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Yuqi Zhang,1,2 Keqian Du,1,2 Xiaoxue Feng,1,2 Jia Xu,1,2 Peijun Xu,1,2 Jianlin Huang1,2 1Department of Rheumatology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Jianlin Huang; Peijun Xu, Department of Rheumatology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, People’s Republic of China, Email hjianl@mail.sysu.edu.cn; xupj@mail.sysu.edu.cnPurpose: This study aimed to compare the rates of disease remission evaluated using various remission criteria, including Boolean2.0, Boolean1.0, clinical disease activity index (CDAI), simplified disease activity index (SDAI), and disease activity score using 28 joints based on C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA).Patients and Methods: A cross-sectional observational analysis was performed using data from patients with RA enrolled in a smart system of disease management group (SSDM). The clinical remission rates of RA patients estimated using the DAS28-CRP, CDAI, SDAI, Boolean1.0 and Boolean2.0 criteria were investigated. Variables were compared using the t-test, Mann–Whitney U-test, or chi-squared test. The agreement between Boolean remission and the DAS28-CRP, CDAI, or SDAI definitions of remission was assessed using McNemar’s test with k coefficient of agreement.Results: A total of 5619 patients were included in the analysis. The mean age of the patients was 56.33 (± 13.01) years, with the majority being female (4491, 79.9%). The rates of remission, as assessed by Boolean2.0, Boolean1.0, DAS28-CRP, CDAI, and SDAI, were 16.6%, 9.7%, 35.2%, 9.1%, and 9.4%, respectively. Comparison with Boolean1.0 criteria revealed higher concordance between Boolean2.0 and DAS28-CRP remission and lower concordance with CDAI and SDAI, regardless of whether the analysis was conducted on the entire population or subgroups based on gender, age or disease duration. Additionally, the administration of different medications may have influenced the rate of Boolean2.0 remission.Conclusion: This study demonstrated a higher concordance between Boolean2.0 criteria and DAS28-CRP remission and a lower concordance with CDAI and SDAI when compared with Boolean1.0 remission criteria.Keywords: Boolean, clinical disease activity index, concordance, disease activity score using 28 joints, remission, simplified disease activity index

Ling-Yun Bao,* Xin-Yue Dao,* Kun Du Department of Neonate, Kun Ming Children’s Hospital, Yunnan, 650021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun Du, Department of Neonate, Kun Ming Children’s Hospital, No. 28 of Shulin Road, Yunnan, 650021, People’s Republic of China, Tel +86 15388843393, Email kdidljtdr_09@outlook.comAbstract: Neonatal respiratory distress syndrome (NRDS) is a common critical disease in neonates. Early diagnosis and timely treatment are crucial. Historically, X-ray imaging was the primary method for diagnosing NRDS. However, this method carries radiation exposure risks, making it unsuitable for dynamic lung condition monitoring. In addition, neonates who are critically ill require bedside imaging, but diagnostic delays are often unavoidable due to equipment transportation and positioning limitations. These challenges have been resolved with the introduction of lung ultrasound (LUS) in neonatal intensive care. The diagnostic efficacy and specificity of LUS for NRDS is superior to that of X-ray. The non-invasive, dynamic, and real-time benefits of LUS also allow for real-time monitoring of lung changes throughout treatment for NRDS, yielding important insights for guiding therapy. In this paper, we examine the ultrasonographic characteristics of NRDS and the recent progress in the application of ultrasound in the diagnosis and treatment of NRDS while aiming to promote wider adoption of this method.Keywords: dynamic monitoring, lung ultrasound, neonates, respiratory distress syndrome, NRDS, point of care ultrasound

Qiong Liu,1,2 Yafei Chen,1 Bo Wang,1 Yinying Chen,3 Bing Li,4 Shuang Guan,1 Kehe Du,5 Xiaoyang Liu,5 Yanan Yu,1 Jun Liu,1 Zhong Wang1 1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Postdoctoral Research Station, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 5iPhase Pharma Services, Beijing, People’s Republic of ChinaCorrespondence: Zhong Wang, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email zhonw@vip.sina.comAim: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach.Methods: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers.Results: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups.Conclusion: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.Keywords: diabetic peripheral neuropathy, Traditional Chinese Medicine, Liu-Wei-Luo-Bi granules, untargeted metabolomics, arginine biosynthesis

Jin Gao,1,2 Tingting Liu,1 Xingyu Xiong,1 Mei Zhao,1 Kun Du,1,2 Jiwei Li2,3 1Department of Neonates; 2Yunnan Province Clinical Research Center for Children’s Health and Disease, Kunming, People’s Republic of China; 3Department of Pathology, Kunming Children’s Hospital, The Affiliated Children’s Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Kun Du; Jiwei Li, Email Dukun@etyy.cn; 360623155@qq.comAbstract: Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi, which is transmitted by larval trombiculid mites. Due to nonspecific clinical presentation, scrub typhus is grossly underdiagnosed in pregnant women, fetuses and neonates. Here, we present a congenital infection case and hope to provide more insight into this disease.Keywords: neonatal scrub typhus, vertical transmission, congenital infection, Orientia tsutsugamushi, meningitis

Kairong Du,&ast; Wei Wu,&ast; Xiaobo Feng, Jianjuan Ke, Hengtao Xie, Yingying Chen Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei Province, Peoples Republic of China&ast;These authors contributed equally to this workCorrespondence: Hengtao Xie; Yingying ChenDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei Province, Peoples Republic of ChinaTel +86-15342344235; +86-13476119947Email heng_823@163.com ; chenyingy@whu.edu.cnBackground: Puerarin, an active compound of radix puerariae, is a major compound used in Chinese herbal medicines and it has been well known for its pharmacological effects, including antioxidant, anti‑inflammatory, neuroprotective and cardioprotective properties. The aim of the present study was to determine the role of puerarin (Pue) in complete Freund’s adjuvant (CFA)-induced trigeminal neuralgia (TN) and the effects of this compound on Sirt1 activity and on the progression of CFA-induced TN.Methods: Mice were injected with CFA on the unilateral face to induce TN. A cell model of inflammation-associated TN was established by interleukin-1β (IL-1β; 10 ng/mL) and tumor necrosis factor-α (TNF-α; 50 ng/mL) stimulation of neurons. Reverse transcription-quantitative PCR and Western blot analyses were performed to analyze mRNA and protein expression levels in trigeminal ganglion and nerve cells. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was used to determine nerve cell apoptosis following IL-1β/TNF-α or Pue treatment.Results: Pue is a conceivable Sirtuin1 (Sirt1) activator used for the prevention of trigeminal nerve injury that attenuates CFA-induced TN and inflammatory cytokine-evoked overactivation of neuronal inflammation and apoptosis. Treatment of mice with inflammatory cytokines induced upregulation of cleaved caspase-3 protein expression, which was neutralized by Pue supplementation. Both in vivo and in vitro experiments led to the conclusion that Pue modulated Sirt1 activation and repressed transforming growth factor-β 1 (TGF-β 1) protein expression and drosophila mothers against decapentaplegic homolog3 (Smad3) phosphorylation in order to exert neuroprotection.Conclusion: The findings suggested that Pue functioned as a potential Sirt1 activator to improve neuroinflammation-induced TN and neuronal apoptosis via the suppression of TGF-β 1/Smad3 activity. The pharmacological activity of Pue provides a new perspective for the effective prevention and treatment of TN.Keywords: apoptosis, inflammation, TGF-β 1/Smad3, trigeminal neuralgia, Sirt1

Yunyun Zhang,1 Hongyu Guan,1 Kang Du,1 Jin Zhao,1 Yaojiang Shi,1 Huan Wang,1 Decai Wang2 1Center for Experimental Economics in Education, Shaanxi Normal University, Xi’an, People’s Republic of China; 2Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Hongyu GuanCenter for Experimental Economics for Education, Shaanxi Normal University, Xi’an, 710119, People’s Republic of ChinaTel +86 186-9188-9621Email guanhongyu2016@163.comBackground: In rural China, children’s vision problems are very common, with many who would benefit from refractive correction not getting the care they need. This study examines whether a health information campaign that involves vision health education and a free trial of health product with free eyeglasses is effective at raising students’ awareness of myopia and promoting students’ eyeglasses usage.Methods: We conducted an in-the-field randomized controlled experiment of a program providing vision health education and subsidized free eyeglasses to myopic children from 168 primary schools in rural Northwestern China in 2012.Results: A total of 2189 students, mean age 10.5 years (49.3% male), participated in the baseline survey. At the baseline, the average correct response rate for visual knowledge among the sample students was 30.1%, and only 15% who needed eyeglasses used them. Seven months after intervention, the average correct response rate for vision knowledge were 48.5% and 48.3% in the education group and the education plus free eyeglasses group respectively, significantly higher than that of the control group. The rate of eyeglasses usage was 36% and 43% in the free eyeglasses group and the education plus free eyeglasses group respectively, significantly higher than that of the control group. The rate of eyeglasses compliance in the free eyeglasses group and the education plus free eyeglasses group was 19% and 26%, which also were significantly higher than the control group.Conclusion: The information campaign combined with subsidized eyeglasses had a better effect both on vision knowledge and eyeglasses usage. The information campaign improved knowledge by providing the right information, and free eyeglasses changed the perceived utility and experience by the students using the product and getting benefits. Information and the free eyeglasses (subsidized) are complements.Keywords: vision health education, subsidies free eyeglasses, health-seeking knowledge, health-seeking behavior

Guoze Wang,1,2,* Kun Du,1,* Zhenjian Xie,3 Renyong Tang,3 Xianbo Jia,1 Shiyi Chen,1 Songjia Lai1 1Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, People’s Republic of China; 2College of Food Science, Guizhou Medical University, Guiyang 550025, People’s Republic of China; 3College of Pharmacy and Biological Engineering, Chengdu University, Chengdu 610106, People’s Republic of China*These authors contributed equally to this workCorrespondence: Songjia Lai Email laisj5794@163.comBackground: Rabbit is a good model for genetic and medical studies in other livestock species. The rabbit shows low adipose tissue deposition, and the phenomena indicates that there is some specificity of adipose deposition during the rabbit growth. However, little is known about genes that regulate the growth of adipose tissue in rabbits.Materials and Methods: Deep RNA-seq and comprehensive bioinformatics analyses were used to characterize the genes of rabbit visceral adipose tissue (VAT) at 35, 85 and 120 days after birth. Differentially expressed genes (DEGs) were identified at the three growth stages by DESeq. To explore the function of the candidate genes, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Six DEGs were randomly selected, and their expression profiles were validated by q-PCR.Results: A total of 20,303 known transcripts and 99,199 new transcripts from 8 RNA sequencing libraries were identified, and 34 differentially expressed genes (DEGs) were screened. GO enrichment and KEGG pathway analyses revealed that the DEGs were mainly involved in lipid metabolism regulation including acylglycerol metabolic process and mobilization, and decomposition of lipids to generate ATP in adipocytes and fatty acid metabolism, included LOC100342322 and LOC100342572. In addition, 133 protein-coding genes that play a role in adipose growth and development were screened, including acyl-CoA synthetase long-chain family member 5 (ACSL5) and fatty acid-binding protein 2 (FABP2). The validation results of six DEGs by q-PCR showed similar trends with the results of RNA-seq.Conclusion: In summary, this study provides the first report of the coding genes profiles of rabbit adipose tissue during different growth stages. These data allow for the identification of candidate genes for subsequent studies on rabbit genetics and regulation of adipose cells, and provide an animal model for studying obesity in humans.Keywords: rabbit, RNA-seq, adipose tissue, growth, protein-coding gene, fat deposition

Juerong Huang,1 Qihui Chen,1 Kang Du,2 Hongyu Guan2 1Beijing Food Safety Policy & Strategy Base, College of Economics and Management, China Agricultural University, Beijing, People’s Republic of China; 2Center for Experimental Economics in Education, Shaanxi Normal University, Xi’an, People’s Republic of ChinaCorrespondence: Qihui ChenBeijing Food Safety Policy & Strategy Research Base, College of Economics and Management, China Agricultural University, No. 17, Qinghua East Road, Haidian District, Beijing 100083, People’s Republic of ChinaEmail chen1006@umn.eduBackground: The high prevalence of myopia among school-age children in China has raised serious concerns about protecting Chinese students’ vision. While the regular performance of the Chinese eye exercises has been adopted as a preventive approach in China since the mid-1960s, these exercises’ effectiveness at protecting students’ vision has remained largely unknown. This study attempts to provide new evidence of the impact of regularly performing the exercises on Chinese students’ visual outcomes, based on a large-scale dataset.Methods: A school-based survey was conducted among 9842 randomly selected students (fourth graders) from 252 primary schools in rural Northwestern China in 2012. To address potential estimation bias, we adopted both an instrumental variable (IV) approach and a bivariate-probit model to estimate the impacts on students’ visual acuity and the incidences of visual impairment and myopia.Results: Both IV and bivariate-probit estimates reveal a detrimental impact of regularly performing the Chinese eye exercises on students’ vision. Compared with students who did not regularly perform the exercises, those who did were 6.2 percentage points more likely to have impaired vision and 7.6 percentage points more likely to be myopic. The estimates are robust to different estimation strategies, various specifications, and the majority of subsamples.Conclusion: Under the assumption that the correct performance of the Chinese eye exercises would not undermine students’ vision, our findings suggest that the commonly-observed incorrect performance of these exercises among Chinese students imposes non-trivial threats to their vision health.Keywords: Chinese eye exercises, visual impairment, myopia, instrumental variables, bivariate-probit, primary school

Songjia Lai,1,* Kun Du,1,* Yu Shi,1 Cao Li,1 Guoze Wang,1,2 Shenqiang Hu,1 Xianbo Jia,1 Jie Wang,1 Shiyi Chen1 1Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, People’s Republic of China; 2The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Songjia LaiFarm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, 211# Huimin Road, Wenjiang 611130, Sichuan, People’s Republic of ChinaEmail laisj5794@163.comAbstract: Obesity has become a widespread disease that is harmful to human health. Fat homeostasis is essentially maintained by fat accumulation and energy expenditure. Studies on brown adipose tissue (BAT) represent a promising opportunity to identify a pharmaceutical intervention against obesity through increased energy expenditure. Long non-coding RNAs (lncRNAs) were thought to be critical regulators in a variety of biological processes. Recent studies have revealed that lncRNAs, including ones that are BAT-specific, conserved, and located at key protein-coding genes, function in brown adipogenesis, white adipose browning (ie, beige adipogenesis), and brown thermogenesis. In this review, we describe lncRNA properties and highlight functional lncRNAs in these biological processes, with the goal of establishing links between lncRNAs and BAT. Based on the advances of lncRNAs in the regulation of BAT, we discussed the advantages of potential lncRNA-based obesity drugs. Further BAT lncRNA-based drug development may provide new exciting approaches to defend obesity by regulation of fat homeostasis.Keywords: obesity, BAT, thermogenesis, lncRNAs

Hongfei Liu,1,2 Kunyu Du,1 Dongli Li,2 Yi Du,2 Jumei Xi,3 Ying Xu,1 Yan Shen,4 Tao Jiang,5 Thomas J Webster6 1School of Pharmacy, Jiangsu University, Zhenjiang 212013, China; 2School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China; 3Health of Nepstar Drugstore Chain Company Limited, Wuxi 214000, China; 4State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; 5The Pharmacy Department, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China; 6Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA Background: Nintedanib is a new tyrosine kinase inhibitor and growth factor antagonist. It can be used to treat idiopathic pulmonary fibrosis diseases. Nintedanib has poor solubility in the intestinal tract environment, which leads to low bioavailability of just 4.7%. Methods: In this study, a nintedanib solid dispersion was prepared by electrospray technology with an optimized formula (nintedanib:PVPK30:Soybean lecithin=1:5:0.25) and electrospray parameters (21 kV voltage, 18 cm receiving distance, 0.3 mL/h solution flow rate, 0.5 mm pinhole inner diameter). Results: The accumulative release rate of the optimized solid dispersion was more than 60% in 30 minutes and 100% in 60 minutes. The size distribution was uniform and the surface observed with scanning electron microscopy (SEM) was smooth. The DSC and X-ray diffraction results showed that nintedanib existed in the solid dispersion through an amorphous form. Nintedanib solid dispersion sustained-release capsules were prepared to prolong drug release, improve patient compliance and reduce side effects. The accumulative release rate from the sustained release capsules was 35.17%, 54.78%, 70.58%, and 93.93% after 2 h, 6 h, 8 h, and 12 h, respectively, having obvious sustained release effects in vitro. The release behavior of solid dispersion sustained-release capsules in vitro was in accordance with the Ritger-Peppas model. The in vivo studies of nintedanib soft capsules, solid dispersion and nintedanib sustained release capsules in SD rats were investigated; the results showed that the Tmax of the soft capsule, solid dispersion and sustained release capsules were 3 h, 2 h, and 6 h, respectively. The Cmax were 2.945 mg/mL, 5.32 mg/mL, and 3.75 mg/mL, respectively, while the AUC0–24 h was 15.124 mg·h/mL, 23.438 mg·h/mL, and 24.584 mg·h/mL, respectively. The relevant bioavailability of the sustained-release capsules was 162.55% compared to the nintedanib soft capsule and 104.89% compared to the nintedanib solid dispersion.Conclusion: The results suggested superior bioavailability and a sustained-release effect from nintedanib sustained-release capsules, as compared to the reference (commercial nintedanib soft capsule). Keywords: nintedanib, electrospray technology, solid dispersion, sustained release capsule, pharmacokinetics

Xueqing Zhang,1,* Jinluan Li,1,* Qingqin Peng,2 Yunxia Huang,1 Lirui Tang,1 Qingyang Zhuang,1 Feifei Lin,1 Xijin Lin,1 Kaixin Du,3 Junxin Wu1 1Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; 2Department of Radiation Oncology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, China; 3Department of Radiation Oncology, Xiamen Humanity Hospital, Xiamen 361000, China *These authors contributed equally to this work Purpose: The inflammatory status of patients with cancer appears to affect cancer progression and patient prognosis. We examined the characteristics of cancer-associated systemic and local inflammation and its impact on the overall survival (OS) of patients with locally advanced rectal cancer (LARC) who received neoadjuvant radiotherapy (nRT). Patients and methods: Seventy-six consecutive LARC patients who received nRT from February 2012 to September 2015 were retrospectively analyzed. The peripheral neutrophil-to-lymphocyte ratio (NLR) was determined at diagnosis, and the CD8+ T-cell count was determined from surgical specimens. Factors associated with OS were identified by univariate and multivariate Cox regression. Results: The median follow-up time was 23.0 months (range: 2–59), and the overall 5-year OS rate was 68.6% (95% CI =46.06–91.14). Patients with a high NLR (≥2.0) and a low CD8+ T-cell count (

Xin Zhong,1,2 Ming-Yan Liu,1,2 Miao He,1,2 Ke Du,1,2 Min-Jie Wei1,2 1Department of Pharmacology, School of Pharmacy, China Medical University, 2Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Shenyang, Liaoning Province, People’s Republic of China Abstract: The association between interleukin-33 (IL-33) gene polymorphisms and late onset Alzheimer’s disease (LOAD) remains controversial in previous studies. Thus, a meta-analysis was conducted to assess the association between the IL-33 polymorphisms (rs11792633 and rs7044343) and LOAD susceptibility. Crude odds ratio (OR) and 95% confidence interval (CI) were used to investigate the relationship strength. Sensitivity analysis was performed, and publication bias was estimated by the Begg’s and Egger’s tests. Overall, six independent studies involving 2,589 patients and 8,414 control samples met our inclusion criteria and were included in this meta-analysis. The results showed that IL-33 rs11792633 polymorphism had statistically significant correlation with a decreased risk of LOAD in heterozygous comparison model (OR =0.64, 95% CI =0.48–0.83), homozygote comparison model (OR =0.83, 95% CI =0.74–0.93), dominant model (OR =0.78, 95% CI =0.67–0.91), recessive model (OR =0.70, 95% CI =0.59–0.84), and allelic model (OR =0.79, 95% CI =0.69–0.91), which were also validated by stratified subgroup analysis. Additionally, there was an apparent association between the IL-33 rs7044343 variant and LOAD risk under four genetic models for overall population (heterozygous comparison model: OR =0.75, 95% CI =0.63–0.89; dominant model: OR =0.83, 95% CI =0.70–0.98; recessive model: OR =0.80, 95% CI =0.68–0.94; allelic model: OR =0.86, 95% CI =0.79–0.94) as well as Caucasian subgroup. In summary, our meta-analysis implicated that IL-33 gene polymorphisms rs11792633 and rs7044343 were significantly associated with the susceptibility of LOAD. Keywords: late onset Alzheimer’s disease, interleukin-33, polymorphism, meta-analysis

An automated microfluidic sample preparation multiplexer (SPM) has been developed and evaluated for Ebola virus detection. Metered air bubbles controlled by microvalves are used to improve bead-solution mixing thereby enhancing the hybridization of the target Ebola virus RNA with capture probes bound to the beads. The method uses thermally stable 4-formyl benzamide functionalized (4FB) magnetic beads rather than streptavidin coated beads with a high density of capture probes to improve the target capture efficiency. Exploiting an on-chip concentration protocol in the SPM and the single molecule detection capability of the antiresonant reflecting optical waveguide (ARROW) biosensor chip, a detection limit of 0.021pfu/mL for clinical samples is achieved without target amplification. This RNA target capture efficiency is two orders of magnitude higher than previous results using streptavidin beads and the limit of detection (LOD) improves 10×. The wide dynamic range of this technique covers the whole clinically applicable concentration range. In addition, the current sample preparation time is ~1h which is eight times faster than previous work. This multiplexed, miniaturized sample preparation microdevice establishes a key technology that intended to develop next generation point-of-care (POC) detection system.