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1.
Medicine (Baltimore) ; 98(48): e18145, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770252

RESUMO

BACKGROUND: Hypotensive resuscitation is an old study. But its benefits and losses are still controversial. In clinic, the method of fluid resuscitation needs more reliable experimental evidence. This study's objective is to systematically evaluate the efficacy of hypotensive resuscitation in patients with traumatic hemorrhagic shock. METHODS AND ANALYSIS: Through October 2019, Web of Science, PubMed, the Cochrane Library, EMBASE, and Clinical Trials will be systematically searched to identify randomized controlled trials exploring the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock. Strict screening and quality evaluation will be independently performed on the obtained literature by 2 researchers; outcome indexes will be extracted, and a meta-analysis will be performed on the data using Revman 5.3 software. ETHICS AND DISSEMINATION: The stronger evidence about the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock will be provided for clinicians. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133169. STRENGTHS OF THIS STUDY: This study is not only a simple combination of data, but also to verify and discuss the reliability of the results, and provide more convincing evidence for clinicians. LIMITATIONS OF THIS STUDY: Firstly, according to the previous literature researching, it is found that the number of relevant randomized controlled trials is small and the quality level of the literature is uneven. Secondly, the efficacy of hypotensive resuscitation is discussed for a long time, different trials may take place at different times. Comparability between different trials is reduced.

2.
PLoS One ; 14(11): e0224773, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751366

RESUMO

OBJECTIVE: To compare the efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B. METHODS: The Web of Science, PubMed, Cochrane Library, EMBASE, Clinical Trials and China National Knowledge Infrastructure(CNKI) databases were electronically searched to collect randomized controlled trials (RCTs) regarding the comparison between tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used for the meta-analysis. RESULTS: Early on, tenofovir had a greater ability to inhibit the hepatitis B virus, I2 = 0% [RR = 1.08, 95% CI (1.03, 1.13), P<0.01] (96 weeks). Entecavir can normalize the ALT levels earlier, I2 = 0% [RR = 0.87, 95% CI (0.77, 0.98), P = 0.02] (48 weeks). However, there was no statistically significant difference between TDF and ETV at 144 weeks. Tenofovir was as effective as entecavir in terms of HBeAg clearance and HBeAg seroconversion, I2 = 0% [RR = 1.05, 95% CI (0.68, 1.62), P = 0.82]; I2 = 69% [RR = 0.93, 95% CI (0.54, 1.61), P = 0.80]. The difference in the incidence of elevated creatine kinase levels was not statistically significant I2 = 0% [RR = 0.66, 95% CI (0.27, 1.60), P = 0.35]. CONCLUSIONS: Tenofovir and entecavir were equally effective in the treatment of patients with nucleos(t)ide analogue-naive chronic hepatitis B. In addition, TDF has an advantage in the incidence of hepatocellular carcinoma. Additional RCTs and a large-sample prospective cohort study should be performed.

3.
J Ethnopharmacol ; : 112425, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31765763

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mucus hypersecretion (MH) is recognized as a key pathophysiological and clinical feature of many airway inflammatory diseases. MUC5AC is a major component of airway mucus. Tanreqing injection (TRQ) is a widely used herbal formula for the treatment of respiratory inflammations for years in China. However, a holistic network pharmacology approach to understanding its therapeutic mechanisms against MH has not been pursued. AIM OF THE STUDY: This study aimed to explore the systems-level potential active compounds and therapeutic mechanisms of TRQ in the treatment of MH. MATERIALS AND METHODS: We established systems pharmacology-based strategies comprising compound screenings, target predictions, and pathway identifications to speculate the potential active compounds and therapeutic targets of TRQ. We also applied compound-target and target-disease network analyses to evaluate the possible action mechanisms of TRQ. Then, lipopolysaccharide (LPS)-induced Sprague-Dawley (SD) rat model was constructed to assess the effect of TRQ in the treatment of MH and to validate the possible molecular mechanisms as predicted in systems pharmacology approach. RESULTS: The comprehensive compound collection successfully generated 55 compound candidates from TRQ. Among them, 11 compounds with high relevance to the potential targets were defined as representative and potential active ingredients in TRQ formula. Target identification revealed 172 potential targets, including pro-inflammatory cytokines of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-8. Pathway analyses uncovered the possible action of TRQ in the regulation of IL-17 signaling pathway and its downstream protein MUC5AC. Then in vivo experiment indicated that TRQ could significantly inhibit LPS stimulated MUC5AC over-production as well as the expression of TNF-α, IL-6, IL-8, and IL-17A, in both protein and mRNA levels. CONCLUSIONS: Based on the systems pharmacology method and in vivo experiment, our work provided a general knowledge on the potential active compounds and possible therapeutic targets of TRQ formula in its anti-MH process. This work might suggest directions for further research on TRQ and provide more insight into better understanding the chemical and pharmacological mechanisms of complex herbal prescriptions in a network perspective.

4.
Medicine (Baltimore) ; 98(47): e17976, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764805

RESUMO

BACKGROUND: According to the centers for disease control and prevention, 14% of American adults have diabetes - 10% know it, and more than 4% go undiagnosed. Sotagliflozin is a new type of diabetes drug This study is to compare the efficacy of Sotagliflozin therapy for Diabetes Mellitus (DM) between week 24 with week 52. METHODS AND ANALYSIS: Through to October 2019, Web of Science, PubMed Database, Cochrane Library, EMBASE, Clinical Trials and CNKI will be searched to identify randomized controlled trials (RCTs) exploring SOTA therapy for DM. Strict screening and quality evaluation will be performed on the obtained literature independently by 2 researchers; outcome indexes will be extracted. The bias risk of the included studies will be evaluated based on Cochrane assessment tool. Meta-analysis will be performed on the data using Revman 5.3 software. We will provide practical and targeted results assessing the lost efficacy of SOTA therapy for DM from week 24 to week 52, to provide reference for clinicians. ETHICS AND DISSEMINATION: The stronger evidence about the lost efficacy of SOTA for DM from week 24 to week 52 will be provided for clinicians. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133027. STRENGTHS AND LIMITATIONS OF THIS STUDY: Whether the efficacy of SOTA could last for a long time is still inconclusive, high quality research is still lacking, and this study attempts to explore this issue; The efficacy of SOTA at different times will be compared by direct comparisons and indirect comparisons, this can lead to more accurate and reliable results; The quality of the included literatures are uneven, and some data might be estimated by calculation, which may affect the quality of this study.

5.
BMJ Open ; 9(11): e034592, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690612

RESUMO

INTRODUCTION: Current strategies for the prevention of acute exacerbations in chronic obstructive pulmonary disease (COPD) are primarily based on clinical measurements but fail to target the pathophysiological mechanisms, namely endotypes, of the disease. Studies identifying endotypes underlying exacerbation susceptibility and discovering specific biomarkers may lead to the development of targeted therapeutics but are lacking. This study aims to assess a broad spectrum of biomarkers at multiple biological levels (genetics, airway inflammation and respiratory microbiome) for their ability in predicting acute exacerbations of COPD, thus enables high-resolution disease endotyping and may lead to precision treatment of the disease. METHODS AND ANALYSIS: In this prospective cohort study, participants with stable COPD (n=600) will be recruited and assessed for demographics, symptom scores, spirometry, medication use and comorbidities at baseline. Blood will be obtained for genotyping variants in a panel of nine genes. Induced sputum will be collected for the profile of microbiota using 16S rRNA gene sequencing, quantification of bacterial load, inflammatory mediators assay and sputum cytometry. Participants will be followed up for their exacerbations till 12 months and reassessed for the clinical measurements as baseline. The primary outcomes are total number of exacerbations, severe exacerbations, moderate exacerbations and time to first exacerbation. The secondary outcomes are changes in lung function and symptom scores. The effect of biomarkers representing genetic variants, airway inflammation and respiratory microbiome on predicting the frequent exacerbator phenotype and exacerbation frequency will be analysed with multivariable modelling, and time to first exacerbation with a Cox regression model. ETHICS AND DISSEMINATION: The study has been approved by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No. 2018-298). The results of the study will be published on peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1800019063.

6.
Sheng Li Xue Bao ; 71(5): 698-704, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646323

RESUMO

The aim of this study was to investigate the relationship between the effects of different doses of X-rays on DNA damage and JAK/STAT signaling pathway activation in A549 cells. The A549 cells were radiated with X-rays at doses of 2, 4, and 8 Gy. The proliferation of A549 cells was detected by CCK8 method. The content of interleukin 6 (IL-6) in culture medium at different time points after irradiation was detected by enzyme-linked immunoassay, and the expression levels of IL-6 receptor (IL-6R) and p53 binding protein 1 (53BP1) were detected by immunofluorescent staining. The expression levels of JAK2, p-JAK2, STAT3 and p-STAT3 were detected by Western blot. The results showed that, compared with the control group, X-ray irradiation reduced the cellular proliferation, up-regulated the expression of 53BP1, increased the IL-6 content in the medium supernatant, and up-regulated the protein expression levels of IL-6R, JAK2, p-JAK2, STAT3, and p-STAT3. The above effects of X-ray irradiation were dose-dependent. These results suggest that the mechanism by which X-rays cause DNA damage in A549 cells may involve activation of the JAK/STAT signaling pathway.


Assuntos
Dano ao DNA/efeitos da radiação , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células A549 , Humanos , Receptores de Interleucina-6/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Raios X
7.
Sci Rep ; 9(1): 13431, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530860

RESUMO

Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases. Yihuo Huatan Formula (YHF), as a proven Chinese Herbal Medicine (CHM), has been verified to be effective in the treatment of stable COPD through years' of practice. Nevertheless, its working mechanism is still unclear. We sought to systematically decipher the mechanism of YHF for treating stable COPD using systems pharmacology-based method that integrates pharmacokinetic screening, target prediction, network analyses, GO and KEGG enrichment analyses. Firstly, a total of 1267 chemicals out of 15 herbal components were included in YHF chemical database. Among them, 180 potential active molecules were screened out through pharmacokinetic evaluation. Then 258 targets of the active molecules were predicted, of which 84 were chosen for further analyses. Finally, the network analyses and GO and KEGG enrichment methods suggested a therapeutic effect of YHF on the alleviation of airway inflammation, decrease of mucus secretion, maintenance of immune homeostasis and benefit of COPD comorbidities, by regulating multiple targets and pathways. The systems pharmacology-based approach helps to understand the underlying working mechanism of YHF in stable COPD from a holistic perspective, and offers an exemplification for systematically uncovering the action mechanisms of CHM.

8.
Medicine (Baltimore) ; 98(34): e16943, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441888

RESUMO

BACKGROUND: Chronic hepatitis b (CHB) is a serious problem worldwide. Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) both are first-line drugs for CHB, but there is debate about which is more appropriate in nucleos(t)ide analogue-naive CHB. OBJECTIVE: To systematically evaluate the effectiveness and safety of tenofovir and ETV in nucleos(t)ide analogue-naive CHB. METHODS: The Web of Science, PubMed, The Cochrane Library, EMBASE, Clinical Trials, and China National Knowledge Infrastructure databases will be electronically searched to collect randomized controlled trials regarding the comparison between tenofovir and ETV in nucleos(t)ide analogue-naive CHB since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software will be used for the meta-analysis. RESULT: We will provide practical and targeted results assessing the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients, try to compare the advantages of TDF and ETV. CONCLUSION: The stronger evidence about the effectiveness and safety of TDF and ETV for nucleos(t)ide analogue-naive CHB patients will be provided for clinicians. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42019134194.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Guanina/uso terapêutico , Humanos , Metanálise como Assunto , Revisão Sistemática como Assunto
9.
Medicine (Baltimore) ; 98(33): e16850, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415414

RESUMO

BACKGROUND: Type 1 Diabetes Mellitus (T1DM) has long required insulin treatment. Sotagliflflozin (SOTA), as a dual SGLT-1/2 inhibitor, has the potential to be the first oral antidiabetic drug (OAD) to be approved for T1DM in the US market. It is important to evaluate the effectiveness of SOTA for T1DM. METHODS: Web of Science, PubMed datebase, Cochrane Library, Embase, Clinical Trials, and CNKI will be searched to identify randomized controlled trials (RCTs) exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluation will be performed on the obtained literature independently by 2 researchers; outcome indexes will be extracted. The bias risk of the included studies will be evaluated based on Cochrane assessment tool. Meta-analysis will be performed on the data using Revman 5.3 software. RESULT: We will provide practical and targeted results assessing the efficacy and safety of SOTA for T1DM patients, to provide reference for clinical use of SOTA. CONCLUSION: The stronger evidence about the efficacy and safety of SOTA for T1DM patients will be provided for clinicians. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133099.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicosídeos/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Administração Oral , Terapia Combinada , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisão Sistemática como Assunto
10.
Medicine (Baltimore) ; 98(28): e16444, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305473

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high morbidity and mortality placing heavy social and economic burden. As a kind of complementary therapy for the treatment of stable COPD, Chinese oral herbal paste has been widely used and studied. The study aims to evaluate the clinical efficacy and safety of herbal paste in the treatment of stable COPD, and to provide evidence for its clinical application. METHODS: We will electronically search databases, including Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, PubMed, Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP), and Chinese Biomedical Database (CBM), from respective inception to June 2019 to collect randomized controlled trials (RCTs) of Chinese oral herbal paste for the treatment of stable COPD. The websites of Chinese clinical trial registry and international clinical trial registry, the reference lists of the retrieved articles, conference proceedings, and gray literature will also be collected. The quality of life, symptom scores, and exacerbation frequency will be measured as primary outcomes. Secondary outcomes include scores of traditional Chinese medicine (TCM) syndrome, clinical effective rates according to criteria in TCM, changes in lung function, 6-minute walking distance, and safety analysis. The Cochrane bias risk assessment and the GRADE method will be used to assess the quality of the original studies included. Merging analysis of data will be performed using Rev Man 5.3 software. RESULTS: The systematic review will provide an evidence on the clinical efficacy and safety of Chinese oral herbal paste for the treatment of stable COPD, and will be submitted for publication in a peer-reviewed journal. CONCLUSION: The study will confirm whether Chinese oral herbal paste is an effective and safe intervention for the prevention and treatment of stable COPD.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Metanálise como Assunto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Revisão Sistemática como Assunto , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Pomadas , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
11.
J Phys Chem A ; 123(32): 6958-6969, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31318549

RESUMO

Uranium(III) compounds are very reactive and exhibit a broad range of chemical-bonding tendencies owing to the spatially diffused valence orbitals of uranium. A systematic study on the geometries, electronic structures, and chemical bonding of NU-XO (X = C, N, O) is performed using relativistic quantum chemistry approaches. The NU-CO and NU-NO complexes have an end-on structure, that is, (NU) (η1-CO) and (NU) (η1-NO), whereas NU-OO adopts a side-on ((NU) (η2-O2)) structure. The electronic structure analysis shows that UN exhibits efficient activation reactivity to molecules, especially to NO and O2, because of the significant U 7s/5f → XO 2π* electron transfer. Thus, the oxidation state of U is +V with the dianion ligand NO2- and O22- in NU-NO and NU-OO, respectively. Instead, U retains its usual +III oxidation state in NU-CO with a neutral CO ligand. The significant stability of NU-XO (X = C, N, O) is determined by the covalent U-X bonding which contains both X → U σ-, π-donation from the X lone pair and U 5f → XO 2π* back-donation contributions. The significant back-donation to the antibonding X-O 2π* orbital results in the obvious weakening of the X-O bonding.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(2): 203-209, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31106540

RESUMO

OBJECTIVE: To explore the mechanism of acupuncture in regulating chronic inflammation through dopamine in rats with chronic obstructive pulmonary disease (COPD). METHODS: 32 SD rats were randomly divided into control, model, sham acupuncture and acupuncture groups (n=8) . COPD condition was induced by eight-week exposure to cigarette smoking and lipopolysaccharides (LPS) of the rats, except for those in the control group. From the beginning of the 7th week, the acupuncture group received bilateral electroacupuncture on the Zusanli (ST-36), while the sham acupuncture group received bilateral electroacupuncture on the non-points, 30 min/time, 1/day, for 2 weeks prior to exposure to cigarette smoking. Post treatment changes in plasma dopamine and inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8)], lung function [total lung capacity (TLC), functional residual capacity (FRC), the 50 µs forced expiratory volume (FEV) vs. forced vital capacity (FVC)( FEV50/FVC), the 100 µs FEV vs. FVC (FEV100/FVC), total airway resistance (RL), lung dynamic compliance (Cdyn)], and the ratio of total alveolus area to tissue area (A/t) and cell counts in the alveolar lavage fluid (BALF) were measured. Pearson correlations between plasma dopamine and the above indicators were calculated. RESULTS: Acupuncture increased plasma dopamine and improved the inflammatory factors, lung function, A/t and BALF cell counts. Compared with the model rats, the rats that received acupuncture had higher levels of TNF-α and IL-1ß, A/t and BALF cell counts, and lung function (FEV50/FVC, FEV100/FVC, RL, Cdyn) (P<0.05). The effects of acupuncture were superior on the ST-36 points compared with the non-points. Significant correlations between lung function (FRC, RL, Cdyn) and inflammatory factors (TNF-α, IL-1ß, IL-6, IL-8) were found (P<0.001) . TLC was correlated with IL-8, IL-1ß and A/t (P<0.05). Plasma dopamine was correlated with FRC, TLC, FEV50/FVC, FEV100/FVC (P<0.05). CONCLUSION: Acupuncture can alleviate inflammation, improve lung function and raise plasma dopamine level in COPD rats, and the effect of acupuncture on lung function may be related to reducing inflammatory factors and increasing dopamine level.


Assuntos
Terapia por Acupuntura , Dopamina/sangue , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Pontos de Acupuntura , Animais , Eletroacupuntura , Interleucinas/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(1): 88-108, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31037911

RESUMO

OBJECTIVE: To assess the association between chronic obstructive pulmonary disease (COPD) comorbidities and clinical characteristics, and to explore the inflammation mechanism. METHODS: 220 stable COPD patients were included. Clinical characteristics and comorbidities were recorded, and blood samples were collected. The relationship among the number and type of comorbidities, Charlson comorbidity index (CCI), clinical characteristics and the levels of plasma inflammatory markers [interleukin (IL)-6, high sensitivity C-reaction protein (hs-CRP), tumor necrosis factor-α (TNF-α), IL-8] were studied. RESULTS: The top five comorbidities were hypertension, metabolic syndrome and diabetes osteoporosis, bronchiectasis and peripheral vascular diseases. The level of plasma IL-6 was greater in higher CCI score (≥4) group compared with lower CCI score (<4) group ( P=0.011). Levels of IL-6 and IL-8 and the number of hospitalization in prior year were positively correlated with CCI and age adjusted CCI (r<0.03, P<0.05). There was a correlation between the COPD comorbidities and systemic inflammatory response (r<0.3, P<0.05). CONCLUSION: Patients with a higher CCI score had more severe symptoms, functional impairment and higher level of inflammatory factors and high frequency of hospital admission due to acute exacerbation. The mechanism by which COPD may play a role in systemic inflammatory response deserves further study.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Biomarcadores , Comorbidade , Humanos , Inflamação , Interleucina-6 , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fator de Necrose Tumoral alfa
14.
Clin Genet ; 96(3): 207-215, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066047

RESUMO

Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous conditions. We launched a nationwide study to determine the frequency of CMD in the Chinese population and assess the status of diagnosis and disease management for CMD in China. Cases were chosen from databases in 34 tertiary academic hospitals from 29 first-level administrative divisions (provinces, municipalities, autonomous regions, and special administrative regions), and medical records were reviewed to confirm the diagnoses. The study included 409 patients, of those patients who consented to genetic testing (n = 340), mutations were identified in 286 of them. The most common forms identified were LAMA2-related CMD (36.4%), followed by COL6-related CMD (23.2%) and α-dystroglycanopathy (21.0%). The forms of CMD related to mutations in LMNA and SEPN1 were less frequent (12.5% and 2.4%, respectively). We also recorded a significant difference in the diagnostic capabilities and disease management of CMD, with this being relatively backward in research centers from less developed regions. We provide, for the first time, comprehensive epidemiologic information of CMD in a large cohort of Chinese people. To our knowledge, this is the largest sample size of its kind so far highlighting the prevalence of CMD in China.

15.
Mol Med Rep ; 19(5): 3441-3448, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30816533

RESUMO

Ataxia­telangiectasia (A­T) is an autosomal recessive chromosome breakage disorder caused by mutations in the ATM serine/threonine kinase (ATM) gene. Typically, it presents in early childhood with progressive cerebellar dysfunction, accompanied by immunodeficiency and oculocutaneous telangiectasia. In the present study, the clinical and genetic findings of a Chinese family affected with A­T in two live siblings, the proband (II­2) and his elder brother (II­1), as well as a fetus (II­3) were reported. General health, clinical neurological, electrophysiological (motor and sensory nerve conduction) and magnetic resonance imaging evaluations revealed that patients II­1 and II­2 had similar symptoms of ataxia, dysarthria, conjunctival hyperemia and elevated serum α­fetoprotein, whereas patient II­1 had earlier A­T onset at 2 years old and more serious problems with movement and intelligence. Targeted sequencing followed by Sanger sequencing revealed that these two patients carried the compound heterozygotes of a novel nonsense mutation c.5170G>T (p.Glu1724Ter) and a known nonsense mutation c.748C>T (p.Arg250Ter) in the ATM gene. Each mutation was inherited from an asymptomatic parent, which therefore confirmed the diagnosis of A­T. Given this, proband's mother performed prenatal diagnosis in her third pregnancy. Unfortunately, the fetus had the same causal mutations as its siblings and the pregnancy was terminated. The findings of the present study expanded the mutation spectrum of the ATM gene and may help in understanding the genetic basis of A­T, in order to guide genetic counseling and prenatal diagnosis.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Estudos de Associação Genética , Aconselhamento Genético , Mutação , Fenótipo , Alelos , Grupo com Ancestrais do Continente Asiático , Ataxia Telangiectasia/fisiopatologia , Biomarcadores , Cerebelo/patologia , Biologia Computacional , Análise Mutacional de DNA , Eletromiografia , Feminino , Genótipo , Humanos , Imagem por Ressonância Magnética , Masculino , Linhagem , Avaliação de Sintomas
16.
Trials ; 20(1): 187, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922355

RESUMO

BACKGROUND: The common cold is a highly prevalent illness with significant impact on society and health care. Common cold with heat syndrome (CCHS) is one of the most common types based on syndrome differentiation by traditional Uighur medicine (TUM), which is widely used in Central Asia. The study is designed to explore the efficacy, safety and optimal therapeutic dosage of Binafuxi granules in treating CCHS. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Participants (n = 240) will be enrolled from five centers across China and randomly assigned to the high-dose group, low-dose group or placebo control group in a 1:1:1 ratio. All eligible patients will receive test drugs twice daily for 3 days. The primary outcome is the time to fever relief. Secondary outcomes include the time to fever clearance, duration of primary symptoms and each symptom and change in TUM symptom score. DISCUSSION: This is the first placebo-controlled randomized clinical trial of a Uighur medicine in treating common cold. It will provide robust evidence on the efficacy and safety of Binafuxi granules in the treatment of CCHS. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IIR-17013379 . Registered on 14 November 2017.


Assuntos
Resfriado Comum/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Administração Oral , Adolescente , Adulto , Idoso , China , Ensaios Clínicos Fase II como Assunto , Resfriado Comum/diagnóstico , Resfriado Comum/fisiopatologia , Resfriado Comum/virologia , Método Duplo-Cego , Esquema de Medicação , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Adv Mater ; 31(16): e1807495, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30811702

RESUMO

Sodium metal anodes are poor due to the reversibility of Na plating/stripping, which hinders their practical applications. A strategy to form a sodiophilic Au-Na alloy interphase on a Cu current collector, involving a sputtered Au thin layer, is shown to enable efficient Na plating/stripping for a certain period of time. Herein, electrochemical behaviors of Na plating on different substrates are explored, and it is revealed that the sodiophilic interphase can be achieved universally by in situ formation of M-Na (M = Au, Sn, and Sb) alloys during Na plating prior to Na bulk deposition in the initial cycle. Moreover, it is found that repetitive alloying-dealloying leads to falling-off of thin film sodiophilic materials and thus limits the lifespan of efficient Na cycling. Therefore, an approach is further developed by employing particles of sodiophilic materials combined with the control over the cutoff potential, which significantly improves the stability of Na plating/stripping process. Especially, the low-cost Cu@Sn-NPs and Cu@Sb-MPs composite current collectors allow Na plating and stripping to cycle for 2000 and 1700 times with the average efficiency of 99.9% at 2 mA cm-2 .

18.
J Am Chem Soc ; 141(4): 1665-1671, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30608680

RESUMO

Perovskite solar cells are strong competitors for silicon-based ones, but suffer from poor long-term stability, for which the intrinsic stability of perovskite materials is of primary concern. Herein, we prepared a series of well-defined cesium-containing mixed cation and mixed halide perovskite single-crystal alloys, which enabled systematic investigations on their structural stabilities against light, heat, water, and oxygen. Two potential phase separation processes are evidenced for the alloys as the cesium content increases to 10% and/or bromide to 15%. Eventually, a highly stable new composition, (FAPbI3)0.9(MAPbBr3)0.05(CsPbBr3)0.05, emerges with a carrier lifetime of 16 µs. It remains stable during at least 10 000 h water-oxygen and 1000 h light stability tests, which is very promising for long-term stable devices with high efficiency. The mechanism for the enhanced stability is elucidated through detailed single-crystal structure analysis. Our work provides a single-crystal-based paradigm for stability investigation, leading to the discovery of stable new perovskite materials.

19.
Angew Chem Int Ed Engl ; 58(10): 3092-3096, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30589160

RESUMO

Lithium metal anodes suffer from poor cycling stability and potential safety hazards. To alleviate these problems, Li thin-film anodes prepared on current collectors (CCs) and Li-free types of anodes that involve direct Li plating on CCs have received increasing attention. In this study, the atomic-scale design of Cu-CC surface lithiophilicity based on surface lattice matching of the bcc Li(110) and fcc Cu(100) faces as well as electrochemical achievement of Cu(100)-preferred surfaces for smooth Li deposition with a low nucleation barrier is reported. Additionally, a purposely designed solid-electrolyte interphase is created for Li anodes prepared on CCs. Not only is a smooth planar Li thin film prepared, but a uniform Li plating/stripping on the skeleton of 3D CCs is achieved as well by high utilization of the surface and cavities of the 3D CCs. This work demonstrates surface electrochemistry approaches to construct stable Li metal-electrolyte interphases towards practical applications of Li anodes prepared on CCs.

20.
Medicine (Baltimore) ; 97(49): e13225, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544381

RESUMO

RATIONALE: Epidermolysis bullosa (EB) refers to a group of rare inherited mechanobullous disorders that present with great clinical and genetic heterogeneity. Its severity ranges from mild blistering to life-threatening. However, the clinical symptoms of different types of EB overlap significantly, especially at an early stage. Thus it is important to clarify the diagnosis for prognostic implications, patient management, and genetic counseling. PATIENT CONCERNS: Here, we report a 10-day-old male neonate from a nonconsanguineous Chinese family. He showed a bulla on the left lower limb lasting for 3 days, erosions around fingertips and toe tips at birth (predominantly on fingers), with the progressive spread of generalized blisters over the body as well as the development of the illness. DIAGNOSIS: The patient was diagnosed with suspected epidermolysis bullosa according to the blisters and erosions of the body as well as the pyogenic fingernails and toenails. INTERVENTIONS: The patient was performed targeted next-generation sequencing (NGS) with 9 candidate known genes, subsequently, his parents were screened for the mutations identified in the patient by Sanger sequencing. Then, prenatal diagnosis with amniotic fluid was performed in the subsequent pregnancy by Sanger sequencing. OUTCOMES: Targeted NGS revealed a previously unreported splice site variant c.822+1G>A (IVS 8) and a known recurrent nonsense variant c.124C>T (p.Arg42Ter, exon 3) in LAMB3 gene. The patient's father possessed a heterozygous c.822+1G>A mutation, his mother possessed a heterozygous c.124C>T mutation. For the subsequent pregnancy, the analyses of amniotic fluid sample indicated that the fetus carried neither of the mutations. LESSONS: Our finding will further enlarge LAMB3 genotype-phenotype correlations spectrum. Targeted capture sequencing is a valuable method to illustrate precise molecular pathology in patients with EB disorders, especially at an early stage of the clinical evaluation of complex disorders to avoid unnecessary and economically wasteful tests.


Assuntos
Moléculas de Adesão Celular/genética , Epidermólise Bolhosa Juncional/genética , Mutação , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Diagnóstico Diferencial , Evolução Fatal , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recém-Nascido , Masculino , Gravidez , Diagnóstico Pré-Natal
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