Search

Xixia Liu,1,2 Yuhan Liao,1 Xiuxiu Wang,1 Donghua Zou,1 Chun Luo,1 Chongdong Jian,1 Yuan Wu1 1Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 2Department of Rehabilitation, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China Abstract: MicroRNA (miRNA) is believed to play a crucial role in the cause and treatment of epilepsy by controlling gene expression. However, it is still unclear how miRNA profiles change after multiple prolonged seizures and aggravation of brain injury in chronic epilepsy (CE). To investigate the role of miRNA in epilepsy, we utilized the CE rat models with pentylenetetrazol (PTZ) and miRNA profiles in the hippocampus. miRNA profiles were characterized using miRNA microarray analysis and were compared with the rats in the sham group, which received 0.9% physiological saline treatment at the same dose. Four up-regulated miRNAs (miR-139–3p, -770–5p, -127–5p, -331–3p) and 5 down-regulated miRNAs (miR-802–5p, -380–5p, -183–5p, -547–5p, -344a/-344a–5p) were found in the CE rats (fold change >1.5, P

Jian-Min Shen,1 Xin-Xin Li,1 Lin-Lan Fan,2 Xing Zhou,3 Ji-Min Han,1 Ming-Kang Jia,1 Liang-Fan Wu,1 Xiao-Xue Zhang,1 Jing Chen1 1School of Life Sciences, 2School of Basic Medical Sciences, Lanzhou University, 3The People’s Hospital of Gansu Province, Lanzhou, Gansu, China Abstract: A novel nanoscale molecular probe is formulated in order to reduce toxicity and side effects of antitumor drug doxorubicin (DOX) in normal tissues and to enhance the detection sensitivity during early imaging diagnosis. The mechanism involves a specific targeting of Arg-Gly-Asp peptide (RGD)-GX1 heterogeneous dimer peptide-conjugated dendrigraft poly-l-lysine (DGL)–magnetic nanoparticle (MNP) composite by αvβ3-integrin/vasculature endothelium receptor-mediated synergetic effect. The physicochemical properties of the nanoprobe were characterized by using transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering (DLS), and vibrating sample magnetometer. The average diameter of the resulting MNP–DGL–RGD-GX1–DOX nanoparticles (NPs) was ~150-160 nm by DLS under simulate physiological medium. In the present experimental system, the loading amount of DOX on NPs accounted for 414.4 mg/g for MNP–DGL–RGD-GX1–DOX. The results of cytotoxicity, flow cytometry, and cellular uptake consistently indicated that the MNP–DGL–RGD-GX1–DOX NPs were inclined to target HepG2 cells in selected three kinds of cells. In vitro exploration of molecular mechanism revealed that cell apoptosis was associated with the overexpression of Fas protein and the significant activation of caspase-3. In vivo magnetic resonance imaging and biodistribution study showed that the MNP–DGL–RGD-GX1–DOX formulation had high affinity to the tumor tissue, leading to more aggregation of NPs in the tumor. In vivo antitumor efficacy research verified that MNP–DGL–RGD-GX1–DOX NPs possessed significant antitumor activity and the tumor inhibitory rate reached 78.5%. These results suggested that NPs could be promising in application to early diagnosis and therapy in hepatocellular carcinoma as a specific nanoprobe. Keywords: heterogeneous dimer peptide (HDP), molecular probe, magnetic nanoparticles (MNPs), targeting, hepatocellular carcinoma (HCC)

Summary Background Many patients with Parkinson's disease have potentially disabling off episodes that are not predictably responsive to levodopa. In this study, we assessed the safety and efficacy of apomorphine sublingual film as an on-demand therapy for off episodes in patients with Parkinson's disease. Methods This randomised, double-blind, placebo-controlled study was done by movement disorder specialists at 32 sites in the USA and one in Canada. Patients with Parkinson's disease who had 2 h or more of off time per day with predictable morning off periods, were responsive to levodopa, and were on stable doses of anti-parkinsonian medication were eligible. In an open-label titration phase, increasing doses of apomorphine sublingual film (10–35 mg) were administered until a tolerable full on response was achieved. Patients were then randomly assigned (1:1) with an interactive web-response system to receive the effective dose of apomorphine sublingual film or matching placebo in a 12-week, double-blind maintenance phase. Randomisation was not stratified, and the block size was four. All patients and study personnel were masked to treatment assignments. The primary endpoint was the in-clinic change from predose to 30 min post-dose in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 (motor) score at week 12, analysed on a modified intention-to-treat population by use of a mixed-effect model for repeated measures. Safety analyses were done on all enrolled patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov , NCT02469090 . Findings Between June 18, 2015, and Dec 11, 2017, 109 patients were enrolled and randomly assigned to receive apomorphine sublingual film (n=54) or placebo (n=55). All patients received the assigned study treatment, and 34 (63%) of 54 patients receiving apomorphine sublingual film and 46 (84%) of 55 receiving placebo completed the study. Least squares mean (SE) change from predose to 30 min post-dose in MDS-UPDRS part 3 score at week 12 was −11·1 (SE 1·46, 95% CI −14·0 to −8·2) with apomorphine sublingual film and −3·5 (1·29, −6·1 to −0·9) with placebo (difference −7·6, SE 1·96, 95% CI −11·5 to −3·7; p=0·0002). Mild-to-moderate oropharyngeal events were the most common side-effect, reported in 17 (31%) of 54 patients receiving apomorphine sublingual film and in four (7%) of 55 patients receiving placebo, leading to treatment discontinuation in nine (17%) patients treated with apomorphine and in one (2%) patient treated with placebo. Other treatment-emergent adverse events were transient nausea (in 15 [28%] patients receiving apomorphine sublingual film), somnolence (seven [13%]), and dizziness (five [9%]). Orthostatic hypotension, syncope, dyskinesia, hallucinations, prolongation of the QT interval, and impulse control disorders were infrequent (prevalence ≤2% of all patients) or did not occur. One patient treated with apomorphine sublingual film (with known cardiac risk factors) had a fatal cardiac arrest. Interpretation Although nearly a third of patients discontinued treatment primarily because of oropharyngeal side-effects, apomorphine sublingual film provided an efficacious, on-demand treatment for off episodes for most patients with Parkinson's disease in this trial. The long-term safety and efficacy of apomorphine sublingual film are currently being investigated. Funding Cynapsus Therapeutics and Sunovion.

© 2020 Elsevier Ltd Implantable electrochemical biosensor is one powerful tool for the accurate and reliable measurements of small molecules in vivo. However, the electrode is inevitably subjected to the protein adsorption when implanted into the living animals, affecting the sensitivity and stability of biosensor. Herein, we designed the multi-walled carbon nanotubes/gelatin-hemoglobin (MWCNTs/gelatin-Hb) core-shell nanobelts constructed on glassy carbon electrode (GC) using the one-step electrospinning technique for studying the effect of protein adsorption on the electrode surface properties. The results of the water contact angle and the scanning electron microscopy (SEM) showed that the electrospun core-shell MWCNTs/gelatin-Hb nanobelts present hydrophilic and certain anti-protein adsorption properties. Direct electron transfer between the Hb molecules in the electrospun core-shell nanobelts and electrode and catalysis of hydrogen peroxide (H2O2) can be still achieved after the electrospun core-shell MWCNTs/gelatin-Hb nanobelts adsorbed protein. Moreover, compared with before protein adsorption (Kmapp =0.0155 mmol/L), the electrospun core-shell MWCNTs/gelatin-Hb nanobelts after protein adsorption still displayed high biological affinity to H2O2 (Kmapp =0.0382 mmol/L). The constructed H2O2 biosensor by using the electrospun core-shell MWCNTs/gelatin-Hb nanobelts showed high sensitivity, great reproducibility and stability after protein adsorption. This study provides a novel design and an effective platform for the development of implantable electrochemical biosensors.

In order to control the wheel–rail coupling vibration of an urban railway system, a combined elastic wheel damping structure is proposed where the key parameters that determine the structural damping and thereby control the vibration of the railway system are explored. The vertical acceleration of the elastic wheels is obtained for a range of stiffness coefficients as the wheel moves on an irregular track, which is calculated by the [Formula: see text] method in the time domain. The results show that the vertical acceleration changes with a V-shaped trend, with an increase of wheel stiffness coefficient, which allows the optimum stiffness coefficient for minimum vertical acceleration of the elastic wheel to be obtained. It is observed that when attempting to suppress wheel vibration, an elastic wheel with a larger stiffness coefficient is needed as the degree of track irregularity reduces. This paper provides new insights into the effect of wheel elasticity on vibration characteristics, and thereby provides directions to improve ride quality and passenger comfort.

Background: Vascular dementia is a common and frequently-occurring disease in the process of human aging. Although the current treatment can delay the deterioration of the disease, it has not a great breakthrough in improving cognitive impairment. Therefore, exploring the potential key molecular targets of VD provide promising strategy for prevention and treatment. Methods: vascular dementia rats were reproduced by permanent middle cerebral artery occlusion (pMCAO) and anoxic injury of HT22 cells were induced by Cobalt Chloride (CoCl 2 , 200μM). The ability of spatial learning and memory was assessed by morris water maze (MWM) test. Histological analysis was performed by HE staining and immunohistochemical staining. The effects of gastrodin on autophagy flux and calcium signal in vascular dementia rats and HT22 cells during hypoxia injury were detected by Western blotting and immunofluorescence. Furthermore, intracellular Ca 2+ levels were quantified using a Ca 2+ quantification kit and were also measured by flow cytometric estimation of Fluo-4 AM. Results: Gastrodin significantly reversed cognitive deficits in vascular dementia rats. The results of immunohistochemical analysis and western blot confirmed that gastrodin could attenuate the levels of LC3, p62 and phosphorylated CaMKII in hippocampus of VD rats. In addition, gastrodin was similar to the early autophagic inhibitor (3-BDO) ameliorating CoCl 2 -induced autophagic flux dysfunction and p62 knockdown by siRNA also promoting autophagic flux patency, but the late autophagy inhibitor (CQ) weakened the improvement effect of gastrodin. Furthermore, gastrodin markedly inhibited CoCl 2 -induced autophagic flux dysfunction by inhibiting [Ca 2+ ] i -dependent CaMKII. Conclusion: Gastrodin is a potential promising candidate for VD by improving autophagy flux dysfunction via increasing lysosome acidification and autophagosome-lysosome fusion mediated by CaMKII-regulated suppression of p62 signaling. Keywords: Gastrodin, Vascular dementia, Neuron injury, Autophagic flux, Ca 2+ , CaMKII

Echocardiography is a key evaluation tool for the diagnosis, prognosis, and guidance of interventional management of numerous cardiovascular conditions, including ischaemia, heart failure, and structural heart diseases. Recent technological advancements have also seen the exploration of artificial intelligence, intracardiac vortex imaging, and three-dimensional printing in echocardiography. With cardiovascular diseases increasing in prevalence worldwide, it is important for clinicians including general practitioners to have updated knowledge of appropriate use of echocardiography. As such, this article reviews the current literature and summarises the latest developments and the general clinical usage of echocardiography.

Publisher's version (útgefin grein), Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18., Competing interests Gad Getz receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig and POLYSOLVER. Hikmat Al-Ahmadie is consultant for AstraZeneca and Bristol-Myers Squibb. Samuel Aparicio is a founder and shareholder of Contextual Genomics. Pratiti Bandopadhayay receives grant funding from Novartis for an unrelated project. Rameen Beroukhim owns equity in Ampressa Therapeutics. Andrew Biankin receives grant funding from Celgene, AstraZeneca and is a consultant for or on advisory boards of AstraZeneca, Celgene, Elstar Therapeutics, Clovis Oncology and Roche. Ewan Birney is a consultant for Oxford Nanopore, Dovetail and GSK. Marcus Bosenberg is a consultant for Eli Lilly. Atul Butte is a cofounder of and consultant for Personalis, NuMedii, a consultant for Samsung, Geisinger Health, Mango Tree Corporation, Regenstrief Institute and in the recent past a consultant for 10x Genomics and Helix, a shareholder in Personalis, a minor shareholder in Apple, Twitter, Facebook, Google, Microsoft, Sarepta, 10x Genomics, Amazon, Biogen, CVS, Illumina, Snap and Sutro and has received honoraria and travel reimbursement for invited talks from Genentech, Roche, Pfizer, Optum, AbbVie and many academic institutions and health systems. Carlos Caldas has served on the Scientific Advisory Board of Illumina. Lorraine Chantrill acted on an advisory board for AMGEN Australia in the past 2 years. Andrew D. Cherniack receives research funding from Bayer. Helen Davies is an inventor on a number of patent applications that encompass the use of mutational signatures. Francisco De La Vega was employed at Annai Systems during part of the project. Ronny Drapkin serves on the scientific advisory board of Repare Therapeutics and Siamab Therapeutics. Rosalind Eeles has received an honorarium for the GU-ASCO meeting in San Francisco in January 2016 as a speaker, a honorarium and support from Janssen for the RMH FR meeting in November 2017 as a speaker (title: genetics and prostate cancer), a honorarium for an University of Chicago invited talk in May 2018 as speaker and an educational honorarium paid by Bayer & Ipsen to attend GU Connect ‘Treatment sequencing for mCRPC patients within the changing landscape of mHSPC’ at a venue at ESMO, Barcelona, on 28 September 2019. Paul Flicek is a member of the scientific advisory boards of Fabric Genomics and Eagle Genomics. Ronald Ghossein is a consultant for Veracyte. Dominik Glodzik is an inventor on a number of patent applications that encompass the use of mutational signatures. Eoghan Harrington is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Yann Joly is responsible for the Data Access Compliance Office (DACO) of ICGC 2009-2018. Sissel Juul is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Vincent Khoo has received personal fees and non-financial support from Accuray, Astellas, Bayer, Boston Scientific and Janssen. Stian Knappskog is a coprincipal investigator on a clinical trial that receives research funding from AstraZeneca and Pfizer. Ignaty Leshchiner is a consultant for PACT Pharma. Carlos López-Otín has ownership interest (including stock and patents) in DREAMgenics. Matthew Meyerson is a scientific advisory board chair of, and consultant for, OrigiMed, has obtained research funding from Bayer and Ono Pharma and receives patent royalties from LabCorp. Serena Nik-Zainal is an inventor on a number of patent applications that encompass the use of mutational signatures. Nathan Pennell has done consulting work with Merck, Astrazeneca, Eli Lilly and Bristol-Myers Squibb. Xose S. Puente has ownership interest (including stock and patents in DREAMgenics. Benjamin J. Raphael is a consultant for and has ownership interest (including stock and patents) in Medley Genomics. Jorge Reis-Filho is a consultant for Goldman Sachs and REPARE Therapeutics, member of the scientific advisory board of Volition RX and Paige.AI and an ad hoc member of the scientific advisory board of Ventana Medical Systems, Roche Tissue Diagnostics, InVicro, Roche, Genentech and Novartis. Lewis R. Roberts has received grant support from ARIAD Pharmaceuticals, Bayer, BTG International, Exact Sciences, Gilead Sciences, Glycotest, RedHill Biopharma, Target PharmaSolutions and Wako Diagnostics and has provided advisory services to Bayer, Exact Sciences, Gilead Sciences, GRAIL, QED Therapeutics and TAVEC Pharmaceuticals. Richard A. Scolyer has received fees for professional services from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia, Myriad, NeraCare GmbH and Amgen. Tal Shmaya is employed at Annai Systems. Reiner Siebert has received speaker honoraria from Roche and AstraZeneca. Sabina Signoretti is a consultant for Bristol-Myers Squibb, AstraZeneca, Merck, AACR and NCI and has received funding from Bristol-Myers Squibb, AstraZeneca, Exelixis and royalties from Biogenex. Jared Simpson has received research funding and travel support from Oxford Nanopore Technologies. Anil K. Sood is a consultant for Merck and Kiyatec, has received research funding from M-Trap and is a shareholder in BioPath. Simon Tavaré is on the scientific advisory board of Ipsen and a consultant for Kallyope. John F. Thompson has received honoraria and travel support for attending advisory board meetings of GlaxoSmithKline and Provectus and has received honoraria for participation in advisory boards for MSD Australia and BMS Australia. Daniel Turner is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Naveen Vasudev has received speaker honoraria and/or consultancy fees from Bristol-Myers Squibb, Pfizer, EUSA pharma, MSD and Novartis. Jeremiah A. Wala is a consultant for Nference. Daniel J. Weisenberger is a consultant for Zymo Research. Dai-Ying Wu is employed at Annai Systems. Cheng-Zhong Zhang is a cofounder and equity holder of Pillar Biosciences, a for-profit company that specializes in the development of targeted sequencing assays. The other authors declare no competing interests.

Background: Most aphids exhibit wing polyphenism in which wingless and winged morphs produce depending on the population density and host plant quality. Although the influence of environmental factors on wing polyphenism of aphids have been extensively investigated, molecular mechanisms underlining morph differentiation (i.e. wing development /degeneration), one downstream aspect of the wing polyphenism , has been poorly understood. Results: We examined the expression levels of the twenty genes involved in wing development network, and only vestigial (vg ) showed significantly different expression levels in both whole-body and wall-body of third instar nymphs, with 5.4- and 16.14- fold higher expression in winged lines compared to wingless lines, respectively in Rhopalosiphum padi . vg expression was higher in winged lines compared to wingless lines in third, fourth instar nymphs and adults. Larger difference expression was observed in third (21.38-fold) and fourth (20.91-fold) instar nymphs relative to adults (3.12-fold). Suppression of vg using RNAi repressed the wing development of third winged morphs. Furthermore, dual luciferase reporter assay revealed that the miR-147 can target the vg mRNA. Modulation of miR-147b levels by microinjection of its agomir (mimic) decreased vg expression levels and repressed wing development. Conclusions : Our findings suggest that vg is essential for wing development in R. padi and that miR-147b modulates its expression. .

In the development of space mission simulation system, the fidelity of real-time scene rendering is one of the key indexes of simulation system. This paper presents a new shader technology based on physical rendering. The technique was validated by rendering tests in the engine. The simulation results show that the method can effectively improve the fidelity of scene rendering and provide technical support for the development of high-fidelity space mission simulation system.

Shao-Ang Cheng,1,* Li-Zhong Liang,2,* Qi-Lian Liang,1 Zhen-Yi Huang,3 Xiao-Xia Peng,1 Xiao-Cui Hong,1 Xing-Bo Luo,1 Gao-Le Yuan,1 Hui-Jie Zhang,1 Liang Jiang4 1Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 2Medical Insurance Office, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 3Department of Finance, Central Hospital of Guangdong Agriculture Reclamation, Zhanjiang 524002, China; 4Interventional Ward, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China *These authors contributed equally to this work Background: To investigate the epidemiological features of breast cancer laterality and molecular subtypes in southern China.Materials and methods: A total of 2,049 cases who were diagnosed with unilateral breast cancer in the past 5 years were classified based on laterality and molecular subtypes. Molecular subtypes were defined in accordance with the 2013 St. Gallen recommendations.Results: Breast cancer was more likely to be diagnosed in the left breast than in the right at a rate of around 5%. In the case of invasive carcinomas, the right breast was more commonly affected than the left in young (

Lu Yang,1,* Ming Xu,2,* Chuan-Bao Cui,1 Peng-Hai Wei,1 Shu-Zhi Wu,1 Zuo-Jie Cen,1 Xing-Xing Meng,1 Qiong-Guang Huang,1 Zhi-Chun Xie1 1Department of Epidemiology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Human Anatomy and Histology and Embryology, Qilu Medical University, Zibo 255213, Shandong Province, People’s Republic of China *These authors contributed equally to this work Background: The current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Materials and methods: Whole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes. Investigation of the potential function of ERCC8 was carried out by gene set enrichment analysis (GSEA) and genome-wide coexpression analysis.Results: ROC analysis suggests that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated and may have potential to distinguish between HBV-related HCC tumor and paracancerous tissues (area under the curve of ROC ranged from 0.623 to 0.744). Survival analysis demonstrated that high ERCC8 expression was associated with a significantly decreased risk of recurrence (adjusted P=0.021; HR=0.643; 95% CI=0.442–0.937) and death (adjusted P=0.049; HR=0.631; 95% CI=0.399–0.998) in HBV-related HCC. Then, we also developed two nomograms for the HBV-related HCC individualized prognosis predictions. GSEA suggests that the high expression of ERCC8 may have involvement in the energy metabolism biological processes. As the genome-wide coexpression analysis and functional assessment of ERCC8 suggest, those coexpressed genes were significantly enriched in multiple biological processes of DNA damage and repair. Conclusion: The present study indicates that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated between HBV-related HCC tumor and paracancerous tissues and that the mRNA expression of ERCC8 may serve as a potential biomarker for the HBV-related HCC prognosis. Keywords: HBV, hepatocellular carcinoma, diagnosis, prognosis, ERCC

Bin Zhu,1 Lei Zhang,2 Xiao Ping Cheng,3 Lei Wang,4 Yue Tian,1 Xi Xi Li,1 Ying Ping Liu,5 Zhi Gang Zhao11Department of Pharmacy, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China; 2Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100050, China; 3Department of Nephrology, Shaanxi Hospital of Traditional Chinese Medical, ShaaXi 710003, China; 4Department of Endocrinology, Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China; 5Obstetrics Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, ChinaBackground: To examine the association of metabolic syndrome (MetS) with carotid artery stenosis (CAS), especially in menopausal women in China.Materials and methods: A cross-sectional study of menopause women aged ≥40 years were enrolled from the Jidong community of Tangshan City between 2013 and 2014 to examine the association between MetS and CAS. Logistic regression analyses were performed to analyze the association between MetS and the presence of CAS.Results: A total of 762 menopause women with mean age 59.3±5.6 years were enrolled in our analysis. Of all the people, 111 participants in CAS group (n=159) and 297 participants in no CAS group (n=603) were diagnosed with MetS meantime. Menopausal women with MetS had increased risk of CAS (OR, 2.383; 95% CI, 1.639–3.464), and the association was further verified by adjusting for confounding factors (OR, 1.949; 95% CI, 1.269–2.994). In addition, age, physical activity (never or moderate), body mass index (>24 kg/m2), and family income (

The current report describes the journey from the sharing of a single, extraordinary experience during a support group conversation to the development of a novel scientific investigation of balance problems in a rarer form of dementia. The story centres around the involvement of people living with or caring for someone with posterior cortical atrophy (often referred to as the visual variant of Alzheimer’s disease) in highlighting hitherto under-appreciated consequences of their condition upon their ability to know ‘Am I the right way up?’. We describe how comments and descriptions of these balance symptoms were collated and communicated, and the involvement of people with posterior cortical atrophy in shaping a series of scientific hypotheses and developing and adapting appropriate experimental materials and procedures. We also reflect more broadly on how we might better recognise, acknowledge and encourage different forms of involvement, and describe several engagement-inspired extensions to the research involving people living with dementia, scientists and artists.

Xiao-Xiao Wang,1,* Fu-Gui Ye,2,* Jie Zhang,1,* Jun-Jing Li,1 Qing-Xia Chen,1 Pei-Yang Lin,1 Chuan-Gui Song1 1Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Breast Surgery, Key Laboratory of Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Neoadjuvant chemotherapy (NAC) plays a pivotal role in the treatment of locally advanced breast cancer (LABC); however, breast cancer is a heterogeneous disease, individual responses to chemotherapy are highly variable. Therefore, the purpose of the current research is to identify biomarkers that can predict the chemotherapeutic response. Patients and methods: We recruited 78 patients with primary breast cancer who underwent taxane- and anthracycline-based NAC; these patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The microRNA microarray was conducted to explore differentially expressed miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) further validated the relationship between miR-4530 and chemosensitivity in breast cancer patients. Results: No significant differences were observed between the two groups regarding the clinicopathological characteristics. miR-4530 showed the most potential involving breast cancer chemosensitivity. Mechanically, RUNX2 was identified one of the direct targets of miR-4530 and responsible for breast cancer chemosensitivity. Conclusion: Our results revealed that elevated serum miR-4530 levels may sensitize breast cancer to taxane- and anthracycline-based NAC by suppressing RUNX2; therefore, this miRNA has the potential to be a new biomarker for predicting breast cancer chemosensitivity. Keywords: miR-4530, serum, neoadjuvant chemotherapy, chemotherapeutic resistance, RUNX2

Liang Jiang,1,* Qi-Lian Liang,2 Wei-Ming Liang,1,* Hui-Jie Zhang,2 Jie Huang,2 Gao-Le Yuan,2 Xiao-Xia Peng,2 Shao-Ang Cheng,2 Zhi-Gang Huang,3 Xiang-Ning Zhang4 1Interventional Ward, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 2Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; 3Department of Epidemiology, School of Public Health, Guangdong Medical University, Dongguan 523808, China; 4Department of Pathophysiology, School of Basic Medical Science, Guangdong Medical University, Dongguan 523808, China *These authors contributed equally to this work Introduction: Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited.Materials and methods: We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot.Result: We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P

Shi-Ming Zhang, Qing-Ge Zhu, Xiao-Xiao Ding, Song Lin, Jing Zhao, Lei Guan, Ting Li, Bing He, Hu-Qin Zhang The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an JiaoTong University, Xi’an, 710049, China Background: The prognostic value of EGFR and KRAS mutations in resected non-small cell lung cancer (NSCLC) has been reported. However, conflicting results were reported in these studies. The effect of mutations in these two genes in resected NSCLC remains controversial.Methods: We searched Internet databases for studies reporting disease-free survival (DFS) and overall survival (OS) in resected NSCLC patients with EGFR or KRAS mutations. A meta-analysis calculating the pooled hazard ratio (HR) for DFS and OS was used to measure the association of EGFR or KRAS mutations with the prognosis of patients after surgery.Results: A total of 9,635 patients from 32 studies were included in this analysis. The combined HR for EGFR mutations on DFS was 0.77 (95% CI 0.66–0.90, p=0.001) and on OS was 0.72 (95% CI 0.66–0.80, p

In his comment to Giuseppe Carlo Marino’s essay about the globalization and crisis of “historical thought”, Eugenio Guccione proposes a historical and philosophical interpretation of the changes in the relationship among political events, roll and the meaning of the human existence, and cultural debate linked to the “globalizing” phenomena, inserting the events and recent evolutions of the historical thought in a larger context of redefinition of the very concept of history.

Myostatin (MSTN) is a negative regulator of skeletal muscle growth. In order to investigate whether there is a correlation between MSTN polymorphisms and chicken production performance, in this study, single nucleotide polymorphisms (SNPs) in MSTN gene were examined across 180 Daheng broilers by direct sequencing of PCR product, and the correlations between the genotype and body weight at the age of 1-10 weeks and carcass traits at the age of 73 day were analyzed. Five SNPs (rs313622770, rs313744840, rs316247861, rs314431084, rs317126751) of MSTN gene were identified across Daheng broiler samples, and four haplotypes were reconstructed based on the five SNPs. Results of association analysis showed that four (rs313622770, rs313744840, rs316247861 and rs317126751) of these SNPs had significant association with some growth traits (p

Xiao Xia Guo,1,* Hong Li Wu,2,* Hong Yun Shi,3 Lei Su,3 Xi Zhang3 1Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, 2Department of Obstetrics and Gynecology, Hebei University Affiliated Hospital, 3Department of Radiation Oncology, Hebei University Affiliated Hospital, Baoding, China *These authors contributed equally to this work Purpose: PARP inhibition is an exciting new anticancer strategy. As the first PARP inhibitor approved for the treatment of advanced BRCA-mutated ovarian cancer, olaparib has proven to be effective in the treatment of several solid tumors. We performed a meta-analysis of published randomized controlled trials to evaluate the efficacy and safety of olaparib in cancer patients. Methods: PubMed, Embase, and oncology-conference proceedings were searched for relevant studies. End points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 adverse events. Pooled hazard ratio (HR)/risk ratio (RR) and 95% CI were calculated using random or fixed-effect models. Results: Eight trials involving 1,957 patients were ultimately identified. The pooled analysis demonstrated that olaparib treatment significantly improved PFS (HR 0.62, 95% CI 0.47–0.82; P=0.001), OS (HR 0.82, 95% CI 0.73–0.93; P=0.001), and ORR (RR 1.38, 95% CI 1.16–1.65; P

Yu Zhang,1,2,* Xiao Xi Zhang,3,* Rui Yan Yuan,1,4,* Tai Ren,1,4 Zi Yu Shao,1,4 Hong Fei Wang,1,4 Wei Long Cai,5 Li Tian Chen,1,4 Xu An Wang,4 Ping Wang2 1Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, People’s Republic of China; 2Department of General Surgery, Hangzhou First People’s Hospital, Hangzhou 310006, People’s Republic of China; 3Shanghai Health Development Research Center, Shanghai 200040, People’s Republic of China; 4Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, People’s Republic of China; 5Department of General Surgery, Huzhou Central Hospital, Zhejiang 313000, People’s Republic of China *These authors contributed equally to this work Background: Cordycepin, the main active ingredient of a traditional Chinese herbal remedy – extracted from Cordyceps sinensis – has been demonstrated as a very effective anti-inflammatory and antitumor drug. The present study investigated its antitumor effect on pancreatic cancer, a highly aggressive cancer with extremely poor prognosis due to malignancy, and clarified its underlying mechanism both in vitro and in vivo. Methods: The antitumor viability of cordycepin on human pancreatic cancer MIAPaCa-2 and Capan-1 cells was determined by colony formation assays. Annexin V/PI double staining and flow cytometry assay were used to investigate whether cordycepin induced apoptosis and cell cycle arrest. The mitochondrial membrane potential (ΔΨm) was analyzed by Rhodamine 123 staining, and expression of related proteins evaluated by Western blot and immunohistochemistry, both on pancreatic cancer cells and tumor xenografts to reveal the potential mechanism for the effect of cordycepin. Furthermore, the in vivo efficacy was examined on nude mice bearing MIAPaCa-2 cell tumors treated by intraperitoneal injection of cordycepin (0, 15, and 50 mg/kg/d) for 28 days. Results: Cordycepin inhibited cell viability, proliferation and colony formation ability and induced cell cycle arrest and early apoptosis of human pancreatic cancer cells (MIAPaCa-2 and Capan-1) in a dose- and time-dependent manner. The same effect was also observed in vivo. Decrease of ΔΨm and upregulation of Bax, cleaved caspase-3, cleaved caspase-9, and cleaved PARP as well as downregulation of Bcl-2 both in vitro and in vivo indicated that the mitochondria-mediated intrinsic pathway was involved in cordycepin’s antitumor effect. Conclusion: Our data showed that cordycepin inhibited the activity of pancreatic cancer both in vitro and in vivo by regulating apoptosis-related protein expression through the mitochondrial pathway and suggest that cordycepin may be a promising therapeutic option for pancreatic cancer. Keywords: cordycepin, pancreatic cancer, proliferation, apoptosis, mitochondrial pathway

Qinchang Chen,1,* Kai Huang,2,* Lingling Li,2 Xixia Lin,2 Cong Ding,2 Junrui Zhang,3 Qingui Chen1 1Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 2Division of Vascular and Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; 3Guangzhou Institute of Standardization, Guangzhou, China *These authors contributed equally to this work Purpose: We aimed to evaluate the association of serum uric acid on admission with long-term outcome of critically ill patients. Materials and methods: We conducted a retrospective cohort study using data extracted from the Medical Information Mart for Intensive Care III database. The primary endpoint was 90-day mortality. Propensity score matching (PSM) was performed, and multivariate Cox regression analysis was used to adjust for potential confounders. Receiver operating characteristic (ROC) curves were also used to assess the mortality predictions. Results: A total of 2,123 patients were included finally with a PSM cohort consisting of 556 90-day non-survivors matched 1:1 with 556 90-day survivors. No statistically significant difference of median admission uric acid was observed between the two groups (survivors 5.50 mg/dL vs non-survivors 5.60 mg/dL, p=0.536). ROC area under the curve was 0.511 (95% confidence interval [CI] 0.477–0.545), suggesting that uric acid had poor discriminative powers for predicting 90-day mortality. No significant association between uric acid and 90-day mortality was found (hazard ratio 1.00, 95% CI 0.98–1.03, p=0.6835). Conclusion: Serum uric acid on intensive care unit admission failed to predict 90-day mortality of critically ill patients. Keywords: uric acid, critical care, mortality, risk factors

Jing Liu,1,2,* Jie Yang,3,* Lin Yu,3,* Chun Rao,2,4,5 Qian Wang,2,4,5 Cuiyun Sun,2,4,5 Cuijuan Shi,2,4,5 Dan Hua,2,4,5 Xuexia Zhou,2,4,5 Wenjun Luo,2,4,5 Run Wang,2,4,5 Weiping Li,1 Shizhu Yu2,4,5 1Department of Neurosurgery and Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen University School of Medicine, Shenzhen 518035, People’s Republic of China; 2Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Tianjin Medical University,Tianjin 300070, People’s Republic of China; 4Department of Neuropathology, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, People’s Republic of China; 5Department of Neuropathology, Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, People’s Republic of China *These authors contributed equally tothiswork Background: Downregulation of miR-361-5p contributes to epithelial–mesenchymal transition of glioma cells. However, the relevance of miR-361-5p to migration and invasion of gliomas remains unknown. Materials and methods: The relationship between miR-361-5p and SND1 expression was analyzed in 120 human gliomas and 8 glioma cell lines by in situ hybridization, immunohistochemistry, and Western blot. Dual-luciferase reporter assay was used to identify SND1 as a target of miR-361-5p. The mechanisms through which miR-361-5p inhibits glioma cell migration and invasion were studied by in vitro assays. Results: miR-361-5p expression was significantly downregulated in glioma tissues and glioma cell lines, and was inversely correlated with glioma grades. However, SND1 expression was positively correlated with glioma grades and inversely correlated with miR-361-5p expression. miR-361-5p overexpression suppressed glioma cell migration and invasion through targeting SND1 and subsequently decreasing MMP-2 expression. In glioma cell lines, SND1 overexpression could partly reverse the antitumor effects of miR-361-5p. Conclusion: The findings provide evidence that miR-361-5p directly targets SND1 to degradation and then reduces MMP-2 gene transcription, thus inhibiting glioma migration and invasion. miR-361-5p is an important tumor suppressor and a novel diagnostic biomarker of glioma, and miR-361-5p and SND1 are potential therapeutic candidates for malignant gliomas. Keywords: miR-361-5p, glioma, SND1, migration, invasion

Jing-hua Pan,1 Hong Zhou,2 Sheng-bin Zhu,1 Jin-lian Huang,1 Xiao-xu Zhao,1 Hui Ding,1 Yun-long Pan1 1Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; 2Department of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China Abstract: RAF kinase is crucially involved in cell proliferation and survival in colorectal cancer (CRC). Patients with metastatic CRC (mCRC) harboring BRAF mutations (BRAFms) not only experience a poor prognosis but also benefit less from therapeutics targeting ERK signaling. With advances in RAF inhibitors and second-generation inhibitors including encorafenib and vemurafenib, which have been approved for treating BRAF-V600E malignancies, the combinatorial therapeutic strategies of RAF inhibitors elicit remarkable responses in patients with BRAF-V600E mCRC. However, the therapeutic efficacy is restricted by resistance, which might be due to RAF dimerization and reactivation of the MAPK pathway. In addition, the next-generation RAF inhibitors, which are characterized by varying structural and biochemical properties, have achieved preclinical and clinical advances. Herein, we summarize the existing mechanism of RAF kinases in CRC, including MAPK feedback reactivation of resistance to RAF inhibitors. We additionally summarize the development of three generations of RAF inhibitors and different therapeutic strategies including the combination of EGFR, BRAF, and PI3K inhibitors for BRAFm CRC treatment. Keywords: BRAF, inhibitor, colorectal cancer, V600E, structure, resistance

Tao Han,1,* Jianjun Chen,1,* Yuting Luan,2,* Xiaoxia Chen,1,* Xiaodan Yang,1 Yue Zhang,1 Gao Li,2 Di Wang,3 Zhendong Zheng1 1Department of Oncology, Cancer Center of People’s Liberation Army, General Hospital of Shenyang Military Region, Shenyang 110840, People’s Republic of China; 2Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110840, People’s Republic of China; 3Department of Pathology, General Hospital of Shenyang Military Region, Shenyang 110840, People’s Republic of China *These authors contributed equally to this work Abstract: Embryonal rhabdomyosarcoma (ERMS) has a low prevalence, poor prognosis, and limited treatment efficacy. We report a case of an 18-year-old male whose disease relapsed in the abdominal cavity after a testicular ERMS curative resection. The patient received eight sequential cycles of rescue therapy using cisplatin and isocyclophosphamide in combination with a vascular targeted drug, Endostar. The therapeutic effect of the combination regimen has been evaluated for complete response. This is the first case to report using Endostar and chemotherapy in relapsed ERMS, and the curative effect results in complete response. Endostar, a new vascular targeted drug, combined with chemotherapy may play a synergistic role and provide a reference for the treatment of ERMS. Keywords: embryonal rhabdomyosarcoma, metastasis, complete response, endogenous angiogenesis inhibitor

This article traces the history of elementary schooling from the nineteenth century to 1948, focusing on «small schools», a seemingly marginal and peripheral element of public education. Such schools have been defined over the decades as: «elementary schools comprised of three sections», «rural schools», «unclassified schools», «merged schools entrusted to a single teacher», «singular multi-class schools». From a historiographical perspective this type of school will be considered beyond the stereotypes that have characterised the reconstruction of educational history in Italy. One such stereotype, which recent archival and documentary research has started to put into question, is the assumption that compulsory schooling coincided with the birth of Italy as a nation-state. The three historical periods presented, devoted to the multi-classroom school in liberal Italy, during fascism, and in the early years of the republic respectively, offer unexpected reflections on choices presently made regarding primary school by those on the educational shop floor, political decision-makers and communities.

This article shows the school situation of the neighborhood of San Jorge, a peripheral, industrial and worker immigration area of Pamplona between 1933 and 1983. It shows initiatives of pressure on the authorities and the importance of social action in the implementation of school facilities and its subsequent use. From the Second Republic to a dictatorial time that evolves towards constant citizen proposals at the end of the sixties, this article revealed the importance of schools for formal education and also for the use of facilities to channel collective activity and group identity within an urbanism that did not foresee spaces of encounter. The interaction between social initiative and official educational policy shows that the involvement of the neighbors was decisive to overcome the shortcomings of disorderly growth.

Hai-Yang Wang,1 Xiao-Xia Zhang,1 Cui-Ping Si,1 Yang Xu,1 Qian Liu,1 He-Tao Bian,1 Bing-Wei Zhang,2 Xue-Lin Li,3 Zhong-Rui Yan1 1Department of Neurology, Jining No1 People’s Hospital, Jining, Shandong Province, China; 2Department of Neurology and Psychiatry, First Affiliate Hospital of Dalian Medical University, Dalian, Liaoning Province, China; 3Department of Intensive Care Unit, Jining No1 People’s Hospital, Jining, Shandong Province, China Objective: Impairments in emotion regulation, and more specifically in cognitive reappraisal, are thought to play a key role in the pathogenesis of anxiety disorders. However, the available evidence on such deficits is inconsistent. To further illustrate the neurobiological underpinnings of anxiety disorder, the present meta-analysis summarizes functional magnetic resonance imaging (fMRI) findings for cognitive reappraisal tasks and investigates related brain areas.Methods: We performed a comprehensive series of meta-analyses of cognitive reappraisal fMRI studies contrasting patients with anxiety disorder with healthy control (HC) subjects, employing an anisotropic effect-size signed differential mapping approach. We also conducted a subgroup analysis of medication status, anxiety disorder subtype, data-processing software, and MRI field strengths. Meta-regression was used to explore the effects of demographics and clinical characteristics. Eight studies, with 11 datasets including 219 patients with anxiety disorder and 227 HC, were identified.Results: Compared with HC, patients with anxiety disorder showed relatively decreased activation of the bilateral dorsomedial prefrontal cortex (dmPFC), bilateral dorsal anterior cingulate cortex (dACC), bilateral supplementary motor area (SMA), left ventromedial prefrontal cortex (vmPFC), bilateral parietal cortex, and left fusiform gyrus during cognitive reappraisal. The subgroup analysis, jackknife sensitivity analysis, heterogeneity analysis, and Egger’s tests further confirmed these findings. Conclusions: Impaired cognitive reappraisal in anxiety disorder may be the consequence of hypo-activation of the prefrontoparietal network, consistent with insufficient top-down control. Our findings provide robust evidence that functional impairment in prefrontoparietal neuronal circuits may have a significant role in the pathogenesis of anxiety disorder. Keywords: anxiety disorder, emotion regulation, cognitive reappraisal, fMRI, prefrontoparietal network, signed differential mapping

Xingxing Chen,1,2,* Fan Xia,1,2,* Jurui Luo,1,2,* Jinli Ma,1,2 Zhaozhi Yang,1,2 Li Zhang,1,2 Yan Feng,1,2 Zhimin Shao,2,3 Xiaoli Yu,1,2 Xiaomao Guo1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 3Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China *These authors contributed equally to this work Background: This study investigated the effect of postmastectomy radiotherapy (PMRT) in patients with stage II–III triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC) and modified radical mastectomy (MRM).Patients and methods: A total of 104 women with stage II–III TNBC who received NAC and MRM at our institution between January 2000 and July 2007 were identified. Patients were divided into 2 groups (PMRT and non-PMRT) for statistical analysis.Results: The median follow-up time was 64months (range 12–123months). The 5year cumulative locoregional recurrence (LRR) and disease recurrence (DR) rates were 26.5% and 49.6%, respectively. Despite their more adverse prognostic features, patients with PMRT had lower 5year cumulative LRR and DR rates than those without PMRT (LRR: 18.3% vs 52.2%, respectively, p=0.0005; DR: 45% vs 69.1%, p=0.0334, respectively). On multivariate analysis of the entire study cohort, forgoing PMRT was significantly associated with developing LRR and DR. Subset analysis revealed that PMRT significantly reduced the 5year LRR rate in patients with pre-chemotherapy clinical stages IIA (8.3% vs 46.2%, p=0.019) and IIIA (16% vs 66.7%, p=0.003). PMRT also significantly reduced the 5year DR rate in patients with pre-chemotherapy clinical stage IIA (24.5% vs 69.3%, p=0.0151) and ≥IIIB (70.8% vs 100%, p=0.0481).Conclusion: In our cohort of patients with TNBC treated with NAC and MRM, PMRT significantly improved locoregional control and disease-free survival in the entire cohort as well as in patients with stage IIA disease. Our results may help in tailoring adjuvant treatment decisions for these particular patient populations. Keywords: triple-negative breast carcinoma, neoadjuvant chemotherapy, surgery, adjuvant radiation therapy, locoregional recurrence, disease recurrence

Xuan-xuan Li,1 Si Shi,2 Lan Rong,1 Mei-qing Feng,2 Liang Zhong1 1Department of Digestive Diseases, Huashan Hospital Affiliated to Fudan University, Shanghai, China; 2School of Pharmacy, Fudan University, Shanghai, China Background: The prevalence of Helicobacter pylori has long been a global health issue. Triple therapy, being the first-line treatment, has caused dysbiosis of the gastrointestinal tract that led to various complications. A novel nanomedicine – liposomal linolenic acid (LipoLLA) – has been proven to have great potential in eradicating H. pylori. However, the possible side effects of LipoLLA due to alteration of the gastrointestinal microbiota remain unknown.Aim: This study focused on the impact of LipoLLA on gastrointestinal microbiota in mice in comparison with triple therapy in order to assess the safety profile.Methods: Mice were divided into five groups: blank control group; H. pylori control group; triple therapy group; low-dose LipoLLA group (25 mg/kg); and high-dose LipoLLA group (50 mg/kg). Fecal samples were collected before and after the intake of corresponding formulas. Gastric tissues were obtained after mice dissection. These samples were analyzed with high-throughput sequencing.Results: The analysis revealed that LipoLLA resulted in minor gut microbiota alteration at different levels. The altered proportions in the high-dose group were higher than that of the low-dose group. On the other hand, the triple therapy group showed dramatic shifts in the major community composition. It displayed a notable boost in the relative abundance of Proteobacteria and Firmicutes along with a decrease in that of Verrucomicrobia and Bacteroidetes. All of them belonged to the major phyla in the microbiome. Triple therapy also led to the growth of the family Enterobacteriaceae, Enterococcaceae, and Clostridiaceae_1 that may be associated with clinical illnesses. Gastric microbiota analysis reached similar conclusions.Conclusion: Our findings indicated that LipoLLA causes minor gastrointestinal microbiota alterations while the triple therapy triggered dramatic changes. Thus, LipoLLA is not only promising but also a safe therapeutic medication to eradicate H. pylori infection. Keywords: nanomedicine, linolenic acid, Helicobacter pylori, gastric microbiota, gut microbiota

Xingxing Shi,* Kai Zhou,* Fei Huang,* Juan Zhang, Chen Wang Department of Prosthodontics, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Background: As a potentially bioactive material, the widespread application of nanosized hydroxyapatite (nano-HAP) in the field of bone regeneration has increased the risk of human exposure. However, our understanding of the interaction between nano-HAP and stem cells implicated in bone repair remains incomplete. Methods: Here, we characterized the adhesion and cellular internalization of HAP nanoparticles (HANPs) with different sizes (20 nm np20 and 80 nm np80) and highlighted the involved pathway in their uptake using human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs). In addition, the effects of HANPs on cell viability, apoptosis response, osteogenic differentiation, and underlying related mechanisms were explored. Results: It was shown that both types of HANPs readily adhered to the cellular membrane and were transported into the cells compared to micro-sized HAP particles (m-HAP; 12 µm). Interestingly, the endocytic routes of np20 and np80 differed, although they exhibited similar kinetics of adhesion and uptake. Our study revealed involvement of clathrin- and caveolin-mediated endocytosis as well as macropinocytosis in the np20 uptake. However, for np80, clathrin-mediated endocytosis and some as-yet-unidentified important uptake routes play central roles in their internalization. HANPs displayed a higher preference to accumulate in the cytoplasm compared to m-HAP, and HANPs were not detected in the nucleolus. Exposure to np20 for 24 h caused a decrease in cell viability, while cells completely recovered with an exposure time of 72 h. Furthermore, HANPs did not influence apoptosis and necrosis of hWJ-MSCs. Strikingly, HANPs enhanced mRNA levels of osteoblast-related genes and stimulated calcium mineral deposition, and this directly correlated with the activation in c-Jun N-terminal kinases and p38 pathways. Conclusion: Our data provide additional insight about the interactions of HANPs with MSCs and suggest their application potential in hard tissue regeneration. Keywords: HANPs, hWJ-MSCs, internalization, osteogenic differentiation, JNK, p38

Fang Hu,* Xiaowei Mao,* Yujun Zhang, Xiaoxuan Zheng, Ping Gu, Huimin Wang, Xueyan ZhangDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC) patients.Methods: We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve and area under the summary receiver operating characteristic curve.Results: Eight eligible publications with 255 advanced NSCLC patients were included in this meta-analysis. Taking tumor tissues as reference, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating tumor cells for detecting the epidermal growth factor receptor mutation status were found to be 0.82 (95% confidence interval [CI]: 0.50–0.95), 0.95 (95% CI: 0.24–1.00), 16.81 (95% CI: 0.33–848.62), 0.19 (95% CI: 0.06–0.64), and 86.81 (95% CI: 1.22–6,154.15), respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89–0.94). The subgroup analysis showed that the factors of blood volume, histological type, EGFR-tyrosine kinase inhibitor therapy, and circulating tumor cell and tissue test methods for EGFR accounted for the significant difference of the pooled specificity. No significant difference was found between the pooled sensitivity of the subgroup.Conclusion: Our meta-analysis confirmed that circulating tumor cells are a good surrogate for detecting epidermal growth factor receptor mutation when tumor tissue is unavailable in advanced NSCLC patients, but more precise techniques are needed to improve their clinical efficiency.Keywords: non-small-cell lung cancer, circulating tumor cell, epidermal growth factor receptor, meta-analysis

During the second half of the nineteenth century, spas were born on the northern part of the Algerian territory, where aboriginals and settlers were living separately. These architecturally specific buildings were intended for both Algerians and Europeans. Often of local traditional inspiration, their look also included characteristics related to their activity and function, and reflected the varied cultural codes of the dual clientele of Algerian and European origin. The present work aims to analyze the architectural style of these establishments and to distinguish the local aesthetic specificities used in this type of building, by considering their functionality and the origin of the users (Europeans or Algerians).

Tianwen Lai,1,* Yanyu Li,1,* Zongjiong Mai,2 Xiaoxia Wen,1 Yingying Lv,1 Zhanqing Xie,3 Quanchao Lv,1 Min Chen,1 Dong Wu,1 Bin Wu1 1Department of Respiratory and Critical Care Medicine, 2Department of Oncology, 3Department of Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Purpose: Fibrosis in peripheral airways is responsible for airflow limitation in chronic obstructive pulmonary disease (COPD). Annexin A1 modulates several key biological events during inflammation. However, little is known about its role in airway fibrosis in COPD. We investigated whether levels of Annexin A1 were upregulated in patients with COPD, and whether it promoted airway fibrosis.Methods: We quantified serum Annexin A1 levels in never-smokers (n=12), smokers without COPD (n=11), and smokers with COPD (n=22). Correlations between Annexin A1 expression and clinical indicators (eg, lung function) were assessed. In vitro, human bronchial epithelial (HBE) cells were exposed to cigarette smoke extract (CSE) and Annexin A1 expression was assessed. Primary human lung fibroblasts were isolated from patients with COPD and effects of Annexin A1 on fibrotic deposition of lung fibroblasts were evaluated.Results: Serum Annexin A1 was significantly higher in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines stage III or IV than in those with GOLD stages I or II (12.8±0.8ng/mL versus 9.8±0.7 ng/mL; p=0.016). Annexin A1 expression was negatively associated with airflow obstruction (forced expiratory volume in one second % predicted; r=−0.72, p

The high variability in turbulence is a significant feature of the realistic atmospheric boundary layer winds which might have strong effects on wind loads on structures submerged in atmospheric boundary layer. This article has been devoted to this matter of science which is of practical importance to wind-engineering design and research. First, the variation of the turbulence intensity of the atmospheric boundary layer flow has been studied using theoretical calculations and meteorological wind measurements. Second, the effects of free-stream turbulence on wind loads on circular cylindrical structures have been revealed at high Reynolds number and equivalent conditions based on field measurements and wind tunnel model tests for wind effects on a large cooling tower. Through these works, it is found that the turbulence intensity for the measured atmospheric boundary layer winds is highly variable due to the significant effect of the mean wind speed, which is not well represented by the traditional empirical formulae. Besides, the free-stream turbulence significantly influences the dynamic characteristics of wind effects on the cooling tower in most cases, and the wind effects for a flow field of high turbulence intensity are generally more unfavorable than those for a flow field of low turbulence intensity.