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1.
Science ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672917

RESUMO

The transition from peri-implantation to gastrulation in mammals entails the specification and organization of the lineage progenitors into a body plan. Technical and ethical challenges have limited understanding of the cellular and molecular mechanisms underlying this transition. Here, we established a culture system that enabled the development of cynomolgus monkey embryos in vitro for up to 20 days. Cultured embryos underwent key primate developmental stages, including lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and primordial germ cell-like cell (PGCLC) differentiation. Single-cell RNA sequencing analysis revealed development trajectories of primitive endoderm, trophectoderm, epiblast lineages, and PGCLCs. Analyzing single-cell chromatin accessibility identified transcription factors specifying each cell type. Our results reveal critical developmental events and complex molecular mechanisms underlying non-human primate embryogenesis in the early post-implantation period with possible relevance to human development.

2.
Hypertension ; : HYPERTENSIONAHA11913700, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31607175

RESUMO

The α1-AR (α1 adrenergic receptor) blockers currently on the market cannot meet clinical needs because of low-selectivity for subtypes of α1-ARs, short half-life, and uncertain role in cardiovascular end point events. The study sought to find a vaccine specifically against α1D-AR (α1D-adrenergic receptor) for treating hypertension. A short peptide ADR-004 (cgiteeagy) belonging to α1D-AR was screened, and the ADRQß-004 vaccine was produced and injected into spontaneously hypertensive rats model (including a short-term study, 10 weeks, and a long-term observation study, 39 weeks) and NG-nitro-l-arginine methyl ester + spontaneously hypertensive rats model (15 weeks). The antihypertensive effect and target organ protection of the ADRQß-004 vaccine were carefully evaluated. The possible immune-mediated damage was detected in normal vaccinated Sprague Dawley rats. The ADR-004 peptide has perfect immunogenicity, and the ADRQß-004 vaccine could induce strong antibody production. In the short-term study, the ADRQß-004 vaccine averagely decreased the systolic blood pressure of spontaneously hypertensive rats up to 15 mm Hg and that of NG-nitro-l-arginine methyl ester+spontaneously hypertensive rats up to 29 mm Hg. In the long-term observation model, the antihypertensive effect of the ADRQß-004 vaccine was quite stable, and the average decline of systolic blood pressure was 22 mm Hg. The ADRQß-004 vaccine effectively prevented vascular structural remodeling, cardiac hypertrophy and fibrosis, and renal injury of hypertensive animals, superior to prazosin at renal level. Moreover, the ADRQß-004 vaccine obviously downregulated the expression of α1D-AR, but not α1A-AR. Additionally, no significant immune-mediated damage was detected in immunized animals. The present results demonstrate that the ADRQß-004 vaccine may provide a novel and promising method for the treatment of hypertension.

3.
Pharmacology ; : 1-7, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31587003

RESUMO

INTRODUCTION: Cynaroside is a biological component isolated from Lonicera japonica Thunb, and it possesses numerous pharmacological activities. However, whether cynaroside affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. The purpose of this study was to investigate the effects of cynaroside on 8 major CYP isoforms in human liver microsomes (HLMs). METHODS: In this study, the inhibitory effects of cynaroside on the 8 human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using HLMs. RESULTS: The results showed that cynaroside inhibited the activity of CYP1A2, 3A4, and 2C9, with IC50 values of 21.74, 15.88, and 16.58 µmol/L, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that cynaroside was not only a noncompetitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.33, 11.60, and 8.09 µmol/L, respectively. In addition, cynaroside is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.049/11.62 µmol/L-1min-1. CONCLUSION: The in vitro studies of cynaroside with CYP isoforms indicate that cynaroside has the potential to cause pharmacokinetic drug interactions with other coadministered drugs metabolized by CYP1A2, 3A4, and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.

4.
J Asian Nat Prod Res ; : 1-7, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588784

RESUMO

Phytochemical investigation of 95% ethanol extract of the fruit of Forsythia suspensa resulted in the isolation of two new furofuran lignan glycoside derivatives pinoresinoside A (1) and phillyrigeninside A (2), along with three known ones. Their structures were established based on extensive spectroscopic data analyses and comparison with literature data. Absolute configuration of 1 was determined by CD method. In addition, compounds 1 and 2 were revealed to show in vitro cytotoxicity against human tumor cell lines (SGC-7901, MCF-7 and HepG2), with IC50 values ranging from 16.77 to 37.35 µM.

5.
Sex Transm Infect ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653680

RESUMO

BACKGROUND: Individuals with risk-loving attitudes may be more likely to participate in high-risk sex and gambling. We investigated whether a lottery-based financial incentive to have a negative syphilis test may attract Chinese men who have sex with men (MSM) who practised risky sexual behaviours. METHODS: In July 2018, a national online cross-sectional survey was conducted in China. We collected information on willingness to participate in a lottery-based financial incentive where men were eligible if they tested negative for syphilis, and the minimum prize that would attract them to participate. We used a validated risk attitude scale which asked about the willingness to take risks in six domains, ranging from 0 (avoids taking risk) to 10 (fully prepared to take risks). To avoid multicollinearity, we used principal components analysis to create a 'risk attitude index'. Bivariable and multivariable logistic regression explored factors associated with willingness to test negative for syphilis. RESULTS: 699 MSM enrolled with a median age of 26 years (IQR: 23-30). 70% self-identified as gay and 52% reported ever testing for syphilis. 64% stated they were likely or very likely to test for syphilis linked with a lottery-based incentive. The median desired amount for the lottery had an expected value of ¥10 (US$1.50, IQR: ¥5-¥30). Men who had greater odds of willingness to participate in the lottery-based incentive were those scoring highest on the risk attitude index (adjusted OR (AOR) 2.6, 95% CI 1.5 to 4.3), those reporting more than one sexual partner in the last 3 months (AOR 1.7, 95% CI 1.2 to 2.4), those who had not used condoms during their last sex (AOR 1.5, 95% CI 1.0 to 2.2) and those who ever had group sex (AOR 1.5, 95% CI 1.0 to 2.2). CONCLUSION: Chinese MSM with higher risk attitudes and who reported riskier sexual behaviours indicated greater interest in the concept of a lottery-based incentive for syphilis testing. A lottery-based incentive may be a promising strategy for promoting condom use among risk-loving men.

6.
J Neurosurg ; : 1-10, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653806

RESUMO

OBJECTIVE: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

7.
Small ; : e1904245, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617305

RESUMO

Perforated ultrathin Pd nanosheets with crystalline/amorphous heterostructures are rationally synthesized to offer a large electrochemically active surface area of 172.6 m2 g-1 and deliver a 5.6 times higher apparent reaction rate in comparison to commercial Pd/C, thus offering a facile confined growth method to generate superior catalysts.

8.
Blood Adv ; 3(19): 2883-2894, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31585952

RESUMO

We developed an in vivo hematopoietic stem cell (HSC) transduction approach that involves HSC mobilization from the bone marrow into the peripheral bloodstream and the IV injection of an integrating, helper-dependent adenovirus (HDAd5/35++) vector system. HDAd5/35++ vectors target human CD46, a receptor that is abundantly expressed on primitive HSCs. Transgene integration is achieved by a hyperactive Sleeping Beauty transposase (SB100x) and transgene marking in peripheral blood cells can be increased by in vivo selection. Here we directed transgene expression to HSC-derived erythroid cells using ß-globin regulatory elements. We hypothesized that the abundance and systemic distribution of erythroid cells can be harnessed for high-level production of therapeutic proteins. We first demonstrated that our approach allowed for sustained, erythroid-lineage specific GFP expression and accumulation of GFP protein in erythrocytes. Furthermore, after in vivo HSC transduction/selection in hCD46-transgenic mice, we demonstrated stable supraphysiological plasma concentrations of a bioengineered human factor VIII, termed ET3. High-level ET3 production in erythroid cells did not affect erythropoiesis. A phenotypic correction of bleeding was observed after in vivo HSC transduction of hCD46+/+/F8-/- hemophilia A mice despite high plasma anti-ET3 antibody titers. This suggests that ET3 levels were high enough to provide sufficient noninhibited ET3 systemically and/or locally (in blood clots) to control bleeding. In addition to its relevance for hemophilia A gene therapy, our approach has implications for the therapy of other inherited or acquired diseases that require high levels of therapeutic proteins in the blood circulation.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31583494

RESUMO

A Gram-stain negative, aerobic, non-flagellated, non-gliding, rod-shaped bacterium, designated strain YLY04T, was isolated from the gut microflora of a sea bass (Dicentrarchus labrax L.) collected from the coast of Yuanyao Wharf, Weihai, China. Growth was found to occur at pH 6.0-9.0 (optimum, 7.0-8.0), 4-37 °C (optimum, 28-30 °C) in the presence of 0-11.0% (w/v) NaCl (optimum, 3.0-4.0%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YLY04T is closely related to Pelagivirga sediminicola BH-SD19T and Roseovarius antarcticus M-S13-148T. Strain YLY04T contains ubiquinone-10 as the sole respiratory quinone and summed feature 8 (C18:1ω7c and/or C18:1ω6c), cyclo-C19:0ω8c, C16:0 and 11-methyl-C18:1ω7c as the major fatty acids. The polar lipids of strain YLY04T were found to consist of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and three unidentified lipids. The DNA G+C content was determined to be 62.7 mol%. The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis, indicated that strain YLY04T represents a novel species within the genus Pelagivirga, for which the name Pelagivirga dicentrarchi sp. nov. is proposed. The type strain is YLY04T (= MCCC 1H00334T = KCTC 62452T).

10.
J Ethnopharmacol ; 248: 112319, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31639488

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Apoptosis plays an important role in cerebral ischemia-reperfusion injury and triggers a series of pathological changes which may even be life-threatening. Astragaloside-IV (AS-IV), a natural compound extracted from Astragalus (Astragalus membranaceus (Fisch.) Bunge., Leguminosae, Huangqi in Chinese), showed neuroprotective effects in the study of cerebral ischemia-reperfusion injury. In this study we investigate the effects of AS-IV on apoptosis induced by transient cerebral ischemia and reperfusion in rats, as well as the associated regulatory factors. METHODS: AS-IV was administrated to male Sprague-Dawley (SD) rats after transient cerebral ischemia and reperfusion surgery (12.5, 25, and 50 mg/kg, once per day, continued for 7 days after surgey). After seven days of continuous administration, neurological function, cerebral infarction volume, and pathological changes of brain tissue were detected. Fas, FasL, Caspase-8, Bax, and Bcl-2 mRNA levels were determined by real-time PCR. Caspase-8, Bid, Cytochrome C (Cyto C), cleaved Caspase-3 proteins were determined by western blot and immunohistochemistry was used to quantify Cyto C. RESULTS: AS-IV significantly attenuated the neurological deficit in rats with ischemica-reperfusion injury, and reduced cerebral infarction and neuronal apoptosis. AS-IV inhibited the mRNA upregulation of Fas, FasL, Caspase-8, and Bax/Bcl-2. Furthermore, the protein level of apoptosis cytokines Caspase-8, Bid, cleaved Caspase-3 and Cyto C were also inhibited after ischemia reperfusion, suggesting that AS-IV might alleviate ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway.

11.
J Zhejiang Univ Sci B ; 20(11): 868-876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595723

RESUMO

Acrolein, known as one of the most common reactive carbonyl species, is a toxic small molecule affecting human health in daily life. This study is focused on the scavenging abilities and mechanism of ferulic acid and some other phenolic acids against acrolein. Among the 13 phenolic compounds investigated, ferulic acid was found to have the highest efficiency in scavenging acrolein under physiological conditions. Ferulic acid remained at (3.04±1.89)% and acrolein remained at (29.51±4.44)% after being incubated with each other for 24 h. The molecular mechanism of the detoxifying process was also studied. Detoxifying products, namely 2-methoxy-4-vinylphenol (product 21) and 5-(4-hydroxy-3-methoxyphenyl)pent-4-enal (product 22), were identified though nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS), after the scavenging process. Ferulic acid showed significant activity in scavenging acrolein under physiological conditions. This study indicates a new method for inhibiting damage from acrolein.

12.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3672-3683, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602939

RESUMO

Sesquiterpenes are a class of terpenoids composed of three isoprene units( 15 carbons). Sesquiterpenoids possess a variety of different structures,including acyclic sesquiterpenes,monocyclic sesquiterpenoids,bicyclic sesquiterpenoids,tricyclic sesquiterpenoids,tetracyclic sesquiterpenoids and macrocyclic sesquiterpenoids. Among them,a large number of monocyclic sesquiterpenoids were isolated and display extensive bioactivities,such as cytotoxic,antioxidant,anti-inflammatory,antibacterial and other activities. In this review,we summarized the progress about the phytochemistry and biological activities of monocyclic sesquiterpenoids( a total of161 compounds) reported from 2014 to 2018( 5 years),including megastigmanes,monocyclofarnesol-type,bisabolane-type,germacrane-type,and other types of monocyclic sesquiterpenoids. Furthermore,several future research perspectives and development of sesquiterpenoids as potential therapeutic agents were discussed as well.


Assuntos
Sesquiterpenos/farmacologia , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Estrutura Molecular
13.
Int J Mol Med ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31638173

RESUMO

The aim of the present study was to investigate the role of microRNA­21 (miR­21) in regulating the classical WNT/ß­catenin signaling pathway by targeting low­density lipoprotein­related receptor 6 (LRP6) in non­alcoholic fatty liver disease (NAFLD). For this purpose, we established a NAFLD model by feeding C57BL/6J mice a methionine­choline­â€‹deficient diet. Antagomir­21 was then injected via the tail vein, and the expression levels of WNT/ß­catenin signaling pathway­related proteins, such as LRP6, glycogen synthase kinase­3ß (GSK3ß), p­ß­catenin, ß­catenin and the downstream protein, peroxisome proliferator­activated receptor Î³ (PPAR­Î³), and lipid metabolism­related genes, including sterol regulatory element­binding transcription factor 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyl transferase 1α (CPT1α) and adenosine 5­monophosphate (AMP)­activated protein kinase α (AMPKα), were detected. The results revealed that in the NAFLD model, LRP6 expression was negatively associated with miR­21 expression. After antagonizing the expression of miR­21, the protein level of LRP6 was increased. In addition, the WNT/ß­catenin signaling pathway was activated, and lipid accumulation and inflammation were alleviated in the liver. However, the expression of PPAR­Î³ was not inhibited following the upregulation of the WNT signaling pathway. Taken together, the results of this study demonstrate that the inhibition of miR­21 expression can alleviate NAFLD by targeting LRP6 to activate the WNT/ß­catenin signaling pathway.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31613580

RESUMO

The major accomplishment of electrochemical energy-storage devices is closely linked to the advent of state-of-the-art techniques to make optimal electrode systems. Herein, we demonstrate a unique popcorn-inspired strategy to develop all-conductive and highly puffed Fe⊂carbon nanopopcorns as superb anodes for rechargeable Ni/Fe batteries. Temperature-dependent systematic studies show that the nanopopcorn evolution mechanism is governed by typical phase variation from Fe2O3 nanospheres to dispersed Fe0 nanodebris, whose formation induces catalytic reconstruction/conversion from hydrocarbons to graphitic nanolayers while triggering the explosion-like instant puffing process beyond 700 °C. The as-built Fe⊂carbon hybrids with favorable loosened structures, open-up/enlarged surface areas, and intrinsically conducting nature enable great electrochemical reactivity and cyclic stability (reversible capacity higher than ∼420 mA h g-1 in all cycles without obvious capacity decay), as well as outstanding rate behaviors (∼300 mA h g-1 is still retained at ∼20 A g-1). Full-cell devices of NiO@carbon (+)//Fe⊂carbon (-) can exhibit Max. energy/power densities of up to ∼140.8 W h kg-1 and ∼15.6 kW kg-1, respectively. This work sheds a fundamental light on arts to configure puffed electrodes for advanced electrodes in various important applications while holding great promise for high-rate/capacity aqueous rechargeable batteries.

15.
ChemSusChem ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31589802

RESUMO

For the first time, graphene-supported N-doped carbon (G@NC) with a high degree of N doping was synthesized by in situ self-assembly of a glucaminium-based ionic liquid on pristine graphene under hydrothermal conditions. This 2D, metal-free nanohybrid exhibited much higher catalytic activity than most reported metal-free catalysts for the oxygen evolution reaction (OER) and even state-of-the-art Ir- and Ru-based catalysts because the high content of graphitic N greatly increased the number of OER-active sites, the pristine graphene significantly promoted the OER activity of the C sites adjacent to the graphitic N atoms, and N-doped graphitic carbon remarkably enhanced the charge-transfer rate. This work not only creates a facile and economical approach to controllably fabricate pristine-graphene-supported carbon with a high N-doping level for the development of highly efficient metal-free OER catalysts but also provides insight into the mechanisms for both the in situ self-assembly and the high OER catalytic activity of G@NC.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31633909

RESUMO

Pyrite FeS2 has long been a research focus as the alternative anode of rechargeable Ni-Fe cells owing to its eye-catching merits of great earth-abundance, attractive electrical conductivity, and output capacity. However, its further progress is impeded by unsatisfactory cyclic behaviors due to still "ill-defined" phase changes. To gain insights into the pyrite working principles/failure factors, we herein design a core-shell hybrid of a FeS2@carbon nanoreactor, an optimal anode configuration approaching the practical usage state. The resultant electrodes exhibit a Max. specific capacity of ∼272.89 mAh g-1 (at ∼0.81 A g-1), remarkably improved cyclic longevity/stability (beyond ∼80% capacity retention after 103 cycles) and superior rate capability (∼146.18 mAh g-1 is remained at ∼20.01 A g-1) in contrast to bare FeS2 counterparts. The as-built Ni-Fe full cells can also output impressive specific energy/power densities of ∼87.38 Wh kg-1/ ∼ 11.54 kW kg-1. Moreover, a refreshed redox reaction working mechanism of "FeS2OH ↔FeS2↔Fe0(in pyrite domains)" is redefined based on real-time electrode characterizations at distinct operation stages. In a total cyclic period, the configured pyrite-based anodes would stepwise undergo three critical stages nominally named "retention", "phase transition/coexistence", and "degradation", each of which is closely related to variations on anodic compositions/structures. Combined with optimal electrode configurations and in-depth clarifications on inherent phase conversions, this focus study may guide us to maximize the utilization efficiency of pyrite for all other aqueous electrochemical devices.

17.
Zhongguo Gu Shang ; 32(8): 696-700, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31533378

RESUMO

OBJECTIVE: To explore long-term outcomes of Chiari osteotomy for Legg-Calvé-Perthes disease in children with type Catterall III or IV, and to analyze clinical effect of osteotomy angle on clinical and radiographic results. METHODS: From March 2005 to July 2013, 26 children with Legg-Calvé-Perthes disease with type Catterall III or IV were treated by Chiari osteotomy, including 17 males and 9 females, aged from 4 to 13 years old with an average of (8.9±2.6) years old. Children were divided into low osteotomy angle group and high osteotomy angle group. according to osteotomy angle. There were 10 children in low osteotomy angle group with an osteotomy angle of 10 degrees, including 8 boys and 2 girls, aged from 4 to 13 years old with an average of (9.2±3.3) years old; while there were 16 children in high osteotomy angle group with an osteotomy angle of 15 degress, including 9 boys and 7 girls, aged from 6 to 12 years old with an average of (8.8±2.1) years old. HHS score before operation and at the latest follow-up were recorded to observe clinical results. CE angle of hip joint, acetabular index, Sharp angle, Shenton's line continuity, femoral head coverage, acetabular depth ratio were recorded to compare radiographic results. Stulberg classification was analyzed to compare reshaping ability of femoral head. RESULTS: Twenty-six children were followed up for 4.5 to 12.0 years with an average of (7.9±1.8) years. All incisions were healed at stage I for 10 to 14 days, with an average of(12.3±1.1) days. No inflammation, skin necrosis and injury of vessel and nerve occurred. All osteotomies achieved bone union for 8 to 13 weeks, with an average of(9.8±1.4) weeks. HHS score increased from 75.8±6.5 before operation to 93.5±2.5 at the latest follow-up in low osteotomy angle group(P<0.05), and form 77.6±6.2 to 97.8±1.6 in high osteotomy angle group (P<0.05). HHS score of high osteotomy angle group at the latest follow-up was higher than that of low osteotomy angle group (P<0.05). The acetabular index decreased from (10.1±2.5)° before operation to (4.5±1.3)° at the latest follow-up in low osteotomy angle group (P<0.05), and from (10.7±3.3)° before operation to (2.0±1.1)° in high osteotomy angle group (P<0.05). The acetabular index of high osteotomy angle group at the latest followup was better than low osteotomy angle group(P<0.05). There was no significant difference in CE angle, Sharp angle, Shenton's continuity, femoral head coverage, acetabular depth ratio between two groups. According to Stulberg classification, the femoral head reshaping ability in high osteotomy angle group was better than that of low osteotomy angle group(P<0.05). CONCLUSIONS: Chiari osteotomy with 15° for Legg-Calvé-Perthes disease in children with type Catterall III or IV could effectively decrease index of acetabulum, and helpful for femoral head reshaping ability, then in further improve clinical effects.


Assuntos
Cabeça do Fêmur , Osteotomia , Acetábulo , Adolescente , Criança , Pré-Escolar , Feminino , Articulação do Quadril , Humanos , Inflamação , Masculino , Resultado do Tratamento
18.
PLoS One ; 14(9): e0222603, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31513669

RESUMO

OBJECTIVES: To examine the morbidities associated with workplace injury and to explore how clinical variables modify the risk of injury recurrence. METHODS: A case-control study was designed using Florida's statewide inpatient, outpatient, and emergency visits data obtained from the Healthcare Cost and Utilization Project. We included adults who were admitted for a workplace injury (WPI) or injury at other places (IOP), and a matched population of random controls without WPI/IOP. The associations between WPI and clinical morbidities were assessed by univariate and multivariable regression, ranking predictors by information gain, area under the receiver operating characteristic (AUROC), and odds ratios. We analyzed WPI recurrence using survival methods (Kaplan-Meier, Cox regression, survival decision trees) and developed prediction models via regularized logistic regression, random forest, and AdTree. Performance was assessed by 10-fold cross-validation comparing AUROC, sensitivity, specificity, and Harrell's c-index. RESULTS: A total of 80,712 WPI, 161,424 IOP, and 161,424 control patients were included; 485 distinct clinical diagnostic and 160 procedure codes were analyzed after filtering. Acute bronchitis and bronchiolitis, sprains and strains of shoulder and upper arm, ankle and foot, or other and unspecified parts of back, accidents caused by cutting and piercing instruments or objects, and overexertion and strenuous movements were identified as important consequences of WPI. The prediction models of injury recurrence identified several key factors, such as insurance type and prior injury events, although none of the models exhibited high predictive performance (best AUROC = 0.60, best c-index = 0.62). CONCLUSIONS: WPI is associated to diverse serious physical comorbidity burden. There are demographic, social and clinical comorbidity components associated to the risk of WPI recurrence, although their predictive value is moderate, which warrants future investigation in other information source domains, e.g. deepening into the environmental and societal sphere.

19.
Theranostics ; 9(21): 6314-6333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534553

RESUMO

Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. Methods: As a proof-of-concept study, a multifunctional SF@MnO2 nanoparticle-based platform was strategically synthesized using SF as a reductant and a template via a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO2 nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO2/ICG/DOX (SMID) nanocomplex. Results: The obtained product was highly reactive with endogenous hydrogen peroxide (H2O2) in tumor microenvironment, which was decomposed into O2 to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO2 and stably conjugated ICG. The concurrent NIR fluorescence and magnetic resonance (MR) imaging in vivo both indicated effective tumor-specific enrichment of SMID nanoparticles via enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. Conclusion: This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31518449

RESUMO

BACKGROUND AND AIM: The effect of real-time analysis of needle-based confocal laser endomicroscopy (nCLE) for gastric subepithelial lesions (SELs) on the diagnostic value is unclear. The study aimed to investigate the diagnostic efficacy of real-time nCLE for gastric SELs and to assess the technical aspects and safety of real-time nCLE. METHODS: Consecutive patients with gastric SELs ≥ 1 cm were prospectively investigated by endoscopic ultrasound (EUS), followed by nCLE. During EUS-nCLE, real-time nCLE diagnosis was made by an expert endoscopist. The procedure-relative adverse events were assessed and recorded. One-month wash-out period later, nCLE videos were reviewed off-line by the same endoscopist. The nCLE diagnoses were compared with corresponding pathological results. Additionally, image quality and interobserver agreements for the criteria were evaluated by three experienced endomicroscopists. RESULTS: Except for one failing to be punctured, 60 patients completed EUS-nCLE procedures successfully. Real-time nCLE had high diagnostic accuracies of ≥ 88.3% for gastric SELs. There were no significant differences between real-time and off-line nCLE diagnoses for gastric SELs (P > 0.05). The overall accuracy of real-time nCLE for diagnosis of gastric SELs was 86.7%. There were no procedure-relative adverse events occurred. In addition, the mean image quality score was 3.6 (1 = poor and 5 = excellent). The interobserver agreement was "almost perfect" for ectopic pancreas and "substantial" for gastrointestinal stromal tumor, leiomyoma and carcinoma. CONCLUSIONS: EUS-nCLE could provide in vivo real-time diagnostic imaging with a high diagnostic accuracy. Meanwhile, real-time nCLE was feasible and had a satisfactory safety profile.

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