Publications by authors named "Chang Zheng"

257 Publications

Prediction of treatment dosage and duration from free-text prescriptions: an application to ADHD medications in the Swedish prescribed drug register.

Evid Based Ment Health 2021 Apr 1. Epub 2021 Apr 1.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Background: Accurate estimation of daily dosage and duration of medication use is essential to pharmacoepidemiological studies using electronic healthcare databases. However, such information is not directly available in many prescription databases, including the Swedish Prescribed Drug Register.

Objective: To develop and validate an algorithm for predicting prescribed daily dosage and treatment duration from free-text prescriptions, and apply the algorithm to ADHD medication prescriptions.

Methods: We developed an algorithm to predict daily dosage from free-text prescriptions using 8000 ADHD medication prescriptions as the training sample, and estimated treatment periods while taking into account several features including titration, stockpiling and non-perfect adherence. The algorithm was implemented to all ADHD medication prescriptions from the Swedish Prescribed Drug Register in 2013. A validation sample of 1000 ADHD medication prescriptions, independent of the training sample, was used to assess the accuracy for predicted daily dosage.

Findings: In the validation sample, the overall accuracy for predicting daily dosage was 96.8%. Specifically, the natural language processing model (NLP1 and NLP2) have an accuracy of 99.2% and 96.3%, respectively. In an application to ADHD medication prescriptions in 2013, young adult ADHD medication users had the highest probability of discontinuing treatments as compared with other age groups. The daily dose of methylphenidate use increased with age substantially.

Conclusions: The algorithm provides a flexible approach to estimate prescribed daily dosage and treatment duration from free-text prescriptions using register data. The algorithm showed a good performance for predicting daily dosage in external validation.

Clinical Implications: The structured output of the algorithm could serve as basis for future pharmacoepidemiological studies evaluating utilization, effectiveness, and safety of medication use, which would facilitate evidence-based treatment decision-making.
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http://dx.doi.org/10.1136/ebmental-2020-300231DOI Listing
April 2021

Synthesis and antimicrobial activity evaluation of imidazole-fused imidazo[2,1-b][1,3,4]thiadiazole analogues.

ChemMedChem 2021 Mar 18. Epub 2021 Mar 18.

Yanbian University, College of Pharmacy, Gongyuan, 133002, Yanji, CHINA.

Three series of new imidazole-fused imidazo[2,1-b][1,3,4]thiadiazole analogues (compounds 20a-g, 21a-g, and 22a-g) were synthesized and their antibacterial and antifungal activities were evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans (C. albicans) over Gram-positive and Gram-negative bacteria. N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)aniline (21a) showed the highest activity against C. albicans (MIC50 = 0.16 µg/mL), 13-fold and 3-fold that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21a and 20e did not show cytotoxicity against human foreskin fibroblast-1 cells, and compound 21a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents.
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http://dx.doi.org/10.1002/cmdc.202100122DOI Listing
March 2021

Assessment of Cesarean Delivery and Neurodevelopmental and Psychiatric Disorders in the Children of a Population-Based Swedish Birth Cohort.

JAMA Netw Open 2021 Mar 1;4(3):e210837. Epub 2021 Mar 1.

Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.

Importance: Recent studies suggest that cesarean delivery (CD) is associated with increased risk of neurodevelopmental disorders in children, although they were unable to control for indications for CD or familial confounding beyond full siblings.

Objective: To examine the association between CD and neurodevelopmental and psychiatric disorders in children.

Design, Setting, And Participants: This Swedish register-based cohort study included 1 179 341 term-birth singletons born between January 1, 1990, and December 31, 2003, and followed up through December 31, 2013. All individuals were linked to their full siblings, maternal and paternal half siblings, and maternal full cousins. Statistical analyses were performed from September 26, 2019, to January 16, 2021.

Exposures: Birth by CD recorded at birth, stratified into planned and intrapartum CD.

Main Outcomes And Measures: Registered diagnoses of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), intellectual disability, tic disorders, communication disorders, learning disorders, and any neurodevelopmental disorder; and psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, depressive disorders, eating disorders, bipolar disorders, psychotic disorders, and any psychiatric disorder.

Results: Of 1 179 341 individuals, 1 048 838 (533 140 boys [50.8%]) were delivered vaginally, 59 514 (30 138 boys [50.6%]) were delived via planned CD, and 70 989 (39 191 boys [55.2%]) were delivered via intrapartum CD. Mean (SD) age at follow-up was 17.7 (4.1) years for vaginal delivery, 16.6 (4.2) years for planned CD, and 16.8 (4.1) years for intrapartum CD. Compared with vaginal delivery, and after controlling for measured covariates (parental and neonatal characteristics, maternal comorbidities, and pregnancy complications), CD was associated with higher risk in children of any neurodevelopmental disorder (planned CD, hazard ratio [HR], 1.17; 95% CI, 1.13-1.22; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.14), ADHD (planned CD, HR, 1.17; 95% CI, 1.12-1.23; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.15), and intellectual disability (planned CD, HR, 1.26; 95% CI, 1.14-1.39; intrapartum CD, HR, 1.17; 95% CI, 1.06-1.28). Only planned CD was associated with a higher risk of ASD (HR, 1.20; 95% CI, 1.10-1.31), communication disorders (HR, 1.14; 95% CI, 1.02-1.28), and learning disorders (HR, 1.15; 95% CI, 1.01-1.30). Cesarean delivery was not associated with the remaining disorders. The associations between CD and any neurodevelopmental disorder, ADHD, ASD, and intellectual disability attenuated in full cousins and paternal half siblings, and further attenuated (became nonsignificant) in maternal half siblings and full siblings (risk of any neurodevelopmental disorder in full siblings, planned CD, HR, 0.93; 95% CI, 0.81-1.06; intrapartum CD, HR, 1.07; 95% CI, 0.96-1.21).

Conclusions And Relevance: The findings of this study suggest that the association between CD and increased risk of neurodevelopmental disorders in the children was most likely explained by unmeasured familial confounding.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936261PMC
March 2021

Lysosome-associated membrane protein 3 misexpression in salivary glands induces a Sjögren's syndrome-like phenotype in mice.

Ann Rheum Dis 2021 Mar 3. Epub 2021 Mar 3.

AAV Biology Section, National Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA

Objectives: Sjögren's syndrome (SS) is an autoimmune sialadenitis with unknown aetiology. Although extensive research implicated an abnormal immune response associated with lymphocytes, an initiating event mediated by salivary gland epithelial cell (SGEC) abnormalities causing activation is poorly characterised. Transcriptome studies have suggested alternations in lysosomal function are associated with SS, but a cause and effect linkage has not been established. In this study, we demonstrated that altered lysosome activity in SGECs by expression of lysosome-associated membrane protein 3 (LAMP3) can initiate an autoimmune response with autoantibody production and salivary dysfunction similar to SS.

Methods: Retroductal cannulation of the submandibular salivary glands with an adeno-associated virus serotype 2 vector encoding LAMP3 was used to establish a model system. Pilocarpine-stimulated salivary flow and the presence of autoantibodies were assessed at several time points post-cannulation. Salivary glands from the mice were evaluated using RNAseq and histologically.

Results: Following LAMP3 expression, saliva flow was significantly decreased and serum anti-Ro/SSA and La/SSB antibodies could be detected in the treated mice. Mechanistically, LAMP3 expression increased apoptosis in SGECs and decreased protein expression related to saliva secretion. Analysis of RNAseq data suggested altered lysosomal function in the transduced SGECs, and that the cellular changes can chemoattract immune cells into the salivary glands. Immune cells were activated via toll-like receptors by damage-associated molecular patterns released from LAMP3-expressing SGECs.

Conclusions: These results show a critical role for lysosomal trafficking in the development of SS and establish a causal relationship between LAMP3 misexpression and the development of SS.
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http://dx.doi.org/10.1136/annrheumdis-2020-219649DOI Listing
March 2021

Breast cancer proliferation and deterioration-associated metabolic heterogeneity changes induced by exposure of bisphenol S, a widespread replacement of bisphenol A.

J Hazard Mater 2021 Feb 19;414:125391. Epub 2021 Feb 19.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Exposure to bisphenol A (BPA) is considered to be associated with the increased incidence of breast cancer. As a widespread replacement of BPA, the effect of bisphenol S (BPS) on breast tumor programming has not been studied. We reported that BPS exposure significantly promoted proliferation and deterioration of breast tumor by nonmonotonic dose response. The mechanisms were investigated by molecular biology and mass spectrometry-based lipidomics, proteomics and imaging. BPS exposure induced the spatially intratumor heterogeneity of morphology-driven lipids and proteins. The more significant proliferation resulted from BPS-10 (10 μg/kg body weight /day) exposure was evidenced by the variations of spatial distribution of lipids related to ceramide-sphingomyelin signaling pathway, proteins related to chromosomal stability and cell proliferation in central necrotic regions of breast tumor. In contrast, the BPS-100 exposure obviously accelerated deterioration of breast tumor by the variations of spatial distribution of proteins that were associated with the stability of nucleic acid structure in peripheral neoplastic regions. Accordingly, dysregulation of metabolism and protein function as well as DNA methylation and hypoxic tumor microenvironment could be applied to predict the possibility of tumorigenesis, proliferation and metastasis that might be caused by other bisphenol analogs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125391DOI Listing
February 2021

Breast cancer proliferation and deterioration-associated metabolic heterogeneity changes induced by exposure of bisphenol S, a widespread replacement of bisphenol A.

J Hazard Mater 2021 Feb 19;414:125391. Epub 2021 Feb 19.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Exposure to bisphenol A (BPA) is considered to be associated with the increased incidence of breast cancer. As a widespread replacement of BPA, the effect of bisphenol S (BPS) on breast tumor programming has not been studied. We reported that BPS exposure significantly promoted proliferation and deterioration of breast tumor by nonmonotonic dose response. The mechanisms were investigated by molecular biology and mass spectrometry-based lipidomics, proteomics and imaging. BPS exposure induced the spatially intratumor heterogeneity of morphology-driven lipids and proteins. The more significant proliferation resulted from BPS-10 (10 μg/kg body weight /day) exposure was evidenced by the variations of spatial distribution of lipids related to ceramide-sphingomyelin signaling pathway, proteins related to chromosomal stability and cell proliferation in central necrotic regions of breast tumor. In contrast, the BPS-100 exposure obviously accelerated deterioration of breast tumor by the variations of spatial distribution of proteins that were associated with the stability of nucleic acid structure in peripheral neoplastic regions. Accordingly, dysregulation of metabolism and protein function as well as DNA methylation and hypoxic tumor microenvironment could be applied to predict the possibility of tumorigenesis, proliferation and metastasis that might be caused by other bisphenol analogs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125391DOI Listing
February 2021

GPER1 Silencing Suppresses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Inhibiting PI3K/AKT-Mediated EMT.

Front Cell Dev Biol 2020 21;8:591239. Epub 2020 Dec 21.

Department of General Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

G protein coupled estrogen receptor (GPER1) is a membrane estrogen receptor, belonging to the seven-transmembrane G protein-coupled receptors family, and has important biological functions in cancer. However, the functional role of GPER1 in gastric cancer (GC) remain incompletely understood. In the present study, we employed gene set enrichment analysis and discovered that GPER1 expression was concomitant with EMT process and was positively correlated with activation of the PI3K/AKT pathway in GC. Knockdown of GPER1 with siRNA suppressed the proliferation, migration, and invasion of AGS and MGC-803 GC cells. Knockdown of GPER1 also downregulated the mesenchymal markers N-cadherin and vimentin, upregulated E-cadherin, an epithelial marker, and suppressed expression of the Snail, Slug and Twist1 transcription factors, indicating that knockdown of GPER1 inhibited EMT. Moreover, 740Y-P, a PI3K activator, reversed the effects of GPER1 knockdown on EMT processes. Overexpression of GPER1 with plasmid can further prove these findings. In summary, these data demonstrate that GPER1 inhibition suppresses the proliferation, migration, and invasion of gastric cancer cells by inhibiting PI3K/AKT-mediated EMT. Our study elucidated the function of GPER1 in gastric cancer, and we identified PI3K/AKT-mediated EMT as a novel mechanism by which GPER1 contributes to proliferation, migration, and invasion of gastric cancer. These data suggest that combining inhibition of GPER1 and PI3K may be a potential therapeutic approach to inhibit gastric cancer metastasis.
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http://dx.doi.org/10.3389/fcell.2020.591239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793665PMC
December 2020

Public Mobility and Social Media Attention in Response to COVID-19 in Sweden and Denmark.

JAMA Netw Open 2021 01 4;4(1):e2033478. Epub 2021 Jan 4.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1001/jamanetworkopen.2020.33478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783540PMC
January 2021

Medications for attention-deficit/hyperactivity disorder in individuals with or without coexisting autism spectrum disorder: analysis of data from the Swedish prescribed drug register.

J Neurodev Disord 2020 12 23;12(1):44. Epub 2020 Dec 23.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77, Stockholm, Sweden.

Background: Clinical studies found that medication for attention-deficit/hyperactivity disorder (ADHD) is effective in coexisting autism spectrum disorder (ASD), but current research is based on small clinical studies mainly performed on children or adolescents. We here use register data to examine if individuals with ADHD and coexisting ASD present differences in the prescribing patterns of ADHD medication when compared to individuals with pure ADHD.

Methods: Data with information on filled prescriptions and diagnoses was retrieved from the Swedish Prescribed Drug Register and the National Patient Register. We identified 34,374 individuals with pure ADHD and 5012 individuals with ADHD and coexisting ASD, aged between 3 and 80 years. The first treatment episode with ADHD medications (≥ 2 filled prescriptions within 90 days) and daily doses of methylphenidate during a 3-year period was measured. Odds ratios (ORs) were calculated for the likelihood of being prescribed ADHD medication in individuals with and without ASD and Wilcoxon rank-sum test was used to compare group differences in dose per day.

Results: Individuals with ADHD and coexisting ASD were less likely to start continuous treatment with ADHD medication (ADHD 80.5%; ADHD with ASD 76.2%; OR, 0.80; 95% confidence interval, 0.75-0.86), were less likely to be prescribed methylphenidate, and were more commonly prescribed second line treatments such as dexamphetamine, amphetamine, or modafinil. No group difference was observed for atomoxetine. In adults with ADHD and coexisting ASD, methylphenidate was prescribed in lower daily doses over three years as compared to individuals with pure ADHD.

Conclusions: The findings indicate that there are differences in the medical treatment of individuals with or without ASD. If these differences are due to different medication responses in ASD or due to other factors such as clinicians' perceptions of medication effects in patients with ASD, needs to be further studied.
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http://dx.doi.org/10.1186/s11689-020-09352-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758935PMC
December 2020

[Effect of Polygonum multiflorum-Andrographis paniculata intercropping system on rhizosphere soil actinomycetes community structure and diversity of P. multiflorum].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(22):5452-5458

Guangdong Provincial Research Center on Good Agricultural Practice & Comprehensive Agricultural Development Engineering Technology of Cantonese Medicinal Materials, Guangzhou Comprehensive Experimental Station Chinese Materia Medica Industry Technology System, Key Laboratory for Production & Development of Cantonese Medicinal Materials Under State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University Guangzhou 510006, China.

To investigate the effect of Polygonum multiflorum-Andrographis paniculata intercropping system on rhizosphere soil actinomycetes of P. multiflorum, the community structure and diversity of soil actinomycetes were studied by using the original soil as the control group and the rhizosphere soil actinomycetes communities of P. multiflorum under monoculture and intercropping systems as the experimental group. In this study 655 221 effective sequences were obtained with an average length of 408 bp. OTU coverage and rarefaction curve showed that the sequencing could represent the real situation of soil actinomycetes. According to the results of alpha diversity analysis, the diversity soil actinomycetes varied as follows: original soil>intercropping soil>monoculture soil. The soil actinomycetes community structure and the relative abundance of dominant genera were significantly changed by both monoculture and intercropping, especially monoculture. OTU clustering and PCA analysis of soil samples showed that all the soil samples were divided into three distinct groups and the original soil was more similar to intercropping soil. In addition, intercropping increased the relative abundance of some beneficial actinomyces, such as Kitasatospora and Mycobacterium, which was beneficial to maintain soil health and reduce the occurrence of soil-borne diseases. The results show that, P. multiflorum-A. paniculata intercropping reduced the change of community structure and the decrease of diversity of soil actinomycetes caused by P. multiflorum monoculture, and made the actinomycete community in rhizosphere soil of P. multiflorum close to the original soil.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200816.103DOI Listing
November 2020

[Analysis of acupoint selection of plaster therapy in treatment of stable chronic obstructive pulmonary disease based on data mining].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(22):5356-5361

Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China.

This article analyze acupoint selection and characteristics of plaster therapy for stable chronic obstructive pulmonary di-sease(COPD) by data mining. The CNKI, VIP, CBM, WanFang, PubMed, EMbase, Cochrane Library were retrieved for collecting clinical studies of plaster therapy for stable COPD. After literature screening, a total of 46 systematic reviews were included. Frequency statistics, cluster analysis, and Apriori correlation analysis were used to analyze the pattern and characteristics of plaster therapy for stable COPD. The result showed that the main acupoints for stable COPD were BL13, Dingchuan, CV22, BL23 and BL20. The acupoints used are mainly concentrated on the chest and back. The most frequently used meridian is the bladder meridian. Analysis of the acupoints yielded 27 correlation rules. And cluster analysis grouped the high frequency acupoints into 5 categories. The results of the study showed that the current choice of acupoints is rather concentrated. "Local acupuncture points" and "matching points with front and back" were the main acupoint selection rules. The choice of acupuncture points reflected the traditional Chinese medicine treatment principle of strengthening healthy Qi to eliminate pathogenic factor, treating both manifestation and root cause of disease, and preventing measure taken after the occurrence of disease.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200803.501DOI Listing
November 2020

[Systematic review and Meta-analysis on efficacy and safety of Buzhong Yiqi Decoction for stable chronic obstructive pulmonary disease].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(22):5344-5355

Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China.

To systematically review the efficacy and safety of Buzhong Yiqi Decoction in the treatment of stable chronic obstructive pulmonary disease(COPD) at the stable stage. Three English databases and four Chinese databases were systematically searched from the database establishment to August 1, 2020. Randomized controlled trials(RCTs) were screened according to the pre-determined inclusion and exclusion criteria, and then the data were extracted. Methodological quality of the included studies was assessed based on Cochrane bias risk tool, and RevMan 5.3 was used for data analysis. A total of 389 articles were retrieved and finally 18 RCTs were included in this study, involving 1 566 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in terms of improving 6-minute walk distance(6 MWD), and delaying the decline of forced expiratory volume in one second(FEV_1) or its % in the expected value as well as the decline in ratio of FEV_1 to forced vital capacity(FVC), Buzhong Yiqi Decoction alone or in combination with conventional Western medicine was superior to conventional therapy Western medicine alone. Subgroup analysis showed that, in terms of reducing traditional Chinese medicine symptom scores, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of reducing the grade of modified medical research council(mMRC), Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of improving 6 MWD, Buzhong Yiqi Decoction combined with conventional treatment or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment alone or Tiotropium Bromide Powder for Inhalation alone. In terms of delaying the decline of FEV_1 or its % in the expected value, Buzhong Yiqi Decoction combined with conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation alone, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. In terms of delaying the decline in FEV_1/FVC, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. Meta-analysis of other outcome measures was not available and no conclusion can be drawn due to the inclusion of only one study. As some studies did not mention the adverse reactions, no safety comments can be made for Buzhong Yiqi Decoction alone or combined with conventional Western medicine. Due to the limitations of the quality and quantity of included studies, the conclusions of this research should be treated with caution. The efficacy of Buzhong Yiqi Decoction for stable COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200904.501DOI Listing
November 2020

[Systematic review and Meta-analysis on efficacy and safety of Liujunzi Decoction combined with Western medicine for stable chronic obstructive pulmonary disease].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(22):5331-5343

Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China.

To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200720.501DOI Listing
November 2020

[Editorial explanation for clinical practice guideline for stable chronic obstructive pulmonary disease with traditional Chinese medicine].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(22):5323-5330

Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China.

As an important auxiliary document in the process of guideline development, the editorial explanation is the extension and complement to the content of the guideline, a basis for fully understanding the technical content of the guideline, an indispensable document for the guideline's traceability. The project team of this guideline, while formulating the Clinical practice guideline for stable chronic obstructive pulmonary disease with traditional Chinese medicine(draft version for comments), also has written the corresponding editorial explanation. In order to enable the relevant medical workers to more accurately understand and apply the guideline, but also to provide readers with a more in-depth understanding of the reasons and processes for the development of the guideline, the paper will give a detailed introduction to the compilation process about the guideline, includes: work overview(project background, task source, drafting and collaboration unit, project team members and their division of labor), main technical content(the basis and principles of guideline development, technical route), main compilation process(the establishment of project team, the formulation of the guideline plan, the project approval and the registration of research programme, the construction of clinical issues and the selection of outcome indicators, evidence search screening and synthesis, evidence evaluation and grading, the formation of recommendations, the writing of exposure draft, external review and self-assessment, etc), expert consensus implementation requirements and measure suggestions(promotion and implementation measures, and post-effect evaluation), other issues need to be explained and so on.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200726.502DOI Listing
November 2020

[Clinical practice guideline for stable chronic obstructive pulmonary disease with traditional Chinese medicine (draft version for comments)].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(22):5309-5322

Xiyuan Hospital,China Academy of Chinese Medical Sciences Beijing 100091,China.

By referring to the standards and procedures of WHQ Handbook for Guideline Development, under the guidance of relevant laws, regulations, and technical documents, in line with the principle of "evidence-based, consensus-based, experience-based", and based on the best available evidences, fully combined with expert experience and patient preferences, we summarized eight clinical questions in this paper: can traditional Chinese medicine(TCM) treatment improve the clinical symptoms and the degree of dyspnea in patients with stable chronic obstructive pulmonary disease(COPD) Can TCM treatment reduce the number of exacerbations in patients with stable COPD? Can TCM treatment improve the exercise tolerance of patients with stable COPD? Can TCM treatment improve the quality of life of patients with stable COPD? Can TCM treatment delay the decline of lung function in patients with stable COPD? Can TCM treatment improve anxiety and depression in patients with stable COPD? Does the point application therapy benefit patients with stable COPD? Can non-pharmacological treatment benefit patients with stable COPD? Based on these eight clinical problems, the cha-racteristics of TCM itself, and actual clinical situation, the recommendations of TCM to treat the stable COPD were formed in this guideline, with intention to provide advice and guidance to clinicians in the use of TCM to treat stable COPD, to relieve symptoms, improve exercise tolerance, improve health status, prevent disease progression, prevent and treat exacerbations, and improve clinical efficacy. Due to the influence of the user's region, nationality, race and other factors, the implementation of this guideline should be based on the actual situations.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200726.503DOI Listing
November 2020

Key Odorant Differences in Fragrant and Oils Revealed by Gas Chromatography-Olfactometry, Odor Activity Values, and Aroma Recombination.

J Agric Food Chem 2020 Dec 23;68(50):14950-14960. Epub 2020 Nov 23.

Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National& Local Joint Engineering Laboratory, Key Laboratory of Oilseeds processing of Ministry of Agriculture, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China.

Fragrant species seed oils (FBO) produced in China are mainly obtained from rapeseed (: ) and mustard seeds (: ). The characterization and differences of aroma profiles between those two species remain unclear. In this study, the volatile compounds in FBOs were systemically extracted by headspace solid-phase microextraction and solvent-assisted flavor evaporation combined with ultrasound and identified by comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry (GC×GC-TOFMS) and gas chromatography-olfactometry (GC-O). Ninety-three odorants were identified as aroma-active compounds with flavor dilution (FD) factors ranging from 1 to 6561. Moreover, 63 key compounds exhibited their odor activity values (OAVs) to be greater than 1. The oils of the two species were successfully recombinated with their key odorants. oils presented stronger pungent-like, pickled-like, and fishy like notes compared to oils. The key odor differences were primarily attributed to the concentration of 3-butenenitrile, 4-(methylsulfanyl)butanenitrile, 5-(methylsulfanyl)pentanenitrile, 3-isothiocyanato-1-propene, 3-methyl-3-butenenitrile, isothiocyanatocyclopropane, (methylsulfanyl)acetonitrile, dimethyl sulfide, dimethyl trisulfide, and 3-(methyldisulfanyl)-1-propene. This work provides a guide for the selection of raw materials and odor markers in fragrant and oils.
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http://dx.doi.org/10.1021/acs.jafc.0c05944DOI Listing
December 2020

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction.

Curr Mol Med 2020 Nov 19. Epub 2020 Nov 19.

Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008. China.

Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.
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http://dx.doi.org/10.2174/1566524020666201120113538DOI Listing
November 2020

A Leptin-Mediated Neural Mechanism Linking Breathing to Metabolism.

Cell Rep 2020 11;33(6):108358

Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address:

Breathing is coupled to metabolism. Leptin, a peptide mainly secreted in proportion to adipose tissue mass, increases energy expenditure with a parallel increase in breathing. We demonstrate that optogenetic activation of LepRb neurons in the nucleus of the solitary tract (NTS) mimics the respiratory stimulation after systemic leptin administration. We show that leptin activates the sodium leak channel (NALCN), thereby depolarizing a subset of glutamatergic (VGluT2) LepRb NTS neurons expressing galanin. Mice with selective deletion of NALCN in LepRb neurons have increased breathing irregularity and central apneas. On a high-fat diet, these mice gain weight with an associated depression of minute ventilation and tidal volume, which are not detected in control littermates. Anatomical mapping reveals LepRb NTS-originating glutamatergic axon terminals in a brainstem inspiratory premotor region (rVRG) and dorsomedial hypothalamus. These findings directly link a defined subset of NTS LepRb cells to the matching of ventilation to energy balance.
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http://dx.doi.org/10.1016/j.celrep.2020.108358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698346PMC
November 2020

[Research progress on chemical constituents and pharmacological effects of Sedum sarmentosum].

Zhongguo Zhong Yao Za Zhi 2020 Sep;45(18):4341-4348

College of Pharmacy, Shandong University of Traditional Chinese Medicine Ji'nan 250355, China.

Sedum sarmentosum is a traditional Chinese medicine with the clinical effects of clearing away heat and detoxification. It has the pharmacological effects of protecting liver, anti-tumor, anti-fibrosis, anti-oxidation, inhibiting lipid accumulation and immunosuppression. Because of its remarkable effect of reducing enzymes and protecting the liver, it is mainly used for the treatment of various types of hepatitis in clinical application. The flavonoids, megastigmanes, alkaloids, sterols, triterpenes and other chemical constituents in S. sarmentosum are the important material basis for its pharmacological action. In this paper, the research progress on the chemical constituents and pharmacological effects of S. sarmentosum were reviewed, and the research status and research direction of S. sarmentosum were analyzed, in order to provide a reference for its further rational development and application.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200623.601DOI Listing
September 2020

Attention-deficit/hyperactivity disorder symptoms and dietary habits in adulthood: A large population-based twin study in Sweden.

Am J Med Genet B Neuropsychiatr Genet 2020 12 7;183(8):475-485. Epub 2020 Oct 7.

School of Medical Sciences, Örebro University, Örebro, Sweden.

Associations between adult attention-deficit/hyperactivity disorder (ADHD) symptoms and dietary habits have not been well established and the underlying mechanisms remain unclear. We explored these associations using a Swedish population-based twin study with 17,999 individuals aged 20-47 years. We estimated correlations between inattention and hyperactivity/impulsivity with dietary habits and fitted twin models to determine the genetic and environmental contributions. Dietary habits were defined as (a) consumption of food groups, (b) consumption of food items rich in particular macronutrients, and (c) healthy and unhealthy dietary patterns. At the phenotypic level, inattention was positively correlated with seafood, high-fat, high-sugar, high-protein food consumptions, and unhealthy dietary pattern, with correlation coefficients ranging from 0.03 (95%CI: 0.01, 0.05) to 0.13 (95% CI: 0.11, 0.15). Inattention was negatively correlated with fruits, vegetables consumptions and healthy dietary pattern, with correlation coefficients ranging from -0.06 (95%CI: -0.08, -0.04) to -0.07 (95%CI: -0.09, -0.05). Hyperactivity/impulsivity and dietary habits showed similar but weaker patterns compared to inattention. All associations remained stable across age, sex and socioeconomic status. Nonshared environmental effects contributed substantially to the correlations of inattention (56-60%) and hyperactivity/impulsivity (63-80%) with dietary habits. The highest and lowest genetic correlations were between inattention and high-sugar food (r = .16, 95% CI: 0.07, 0.25), and between hyperactivity/impulsivity and unhealthy dietary pattern (r = .05, 95% CI: -0.05, 0.14), respectively. We found phenotypic and etiological overlap between ADHD and dietary habits, although these associations were weak. Our findings contribute to a better understanding of common etiological pathways between ADHD symptoms and various dietary habits.
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http://dx.doi.org/10.1002/ajmg.b.32825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702140PMC
December 2020

Serious Transport Accidents in Tourette Syndrome or Chronic Tic Disorder.

Mov Disord 2021 01 24;36(1):188-195. Epub 2020 Sep 24.

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Background: It is unknown whether individuals with tic disorders are at increased risk for serious transport accidents.

Objectives: The aim of this study was to investigate the risk for injuries or death caused by transport and motor vehicle accidents in individuals with Tourette syndrome or chronic tic disorder.

Methods: This population-based, sibling-controlled cohort study included all individuals aged ≥18 years living in Sweden between 1997 and 2013 (N = 6,127,290). A total of 3449 individuals had a registered diagnosis of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. We also identified 2191 families with full siblings discordant for tic disorders. Cox proportional hazards regression modeling was used to estimate the risk for injuries or deaths as a result of transport accidents in individuals with a lifetime diagnosis of Tourette syndrome or chronic tic disorder compared with unexposed individuals and siblings.

Results: Individuals with tic disorders had a higher risk for transport injuries or death compared with the general population (adjusted hazard ratio, 1.50 [95% confidence interval: 1.33-1.69]) and their unaffected siblings (adjusted hazard ratio, 1.41 [95% confidence interval: 1.18-1.68]). The risks were similar across sexes. The exclusion of most psychiatric comorbidities did not alter the magnitude of the estimates. However, the risks were no longer significant after exclusion of individuals with comorbid attention deficit hyperactivity disorder.

Conclusions: The marginally increased risk for serious transport accidents in tic disorders is mainly driven by attention deficit hyperactivity disorder comorbidity. Improved detection and management of attention deficit hyperactivity disorder symptoms in this patient group are warranted. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891379PMC
January 2021

Multimaterial three-dimensional printing in brachytherapy: Prototyping teaching tools for interstitial and intracavitary procedures in cervical cancers.

Brachytherapy 2020 Nov - Dec;19(6):767-776. Epub 2020 Sep 4.

Department of Radiation Oncology, Duke University Medical Center, Durham, NC. Electronic address:

Purpose: As the utilization of brachytherapy procedures continues to decline in clinics, a need for accessible training tools is required to help bridge the gap between resident comfort in brachytherapy training and clinical practice. To improve the quality of intracavitary and interstitial high-dose-rate brachytherapy education, a multimaterial, modular, three-dimensionally printed pelvic phantom prototype simulating normal and cervical pathological conditions has been developed.

Methods And Materials: Patient anatomy was derived from pelvic CT and MRI scans from 50 representative patients diagnosed with localized cervical cancer. Dimensions measured from patients' uterine body and uterine canal sizes were used to construct a variety of uteri based off of the averages and standard deviations of the subjects in our study. Soft-tissue anatomy was three-dimensionally printed using Agilus blends (shore 30 and 70) and modular components using Vero (shore 85).

Results: The kit consists of four uteri, a standard bladder, a standard rectum, two embedded gross tumor volumes, and four clip-on gross tumor volume attachments. The three anteverted uteri in the kit are based on the smallest, the average, and the largest dimensions from our patient set, whereas the retroverted uterus assumes average dimensions.

Conclusions: This educational high-dose-rate gynecological pelvic phantom is an accessible and cost-effective way to improve radiation oncology resident training in intracavitary/interstitial brachytherapy cases. Implementation of this phantom in resident education will allow for more thorough and comprehensive physician training through its ability to transform the patient scenario. It is expected that this tool will help improve confidence and efficiency when performing brachytherapy procedures in patients.
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http://dx.doi.org/10.1016/j.brachy.2020.07.013DOI Listing
September 2020

A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma.

PeerJ 2020 5;8:e9658. Epub 2020 Aug 5.

Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, China.

Background: Immune cells in the tumor microenvironment are an important prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, information on the heterogeneity and risk stratification of these cells is limited. We sought to develop a novel immune model to evaluate the prognostic intra-tumoral immune landscape of patients with DLBCL.

Methods: The ESTIMATE and CIBERSORT algorithms were used to estimate the numbers of 22 infiltrating immune cells based on the gene expression profiles of 229 patients with DLBCL who were recruited from a public database. The least absolute shrinkage and selection operator (Lasso) penalized regression analyses and nomogram model were used to construct and evaluate the prognostic immunoscore (PIS) model for overall survival prediction. An immune gene prognostic score (IGPS) was generated by Gene Set Enrichment Analysis (GSEA) and Cox regression analysis was and validated in an independent NCBI GEO dataset (GSE10846).

Results: A higher proportion of activated natural killer cells was associated with a poor outcome. A total of five immune cells were selected in the Lasso model and DLBCL patients with high PIS showed a poor prognosis (hazard ratio (HR) 2.16; 95% CI [1.33-3.50];  = 0.002). Differences in immunoscores and their related outcomes were attributed to eight specific immune genes involved in the cytokine-cytokine receptor interaction and chemokine signaling pathways. The IGPS based on a weighted formula of eight genes is an independent prognostic factor (HR: 2.14, 95% CI [1.40-3.28]), with high specificity and sensitivity in the validation dataset.

Conclusions: Our findings showed that a PIS model based on immune cells is associated with the prognosis of DLBCL. We developed a novel immune-related gene-signature model associated with the PIS model and enhanced the prognostic functionality for the prediction of overall survival in patients with DLBCL.
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http://dx.doi.org/10.7717/peerj.9658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414766PMC
August 2020

Association of Opioid Prescription Initiation During Adolescence and Young Adulthood With Subsequent Substance-Related Morbidity.

JAMA Pediatr 2020 Aug 10. Epub 2020 Aug 10.

Department of Psychological and Brain Sciences, Indiana University, Bloomington.

Importance: Concerns about adverse outcomes associated with opioid analgesic prescription have led to major guideline and policy changes. Substantial uncertainty remains, however, regarding the association between opioid prescription initiation and increased risk of subsequent substance-related morbidity.

Objective: To examine the association of opioid initiation among adolescents and young adults with subsequent broadly defined substance-related morbidity.

Design, Setting, And Participants: This cohort study analyzed population-register data from January 1, 2007, to December 31, 2013, on Swedish individuals aged 13 to 29 years by January 1, 2013, who were naive to opioid prescription. To account for confounding, the analysis compared opioid prescription recipients with recipients of nonsteroidal anti-inflammatory drugs as an active comparator, compared opioid-recipient twins and other multiple birth individuals with their nonrecipient co-multiple birth offspring (co-twin control), examined dental prescription as a specific indication, and included individual, parental, and socioeconomic covariates. Data were analyzed from March 30, 2019, to January 22, 2020.

Exposures: Opioid prescription initiation, defined as first dispensed opioid analgesic prescription.

Main Outcomes And Measures: Substance-related morbidity, assessed as clinically diagnosed substance use disorder or overdose identified from inpatient or outpatient specialist records, substance use disorder or overdose cause of death, dispensed pharmacotherapy for alcohol use disorder, or conviction for substance-related crime.

Results: Among the included cohort (n = 1 541 862; 793 933 male [51.5%]), 193 922 individuals initiated opioid therapy by December 31, 2013 (median age at initiation, 20.9 years [interquartile range, 18.2-23.6 years]). The active comparator design included 77 143 opioid recipients without preexisting substance-related morbidity and 229 461 nonsteroidal anti-inflammatory drug recipients. The adjusted cumulative incidence of substance-related morbidity within 5 years was 6.2% (95% CI, 5.9%-6.5%) for opioid recipients and 4.9% (95% CI, 4.8%-5.1%) for nonsteroidal anti-inflammatory drug recipients (hazard ratio, 1.29; 95% CI, 1.23-1.35). The co-twin control design produced comparable results (3013 opioid recipients and 3107 nonrecipients; adjusted hazard ratio, 1.43; 95% CI, 1.02-2.01), as did restriction to analgesics prescribed for dental indications and additional sensitivity analyses.

Conclusions And Relevance: Among adolescents and young adults analyzed in this study, initial opioid prescription receipt was associated with an approximately 30% to 40% relative increase in risk of subsequent substance-related morbidity in multiple designs that adjusted for confounding. These findings suggest that this increase may be smaller than previously estimated in some other studies.
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http://dx.doi.org/10.1001/jamapediatrics.2020.2539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418042PMC
August 2020

Grid-based electron-solid interaction simulation for characterizing high-dimensional microstructures.

Ultramicroscopy 2020 Oct 2;217:113070. Epub 2020 Jul 2.

Department of Civil Engineering, Monash University, Clayton 3068, Australia. Electronic address:

Three-dimensional (3D) micro- and nanostructural characterization using scanning electron microscope (SEM) and electron-solid interaction simulations (ESIS) has attracted broad interest in various research fields. However, 3D SEM-ESIS still faces key challenges in characterizing and modelling complex microstructures. In this paper, a new grid-based simulation scheme is developed to enable ESIS of complex microstructures. In contrast to the widely used region-based approach, the scheme presented here uses a grid of points to represent the spatial distribution of sample compositions, which allows numerical investigation of the effect of various geometric features such as interfacial diffusion zones and complex pores in the samples. The simulation results suggest that the interfacial diffusion zone and porosity significantly influence the scattering signals. It is believed that the presented scheme acts as a useful interpretation tool in understanding a wide range of materials and paves the way to SEM-based 3D reconstruction.
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http://dx.doi.org/10.1016/j.ultramic.2020.113070DOI Listing
October 2020

History of violence/maltreatment and psychogenic non-epileptic seizures.

Seizure 2020 Oct 14;81:8-12. Epub 2020 Jul 14.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Purpose: To study the association of earlier violence/maltreatment with the occurrence of PNES in a nationwide population sample.

Methods: This is a nested case-control study performed using Swedish nationwide registers. Cases were all individuals born in Sweden between 1941 and 2009 with incident PNES between 2001 and 2013 while resident in Sweden according to the Swedish Patient Register. For each case, 10 controls, alive and PNES-free at time of PNES diagnosis of the matched case, were randomly selected from the Swedish Total Population Register, matched on age and sex. To test the specificity of the association, we conducted two similar analyses for epilepsy and dissociative disorder with motor symptoms or deficit, as comparators to PNES. Registers were examined in search of all coded diagnoses of child maltreatment or violence episodes before the index date among the cases and controls.

Results: 885 patients received a first diagnosis of PNES. 7.6 % of cases had a history of violence/maltreatment, compared to 1.1 % of controls, giving a crude OR of 7.9 (95 % CI: 3.7-11.0). The ORs decreased but remained significant after adjustment for socio-economic factors (OR = 6.3, 95 % CI: 4.4-9.0) and psychiatric comorbidities (OR = 5.2, 95 % CI: 3.5-7.9). The association was also evident for epilepsy and dissociative disorder, although of lower magnitude.

Conclusion: Patients with PNES have a history of violence/maltreatment more frequently than the rest of the population. This association can be influenced by socio-economic factors and the presence of concurrent psychiatric disturbances.
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http://dx.doi.org/10.1016/j.seizure.2020.07.012DOI Listing
October 2020

R-spondin2 Suppresses the Progression of Hepatocellular Carcinoma via MAPK Signaling Pathway.

Mol Cancer Res 2020 10 24;18(10):1491-1499. Epub 2020 Jun 24.

Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

The family plays important roles in embryonic development, including in humans. However, information on the relationship between R-spondin2 and hepatocellular carcinoma (HCC) is lacking. This study aimed was to explore the mechanisms of R-spondin2 action in the progression of HCC. By analyzing R-spondin2 expression levels in HCC tissues by IHC and database, we identified that HCC tissues had lower expression levels of R-spondin2, correlated with a poor prognosis. We also established -overexpressing and knockdown cell lines and measured their viabilities and invasion abilities and their oncogenic capacity . Human mRNA microarray analysis was performed to screen for mRNAs that were differentially expressed between -overexpressing and control HCC cells. Microarray and Western blot analyses showed significant changes in the MAPK signaling pathway after transfection. Furthermore, experiments indicated that knockdown increased the tumorigenicity of HCC cells after subcutaneous implantation in mice. Altogether, our results indicate that the , which might be a novel tumor suppressor gene, were responsible for inhibiting the proliferation and invasion of HCC via the MAPK signaling pathway. IMPLICATIONS: gene might be a novel tumor suppressor gene providing new clues to clarify the biological behavior of HCC and thus reduce patient mortality and prolong survival.
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http://dx.doi.org/10.1158/1541-7786.MCR-19-0599DOI Listing
October 2020

Comedication and Polypharmacy With ADHD Medications in Adults: A Swedish Nationwide Study.

J Atten Disord 2020 Jun 1:1087054720923725. Epub 2020 Jun 1.

Karolinska Institutet, Stockholm, Sweden.

Evidence regarding comedication among individuals with ADHD is lacking, especially in adults. This study investigated comedication and polypharmacy with ADHD medications in adults. We identified adults dispensed with ADHD medications during 2013 in Sweden and matched them to controls. Logistic regression was used to calculate odds ratios (ORs) of receiving other medications. Individuals receiving ADHD medications had higher risk of receiving any major classes of somatic medications (ORs ranged from 4.1, 95% confidence interval [CI] = [4.0, 4.3], to 7.4, 95% CI = [6.5, 8.5] across age groups). They were more likely to receive respiratory system, alimentary tract and metabolic system, and cardiovascular system medications. In addition, they had higher risk of receiving any other psychotropic medications. The proportion of polypharmacy with five or more medication classes increased from 10.1% to 60.4% from 18 to 64 years. Comedication was more common in adults receiving ADHD medications. Potential benefits and harms of comedication and polypharmacy require further research. [] .
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http://dx.doi.org/10.1177/1087054720923725DOI Listing
June 2020

Associations between selective serotonin reuptake inhibitors and violent crime in adolescents, young, and older adults - a Swedish register-based study.

Eur Neuropsychopharmacol 2020 07 29;36:1-9. Epub 2020 May 29.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 17165 Solna, Stockholm, Sweden.

This study identified individuals ever dispensed a selective serotonin reuptake inhibitor (SSRI) aged 15-60 years during 2006-2013, using Swedish national registers. The outcome was violent crime conviction. The main statistical analyses assessed risks of violent crime during periods on compared to off SSRI treatment within individuals. Further analyses investigated risk over time in relation to treatment initiation and discontinuation. The study identified 785,337 individuals (64.2% female), experiencing 32,203 violent crimes in 5,707,293 person-years. Between-individual analyses found statistically significantly elevated Hazard Ratios (HRs) overall (HR = 1.10), and in 15-24 and 25-34 year-olds (HR = 1.19 and 1.16), but non-significant HRs in 35-44 and 45-60-year-olds (HR = 1.02 and 1.04). In within-individual analyses, where 2.6% of SSRI users were informative, hazards were elevated overall (HR = 1.26, 95% CI = 1.19, 1.34), and across age groups (HR of 1.35 [95% CI = 1.19, 1.54] in 25-34-year-olds to 1.15 [95% CI = 0.99, 1.33] in 35-44-year-olds). In the overall cohort, the within-individual HRs were significantly elevated throughout treatment (HRs of 1.24 to 1.35) and for up to 12 weeks post-discontinuation (HRs of 1.37 and 1.20). While questions on causality remain, these results indicate that there may be an increased risk of violent crime during SSRI treatment in a small group of individuals. It may persist throughout medicated periods, across age groups, and after treatment discontinuation. Further confirmation is needed from studies with different designs, and clinical focus should be on high-risk individuals, as a majority of SSRI-users (around 97% in our cohort) will not commit violent crimes.
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http://dx.doi.org/10.1016/j.euroneuro.2020.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347007PMC
July 2020

Maternal pre-pregnancy overweight/obesity and the risk of attention-deficit/hyperactivity disorder in offspring: a systematic review, meta-analysis and quasi-experimental family-based study.

Int J Epidemiol 2020 06;49(3):857-875

School of Medical Sciences, Örebro University, Örebro, Sweden.

Background: Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden.

Methods: We searched PubMed, Embase and PsycINFO during 1975-2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding.

Results: Eight cohorts with a total of 784 804 mother-child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25-1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84-2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28-1.34), HRobesity = 1.92 (1.87-1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19-1.25), HRobesity = 1.60 (1.55-1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98-1.23), HRobesity = 1.44 (1.22-1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92-1.11), HRobesity = 1.10 (0.94-1.27)].

Conclusion: Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding.
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http://dx.doi.org/10.1093/ije/dyaa040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394963PMC
June 2020