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1.
Adv Ther ; 36(6): 1485-1496, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004325

RESUMO

INTRODUCTION: China has the largest number of diabetic patients in the world. In the past 2 decades, the prevalence of diabetes in China has increased dramatically, and the current status of diabetes control in the diabetic population is not satisfactory. Although insulin is currently recognized in diabetes treatment guidelines as the therapeutic option for patients not adequately controlled by diet/exercise and oral agents, the proportion of patients with type 2 diabetes using insulin is still very low, and the time when insulin therapy is initiated is relatively late. In using insulin injections, concerns about the complexity of the treatment regimen, a fear of needles, and other psychological barriers can affect insulin treatment, impacting on patient compliance and potentially resulting in a poor treatment response. Another type of insulin injection device that has become available recently, the needle-free injector, is now being used in clinical practice because of its unique features and patients' injection experiences. The aims of this study are to investigate the efficacy and safety of the needle-free injector-based insulin treatment in blood glucose control in patients with type 2 diabetes, as compared with a conventional needle-based insulin treatment, and to evaluate patient satisfaction with the different insulin delivery methods. METHODS AND PLANNED OUTCOMES: A prospective, multicenter, randomized, open-label, parallel-group clinical trial was designed and implemented in China. A total of 420 patients with type 2 diabetes from ten research centers will be enrolled in the study. The primary efficacy endpoint is the change in the glycosylated hemoglobin (HbA1c) level from baseline to after 16 weeks of treatment after randomization. Secondary efficacy endpoints include measurements of blood glucose concentrations, the rate of achieving the target HbA1c level of less than 7%, patients' quality-of-life (as determined by the SF-36 questionnaire), the insulin dose administered, compliance with insulin therapy, and patients' satisfaction with their injection device. ETHICS AND DISSEMINATION: The study was approved by the Independent Ethics Committee (IEC) of Peking University Peoples Hospital and was conducted in accordance with the moral, ethical, and scientific principles of the declaration of Helsinki and the provisions of good clinical practice (GCP) in China. Written informed consent will be obtained from all participants before any study-related procedures are implemented. It is hoped that the study will provide evidence for the clinical application of the needle-free injector by providing data on its efficacy and safety, as compared with a conventional insulin pen, in the Chinese type 2 diabetes population. When available, the results will be published in an international peer-reviewed journal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03243903. Registration date, August 9, 2017. FUNDING: Beijing QS Medical Technology Co., Ltd.

2.
PLoS One ; 10(3): e0120586, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25793984

RESUMO

Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1ß. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1ß secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.


Assuntos
Proteína HMGB1/metabolismo , Inflamação/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Resistência ao Cisalhamento , Transdução de Sinais , Estresse Mecânico , Proteína HMGB1/antagonistas & inibidores , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/metabolismo , Transporte Proteico , Fatores de Tempo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
3.
Chem Commun (Camb) ; 51(4): 689-92, 2015 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25418674

RESUMO

We propose a strategy to control directly the orientation of hemin plane via experimental models, Hemin-His model and Hemin-MHN model with ODT. Electrochemical results show that electron communication is largely enhanced when the hemin plane is near to parallel to the electrode surface by histidine ligation in Hemin-His model, while the electron transport of hemin in Hemin-MHN model with ODT becomes relatively difficult.


Assuntos
Hemina/química , Técnicas Eletroquímicas , Eletrodos , Transporte de Elétrons , Elétrons , Histidina/química , Modelos Moleculares
4.
Acta Crystallogr C Struct Chem ; 70(Pt 7): 715-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24992118

RESUMO

A novel manganese coordination polymer, poly[(µ5-thiophene-3,4-dicarboxylato)manganese(II)], [Mn(C6H2O4S)]n, was synthesized hydrothermally using 3,4-thiophenedicarboxylate (3,4-tdc(2-)) as the organic linker. The asymmetric unit of the complex contains an Mn(2+) cation and one half of a deprotonated 3,4-tdc(2-) anion, both residing on a twofold axis. Each Mn(2+) centre is six-coordinated by O atoms of bridging/chelating carboxylate groups from five 3,4-tdc(2-) anions, forming a slightly distorted octahedron. The Mn(2+) centres are bridged by 3,4-tdc(2-) anions to give an infinite two-dimensional layer which incorporates one-dimensional Mn-O gridlike chains, and in which the 3,4-tdc(2-) anion adopts a novel hexadentate chelating and µ5-bridging coordination mode. The fully deprotonated 3,4-tdc(2-) anion exhibits unexpected efficiency as a ligand towards the Mn(2+) centres, which it coordinates through all of its carboxylate O atoms to provide the novel coordination mode. The IR spectrum of the complex is also reported.

5.
J Chromatogr A ; 1342: 86-91, 2014 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-24709591

RESUMO

The effect of low concentrations of sodium dodecyl sulfate (SDS) on the separation of palonosetron hydrochloride (PALO) stereoisomers by micellar electrokinetic chromatography (MEKC) has been investigated. It was found that the addition of SDS prolongs the migration time and the migration order of four stereoisomers changes regularly with the SDS concentration. Good separations for all the four stereoisomers were achieved at appropriate SDS concentration. The effect of SDS on the electromigration (mobilities) of PALO stereoisomers has been studied, in order to explain its effect on the separation by MEKC. It was found that low concentrations of SDS added into the separation media forms negatively charged complexes with PALO stereoisomers and hence reverses their electromigration direction. Furthermore, the migration order between two enantiomeric pairs is also reversed because the enantiomeric pair with a bigger positive mobility than that of another pair turns to have a bigger negative mobility when bound with SDS. Based on these results, the effect of SDS on the MEKC separation of PALO stereoisomers was elucidated reasonably. The performance of the developed chiral MEKC method was validated by the analysis of a real sample.


Assuntos
Isoquinolinas/química , Quinuclidinas/química , Dodecilsulfato de Sódio/química , Cromatografia Capilar Eletrocinética Micelar/métodos , Micelas , Palonossetrom , Estereoisomerismo
6.
Analyst ; 138(19): 5777-82, 2013 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-23912152

RESUMO

With the advantages of in situ analysis and high surface sensitivity, surface-enhanced infrared absorption spectroscopy in attenuated total reflection mode (ATR-SEIRAS) combined with electrochemical methods has been employed to examine the interfacial direct electron transfer activity and adsorption kinetics of cytochrome c (cyt c). This work presents data on cyt c adsorption onto negatively charged mercaptohexanoic acid (MHA) and positively charged 6-amino-1-hexanethiol (MHN) self-assembled monolayers (SAMs) on gold nanofilm surfaces. The adsorbed cyt c displays a higher apparent electron transfer rate constant (33.5 ± 2.4 s(-1)) and apparent binding rate constant (73.1 ± 5.2 M(-1) s(-1)) at the MHA SAMs surface than those on the MHN SAMs surface. The results demonstrate that the surface charge density determines the protein adsorption kinetics, while the surface charge character determines the conformation and orientation of proteins assembled which in turn affects the direct electron transfer activity.


Assuntos
Adsorção/fisiologia , Citocromos c/química , Citocromos c/metabolismo , Transporte de Elétrons/fisiologia , Animais , Cavalos , Conformação Proteica , Estrutura Secundária de Proteína , Propriedades de Superfície
7.
Chem Commun (Camb) ; 49(78): 8788-90, 2013 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-23958636

RESUMO

Ferric ions show high affinity to the kinase-generated phosphorylated sites of peptides. Thus, the high electrocatalytic activity of the coordinated ferric ions toward the reduction of hydrogen peroxide can be used for sensitive label-free monitoring of protein kinase activity and inhibition.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Compostos Férricos/metabolismo , Peróxido de Hidrogênio/metabolismo , Peptídeos/metabolismo , Sequência de Aminoácidos , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Técnicas Eletroquímicas/métodos , Ensaios Enzimáticos/métodos , Íons/metabolismo , Oxirredução , Peptídeos/química , Fosforilação
8.
Chem Commun (Camb) ; 48(88): 10859-61, 2012 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-23023396

RESUMO

It is proposed that direct electron transfer is dependent on the orientation of the heme plane in cytochrome c (cyt c) assembled on electrode surfaces. Orientation with the heme plane in cyt c parallel to the gold electrode surface favors the direct electron transfer, while vertical orientation of the heme plane makes the direct electron transfer difficult. A preferable electron transport pathway for cyt c is through the axial ligand (His-18) of the heme center rather than the porphyrin ring.


Assuntos
Citocromos c/química , Ouro/química , Heme/química , Adsorção , Eletroquímica , Eletrodos , Propriedades de Superfície , Molhabilidade
9.
Ying Yong Sheng Tai Xue Bao ; 23(11): 3016-20, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23431784

RESUMO

Different origins Bt cotton cultivars, including DP410B (conventional cultivar) and Daiza No. 1 (hybridized cultivar) from US and Sikang No. 1 (conventional cultivar) and Sikang No. 3 (hybridized cultivar) from China, were taken as the test materials to investigate the effects of high temperature (37 degrees C) and different humidity (50%, 70%, and 90%) on the leaf Bt protein expression of Bt cotton. At high temperature, temperature and humidity had no significant effects on the leaf Bt protein expression of the cultivars at peak squaring stage. At peak flowering stage, as compared with the control (25-30 degrees C and 60%-70% humidity), 37 degrees C and 50% humidity decreased the leaf Bt protein content of conventional cultivars significantly by 2.6%-3.0%. At peak bolling stage, compared with the control, 37 degrees C and 50% humidity decreased the leaf Bt protein content of DP410B, Sikang No. 1, and Sikang No. 3 significantly by 3.3%-5.8%. Among the four cultivars, DP410B and Daiza No. 1 had the highest leaf Bt protein content, while Sikang No. 1 had the lowest one.


Assuntos
Proteínas de Bactérias/metabolismo , Endotoxinas/metabolismo , Gossypium/metabolismo , Proteínas Hemolisinas/metabolismo , Temperatura Alta , Umidade , Controle Biológico de Vetores/métodos , Folhas de Planta/metabolismo , Animais , Gossypium/genética , Plantas Geneticamente Modificadas
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(11): 2911-3, 2010 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-21284151

RESUMO

By adding the thulium oxide nanoparticles (NP) of Gd2 O3 and Eu2O3 and Nd2O3 to polymer dispersed liquid crystals (PDLC), and the transmittances of PDLC and NP-PDLC changing with voltage in visible light was tested, and the thulium oxide modulation for PDLC was studied. The results show that transmittance of Gd2O3-NP-PDLC decreases with increasing voltage when the voltage is less than 10 V. The relaxation phenomenon of the sample appears at 15 V, and its transmittance curve fluctuates slightly around that at 10 V. The transmittance of Gd2O3-NP-PDLC increases rapidly at 20 V, and its filter phenomenon emerges. And the transmittance of Eu2O3-NP-PDLC decreases with increasing voltage, but the decrease is only slight. And the transmittance of Nd2O3-NP-PDLC changes with voltage insignificantly.

11.
Zhonghua Liu Xing Bing Xue Za Zhi ; 30(12): 1243-7, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20193306

RESUMO

OBJECTIVE: To understand the distribution of birth weight among premature infants and the associated social factors. METHODS: The study population consisted of 97 537 women who delivered singleton live birth of 20 to 41 gestational weeks in 4 counties/cities, Jiangsu and Zhejiang provinces, China from 1995 to 2000. Chi-square test was employed to test the difference of proportions between respective groups. One- way ANOVA was used to test the differences regarding the mean of gestational weeks at the first prenatal visit and the mean of prenatal visits between the two groups. Multivariate logistic regression was conducted to examine the factors associated with premature birth. RESULTS: Women aged 35 years had higher (8.8%) premature incidence than those aged less than 24 years (5.6%), 25 - 29 years (4.6%), or 30 - 34 years (4.5%, P < 0.001). Women with height less than 149 cm had higher (6.8%) premature incidence than those with height taller than 150 cm (5.0%). Women whose BMI were at least 28 and 24 - 28 had higher (5.5%, 5.5%) premature incidences than those whose BMI were 18.5 - 24.0 (5.0%), < 18.5 (4.6%, P < 0.001). The incidence of premature birth was 6.0% among women without previous pregnancy, higher than that among those women with 4 times of pregnancies (5.7%), 2 times of pregnancies (4.3%), and 3 times of pregnancies (4.0%). Parous women with at least two deliveries had higher (9.3%) premature incidence than the primiparous women (5.2%) and whose women with only one delivery (4.5%, P < 0.001). Women who received early prenatal care had lower 4.7% premature incidence than those who did not receive the service (6.1%). The mean times of prenatal visits among women with premature births was 8.53, less than that of those with full term delivery (10.97). Women with less than four times of prenatal visit had higher (18.9%) premature incidence than those with at least five prenatal visits (4.9%). Multivariate logistic regression showed that premature delivery risk was associated with age, height, BMI, gravidity, parity, early prenatal care, the mean of gestational weeks at first prenatal visit and the mean number of prenatal visits etc. CONCLUSION: Premature delivery risk was associated with factors as age, height, BMI, gravidity, parity, early prenatal care, the mean of gestational weeks at first prenatal visit, the mean number of prenatal visits etc.


Assuntos
Peso ao Nascer , Recém-Nascido Prematuro , Fatores Socioeconômicos , Adulto , China/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Prematuro/epidemiologia , Gravidez , Fatores de Risco
12.
Molecules ; 12(5): 979-87, 2007 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-17873833

RESUMO

A new type of NADH model compound with good reactivity and enantioselectivity has been synthesized in good yields by an efficient and convenient synthetic method. The structures of these model compounds were confirmed by 1H and 13C-NMR and MS.


Assuntos
Formiatos/síntese química , Ácidos Mandélicos/química , NAD/química , Formiatos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estereoisomerismo
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