FC will be considered. The primary outcome is a measurement of the weekly stool frequency [including bowel movement (BM), spontaneous bowel movement (SBM), and complete SBM]. There will be at least 2 reviewers in charge of study selection, data extraction, risk of bias assessment. Bayesian network meta-analysis will be conducted using ADDIS (Aggregate Data Drug Information System) V.1.16.8. Meta-regression and subgroup analyses will also be performed, if feasible, to address the potential causes of inconsistency and heterogeneity. Furthermore, the strength of evidence will be appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

Discussion: In this study, we will provide evidence-based hierarchies for the effectiveness and safety of acupuncture therapies to manage constipated patients, assisting healthcare providers, physicians, and patients in making more informed treatment decisions.

Trial Registration: This study has been registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) with a registration number CRD42021227920.
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http://dx.doi.org/10.21037/apm-21-811DOI Listing
July 2021
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