329 results on '"Wen, Shan"'
Search Results
2. A novel Multi-Level Refined (MLR) knowledge graph design and chatbot system for healthcare applications.
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Huei-Chia Hsueh, Shuo-Chen Chien, Chih-Wei Huang, Hsuan-Chia Yang, Usman Iqbal, Li-Fong Lin, and Wen-Shan Jian
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Medicine ,Science - Abstract
Imagine having a knowledge graph that can extract medical health knowledge related to patient diagnosis solutions and treatments from thousands of research papers, distilled using machine learning techniques in healthcare applications. Medical doctors can quickly determine treatments and medications for urgent patients, while researchers can discover innovative treatments for existing and unknown diseases. This would be incredible! Our approach serves as an all-in-one solution, enabling users to employ a unified design methodology for creating their own knowledge graphs. Our rigorous validation process involves multiple stages of refinement, ensuring that the resulting answers are of the utmost professionalism and solidity, surpassing the capabilities of other solutions. However, building a high-quality knowledge graph from scratch, with complete triplets consisting of subject entities, relations, and object entities, is a complex and important task that requires a systematic approach. To address this, we have developed a comprehensive design flow for knowledge graph development and a high-quality entities database. We also developed knowledge distillation schemes that allow you to input a keyword (entity) and display all related entities and relations. Our proprietary methodology, multiple levels refinement (MLR), is a novel approach to constructing knowledge graphs and refining entities level-by-level. This ensures the generation of high-quality triplets and a readable knowledge graph through keyword searching. We have generated multiple knowledge graphs and developed a scheme to find the corresponding inputs and outputs of entity linking. Entities with multiple inputs and outputs are referred to as joints, and we have created a joint-version knowledge graph based on this. Additionally, we developed an interactive knowledge graph, providing a user-friendly environment for medical professionals to explore entities related to existing or unknown treatments/diseases. Finally, we have advanced knowledge distillation techniques.
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- 2024
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3. A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies
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Monika Kumari, Ruei-Min Lu, Mu-Chun Li, Jhih-Liang Huang, Fu-Fei Hsu, Shih-Han Ko, Feng-Yi Ke, Shih-Chieh Su, Kang-Hao Liang, Joyce Pei-Yi Yuan, Hsiao-Ling Chiang, Cheng-Pu Sun, I.-Jung Lee, Wen-Shan Li, Hsing-Pang Hsieh, Mi-Hua Tao, and Han-Chung Wu
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COVID-19 ,SARS-CoV-2 ,Therapeutics ,mRNA vaccines ,Small molecule antiviral drugs ,Neutralizing antibodies ,Medicine - Abstract
Abstract The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.
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- 2022
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4. Changing surface ocean circulation caused the local demise of echinoid Scaphechinus mirabilis in Taiwan during the Pleistocene–Holocene transition
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Sze Ling Ho, Jia-Kang Wang, Yu-Jou Lin, Ching-Ren Lin, Chen-Wei Lee, Chia-Hsin Hsu, Lo-Yu Chang, To-Hsiang Wu, Chien-Chia Tseng, Hsiao-Jou Wu, Cédric M. John, Tatsuo Oji, Tsung-Kwei Liu, Wen-Shan Chen, Peter Li, Jiann-Neng Fang, and Jih-Pai Lin
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Medicine ,Science - Abstract
Abstract Abundant fossil specimens of Scaphechinus mirabilis, now occurring mostly in temperate waters, have been found in the Toukoshan Formation (Pleistocene) in Miaoli County, Taiwan. Environmental changes leading to its extirpation (local extinction) have thus far been elusive. Here, we reconstruct past environmental and oceanic conditions off northwest Taiwan by analyzing clumped isotopes, as well as stable oxygen isotopes, of well-preserved fossil echinoid tests collected from the Toukoshan Formation. Radiocarbon dates suggest that these samples are from Marine Isotope Stage 3 (MIS 3). Paleotemperature estimates based on clumped isotopes indicate that fossil echinoids were living in oceanic conditions that range from 9 to 14 °C on average, comparable with the estimate derived for a modern sample from Mutsu Bay, Japan. Notably, this temperature range is ~ 10 °C colder than today’s conditions off northwest Taiwan. The substantially lower temperatures during ~ 30 ka (MIS 3) compared to the modern conditions might be due to the rerouting of surface currents off northwest Taiwan when the sea level was ~ 60 m lower than today, in addition to the cooling caused by a lower atmospheric CO2 level during the Last Glacial Period. Colder waters brought here by the China Coastal Current (CCC) and the existence of shallow subtidal zones termed “Miaoli Bay” (mainly located in the present-day Miaoli county) during MIS 3 plausibly sustained generations of S. mirabilis, yielding tens of thousands of fossil specimens in the well-preserved fossil beds. The likely extirpation driver is the drastic change from a temperate climate to much warmer conditions in the shallow sea during the Pleistocene–Holocene transition.
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- 2022
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5. A high-throughput pipeline for scalable kit-free RNA extraction
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Ping Han, Maybelle K. Go, Jeng Yeong Chow, Bo Xue, Yan Ping Lim, Michael A. Crone, Marko Storch, Paul S. Freemont, and Wen Shan Yew
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Medicine ,Science - Abstract
Abstract An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications.
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- 2021
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6. Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study
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Shou-Sheng Chu, Yu-Hsuan Kuo, Wen-Shan Liu, Shih-Chang Wang, Chung-Han Ho, Yi-Chen Chen, Ching-Chieh Yang, and Hung-Chang Wu
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Medicine ,Science - Abstract
Abstract Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) patients. This study aims to determine whether combining radiotherapy with sorafenib administration increases its efficacy. The study cohort included 4763 patients with diagnosed advanced HCC who received sorafenib between January 2012 and December 2015, as reported in medical records in the Taiwan Cancer Registry database. The effect of sorafenib with or without radiotherapy on survival was calculated using the Kaplan–Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Patients receiving sorafenib plus radiotherapy had greater 1-year survival than did those receiving sorafenib alone (P
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- 2021
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7. Using HJ-CCD image and PLS algorithm to estimate the yield of field-grown winter wheat
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Peng-Peng Zhang, Xin-Xing Zhou, Zhi-Xiang Wang, Wei Mao, Wen-Xi Li, Fei Yun, Wen-Shan Guo, and Chang-Wei Tan
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Medicine ,Science - Abstract
Abstract Remote sensing has been used as an important means of estimating crop production, especially for the estimation of crop yield in the middle and late growth period. In order to further improve the accuracy of estimating winter wheat yield through remote sensing, this study analyzed the quantitative relationship between satellite remote sensing variables obtained from HJ-CCD images and the winter wheat yield, and used the partial least square (PLS) algorithm to construct and validate the multivariate remote sensing models of estimating the yield. The research showed a close relationship between yield and most remote sensing variables. Significant multiple correlations were also recorded between most remote sensing variables. The optimal principal components numbers of PLS models used to estimate yield were 4. Green normalized difference vegetation index (GNDVI), optimized soil-adjusted vegetation index (OSAVI), normalized difference vegetation index (NDVI) and plant senescence reflectance index (PSRI) were sensitive variables for yield remote sensing estimation. Through model development and model validation evaluation, the yield estimation model’s coefficients of determination (R2) were 0.81 and 0.74 respectively. The root mean square error (RMSE) were 693.9 kg ha−1 and 786.5 kg ha−1. It showed that the PLS algorithm model estimates the yield better than the linear regression (LR) and principal components analysis (PCA) algorithms. The estimation accuracy was improved by more than 20% than the LR algorithm, and was 13% higher than the PCA algorithm. The results could provide an effective way to improve the estimation accuracy of winter wheat yield by remote sensing, and was conducive to large-area application and promotion.
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- 2020
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8. Concomitant Hepatectomy and Atrial Thrombectomy under Cardiopulmonary Bypass versus Staged Hepatectomy in the Treatment for Hepatocellular Carcinoma with Large Right Atrial Tumor Thrombi
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Wen-Shan Chao, Ching-Hui Shen, Shao-Ciao Luo, Feng-Hsu Wu, Hao-Ji Wei, Chu-Leng Yu, Cheng-Chung Wu, Yun Yen, and Fang-Ku P’eng
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hepatocellular carcinoma ,large right atrial tumor thrombi ,cardiopulmonary bypass ,atrial thrombectomy ,hepatectomy ,Medicine - Abstract
(1) Background: Hepatocellular carcinoma (HCC) with a large right atrium tumor thrombus (RATT) is a rare and critical presentation. Emergency hepatectomy and thrombectomy under cardiopulmonary bypass (CPB) is life-saving and potentially curative. The aim of this study is to propose an appropriate approach for this condition. (2) Methods: In period A (1998 to 2010, n = 7), hepatectomy and thrombectomy were concomitantly performed, and staged hepatectomy was performed in period B (2011 to 2018, n = 17). (3) Results: The median overall survival time (MOST) in the published studies was 14 months. Moreover, the blood loss, blood transfusion rate, length of ICU stays, and hospital costs were significantly reduced in period B. The MOSTs of patients in period A (n = 6) and period B (n = 17) were 14 vs. 18 months (p = 0.099). The median disease-free survival times (MDFTs) in period A (n = 6) and period B (n = 15) were 8 vs. 14 months (p = 0.073), while the MOSTs in period A and period B were 14 vs. 24 months (p = 0.040). (4) Conclusions: Emergency thrombectomy under CPB and staged hepatectomy 4–6 weeks later may be an appropriate approach for HCC with large RATT. However, the optimal waiting interval requires further investigation.
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- 2022
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9. A novel method to retrieve alerts from a homegrown Computerized Physician Order Entry (CPOE) system of an academic medical center: Comprehensive alert characteristic analysis.
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Shuo-Chen Chien, Yen-Po Harvey Chin, Chang Ho Yoon, Md Mohaimenul Islam, Wen-Shan Jian, Chun-Kung Hsu, Chun-You Chen, Po-Han Chien, and Yu-Chuan Jack Li
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Medicine ,Science - Abstract
BackgroundThe collection and analysis of alert logs are necessary for hospital administrators to understand the types and distribution of alert categories within the organization and reduce alert fatigue. However, this is not readily available in most homegrown Computerized Physician Order Entry (CPOE) systems.ObjectiveTo present a novel method that can collect alert information from a homegrown CPOE system (at an academic medical center in Taiwan) and conduct a comprehensive analysis of the number of alerts triggered and alert characteristics.MethodsAn alert log collector was developed using the Golang programming language and was implemented to collect all triggered interruptive alerts from a homegrown CPOE system of a 726-bed academic medical center from November 2017 to June 2018. Two physicians categorized the alerts from the log collector as either clinical or non-clinical (administrative).ResultsOverall, 1,625,341 interruptive alerts were collected and classified into 1,474 different categories based on message content. The sum of the top 20, 50, and 100 categories of most frequently triggered alerts accounted for approximately 80, 90 and 97 percent of the total triggered alerts, respectively. Among alerts from the 100 most frequently triggered categories, 1,266,818 (80.2%) were administrative and 312,593 (19.8%) were clinical alerts.ConclusionWe have successfully developed an alert log collector that can serve as an extended function to retrieve alerts from a homegrown CPOE system. The insight generated from the present study could also potentially bring value to hospital system designers and hospital administrators when redesigning their CPOE system.
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- 2021
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10. Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery
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R. N. V. Krishna Deepak, Ravi Kumar Verma, Yossa Dwi Hartono, Wen Shan Yew, and Hao Fan
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lipid GPCR ,ligand access ,orthosteric and allosteric binding sites ,drug discovery ,antibody ,computational methods ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Great progress has been made over the past decade in understanding the structural, functional, and pharmacological diversity of lipid GPCRs. From the first determination of the crystal structure of bovine rhodopsin in 2000, much progress has been made in the field of GPCR structural biology. The extraordinary progress in structural biology and pharmacology of GPCRs, coupled with rapid advances in computational approaches to study receptor dynamics and receptor-ligand interactions, has broadened our comprehension of the structural and functional facets of the receptor family members and has helped usher in a modern age of structure-based drug design and development. First, we provide a primer on lipid mediators and lipid GPCRs and their role in physiology and diseases as well as their value as drug targets. Second, we summarize the current advancements in the understanding of structural features of lipid GPCRs, such as the structural variation of their extracellular domains, diversity of their orthosteric and allosteric ligand binding sites, and molecular mechanisms of ligand binding. Third, we close by collating the emerging paradigms and opportunities in targeting lipid GPCRs, including a brief discussion on current strategies, challenges, and the future outlook.
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- 2021
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11. Application of Artificial Intelligence in COVID-19 Pandemic: Bibliometric Analysis
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Md. Mohaimenul Islam, Tahmina Nasrin Poly, Belal Alsinglawi, Li-Fong Lin, Shuo-Chen Chien, Ju-Chi Liu, and Wen-Shan Jian
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COVID-19 ,artificial intelligence ,machine learning ,bibliometric analysis ,health ,coronavirus ,Medicine - Abstract
The application of artificial intelligence (AI) to health has increased, including to COVID-19. This study aimed to provide a clear overview of COVID-19-related AI publication trends using longitudinal bibliometric analysis. A systematic literature search was conducted on the Web of Science for English language peer-reviewed articles related to AI application to COVID-19. A search strategy was developed to collect relevant articles and extracted bibliographic information (e.g., country, research area, sources, and author). VOSviewer (Leiden University) and Bibliometrix (R package) were used to visualize the co-occurrence networks of authors, sources, countries, institutions, global collaborations, citations, co-citations, and keywords. We included 729 research articles on the application of AI to COVID-19 published between 2020 and 2021. PLOS One (33/729, 4.52%), Chaos Solution Fractals (29/729, 3.97%), and Journal of Medical Internet Research (29/729, 3.97%) were the most common journals publishing these articles. The Republic of China (190/729, 26.06%), the USA (173/729, 23.73%), and India (92/729, 12.62%) were the most prolific countries of origin. The Huazhong University of Science and Technology, Wuhan University, and the Chinese Academy of Sciences were the most productive institutions. This is the first study to show a comprehensive picture of the global efforts to address COVID-19 using AI. The findings of this study also provide insights and research directions for academic researchers, policymakers, and healthcare practitioners who wish to collaborate in these domains in the future.
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- 2021
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12. Prospective Evaluation of International Prediction of Pregnancy Complications Collaborative Network Models for Prediction of Preeclampsia: Role of Serum sFlt-1 at 11–13 Weeks’ Gestation
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Wen Shan Sim, Shuk Yi Annie Hui, Mahesh Choolani, Runmei Ma, Noppadol Chaiyasit, Daljit Singh Sahota, Tuangsit Wataganara, Piya Chaemsaithong, Liona C. Poon, and Y. M. Wah
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Adult ,Placental growth factor ,medicine.medical_specialty ,Mean arterial pressure ,Blood Pressure ,Preeclampsia ,Pre-Eclampsia ,Pregnancy ,medicine.artery ,Internal Medicine ,medicine ,Humans ,Prospective Studies ,Uterine artery ,reproductive and urinary physiology ,Placenta Growth Factor ,Vascular Endothelial Growth Factor Receptor-1 ,Obstetrics ,business.industry ,Gestational age ,medicine.disease ,female genital diseases and pregnancy complications ,Pregnancy Trimester, First ,Blood pressure ,embryonic structures ,Gestation ,Female ,business ,Biomarkers - Abstract
The study aimed to investigate whether serum sFlt-1 (soluble fms-like tyrosine kinase-1) at 11-13 weeks’ gestation in pregnancies that subsequently developed preeclampsia was different from those without preeclampsia and compare screening performance of the International Prediction of Pregnancy Complications (IPPIC) reported models, which include various combinations of maternal factors, systolic blood pressure, diastolic blood pressure, PlGF (placental growth factor) and sFlt-1 and the competing risk (CR) models, which include various combinations of maternal factors, mean arterial pressure (MAP) and PlGF for predicting any-onset, early-onset, and late-onset preeclampsia. This was a prospective multicenter study in 7877 singleton pregnancies. The differences of the predictive performance between the IPPIC and CR models were compared. There were 141 women (1.79%) who developed preeclampsia, including 13 cases (0.17%) of early-onset preeclampsia and 128 cases (1.62%) of late-onset preeclampsia. In pregnancies that developed preeclampsia compared to unaffected pregnancies, median serum sFlt-1 levels and its MoMs were not significantly different ( p >0.05). There was no significant association between gestational age at delivery and log 10 sFlt-1 and log 10 sFlt-1 MoM ( p >0.05). The areas under the curve of CR models were significantly higher than the IPPIC models for the prediction of any-onset and late-onset preeclampsia but not for early-onset preeclampsia. In conclusion, there are no significant differences in the maternal serum sFlt-1 levels at 11-13 weeks’ gestation between women who subsequently develop preeclampsia and those who do not. Moreover, the CR models for the prediction of any-onset and late-onset preeclampsia perform better than the IPPIC reported model.
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- 2022
13. A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo
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Shi-Jie Zhang, Yi-Fang Li, Rui-Rong Tan, Bun Tsoi, Wen-Shan Huang, Yi-Hua Huang, Xiao-Long Tang, Dan Hu, Nan Yao, Xuesong Yang, Hiroshi Kurihara, Qi Wang, and Rong-Rong He
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Hyperglycemia ,Eye malformation ,Pax6 ,Oxidative stress ,Chick embryo ,Medicine ,Pathology ,RB1-214 - Abstract
Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. Results showed that 47.3% of embryonic eye malformation happened on EDD 5. In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. Among these genes, the expression of Pax6 was the most vulnerable to hyperglycemia, being suppressed by 70%. A reduction in Pax6 gene expression induced eye malformation in chick embryos. However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation.
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- 2016
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14. Identification of core genes and pathways in major depressive disorder by bioinformatic methods
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Wen-Shan Yang and Yuan Hu
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signaling pathway ,major depressive disorder ,differentially-expressed genes ,Medicine ,bioinformatics - Abstract
Objective: This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus (GEO) public database of the National Center for Biotechnology Information (NCBI) website. Methods: The whole-transcriptome brain expression profile dataset (GSE101521) was obtained from the GEO database. Differentially-expressed genes (DEGs) in normal group (non-psychiatric human) and MDD group (depressive patients) were identified applying Networkanalyst online database. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to function annotation and enrichment analysis. After that, STRING online database was conducted to protein–protein interaction (PPI) network, and Cytoscape.3.7.2 software was performed to module analysis. Results: Out of the 41 DEGs identified from normal tissue samples and MDD, 39 were upregulated and 2 were downregulated. GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response, and KEGG pathway analysis suggested that the most chiefly pathway related to MDD were IL-17 signaling pathway, TNF signaling pathway and NOD-like receptor signaling pathway. Six hub genes (IL6, CXCL8, IL1B, FOS, CCL2 and CXCL2) were identified by PPI network and module analysis. Conclusion: Our current study detected novel markers and targets involved immune system, which are involved in pivotal biological mechanisms related to the pathogenesis of major depression. Looking forward, these findings still need to be validated in future experimental studies.
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- 2021
15. Contralateral lymph node recurrence rate and its prognostic factors in stage IVA-B well-lateralized oral cavity cancer
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Yu-Chang Hu, Ju-Chun Chien, Chien-Yu Huang, Kuo-Chen Chang, Wen-Shan Liu, Yu-Hsien Huang, and Bor-Hwang Kang
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Adult ,Male ,medicine.medical_specialty ,Nodal irradiation ,Perineural invasion ,Oral cavity ,03 medical and health sciences ,0302 clinical medicine ,Median follow-up ,medicine ,Humans ,Neoplasm Invasiveness ,Stage (cooking) ,030223 otorhinolaryngology ,Lymph node ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Aged, 80 and over ,Gingival Neoplasms ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Mouth Mucosa ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Neck Dissection ,Female ,Mouth Neoplasms ,Radiotherapy, Adjuvant ,Lymph Nodes ,Neoplasm Recurrence, Local ,NODAL ,business - Abstract
Purpose To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. Materials and methods Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. Results From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. Conclusions Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.
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- 2021
16. Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery
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R. N. V. Krishna Deepak, Ravi Kumar Verma, Yossa Dwi Hartono, Wen Shan Yew, and Hao Fan
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lysophosphatidic acid receptor ,platelet-activating factor receptor ,Pharmaceutical Science ,ligand access ,cannabinoid receptor ,Review ,drug discovery ,lipid GPCR ,RS1-441 ,leukotriene receptor ,computational methods ,Pharmacy and materia medica ,antibody ,prostaglandin receptor ,sphingosine-1-phosphate receptor ,orthosteric and allosteric binding sites ,Molecular Medicine ,Medicine ,free fatty acid receptor - Abstract
Great progress has been made over the past decade in understanding the structural, functional, and pharmacological diversity of lipid GPCRs. From the first determination of the crystal structure of bovine rhodopsin in 2000, much progress has been made in the field of GPCR structural biology. The extraordinary progress in structural biology and pharmacology of GPCRs, coupled with rapid advances in computational approaches to study receptor dynamics and receptor-ligand interactions, has broadened our comprehension of the structural and functional facets of the receptor family members and has helped usher in a modern age of structure-based drug design and development. First, we provide a primer on lipid mediators and lipid GPCRs and their role in physiology and diseases as well as their value as drug targets. Second, we summarize the current advancements in the understanding of structural features of lipid GPCRs, such as the structural variation of their extracellular domains, diversity of their orthosteric and allosteric ligand binding sites, and molecular mechanisms of ligand binding. Third, we close by collating the emerging paradigms and opportunities in targeting lipid GPCRs, including a brief discussion on current strategies, challenges, and the future outlook.
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- 2022
17. Investigation of the proton relay system operative in human cystosolic aminopeptidase P.
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Hui-Chuan Chang, Camy C-H Kung, Tzu-Ting Chang, Shu-Chuan Jao, Yu-Ting Hsu, and Wen-Shan Li
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Medicine ,Science - Abstract
Aminopeptidase P, a metalloprotease, targets Xaa-Proline peptides for cleavage [1-4]. There are two forms of human AMPP, a membrane-bound form (hmAMPP) and a soluble cytosolic form (hcAMPP)[5]. Similar to the angiotensin-I-converting enzyme, AMPP plays an important role in the catabolism of inflammatory and vasoactive peptides, known as kinins. The plasma kinin, bradykinin, was used as the substrate to conduct enzymatic activity analyses and to determine the Michaelis constant (Km) of 174 μM and the catalytic rate constant (kcat) of 10.8 s-1 for hcAMPP. Significant differences were observed in the activities of Y527F and R535A hcAMPP mutants, which displayed a 6-fold and 13.5-fold for decrease in turnover rate, respectively. Guanidine hydrochloride restored the activity of R535A hcAMPP, increasing the kcat/Km 20-fold, yet it had no impact on the activities of the wild-type or Y527F mutant hcAMPPs. Activity restoration by guanidine derivatives followed the order guanidine hydrochloride >> methyl-guanidine > amino-guanidine > N-ethyl-guanidine. Overall, the results indicate the participation of R535 in the hydrogen bond network that forms a proton relay system. The quaternary structure of hcAMPP was determined by using analytical ultracentrifugation (AUC). The results show that alanine replacement of Arg535 destabilizes the hcAMPP dimer and that guanidine hydrochloride restores the native monomer-dimer equilibrium. It is proposed that Arg535 plays an important role in hcAMMP catalysis and in stabilization of the catalytically active dimeric state.
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- 2018
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18. Congenital disorder of glycosylation caused by mutation of ATP6AP1 gene (c.1036G>A) in a Chinese infant: A case report
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Mei-Xiong Yang, Zi-Li Lv, Li Huang, Lian-Cheng Lan, Xiu-Qi Chen, Qing Tang, Xia Yang, and Qing-Wen Shan
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Genetics ,congenital, hereditary, and neonatal diseases and abnormalities ,business.industry ,General Medicine ,medicine.disease ,carbohydrates (lipids) ,ATP6AP1 Gene ,ATP6AP1 mutation ,Cognitive impairment ,Mutation (genetic algorithm) ,Case report ,medicine ,Immunodeficiency ,lipids (amino acids, peptides, and proteins) ,Congenital disorders of glycosylation ,Hepatopathy ,business ,Congenital disorder of glycosylation - Abstract
BACKGROUND The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases (V-ATPase) is located on chromosome Xq28. Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation (CDG). CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs. Therefore, the clinical presentation of patients with ATP6AP1-CDG varies widely. In this report, we present a case of ATP6AP1-CDG in a Chinese infant, with clinical features and genotype. CASE SUMMARY An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital. A post-admission examination at our hospital revealed abnormalities in the infant’s liver, brain, and immune system. Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A (p.E346K) in exon 9 of the ATP6AP1 gene. This variant of the ATP6AP1 gene has not been reported in East Asian countries until now. CONCLUSION Based on the infant’s clinical manifestations and the results of genetic detection, he was clearly diagnosed with ATP6AP1-CDG. The clinical manifestations of children with CDG vary widely. Genetic testing analysis helps in the clinical diagnosis of children with CDG.
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- 2021
19. Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3 rd Month Virological Response to Entecavir Therapy: A Study of Strict Defined Hepatitis B virus Induced Cirrhosis
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Yang Xu, Xiao-Ning Wu, Yi-Wen Shi, Wei Wei, Ai-Ting Yang, Ya-Meng Sun, Wen-Shan Zhao, and Hong You
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Area Under Receiver Operating Characteristic Curve ,Baseline Parameters ,Cirrhosis ,Entecavir ,Hepatitis B viral ,Medicine - Abstract
Background: Cirrhosis is a common complication of chronic hepatitis B. It remains unclear if viral and biochemical parameters at baseline affect virological response to entecavir and therefore warrant investigation. In the present study, we aimed to evaluate the efficacy of entecavir therapy by monitoring virological response at the end of the 3 rd month of treatment and try to figure out whether baseline factors could help predict it in a cohort of hepatitis B virus (HBV) compensated cirrhosis patients and to determine the cut-off value of a predicting parameter. Methods: A total of 91 nucleos(t)ide-naïve patients with HBV induced cirrhosis (compensatory stage) were enrolled in a prospective cohort. HBV DNA and alanine aminotransferase (ALT) were tested at baseline and monitored every 3-6 months after starting therapy. Results: Of all 91 patients, the median follow-up time was 12 (9-24) months. Overall, 64 patients (70.3%) achieved virological response in the 3 rd month. Univariate analysis showed that the 3 rd month virological response can be predicted by baseline HBV DNA levels (P < 0.001, odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.44-3.15), ALT value (P = 0.023, OR: 1.01, 95% CI: 1.00-1.01) and hepatitis B e antigen (HBeAg) negativity (P = 0.016, OR: 0.30, 95% CI: 0.11-0.80). Multiple regression analysis showed baseline HBV DNA level was the only parameter related to full virological response. Higher baseline HBV DNA strata indicated a higher probability that HBV DNA remains detectable at the 3 rd month (P = 0.001). Area under receiver operating characteristic curve for determining the 3 rd month virological response by baseline HBV DNA was 77.6% (95% CI: 66.7-85.2%), with a best cut-off value of 5.8 log 10 . Conclusions: Baseline HBV DNA, HBeAg negativity, and ALT were independent factors contributing to virological response at the 3 rd month. Further, multiple regression showed that HBV DNA level was the only parameter predicting full virological response as early as the 3 rd month, in this cirrhosis cohort.
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- 2015
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20. Hybrid robot-assisted gait training for motor function in subacute stroke: a single-blind randomized controlled trial
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Shih-Wei Huang, Yen-Nung Lin, Hung Chou Chen, Wen-Shan Jian, Yi-Chun Kuan, and Li-Fong Lin
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medicine.medical_specialty ,business.industry ,Subacute stroke ,Rehabilitation ,Stroke Rehabilitation ,Health Informatics ,Robotics ,Motor function ,law.invention ,Stroke ,Physical medicine and rehabilitation ,Polymethacrylic Acids ,Randomized controlled trial ,Gait training ,law ,Organometallic Compounds ,Humans ,Robot ,Medicine ,Single-Blind Method ,Single blind ,business ,Gait ,Retrospective Studies - Abstract
Background Robot-assisted gait training (RAGT) is a practical treatment that can complement conventional rehabilitation by providing high-intensity repetitive training for patients with stroke. RAGT systems are usually either of the end-effector or exoskeleton types. We developed a novel hybrid RAGT system that leverages the advantages of both types. Objective This single-blind randomized controlled trial evaluated the beneficial effects of the novel RAGT system both immediately after the intervention and at the 3-month follow-up in nonambulatory patients with subacute stroke. Methods We recruited 40 patients with subacute stroke who were equally randomized to receive conventional rehabilitation either alone or with the addition of 15 RAGT sessions. We assessed lower-extremity motor function, balance, and gait performance by using the following tools: active range of motion (AROM), manual muscle test (MMT), the Fugl–Meyer Assessment (FMA) lower-extremity subscale (FMA-LE) and total (FMA-total), Postural Assessment Scale for Stroke (PASS), Berg Balance Scale (BBS), Tinetti Performance-Oriented Mobility Assessment (POMA) balance and gait subscores, and the 3-m and 6-m walking speed and Timed Up and Go (TUG) tests. These measurements were performed before and after the intervention and at the 3-month follow-up. Results Both groups demonstrated significant within-group changes in the AROM, MMT, FMA-LE, FMA-total, PASS, BBS, POMA, TUG, and 3-m and 6-m walking speed tests before and after intervention and at the 3-month follow-up (p p = 0.014) and total (p = 0.002) assessments. Conclusion Although the novel hybrid RAGT is effective, strong evidence supporting its clinical effectiveness relative to controls in those with substantial leg dysfunction after stroke remains elusive. Trial registration The study was registered with an International Standard Randomized Controlled Trial Number, ISRCTN, ISRCTN15088682. Registered retrospectively on September 16, 2016, at https://www.isrctn.com/ISRCTN15088682
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- 2022
21. Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder
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Ping Huang, Hengfen Li, Hong-Zeng Zhao, Shao-Jie Kou, Chang-Hong Wang, Xunan Wang, Zhi-Rong Li, De-En Sang, Xian-Zhang Hu, Zongya Zhao, Xiao-Wen Shan, Li-Jing Shi, Hong-Kai Lian, and Jian-Dong Ma
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0301 basic medicine ,medicine.medical_specialty ,genetic structures ,medicine.diagnostic_test ,business.industry ,Left amygdala ,Parietal lobe ,Posterior parietal cortex ,Amygdala ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,Text mining ,Pharmacotherapy ,medicine.anatomical_structure ,Internal medicine ,medicine ,Cardiology ,business ,Functional magnetic resonance imaging ,Molecular Biology ,030217 neurology & neurosurgery ,Anterior cingulate cortex - Abstract
It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.
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- 2021
22. Screening potential FDA-approved inhibitors of the SARS-CoV-2 major protease 3CLpro through high-throughput virtual screening and molecular dynamics simulation
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Hai-Xia Zhang, Wen-Shan Liu, Jia-Qiu Li, Chuan-Hua Ding, Han-Gao Li, and Rui-Rui Wang
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chemistry.chemical_classification ,Aging ,Virtual screening ,Protease ,Chemistry ,Drug discovery ,viruses ,medicine.medical_treatment ,virus diseases ,Cell Biology ,medicine.disease_cause ,Molecular Docking Simulation ,Enzyme ,Biochemistry ,Indinavir ,Docking (molecular) ,medicine ,Coronavirus ,medicine.drug - Abstract
It has been confirmed that the new coronavirus SARS-CoV-2 caused the global pandemic of coronavirus disease 2019 (COVID-19). Studies have found that 3-chymotrypsin-like protease (3CLpro) is an essential enzyme for virus replication, and could be used as a potential target to inhibit SARS-CoV-2. In this work, 3CLpro was used as the target to complete the high-throughput virtual screening of the FDA-approved drugs, and Indinavir and other 10 drugs with high docking scores for 3CLpro were obtained. Studies on the binding pattern of 3CLpro and Indinavir found that Indinavir could form the stable hydrogen bond (H-bond) interactions with the catalytic dyad residues His41-Cys145. Binding free energy study found that Indinavir had high binding affinity with 3CLpro. Subsequently, molecular dynamics simulations were performed on the 3CLpro and 3CLpro-Indinavir systems, respectively. The post-dynamic analyses showed that the conformational state of the 3CLpro-Indinavir system transformed significantly and the system tended to be more stable. Moreover, analyses of the residue interaction network (RIN) and H-bond occupancy revealed that the residue-residue interaction at the catalytic site of 3CLpro was significantly enhanced after binding with Indinavir, which in turn inactivated the protein. In short, through this research, we hope to provide more valuable clues against COVID-19.
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- 2021
23. Simultaneous Reduction of Volume and Dose in Clinical Target Volume for Nasopharyngeal Cancer Patients
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Wen-Shan Liu, Yaoh-Shiang Lin, Ching-Chih Lee, Kuo-Wang Tsai, Wei-Lun Huang, Ching-Chieh Yang, Bor-Hwang Kang, Yu-Chang Hu, Kuo-Ping Chang, and Hsiu-Min Chen
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Endpoint Determination ,Planning target volume ,Gastroenterology ,Disease-Free Survival ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Adverse effect ,Aged ,Retrospective Studies ,Nasopharyngeal cancer ,Radiation ,business.industry ,Proportional hazards model ,Dose-Response Relationship, Radiation ,Nasopharyngeal Neoplasms ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Dysphagia ,Comorbidity ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,business - Abstract
To compare the treatment outcome and severe late adverse effects (AEs) between conventional volume and dose (CVD) and simultaneously reduced volume and dose (SRVD) of clinical target volume treatments in patients with nasopharyngeal carcinoma.This retrospective cohort study enrolled patients with nonmetastatic stage II to IV nasopharyngeal cancer from a single institute. Survival endpoints and severe (≥grade 3) late AEs and comorbidity were compared between groups. The correlation of severe late AEs, comorbidity, and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression methods.From January 2012 to June 2017, this study enrolled 178 patients, 64 in the CVD group and 114 in the SRVD group. The 2 groups did not differ significantly in patient characteristics except for mean follow-up time (37.6 vs 48.8 months; P = .01). The SRVD group did not significantly differ from the CVD group in local control survival (82.0% vs 78.4%; P = .85), regional control survival (89.9% vs 86.0%; P = .62), or disease-free survival (76.4% vs 66.9%; P = .67). The SRVD group had significantly better OS (93.9% vs 67.0%; P.001) and salvage survival (79.3% vs 20.7%; P.01) and a significantly lower ratio of severe lung infection (1 of 113 vs 5 of 59; P = .02). The SRVD group had a significantly lower risk of mortality (hazard ratio [HR], 0.3; P = .03). The factors associated with a significantly higher risk of mortality were N3 (regional lymph node stage status of N3) (HR, 3.0; P = .02); comorbidities of diabetes, coronary artery disease, or chronic kidney disease (grades 2-3) (HR, 3.8; P = .009), and severe lung infection (HR, 6.3; P = .007).Simultaneously reduced volume and dose of clinical target volumes did not impair locoregional control or disease-free survival. The benefits of SRVD treatment may include significant reduction in severe late AEs, particularly lung infection, dysphagia, and xerostomia. However, additional studies with longer patient follow-up are required to confirm these benefits.
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- 2021
24. Postoperative radiotherapy is associated with improved survival in pT1-2N1 oral and oropharyngeal cancer without adequate neck dissection
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Wen-Shan Liu, Ching-Chih Lee, Bor-Hwang Kang, Chun-Hao Yin, and Ching-Chieh Yang
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Adult ,Male ,lcsh:Medical physics. Medical radiology. Nuclear medicine ,medicine.medical_specialty ,Survival ,medicine.medical_treatment ,lcsh:R895-920 ,Neck dissection ,Gastroenterology ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,030223 otorhinolaryngology ,Aged ,Neoplasm Staging ,Oropharyngeal cancer ,Radiotherapy ,business.industry ,Research ,Oral cancer ,Hazard ratio ,Confounding ,Cancer ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Primary tumor ,Combined Modality Therapy ,Confidence interval ,Radiation therapy ,Oropharyngeal Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,Female ,Mouth Neoplasms ,business - Abstract
Background To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection. Methods In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection. Results Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49–0.84) in those with Conclusion Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.
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- 2021
25. Comparison of the antioxidant activities of nonfumigated and sulphur-fumigated Chrysanthemum morifolium cv. Hang-ju induced by oxidative stress
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Jing-Jing Zhu, Qi Huang, Shanshan Liu, Wen-Shan Qu, Fujiang Chu, Hongyan Ma, Zhi-Min Wang, Xinlin Lv, Yu-Yun Zhu, and Linyuan Li
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Male ,Antioxidant ,huvecs ,Chrysanthemum ,medicine.medical_treatment ,Fumigation ,Pharmaceutical Science ,chemistry.chemical_element ,medicine.disease_cause ,030226 pharmacology & pharmacy ,01 natural sciences ,Antioxidants ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,compositae ,Drug Discovery ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Pharmacology ,biology ,Dose-Response Relationship, Drug ,Chemistry ,Plant Extracts ,hyperlipidaemia ,Chrysanthemum morifolium ,lcsh:RM1-950 ,apoptosis ,General Medicine ,biology.organism_classification ,Sulfur ,0104 chemical sciences ,Rats ,010404 medicinal & biomolecular chemistry ,Horticulture ,Oxidative Stress ,lcsh:Therapeutics. Pharmacology ,Complementary and alternative medicine ,drying process ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Oxidative stress ,Research Article - Abstract
Context The traditional drying method, sun drying, for Chrysanthemum morifolium Ramat. cv. Hang-ju (Compositae) (HJ) is widely replaced by sulphur fumigation (SF), which has an unknown effect on its efficacy. Objective To investigate protective effects of nonfumigated HJ (NHJ) and sulphur-fumigated HJ (SHJ) water extracts against oxidative stress and lipid peroxidation. Materials and methods Sprague-Dawley rats were administered high-fat diet to induce hyperlipidaemia and randomly divided into eight groups (n = 6): control, fenofibrate, NHJ and SHJ extracts (1, 2 or 4 g crude drugs/kg/d; intragastric administration for 8 weeks). Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected. Human umbilical vein endothelial cells (HUVECs) were treated with NHJ and SHJ extracts (50, 100 or 200 μg/mL) for 24 h, followed by oxidized low-density lipoprotein (ox-LDL, 20 μg/mL) for 2 h in vitro. Cellular reactive oxygen species (ROS), SOD and MDA levels and apoptosis were evaluated. Results NHJ was more effective than SHJ in decreasing serum TG, TC, LDL-C, LDL/HDL and MDA while increasing serum HDL-C and SOD levels at high doses. SHJ (IC50=19.9 mg/mL) suppressed HUVEC growth stronger than NHJ (IC50=186.7 mg/mL). At 200 μg/mL, NHJ was more effective than SHJ in downregulating ROS and MDA levels, reducing HUVECs apoptosis rate and elevating SOD activity in ox-LDL-treated HUVECs. Conclusions SF causes oxidative damage and attenuates antioxidative activity in ox-LDL-treated HUVECs, which promotes lipid peroxidation. SF is not recommended for processing HJ.
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- 2021
26. Sialyltransferase Inhibitors Suppress Breast Cancer Metastasis
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Tzu-Ting Chang, Han-En Tsai, Wei-Sheng Chen, Chih-Wei Fu, Wen-Shan Li, Pei-Wen Hsiao, and Chia-Ling Chen
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Talin ,Integrins ,Angiogenesis ,Sialyltransferase ,Integrin ,Breast Neoplasms ,01 natural sciences ,Catalysis ,Metastasis ,Animals, Genetically Modified ,03 medical and health sciences ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,Neoplasm Metastasis ,Phosphorylation ,Zebrafish ,Paxillin ,Glycoproteins ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,NF-kappa B ,Cell migration ,medicine.disease ,Sialyltransferases ,0104 chemical sciences ,Isoenzymes ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Focal Adhesion Protein-Tyrosine Kinases ,Cancer cell ,Cancer research ,biology.protein ,Molecular Medicine ,Female ,Signal transduction ,Signal Transduction - Abstract
We report the synthesis and evaluation of a series of cell-permeable and N- versus O-selective sialyltransferase inhibitors. Inhibitor design entailed the functionalization of lithocholic acid at C(3) and at the cyclopentane ring side chain. Among the series, FCW34 and FCW66 were shown to inhibit MDA-MB-231 cell migration as effectively as ST3GALIII-gene knockdown did. FCW34 was shown to inhibit tumor growth, reduce angiogenesis, and delay cancer cell metastasis in animal models. Furthermore, FCW34 inhibited vessel development and suppressed angiogenic activity in transgenic zebrafish models. Our results provide clear evidence that FCW34-induced sialyltransferase inhibition reduces cancer cell metastasis by decreasing N-glycan sialylation, thus altering the regulation of talin/integrin/FAK/paxillin and integrin/NFκB signaling pathways.
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- 2020
27. The emerging role of the MiR-1272-ADAM9-CDCP1 signaling pathway in the progression of glioma
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Xiao-Mei Luo, Gui-Feng Lu, Min Hu, Zhi-Shui Jiang, Sky Dominguez, Yuan-Shou Chen, Xin Yang, Fei Geng, Wen-Shan Lai, Lian-Hua Shen, De-Ying Kong, and Yu-Jun Luo
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Aging ,miR-1272 ,ADAM9 ,CDCP1 ,Brain tumor ,Astrocytoma ,Biology ,Cell Line ,Antigens, Neoplasm ,Cell Movement ,Cell Line, Tumor ,Glioma ,medicine ,Humans ,neoplasms ,Cell Proliferation ,Brain Neoplasms ,Cell growth ,Membrane Proteins ,Cell Biology ,Cell cycle ,medicine.disease ,G1 Phase Cell Cycle Checkpoints ,nervous system diseases ,ADAM Proteins ,MicroRNAs ,Disease Progression ,Cancer research ,Ectopic expression ,Signal transduction ,Glioblastoma ,Cell Adhesion Molecules ,Signal Transduction ,Research Paper - Abstract
Glioma is a primary, malignant, and aggressive brain tumor in adults. To develop new therapeutic strategies for glioma, we must determine its underlying mechanisms. In the present study, we aimed to investigate the potential role of miR-1272-ADAM9-CDCP1 signaling in the progression of glioma. We found that ectopic expression of miR-1272 produced significant inhibitory effects on cell proliferation and migration and was associated with cell cycle G0/G1 arrest in A172 and SHG44 glioma cells. Using the luciferase reporter assay, we identified ADAM9 as a target of miR-1272. The expression of ADAM9 was markedly decreased or increased after overexpression or inhibition, respectively, of miR-1272 in glioma cells. Moreover, overexpression of ADAM9 reversed the inhibitory effects of miR-1272 on glioma cell progression. Furthermore, CDCP1 served as a potential downstream molecule of miR-1272/ADAM9 signaling in glioma and promoted the proliferation and migration of glioma. Results derived from clinical samples and online databases confirmed correlations between the expression of ADAM9 and CDCP1 and both the severity and prognosis of glioma. In conclusion, these results suggest that miR-1272 and CDCP1 may act as novel regulators in glioma. The miR-1272/ADAM9/CDCP1 pathway may serve as a potential candidate pathway for the prevention of glioma.
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- 2020
28. Correlation Between Previous Caesarean Section and Adverse Maternal Outcomes Accordingly With Robson Classification: Systematic Review and Meta-Analysis
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Shazia Jamshed, Shuo-Chen Chien, Afifa Tanweer, Rahma-Novita Asdary, Muhammad Hardhantyo, David Greenfield, Chia-Hui Chien, Shuen-Fu Weng, Wen-Shan Jian, and Usman Iqbal
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Medicine (General) ,public health practice ,R5-920 ,genetic structures ,adverse maternal outcomes ,Medicine ,global health ,General Medicine ,Systematic Review ,previous caesarean section ,World Health Organisation - Robson Classification ,women's health - Abstract
Background: The increasing rates of Caesarean section (CS) beyond the WHO standards (10–15%) pose a significant global health concern.Objective: Systematic review and meta-analysis to identify an association between CS history and maternal adverse outcomes for the subsequent pregnancy and delivery among women classified in Robson classification (RC).Search Strategy: PubMed/Medline, EbscoHost, ProQuest, Embase, Web of Science, BIOSIS, MEDLINE, and Russian Science Citation Index databases were searched from 2008 to 2018.Selection Criteria: Based on Robson classification, studies reporting one or more of the 14 adverse maternal outcomes were considered eligible for this review.Data Collection: Study design data, interventions used, CS history, and adverse maternal outcomes were extracted.Main Results: From 4,084 studies, 28 (n = 1,524,695 women) met the inclusion criteria. RC group 5 showed the highest proportion among deliveries followed by RC10, RC7, and RC8 (67.71, 32.27, 0.02, and 0.001%). Among adverse maternal outcomes, hysterectomy had the highest association after preterm delivery OR = 3.39 (95% CI 1.56–7.36), followed by Severe Maternal Outcomes OR = 2.95 (95% CI 1.00–8.67). We identified over one and a half million pregnant women, of whom the majority were found to belong to RC group 5.Conclusions: Previous CS was observed to be associated with adverse maternal outcomes for the subsequent pregnancies. CS rates need to be monitored given the prospective risks which may occur for maternal and child health in subsequent births.
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- 2022
29. Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.
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Wei-Hsin Ting, Ming-Nan Chien, Fu-Sung Lo, Chao-Hung Wang, Chi-Yu Huang, Chiung-Ling Lin, Wen-Shan Lin, Tzu-Yang Chang, Horng-Woei Yang, Wei-Fang Chen, Ya-Ping Lien, Bi-Wen Cheng, Chao-Hsu Lin, Chia-Ching Chen, Yi-Lei Wu, Chen-Mei Hung, Hsin-Jung Li, Chon-In Chan, and Yann-Jinn Lee
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Medicine ,Science - Abstract
Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.
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- 2016
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30. DORSCON Orange: An Approach to Challenges in a Busy Antenatal Diagnostic Centre in the Midst of a Global Pandemic
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Hak Koon Tan, June Vk Tan, George S. H. Yeo, Glenda Sl Chong, Chee Wai Ku, Kok Hian Tan, Wen Shan Sim, Shephali Tagore, and Valencia R Y Zhang
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Coronavirus disease 2019 (COVID-19) ,Physical Distancing ,Personnel Staffing and Scheduling ,Hospitals, Maternity ,030204 cardiovascular system & hematology ,Ultrasonography, Prenatal ,Obstetric care ,Patient Isolation ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Pandemic ,Health care ,Humans ,Medicine ,Infection control ,030212 general & internal medicine ,Personal Protective Equipment ,Obstetrics ultrasound ,Singapore ,business.industry ,Fetoscopy ,COVID-19 ,Outbreak ,Prenatal Care ,General Medicine ,medicine.disease ,Chorionic Villi Sampling ,Amniocentesis ,Female ,Medical emergency ,business ,Delivery of Health Care ,Response system - Abstract
The WHO declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Lessons from SARS epidemic led Singapore to develop stringent infection control protocols in preparation for future pandemics. However, unlike SARS, COVID-19 appears to be more transmissible and is predicted to continue for longer. As of 14 June 2020, there have been 40,197 positive cases with 26 deaths in Singapore, and KK Women’s and Children’s Hospital (KKH) has managed a total of 73 cases. Obstetrics ultrasound is an indispensable medical service and must continue to operate during a pandemic. A key balance must be struck between keeping patients and healthcare workers safe while being able to provide quality and prompt obstetric care. Our Antenatal Diagnostic Centre (ADC) in KKH developed new strategies to adapt to the pandemic when the national Disease Outbreak Response System Condition (DORSCON) was raised from yellow to orange on 7 February 2020. In this paper, we discuss our clinical workflow to reduce the risk of transmission amongst patients and staff while minimising disruption to our services.
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- 2020
31. Effects of low temperature in spring on fertility of pollen and formation of grain number in wheat
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Wen-Shan Guo, Jin-Feng Ding, Yuxue Zhang, Shengnan Su, Chun-yan Li, Min Zhu, Quan Ma, Xinkai Zhu, and Yun Gao
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geography ,geography.geographical_feature_category ,media_common.quotation_subject ,Grain number ,Fertility ,Plant Science ,Biology ,medicine.disease_cause ,Agronomy ,Pollen ,Spring (hydrology) ,medicine ,Agronomy and Crop Science ,Biotechnology ,media_common - Published
- 2020
32. Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case–control sample
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Luan-Yin Chang, Hsin Chi, Chiung-Ling Lin, Lung Chang, Tzu-Yang Chang, Fu-Yuan Huang, Ya-Ping Lien, Yann-Jinn Lee, Daniel Tsung-Ning Huang, Wen-Shan Lin, Ming-Ren Chen, Nan-Chang Chiu, and Kuender D. Yang
- Subjects
Male ,lcsh:Medicine ,Genome-wide association study ,Diseases ,Pathogenesis ,Gene Frequency ,Odds Ratio ,Child ,lcsh:Science ,Genetics ,education.field_of_study ,Multidisciplinary ,Molecular medicine ,Middle Aged ,Child, Preschool ,Female ,Systemic vasculitis ,Adult ,Adolescent ,Genotype ,Population ,Immunology ,Taiwan ,Single-nucleotide polymorphism ,Biology ,Mucocutaneous Lymph Node Syndrome ,Polymorphism, Single Nucleotide ,Article ,Young Adult ,Medical research ,Asian People ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,education ,Alleles ,Genetic association ,Aged ,lcsh:R ,Genetic Variation ,Infant ,Odds ratio ,medicine.disease ,Risk factors ,Case-Control Studies ,Kawasaki disease ,lcsh:Q ,Biomarkers ,Genome-Wide Association Study - Abstract
Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10–5; C allele, OR = 1.32, P = 8.1 × 10–4). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.
- Published
- 2020
33. Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down‐regulating BRD4
- Author
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Ran Yan, Ruimin Sun, Jihong Yao, Yanwen Lan, Ning Zhang, Yan Zhao, Ruiwen Wang, Zhanyu Wang, Wen Shan, and Junyi Chu
- Subjects
Male ,0301 basic medicine ,Alcoholic liver disease ,Cirrhosis ,medicine.medical_treatment ,Down-Regulation ,chemical and pharmacologic phenomena ,Pharmacology ,Protective Agents ,HMGB1 ,Chronic liver disease ,Pathogenesis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,HMGB1 Protein ,Rats, Wistar ,Liver Diseases, Alcoholic ,Cells, Cultured ,Cell Nucleus ,Inflammation ,Liver injury ,biology ,business.industry ,Nuclear Proteins ,Original Articles ,Cell Biology ,medicine.disease ,SAA ,Rats ,030104 developmental biology ,Cytokine ,Liver ,030220 oncology & carcinogenesis ,Lactates ,biology.protein ,Cytokines ,BRD4 ,Molecular Medicine ,Original Article ,Steatohepatitis ,business ,Signal Transduction ,Transcription Factors ,alcoholic liver disease - Abstract
Alcoholic liver disease (ALD) is the major cause of chronic liver disease and a global health concern. ALD pathogenesis is initiated with liver steatosis, and ALD can progress to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Salvianic acid A (SAA) is a phenolic acid component of Danshen, a Chinese herbal medicine with possible hepatoprotective properties. The purpose of this study was to investigate the effect of SAA on chronic alcoholic liver injury and its molecular mechanism. We found that SAA significantly inhibited alcohol‐induced liver injury and ameliorated ethanol‐induced hepatic inflammation. These protective effects of SAA were likely carried out through its suppression of the BRD4/HMGB1 signalling pathway, because SAA treatment largely diminished alcohol‐induced BRD4 expression and HMGB1 nuclear translocation and release. Importantly, BRD4 knockdown prevented ethanol‐induced HMGB1 release and inflammatory cytokine production in AML‐12 cells. Similarly, alcohol‐induced pro‐inflammatory cytokines were blocked by HMGB1 siRNA. Collectively, our results reveal that activation of the BRD4/HMGB1 pathway is involved in ALD pathogenesis. Therefore, manipulation of the BRD4/HMGB1 pathway through strategies such as SAA treatment holds great therapeutic potential for chronic alcoholic liver disease therapy.
- Published
- 2020
34. HLA‐DQ genotype and biochemical characterization of anti‐transglutaminase 2 antibodies in patients with type 1 diabetes mellitus in Taiwan
- Author
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Yi‐Wen Yang, Thung-S. Lai, Wei-Hsin Ting, Yann-Jinn Lee, Fu-Sung Lo, Chiung-Ling Lin, Wen-Shan Lin, Yu-Ting Hsieh, Chi-Yu Huang, Cheng-Jui Lin, and Chen‐Chung Chu
- Subjects
Male ,0301 basic medicine ,Adolescent ,Genotype ,Tissue transglutaminase ,Taiwan ,Human leukocyte antigen ,Biochemistry ,Gliadin ,03 medical and health sciences ,0302 clinical medicine ,GTP-Binding Proteins ,HLA-DQ Antigens ,HLA-DQ ,Genetics ,Humans ,Medicine ,Protein Glutamine gamma Glutamyltransferase 2 ,Child ,Molecular Biology ,Autoantibodies ,Type 1 diabetes ,Transglutaminases ,biology ,business.industry ,Autoantibody ,Endothelial Cells ,Infant ,nutritional and metabolic diseases ,medicine.disease ,Immunoglobulin A ,Celiac Disease ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,Epitope mapping ,Child, Preschool ,Immunology ,biology.protein ,Female ,Antibody ,business ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Human Leukocyte Antigen (HLA)-DQ2 and HLA-DQ8 are genetic risk factors for Type 1 Diabetes Mellitus (T1DM) and Celiac disease (CD) in Caucasians, but their association with Taiwanese Han population is unknown. We screened 532 Taiwanese T1DM patients for CD biomarkers including anti-tissue transglutaminase (TGM2), anti-gliadin and anti-neoepitope antibodies (Abs), sequencing DQB1 genotypes, and characterized the TGM2 Abs. We report that 3.76% of Taiwanese patients had TGM2-Abs and all had no CD's symptoms. In contrast to Caucasian's CD patients, DQ2/DQ8 only constituted ~4/5 of TGM2-Abs positive patients, while the other ~1/5 patients belonged to different HLA genotypes. Either anti-gliadin or anti-neoepitope Abs coexisted with ~3/4 of TGM2-Abs positive patients that were likely due to gluten-ingestion, while the cause of TGM2-Abs production for other ~1/4 of patients was unknown. Purified anti-TGM2 IgA (TGA) and anti-TGM2 IgG (TGG) could bind on endothelial cells surface, recognized native better than denatured forms of TGM2, and TGA inhibited TGM2's transamidation activity by up to 80% but TGG had no effects. Epitope mapping of all TGM2-Abs positive sera demonstrated that TGM2-Abs had heterogeneity in specificities. This is the first study on the differences between Taiwanese Han group and Caucasian in HLA genotypes and properties of TGM2-Abs.
- Published
- 2020
35. Benzenesulfonamide Derivatives as Calcium/Calmodulin-Dependent Protein Kinase Inhibitors and Antiviral Agents against Dengue and Zika Virus Infections
- Author
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Li Wei Chu, Yi Ling Lee, Yueh Hsin Ping, Wen-Shan Li, Yi-Ling Lin, Wei Chia Chen, and Yogy Simanjuntak
- Subjects
Viremia ,Dengue virus ,medicine.disease_cause ,Antiviral Agents ,01 natural sciences ,Dengue fever ,Zika virus ,Dengue ,Mice ,Structure-Activity Relationship ,03 medical and health sciences ,Catalytic Domain ,Ca2+/calmodulin-dependent protein kinase ,Drug Discovery ,medicine ,Animals ,Humans ,Protein kinase A ,Protein Kinase Inhibitors ,030304 developmental biology ,Sulfonamides ,0303 health sciences ,Molecular Structure ,biology ,Zika Virus Infection ,Chemistry ,Kinase ,Proteins ,Outbreak ,Zika Virus ,Dengue Virus ,medicine.disease ,biology.organism_classification ,Virology ,0104 chemical sciences ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Drug Design ,Molecular Medicine ,Protein Binding - Abstract
Emerging and resurging mosquito-borne flaviviruses are an important public health challenge. The increased prevalence of dengue virus (DENV) infection has had a significant socioeconomic impact on epidemic countries. The recent outbreak of Zika virus (ZIKV) has created an international public health emergency because ZIKV infection has been linked to congenital defects and Guillain-Barre syndrome. To develop potentially prophylactic antiviral drugs for combating these acute infectious diseases, we have targeted the host calcium/calmodulin-dependent kinase II (CaMKII) for inhibition. By using CaMKII structure-guided inhibitor design, we generated four families of benzenesulfonamide (BSA) derivatives for SAR analysis. Among these substances, N-(4-cycloheptyl-4-oxobutyl)-4-methoxy-N-phenylbenzenesulfonamide (9) showed superior properties as a lead CaMKII inhibitor and antiviral agent. BSA 9 inhibited CaMKII activity with an IC50 value of 0.79 μM and displayed EC50 values of 1.52 μM and 1.91 μM against DENV and ZIKV infections of human neuronal BE(2)C cells, respectively. Notably, 9 significantly reduced the viremia level and increased animal survival time in mouse-challenge models.
- Published
- 2020
36. Oxidative trimerization of indoles via water-assisted visible-light photoredox catalysis and the study of their anti-cancer activities
- Author
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Bor-Cherng Hong, Chia-Ling Chen, Gene-Hsiang Lee, Li-Ting Cheng, Wen-Shan Li, and Sheng-Qi Luo
- Subjects
Indoles ,Light ,Antineoplastic Agents ,Oxidative phosphorylation ,Biochemistry ,Catalysis ,Structure-Activity Relationship ,Cell Line, Tumor ,medicine ,Humans ,Physical and Theoretical Chemistry ,Cell Proliferation ,Indole test ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Water ,Photoredox catalysis ,Cancer ,Photochemical Processes ,medicine.disease ,Combinatorial chemistry ,Fluorescence ,Water assisted ,Drug Screening Assays, Antitumor ,Oxidation-Reduction ,Human cancer ,Visible spectrum - Abstract
Incorporation of water has been revealed to successfully facilitate visible-light photoredox catalysis of indole leading to increased production of C2-quaternary indolinone. The water-promoted photoreaction of indole under catalyst-free conditions by a household compact fluorescence light was also demonstrated. The antiproliferative activity of the synthesized indolinones was evaluated against three human cancer cell lines.
- Published
- 2020
37. Comparison of FDG-PET/CT for Cancer Detection in Populations With Different Risks of Underlying Malignancy
- Author
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Hung-Pin Chan, Chin Hu, Nan-Jing Peng, Wen-Shiung Liou, Yu-Li Chiu, and Wen-Shan Liu
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Standardized uptake value ,Malignancy ,Asymptomatic ,General Biochemistry, Genetics and Molecular Biology ,Fluorodeoxyglucose F18 ,Neoplasms ,Positron Emission Tomography Computed Tomography ,Cancer screening ,medicine ,Humans ,Stage (cooking) ,Early Detection of Cancer ,Retrospective Studies ,Pharmacology ,PET-CT ,business.industry ,Cancer ,Glucose analog ,Middle Aged ,Prognosis ,medicine.disease ,Female ,Radiology ,Radiopharmaceuticals ,medicine.symptom ,business ,Follow-Up Studies ,Research Article - Abstract
Background/Aim: Whole-body positron-emission tomography/computed tomography with the glucose analog 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) has been used to screen examinees for underlying malignancy in many countries. The aim of this study was to compare the potential value of FDG-PET/CT application in asymptomatic individuals with those with suspected malignancy. Patients and Methods: A total of 9,408 examinees underwent whole-body FDG-PET/CT at our hospital from July 2006 to August 2013. Three thousand and seven hundred asymptomatic individuals and 848 individuals with laboratory and clinical/radiologicaI suspicion of malignancy who had undergone FDG-PET/CT for cancer screening were recruited. The final confirmation of cancer and outcomes were based on a pathological report and continuous follow-up. Results: Forty-five out of 3,700 asymptomatic individuals (1.2%) had proven malignancy, and 42 of them (93.3%) were found by FDG-PET/CT. Two hundred and twelve out of 848 with suspected malignancy (25%) had proven malignancy, and 196 of them (92.5%) were detected by FDG-PET/CT. Most of these cancers in asymptomatic individuals were clinically at an early stage. The discovery rate in asymptomatic individuals and those with suspected malignancy was 1.1% and 23.1%, respectively. The overall survival of patients with cancer diagnosed with PET/CT was higher than those with suspected malignancy (78.6% vs. 48.5%, p
- Published
- 2019
38. A New Compound Heterozygous Mutation Of BSCL2 In A Chinese Zhuang Ethnic Family With Congenital Generalized Lipodystrophy
- Author
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Qing-wen Shan, Faquan Lin, Shou-dong Li, Yuanyuan Qin, Jie Yan, Liqun Xiang, and Xuan Zhang
- Subjects
Pharmacology ,Proband ,Genetics ,business.industry ,BSCL2 ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Compound heterozygosity ,medicine.disease ,Congenital generalized lipodystrophy ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Mutation (genetic algorithm) ,Internal Medicine ,medicine ,Heterozygous carrier ,business ,Exome sequencing - Abstract
Purpose This study aims to report the clinical features of an infant with CGL in a Chinese Zhuang ethnic family, whose family members were discovered to carry new pathogenic mutations in the BSCL2. Patients and methods In this study, we report clinical and molecular investigations of CGL disease in a family of 4 members (parents and two sons). We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. Results The proband presented with skin pigmentation, hypertriglyceridemia and diabetes. WES identified a previously unreported compound heterozygous mutation in the BSCL2 (c.545_546insCCG heterozygous mutation and exon 3 heterozygous deletion) in the proband. His mother is a heterozygous carrier of the c.545_546insCCG mutation and his father and brother are carriers of the exon 3 heterozygous deletion. Conclusion Compound heterozygous mutation of the BSCL2 (new c.545_546insCCG heterozygous mutation and new exon 3 heterozygous deletion) was detected in the proband with characteristic clinical manifestations of CGL2.
- Published
- 2019
39. Facial Thread Lifting Complications in China: Analysis and Treatment
- Author
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Ze-Hui Li, Wen-Shan Xing, Xue-Ying Chen, Yi-Lin Li, and Jintian Hu
- Subjects
medicine.medical_specialty ,RD1-811 ,business.industry ,Facial anatomy ,Thread (computing) ,Surgical operation ,medicine.disease ,Facial paralysis ,Surgery ,Polydioxanone ,chemistry.chemical_compound ,Hematoma ,chemistry ,Medicine ,Outpatient clinic ,Cosmetic ,Original Article ,business ,After treatment - Abstract
Background:. Facial thread lifting technology has been applied for more than 30 years, with relatively few complications. In 2014, China approved polydioxanone thread (an absorbable barbed thread) for large-scale nonsurgical facial lifting. However, due to surgeons’ lack of overall experience, the complications of polydioxanone thread facelift have been relatively high. Methods:. From April 2014 to January 2020, a total of 190 patients with postoperative complications of facelifts were treated after they underwent thread lifting in other hospitals. Of these, 189 patients were women and one was a man; the age of patients ranged from 28 to 62 years, with an average age of 37.4 years. Results:. Patients were mainly treated in our outpatient clinic for the following complications: skin dimpling (77 cases, 40.5%); contour irregularity (32 cases, 16.8%); visible threads (31 cases, 16.3%); thread extrusion (10 cases, 5.3%); infection (17 cases, 8.9%); swelling (nine cases, 4.7%); incomplete facial paralysis (five cases, 2.6%); hyperpigmentation (four cases, 2.1%); hematoma (four cases, 2.1%); allergy (one case, 0.05%). Follow-up was scheduled 1–24 weeks after treatment. Conclusions:. The most common complications of facial thread lifting are, in the following order, skin dimpling, contour irregularity, visible threads, and thread extrusion. The reasons for complications are mainly unfamiliarity with facial anatomy, unskilled surgical operation, and misunderstanding of the facial aesthetics of Asian women.
- Published
- 2021
40. Sialyltransferase Inhibitors for the Treatment of Cancer Metastasis: Current Challenges and Future Perspectives
- Author
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Chih-Wei Fu, Ser John Lynon P Perez, and Wen-Shan Li
- Subjects
sialyltransferase ,Sialyltransferase ,Pharmaceutical Science ,Motility ,Organic chemistry ,Review ,Analytical Chemistry ,Metastasis ,chemistry.chemical_compound ,QD241-441 ,In vivo ,Neoplasms ,cancer metastasis ,Drug Discovery ,sialyltransferase inhibitors ,Medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,drug design and development ,Gene knockdown ,biology ,business.industry ,hypersialylation ,medicine.disease ,In vitro ,Sialyltransferases ,Sialic acid ,chemistry ,Chemistry (miscellaneous) ,Tumor progression ,biology.protein ,Cancer research ,Molecular Medicine ,business - Abstract
Potent, cell-permeable, and subtype-selective sialyltransferase inhibitors represent an attractive family of substances that can potentially be used for the clinical treatment of cancer metastasis. These substances operate by specifically inhibiting sialyltransferase-mediated hypersialylation of cell surface glycoproteins or glycolipids, which then blocks the sialic acid recognition pathway and leads to deterioration of cell motility and invasion. A vast amount of evidence for the in vitro and in vivo effects of sialyltransferase inhibition or knockdown on tumor progression and tumor cell metastasis or colonization has been accumulated over the past decades. In this regard, this review comprehensively discusses the results of studies that have led to the recent discovery and development of sialyltransferase inhibitors, their potential biomedical applications in the treatment of cancer metastasis, and their current limitations and future opportunities.
- Published
- 2021
41. Antidepressant effect of electroacupuncture on modulating the expression of c-Fos/AP-1 through the JNK signaling pathway
- Author
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Ji-Hong Wu, Peng-Fei Liu, Bing-Cong Zhao, Ya-Huan Li, Tuya Bao, Si-Min Qi, Hui-Wu Jiang, Yang Sun, Song-Xiao Quan, Xiang Li, Yu Wang, Tao Zhang, Huili Jiang, Xing-Zhou Gao, and Wen-Shan Li
- Subjects
Pituitary gland ,Histology ,Electroacupuncture ,MAP Kinase Signaling System ,medicine.medical_treatment ,Pharmacology ,c-Fos ,Open field ,medicine ,Animals ,Ecology, Evolution, Behavior and Systematics ,biology ,Kinase ,Chemistry ,Depression ,Antidepressive Agents ,Rats ,Transcription Factor AP-1 ,medicine.anatomical_structure ,Hypothalamus ,biology.protein ,Antidepressant ,Anatomy ,Signal transduction ,Proto-Oncogene Proteins c-fos ,Biotechnology - Abstract
The effectiveness and safety of electroacupuncture (EA) for depression have been identified by abundant clinical trials and experimental findings. The c-Jun-NH(2)-terminal kinase (JNK) signaling pathway is considered to be involved in the antidepressant mechanism of EA. However, the antidepressant effect of EA via modulating the expression of c-Fos/activator protein-1 (AP-1) under the condition of JNK inhibition remains unexplored. In this study, we investigated the antidepressant effect and possible mechanism of EA in regulating the expression of c-Fos/AP-1 under the condition of JNK inhibition by SP600125 in rats exposed to chronic unpredictable mild stress (CUMS). The depression-like behaviors were evaluated by the body weight, sucrose preference test (SPT), and open field test (OFT). The expression levels of c-Jun in the hypothalamus, c-Fos in the pituitary gland, and c-Fos and AP-1 in the serum of CUMS induced rat model of depression were detected by ELISA. The results indicated that treatment with EA and fluoxetine can reverse the CUMS-induced depression-like behaviors in rats and can up-regulate the expression levels of c-Jun in the hypothalamus, c-Fos in the pituitary gland, and c-Fos and AP-1 in the serum. Of note, the data demonstrated that SP600125, the inhibitor of JNK signaling pathway, can exert synergistic effect with EA in regulating CUMS-induced abnormal activation of the JNK signaling pathway. The antidepressant effect of EA might be mediated by modulating the expression of c-Fos/AP-1.摘要:目前电针抗抑郁的有效性和安全性得到大量临床研究和实验结果的证实,JNK信号通路被认为是参与了电针抗抑郁的机制过程。然而,电针通过在阻断JNK信号通路条件下调节c-Fos/AP-1表达的抗抑郁机制尚未阐明。在本研究中,我们主要探究电针通过SP600125抑制JNK信号通路条件下调节慢性温和不可预知性应激(CUMS)抑郁模型c-Fos/AP-1表达的抗抑郁效应机制。通过体重监测、糖水偏好实验和旷场实验评价抑郁样行为;采用酶联免疫吸附剂测定技术(ELISA)检测下丘脑c-Jun、垂体c-Fos及血清c-Fos、AP-1水平。结果显示,电针及氟西汀干预显著改善了CUMS诱导的大鼠抑郁样行为,并逆转了CUMS诱导的下丘脑水平c-Jun、垂体c-Fos及血清c-Fos、AP-1上调表达。值得注意的是,研究数据表明JNK信号通路特异性阻断剂SP600125同电针一起在调节CUMS诱导的JNK信号通路异常激活上起到协同作用,电针抗抑郁效应可能是通过调节应激诱导的c-Fos/AP-1表达介导的。.
- Published
- 2021
42. A simple noninvasive model to predict significant fibrosis in children with chronic hepatitis B
- Author
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Zi-Li Lv, Xiu-Qi Chen, Qing-Wen Shan, Kang-Ling Zhang, and Qing Tang
- Subjects
Liver Cirrhosis ,Male ,Biopsy ,Gastroenterology ,Severity of Illness Index ,chemistry.chemical_compound ,0302 clinical medicine ,Liver Function Tests ,Fibrosis ,030212 general & internal medicine ,Child ,biology ,medicine.diagnostic_test ,General Medicine ,Prognosis ,Liver ,030220 oncology & carcinogenesis ,Liver biopsy ,Child, Preschool ,Disease Progression ,Female ,Viral load ,Research Article ,medicine.medical_specialty ,Bilirubin ,Aspartate transaminase ,Observational Study ,03 medical and health sciences ,Hepatitis B, Chronic ,children ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,liver biopsy ,Retrospective Studies ,Models, Statistical ,Receiver operating characteristic ,business.industry ,Platelet Count ,fibrosis ,Gold standard (test) ,medicine.disease ,Confidence interval ,chemistry ,ROC Curve ,biology.protein ,Feasibility Studies ,diagnostic model ,business ,hepatitis B virus - Abstract
To develop a noninvasive model to predict significant fibrosis in children with chronic hepatitis B (CHB). A total of 116 CHB pediatric patients who underwent liver biopsy were included in the study. Liver histology, which is the gold standard for assessing fibrosis, was performed. Blood routine examination, coagulation function, liver biochemistry, viral serology, and viral load were analyzed. Receiver operating characteristic curve analysis was used to analyze the sensitivity and specificity of all possible cut-off values. Based on the correlation and difference analyses, 7 available clinical parameters (total bile acid, gamma-glutamyl transpeptidase [GGT], aspartate transaminase, direct bilirubin to total bilirubin ratio, alanine aminotransferase, prealbumin [PA], and cholinesterase) were included in the modeling analysis. A model to predict significant liver fibrosis was derived using the 2 best parameters (PA and GGT). The original model was Y=−1.803 ln PA(mg/L)+0.769lnGGT(U/L)+6.436. After the mathematical calculation, the G index=600 × GGT/PA2 predicted significant fibrosis, with an area under the receiving operating characteristics (AUROC) curve of 0.733, 95% confidence interval (0.643–0.811). The AUROC of the G index (0.733) was higher than that of aminotransferase to platelet ratio index (APRI) (0.680) and Fibrosis index based on 4 factors (FIB-4) (0.601) in predicting significant fibrosis in children with CHB. If the values of the G index were outside the range of 0.28 to 1.16, 52% of children with CHB could avoid liver biopsy, with an overall accuracy of 75%. The G index can predict and exclude significant fibrosis in children with CHB, and it may reduce the need for liver biopsy in children with CHB.
- Published
- 2021
43. The Divergent Immunomodulatory Effects of Short Chain Fatty Acids and Medium Chain Fatty Acids
- Author
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Wen Shan Yew, Zhaohong Tan, Sharada Ravikumar, Qi Hui Sam, Hua Ling, Matthew Wook Chang, and Louis Yi Ann Chai
- Subjects
QH301-705.5 ,microbiome ,Endogeny ,Inflammation ,Catalysis ,Article ,Inorganic Chemistry ,Butyric acid ,Immunomodulation ,chemistry.chemical_compound ,Immune system ,GPR84 ,medicine ,cytokine ,Humans ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Candida ,medium chain fatty acids ,Organic Chemistry ,Fatty Acids ,General Medicine ,Decanoic acid ,Fatty Acids, Volatile ,Hypoxia-Inducible Factor 1, alpha Subunit ,immunity ,Computer Science Applications ,Diet ,Gastrointestinal Microbiome ,Toll-Like Receptor 4 ,Chemistry ,TLR2 ,chemistry ,Biochemistry ,inflammation ,TLR4 ,Butyric Acid ,Cytokines ,medicine.symptom ,Inflammation Mediators ,short chain fatty acids ,Biomarkers - Abstract
Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 to 10 carbon, medium chain fatty acids (MCFA), derived primarily from diet, are less understood. Here, we demonstrated that SCFA and MCFA have divergent immunomodulatory propensities. SCFA down-attenuated host pro-inflammatory IL-1β, IL-6, and TNFα response predominantly through the TLR4 pathway, whereas MCFA augmented inflammation through TLR2. Butyric (C4) and decanoic (C10) acid displayed most potent modulatory effects within the SCFA and MCFA, respectively. Reduction in TRAF3, IRF3 and TRAF6 expression were observed with butyric acid. Decanoic acid induced up-regulation of GPR84 and PPARγ and altered HIF-1α/HIF-2α ratio. These variant immune characteristics of the fatty acids which differ by just several carbon atoms may be attributable to their origins, with SCFA being primarily endogenous and playing a physiological role, and MCFA exogenously from the diet.
- Published
- 2021
44. Biosynthesis of Nature-Inspired Unnatural Cannabinoids
- Author
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Yan Ping Lim, Wen Shan Yew, Maybelle K. Go, Yossa Dwi Hartono, Hao Fan, and Kevin Jie Han Lim
- Subjects
cannabinoids biosynthesis ,drug design ,natural products ,medicine.medical_treatment ,Cannabis sativa ,Pharmaceutical Science ,Organic chemistry ,Computational biology ,Review ,Biology ,Protein Engineering ,Analytical Chemistry ,Metabolic engineering ,03 medical and health sciences ,Synthetic biology ,0302 clinical medicine ,QD241-441 ,cannabinoid receptors ,Drug Discovery ,medicine ,Physical and Theoretical Chemistry ,Nature inspired ,Receptors, Cannabinoid ,030304 developmental biology ,Cannabis ,0303 health sciences ,Cannabinoids ,synthetic enzymology ,Dimethylallyltranstransferase ,Biosynthetic Pathways ,Chemistry (miscellaneous) ,Molecular Medicine ,Cannabinoid ,metabolic engineering ,030217 neurology & neurosurgery - Abstract
Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthetic biology has presented a solution to this through metabolic engineering in heterologous hosts. Through genetic manipulation, rare phytocannabinoids that are produced in low yields in the plant can now be synthesized in larger quantities for therapeutic and commercial use. Additionally, an exciting avenue of exploring new chemical spaces is made available as novel derivatized compounds can be produced and investigated for their bioactivities. In this review, we summarized the biosynthetic pathways of phytocannabinoids and synthetic biology efforts in producing them in heterologous hosts. Detailed mechanistic insights are discussed in each part of the pathway in order to explore strategies for creating novel cannabinoids. Lastly, we discussed studies conducted on biological targets such as CB1, CB2 and orphan receptors along with their affinities to these cannabinoid ligands with a view to inform upstream diversification efforts.
- Published
- 2021
45. Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway
- Author
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Chang-Qing Guo, Yi Zhang, Bin Li, Xiaowei Shi, Yang Gao, Tong Wang, Wen-Shan Xie, Qi Shu, Chunjiu Wang, Xue Yang, Yan Guo, Xin-Yi Fu, Xi-Lin Chen, and Jia-Yi Zhang
- Subjects
0301 basic medicine ,musculoskeletal diseases ,medicine.medical_specialty ,Article Subject ,Osteoarthritis ,Bone resorption ,Other systems of medicine ,03 medical and health sciences ,0302 clinical medicine ,Osteoprotegerin ,Osteoclast ,Internal medicine ,medicine ,030203 arthritis & rheumatology ,biology ,business.industry ,Cartilage ,Osteoblast ,medicine.disease ,Resorption ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Complementary and alternative medicine ,RANKL ,biology.protein ,business ,RZ201-999 ,Research Article - Abstract
Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF- κ B receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.
- Published
- 2021
46. Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation
- Author
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Run-Ling Wang, Wen-Shan Liu, Xing-Hua Lu, Wei-Ya Li, Ying Ma, Wen-Yan Jin, and Liang Zhou
- Subjects
medicine.medical_treatment ,Integrin ,Allosteric regulation ,Phosphatase ,Apoptosis ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,01 natural sciences ,Cancer immunotherapy ,Downregulation and upregulation ,Cell Movement ,Neoplasms ,0103 physical sciences ,Drug Discovery ,Cell Adhesion ,medicine ,Humans ,Enzyme Inhibitors ,Physical and Theoretical Chemistry ,Cell Proliferation ,010304 chemical physics ,biology ,Chemistry ,Growth factor ,Cell Differentiation ,In vitro ,0104 chemical sciences ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,010404 medicinal & biomolecular chemistry ,Biochemistry ,Docking (molecular) ,biology.protein - Abstract
SHP2 phosphatase, encoded by the PTPN11 gene, is a non-receptor PTP, which plays an important role in growth factor, cytokine, integrin, hormone signaling pathways, and regulates cellular responses, such as proliferation, differentiation, adhesion migration and apoptosis. Many studies have reported that upregulation of SHP2 expression is closely related to human cancer, such as breast cancer, liver cancer and gastric cancer. Hence, SHP2 has become a promising target for cancer immunotherapy. In this paper, we reported the identification of compound 1 as SHP2 inhibitor. Fragment-based ligand design, De novo design, ADMET and Molecular docking were performed to explore potential selective SHP2 allosteric inhibitors based on SHP836. The results of docking studies indicated that the selected compounds had higher selective SHP2 inhibition than existing inhibitors. Compound 1 was found to have a novel selectivity against SHP2 with an in vitro enzyme activity IC50 value of 9.97 μM. Fluorescence titration experiment confirmed that compound 1 directly bound to SHP2. Furthermore, the results of binding free energies demonstrated that electrostatic energy was the primary factor in elucidating the mechanism of SHP2 inhibition. Dynamic cross correlation studies also supported the results of docking and molecular dynamics simulation. This series of analyses provided important structural features for designing new selective SHP2 inhibitors as potential drugs and promising candidates for pre-clinical pharmacological investigations.
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- 2019
47. Characterisation of the bacterial biosensor GMG in E‐coli BL21 (DE3)
- Author
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Maybelle K. Go, Yew Wen Shan, and Rashmi Rajasabhai
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on output ,not gate gold ,Operon ,enzymes ,macromolecular substances ,medicine.disease_cause ,nanobiotechnology ,Green fluorescent protein ,inductively coupled plasma-mass spectrometry ,mf-lon protease ,molecular biophysics ,medicine ,biochemistry ,genetics ,Inducer ,genetic circuit ,cellular biophysics ,microorganisms ,lcsh:QH301-705.5 ,Escherichia coli ,Chromatography ,plate reader data ,biology ,Chemistry ,gold concentration ,Molecular biophysics ,technology, industry, and agriculture ,gold ,biosensors ,biology.organism_classification ,single multi-stage assay ,gol-mflon-gfp ,food safety ,orthogonal inverter system ,biosensor gol- mf ,lcsh:Biology (General) ,Salmonella enterica ,gold detection ,au ,escherichia coli ,e-coli bl21 ,Biosensor ,bacterial biosensor gmg ,gold biosensor ,goltsb operon ,Plate reader - Abstract
In this work, a gold biosensor has been constructed and characterised in Escherichia coli ( E. coli ). Though gold biosensors have been previously reported, a NOT gate gold biosensing genetic circuit was constructed using an orthogonal inverter system as an alternative to a circuit where output is contingent solely on input. This enables the detection of changes in gold concentration whereby circuit remains OFF in presence of inducer and ON in absence of inducer. The proposed biosensor is an alternative to conventional forms of gold detection such as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The constructed biosensor is a collection of components – golTSB operon (isolated from Salmonella enterica ), mf -Lon protease (isolated from Mesoplasma florum ) and associated ssrA degradation tag with GFP acting as a reporter. The minimum time and concentration required by the biosensor gol- mf lon-GFP (GMG) to achieve the ON output is characterised here using plate reader data derived from a single multi-stage assay.
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- 2019
48. Distal locked or unlocked nailing for stable intertrochanteric fractures? A meta‐analysis
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Wen-Shan Yan, Peng Zhang, Ming Sun, Deng-Yue Ma, and Wei-Li Cao
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medicine.medical_specialty ,Deep vein ,Nonunion ,Bone Nails ,Cochrane Library ,law.invention ,Intramedullary rod ,03 medical and health sciences ,0302 clinical medicine ,law ,Humans ,Medicine ,Hip Fractures ,business.industry ,General Medicine ,medicine.disease ,Confidence interval ,Fracture Fixation, Intramedullary ,Surgery ,medicine.anatomical_structure ,Harris Hip Score ,030220 oncology & carcinogenesis ,Meta-analysis ,Relative risk ,030211 gastroenterology & hepatology ,business - Abstract
Background To date, there are just several studies comparing distal locked nails with distal unlocked nails in treating intertrochanteric fractures. We report the first meta-analysis about this issue. Methods Systematic search was conducted for studies in PubMed, Embase and Cochrane Library. Meta-analyses were performed regarding intra operative outcomes, complications and functional outcomes. Results Pooled results showed insignificant difference between distal locking group and distal unlocking group in hip pain (relative risk (RR) 1.14, 95% confidence interval (CI) 0.59-2.19), distal tip fracture (RR 1.08, 95% CI 0.37-3.11), lag screw cut-out (RR 1.60, 95% CI 0.54-4.78), delayed or nonunion (RR 1.32, 95% CI 0.25-7.06), deep vein thrombosis (RR 1.06, 95% CI 0.23-4.84), wound infection (RR 0.58, 95% CI 0.28-1.22), Harris hip score (standard mean deviation (SMD) 0.03, 95% CI -0.15 to 0.21) and walking ability. However, significant difference was detected in operation time (SMD 0.77, 95% CI 0.36-1.17), fluoroscopy exposure time (SMD 1.02, 95% CI 0.52-1.52), blood loss (SMD 0.80, 95% CI 0.62-0.99) and total incision length (SMD 1.16, 95% CI 0.86-1.47). Result of trial sequential analysis indicated conclusive evidence. Conclusion Current evidence indicates that the distal locked intramedullary nails should not be recommended as routine choice for stable intertrochanteric fractures.
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- 2019
49. Role of social anxiety on high engagement and addictive behavior in the context of social networking sites
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Joyce Yen Feng, Tony Szu Hsieh Lee, Hong Ren Chen, and Wen-Shan Lin
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education.field_of_study ,Gratification ,05 social sciences ,Social anxiety ,Population ,Context (language use) ,02 engineering and technology ,Relationship maintenance ,Library and Information Sciences ,medicine.disease ,Social support ,020204 information systems ,0502 economics and business ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,050211 marketing ,Social media ,Addictive behavior ,Psychology ,education ,Social psychology ,Information Systems - Abstract
Purpose The purpose of this paper is to tackle the problem of technology addiction by investigating the differences between the antecedences of addictive (problematic technology usage) and high-engagement behavior (non-problematic technology usage). The case of social networking site usage (SNS, e.g. Facebook, Instagram or Twitter) is taken as the case out of the reason of prevalent user population. Design/methodology/approach It is revealed that people tend to use SNS not only for building a relationship, but also for communicating. In other words, there are inner needs of adopting the SNS technology. However, no clear definitions can be followed for determining the problematic SNS usage, addictive behavior and the high-engagement behavior. Therefore, this study adopts the notion of uses and gratification theory (U&G theory) for investigating the SNS usage behavior. Also, the social anxiety is also first introduced to integrate into the research for an empirical study. Findings Results reveal that gratification sought and relationship maintenance are associated with the addictive behavior, whereas the relationship maintenance is significantly related to high-engagement behavior. Research limitations/implications First, the selected data represents a sample of SNW users in the Asian Pacific region and mainly from the group of young college users. Therefore, caution must be taken when generalizing the findings to other SNW users or groups. Second, the time aspect related to social media dependence may need to be considered in future studies. Third, the authors found marginal support for the influence of intentions of high engagement¸ and future studies may consider applying other theories that could better explain these types of behavior. Practical implications The results of this study provide strong evidence that inner anxiety perceived by users should not be neglected while tackling the problematic internet use due to SNW addiction because it can strengthen the force for depending on SNW for seeking social support. Apart from the value of perceived enjoyment as asserted in previous studies, this study opens up a new opportunity to tackle SNW dependence. Social implications The key implication of this research is that the impact of the mental health of users on SNW problematic should not be overlooked . The higher the level of anxiety perceived, the more likely is the SNW dependence. Therefore, the online behavior depending on psychological health should be addressed because it may be a critical point for assisting users to adopt SNW wisely. Originality/value This study confirms that social anxiety people experience in real (offline) life has impacts on online behavior of SNS usage (online). It suggests that the difference between users as the perceived level of social anxiety can trigger different levels of SNS usage. Second, U&G theory is proven valid in understanding SNS addiction. Third, relationship maintenance through the use of SNS reveals its dissimilar effects on SNS addiction and high engagement.
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- 2019
50. A meta-analysis of the effectiveness of yoga-based interventions for maternal depression during pregnancy
- Author
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Donovan Yutong Lim, Hwei Wuen Chan, Wee-Song Yeo, Nandini Venkatanarayanan, Wen-Shan Sim, Wayren Loke, and Qin Xiang Ng
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medicine.medical_specialty ,Psychological intervention ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Humans ,Medicine ,030212 general & internal medicine ,Depression (differential diagnoses) ,Depression ,business.industry ,Yoga ,Prenatal Care ,Small sample ,medicine.disease ,Maternal depression ,Pregnancy Complications ,Treatment Outcome ,Mood ,Complementary and alternative medicine ,Strictly standardized mean difference ,Meta-analysis ,Physical therapy ,Female ,business ,030217 neurology & neurosurgery - Abstract
Prompt and effective treatment of maternal depression during pregnancy is important as it is an independent predictor of negative maternal and fetal outcomes. Yoga is an increasingly popular non-pharmacological modality. This study thus aimed to undertake a meta-analysis of the efficacy of yoga-based interventions for maternal depression during pregnancy. A total of 8 clinical studies were systematically reviewed, and 6 studies with a total of 405 pregnant mothers were included in the final meta-analysis. Applying per-protocol analysis and a random-effects model, the pooled standardized mean difference (SMD) from baseline depressive score was −0.452 (95% CI: −0.816 to −0.880, P = 0.015), supporting a statistically significant beneficial effect of yoga-based interventions on mood. Overall, yoga-based interventions are a promising non-pharmacological option, however, most trials examined were preliminary, recruited only participants with mild depression, did not blind study participants and had relatively small sample sizes. Larger randomized, controlled trials should be encouraged.
- Published
- 2019
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