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1.
Mol Med Rep ; 22(6): 5041-5052, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174052

RESUMO

The authors' previous study demonstrated that miR­128 may exert an inhibitory effect on the osteogenic differentiation of bone marrow­derived mesenchymal stem cells (BM­MSCs), but its downstream mechanisms remain to be elucidated. The aim of the present study was to investigate the microRNA (miRNA/miR) and mRNA profiles of differentiated and undifferentiated BM­MSCs and explore new downstream targets for miR­128. The sequencing datasets of GSE107279 (miRNA) and GSE112318 (mRNA) were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using the DESeq2 method. The target genes of DEMs were predicted by the miRwalk 2.0 database. The hub target genes of miR­128 were screened by constructing the protein­protein interaction (PPI) network and module analysis. The expression levels of miR­128 and crucial target genes were validated by reverse transcription­quantitative (RT­q) PCR before or after transfection of miR­128 mimics to BM­MSCs. The miRNA expression profile analysis identified miR­128 as one of the significantly downregulated DEMs (total 338) in differentiated BM­MSCs compared with the undifferentiated control. A total of 103 predicted target genes of miR­128­3p were overlapped with upregulated DEGs. By calculating the topological properties of each protein in the PPI network, 6 upregulated genes (KIT, NTRK2, YWHAB, GAB1, AXIN1 and RUNX1; fold change was the highest for NTRK2) were considered to be hub genes. Of these, 4 were enriched in module 4 (RUNX1, KIT, GAB1 and AXIN1; RUNX1 was particularly crucial as it can interact with the others), while one was enriched in module 7 (YWHAB). The expression levels of miR­128 and these 6 target genes during the osteogenic differentiation were experimentally confirmed by RT­qPCR. In addition, the expression levels of these 6 genes were significantly reversed after transfection of miR­128­3p mimics into rat BM­MSCs compared with the miR­control group. These findings indicated that miR­128­3p may inhibit the osteoblast differentiation of BM­MSCs by downregulation of these 6 genes, particularly RUNX1, YWHAB and NTRK2.

2.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4500-4509, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164381

RESUMO

Network Meta-analysis has been widely applied in the field of traditional Chinese medicine(TCM) due to its unique advantages. This study aimed to conduct a visual analysis on the state of the application network Meta-analysis in the field of traditional Chinese medicine. Databases of CNKI and Web of Science were retrieved to identify the qualified literatures and then screen out their titles and abstracts. Institutions, authors, cited references, and keywords were analyzed using the information visualization analysis software CiteSpace. Finally, 79 English and 186 Chinese articles were included. The results indicated that the literatures were mainly published in Chinese, and the number of articles was increased rapidly since 2015. Cooperation between institutions and authors were mainly concentrated inside the institutions. The most important four institutions were four universities who attached more importance to evidence-based medical education and academic exploration. The keywords beside the method of network Meta-analysis could be summarized into three types: the main interventions in traditional Chinese medicine(Chinese herbal injection, herb medicine, acupuncture, etc.), disease types(cancer, circulatory system disease, bone joint disease, urinary system disease, etc.) and the outcome of interests(efficacy, safety, symptom, survive, mortality, etc.), which reflected the current research hotspots to certain extent. In addition, the most cited articles were methodology articles, including the introduction of methodology and the guides of application software, suggesting that the exploration of methodological articles will be extremely concerned.


Assuntos
Terapia por Acupuntura , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Metanálise em Rede , Publicações , Projetos de Pesquisa
3.
Genet Epidemiol ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038041

RESUMO

Multiple methods have been proposed to aggregate genetic variants in a gene or a region and jointly test their association with a trait of interest. However, these joint tests do not provide estimates of the individual effect of each variant. Moreover, few methods have evaluated the joint association of multiple variants with DNA methylation. We propose a method based on linear mixed models to estimate the joint and individual effect of multiple genetic variants on DNA methylation leveraging genomic annotations. Our approach is flexible, can incorporate covariates and annotation features, and takes into account relatedness and linkage disequilibrium (LD). Our method had correct Type-I error and overall high power for different simulated scenarios where we varied the number and specificity of functional annotations, number of causal and total genetic variants, frequency of genetic variants, LD, and genetic variant effect. Our method outperformed the family Sequence Kernel Association Test and had more stable estimations of effects than a classical single-variant linear mixed-effect model. Applied genome-wide to the Framingham Heart Study data, our method identified 921 DNA methylation sites influenced by at least one rare or low-frequency genetic variant located within 50 kilobases (kb) of the DNA methylation site.

4.
Immunity ; 53(4): 745-758.e4, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33010223

RESUMO

Innate immune responses rely on rapid and precise gene regulation mediated by accessibility of regulatory regions to transcription factors (TFs). In natural killer (NK) cells and other innate lymphoid cells, competent enhancers are primed during lineage acquisition, and formation of de novo enhancers characterizes the acquisition of innate memory in activated NK cells and macrophages. Here, we investigated how primed and de novo enhancers coordinate to facilitate high-magnitude gene induction during acute activation. Epigenomic and transcriptomic analyses of regions near highly induced genes (HIGs) in NK cells both in vitro and in a model of Toxoplasma gondii infection revealed de novo chromatin accessibility and enhancer remodeling controlled by signal-regulated TFs STATs. Acute NK cell activation redeployed the lineage-determining TF T-bet to de novo enhancers, independent of DNA-sequence-specific motif recognition. Thus, acute stimulation reshapes enhancer function through the combinatorial usage and repurposing of both lineage-determining and signal-regulated TFs to ensure an effective response.

5.
Sci Rep ; 10(1): 18504, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097739

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

6.
ESC Heart Fail ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32954647

RESUMO

AIMS: Qishen Yiqi dripping pills (QSYQ) may be beneficial in patients with ischaemic heart failure (IHF). We aimed to assess the efficacy and safety of QSYQ administered together with guideline-directed medical therapy in patients with IHF. METHODS AND RESULTS: This prospective randomized, double-blind, multicentre placebo-controlled study enrolled 640 patients with IHF between March 2012 and August 2014. Patients were randomly assigned to receive 6 months of QSYQ or placebo in addition to standard treatment. The primary outcome was 6 min walking distance at 6 months. Among the 638 IHF patients (mean age 65 years, 72% men), the 6 min walking distance increased from 336.15 ± 100.84 to 374.47 ± 103.09 m at 6 months in the QSYQ group, compared with 334.40 ± 100.27 to 340.71 ± 104.57 m in the placebo group (mean change +38.32 vs. +6.31 m respectively; P < 0.001). The secondary outcomes in composite clinical events, including all-cause mortality and emergency treatment/hospitalization due to heart failure, were non-significantly lower at 6 months with QSYQ compared with placebo (13% vs. 17%; P = 0.45), and the change of brain natriuretic peptide was non-significantly greater with QSYQ compared with placebo (median change -14.55 vs. -12.30 pg/mL, respectively; P = 0.21). By contrast, the Minnesota Living with Heart Failure Questionnaire score significantly improved with QSYQ compared with placebo (-11.78 vs. -9.17; P = 0.004). Adverse events were minor and infrequent with QSYQ, similar to the placebo group. CONCLUSIONS: Treatment with QSYQ for 6 months in addition to standard therapy improved exercise tolerance of IHF patients and was well tolerated.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32993957

RESUMO

Small cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor survival. To identify genes that differentially expressed in SCLC with tumor promotion activity as candidate therapeutic targets, we analyzed the expression of 50 RhoGEFs family genes in published microarray data of SCLC and normal tissues (Gene Expression Omnibus (GEO) dataset GSE43346). We identified ARHGEF19, a member of RhoGEFs family, as an overexpressed oncogene in SCLC. ARHGEF19 is up-regulated in SCLC tissues and ranks first in RhoGEFs family genes. Enforced ARHGEF19 expression promotes SCLC cell proliferation in vitro and its knockdown decreases cell proliferation in vitro and in vivo. ARHGEF19-DH and -PD domain interacts with HRAS and activates the MAPK/ERK pathway in SCLC cells and SCLC xenografts. Our study presents evidences that ARHGEF19 overexpression promotes SCLC cell growth and activates the MAPK/ERK pathway. These findings would shed light on the development of new therapeutics for SCLC management.

8.
Ther Innov Regul Sci ; 54(5): 1236-1255, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32865809

RESUMO

Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB's instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial's scientific integrity.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/tratamento farmacológico , Confiabilidade dos Dados , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , China , Comitês de Monitoramento de Dados de Ensaios Clínicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Tempo , Resultado do Tratamento
9.
Bioorg Med Chem ; 28(19): 115682, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32912428

RESUMO

RIWVIWRR-NH2 (Bac8c) is a natural antimicrobial peptide (AMP) exhibiting great antibacterial activity against Gram-negative and Gram-positive bacteria. In this work, lipoic acid was used as a fatty acid hydrophobic ligand to modify Bac8c (LA-Bac8c) to further improve its antimicrobial properties. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) assays showed that LA-Bac8c exhibited lower MIC (MBC) values against Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) than Bac8c. Similar results were reflected in the antibiofilm activity towards S. aureus and MRSA, and LA-Bac8c showed better activity to the biofilm which has been formed or is being formed. In addition to this, the obvious interaction between bacteria/biofilm and LA-Bac8c was observed by microscopy. LA-Bac8c displayed strong membrane depolarization and outer membrane permeabilizing ability, and the cell membrane treated with LA-Bac8c was destroyed to the leakage of bacteria cellular components. All these data indicated LA-Bac8c could be used as a useful antimicrobial peptide with wide application prospect.

10.
BMC Musculoskelet Disord ; 21(1): 506, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736553

RESUMO

BACKGROUND: Ti-Ni shape-memory patella concentrator (TNSMPC) has been designed as an alternative approach for fixation of patella fracture, which has some advantages like higher hardness, higher tenacity, better wearing resistance, excellent corrosion resistance and desired histocompatibility. The present study was to investigate the efficiency of TNSMPC combined with cannulated compression screws in the treatment of comminuted patella fractures. METHODS: Between January 2014 and December 2017, 54 patients of C2 and C3 patella fractures underwent open reduction and internal fixation with TNSMPC combined with cannulated compression screws. All the patients got standard postoperative rehabilitation programs and were regularly followed up for at least 12 months after the operation. X-rays, knee functions and life quality were evaluated during the follow-up. RESULTS: All the patients achieved bone healing and recovery of knee function with low incidence of complications according to outcomes of X-rays and questionnaires. The average operation time and blood loss during surgery were 77.5 ± 25.12 min and 24.25 ± 4.70 ml respectively. The Knee Outcome Survey Activities of Daily Living Scale, the range of motion and the 36-item short-form heath survey after the operation were all improved. According to the Bostman's criteria, the excellent to good rate was 92.6%. CONCLUSION: TNSMPC combined with cannulated compression screws is an effective internal fixation method for C2 and C3 patella fracture with excellent clinical outcomes. In addition, the operation does not increase extra technique difficulty or tissue damage relatively, which is worth promotion.

11.
Circ Res ; 127(9): 1182-1194, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-32781905

RESUMO

RATIONALE: Mean platelet volume (MPV) and platelet count (PLT) are platelet measures that have been linked to cardiovascular disease (CVD) and mortality risk. Identifying protein biomarkers for these measures may yield insights into CVD mechanisms. OBJECTIVE: We aimed to identify causal protein biomarkers for MPV and PLT among 71 CVD-related plasma proteins measured in FHS (Framingham Heart Study) participants. METHODS AND RESULTS: We conducted integrative analyses of genetic variants associated with PLT/MPV with protein quantitative trait locus variants associated with plasma proteins followed by Mendelian randomization to infer causal relations of proteins for PLT/MPV. We also tested protein-PLT/MPV association in FHS participants. Using induced pluripotent stem cell-derived megakaryocyte clones that produce functional platelets, we conducted RNA-sequencing and analyzed expression differences between low- and high-platelet producing clones. We then performed small interfering RNA gene knockdown experiments targeting genes encoding proteins with putatively causal platelet effects in megakaryocyte clones to examine effects on platelet production. In protein-trait association analyses, ten proteins were associated with MPV and 31 with PLT. Mendelian randomization identified 4 putatively causal proteins for MPV and 4 for PLT. GP-5 (Glycoprotein V), GRN (granulin), and MCAM (melanoma cell adhesion molecule) were associated with PLT, while MPO (myeloperoxidase) showed significant association with MPV in both analyses. RNA-sequencing analysis results were directionally concordant with observed and Mendelian randomization-inferred associations for GP-5, GRN, and MCAM. In siRNA gene knockdown experiments, silencing GP-5, GRN, and MPO decreased PLTs. Genome-wide association study results suggest several of these may be linked to CVD risk. CONCLUSIONS: We identified 4 proteins that are causally linked to PLTs. These proteins may also have roles in the pathogenesis of CVD via a platelet/blood coagulation-based mechanism.

13.
Cytotherapy ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32861622

RESUMO

BACKGROUND AIMS: The efficacy of CD19-targeted chimeric antigen receptor T (CAR T) cells for treatment of relapsed B-cell malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the long-term outcomes of these patients remain inconclusive. METHODS: The authors focused on the survival of 35 patients with B-cell acute lymphoblastic leukemia who relapsed after allo-HSCT and received CAR T cells. RESULTS: Of the 34 eligible patients, 30 achieved minimal residual disease-negative complete remission (CR), with a total CR rate of 85.7% (79.8-91.6%). There were 14 patients who received various forms of additional therapy after achieving CR. After a median follow-up of 20.7 months, it was noted that 17 patients had relapsed at a median of 4.5 months (2-34 months). The cumulative recurrence rate (RR) at 18 months was 68.3% (57.6-79.0%). Additional treatment did not reduce the RR but seemed to delay the time to relapse (mean: 5.9 months vs 13.1 months; P = 0.046). Patients with a lower tumor burden (≤10%) had a lower RR (25.0% vs 78.6% at 12 months; P = 0.006). The overall survival (OS) rate for the CR patients was 30.0% (20.3-29.7%) at 18 months, with a median OS of 12.7 months. CONCLUSIONS: The authors' study indicated that for patients who relapsed after HSCT, although a high CR rate was achieved after CAR T therapy, the long-term efficacy was unsatisfactory. It is necessary to optimize additional treatment, including a second HSCT, to further improve long-term efficacy after CAR T infusion.

14.
Biomed Environ Sci ; 33(7): 484-492, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32807267

RESUMO

Objective: Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection. Methods: Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted. Results: A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination. Conclusions: Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.


Assuntos
Anticorpos Anti-Hepatite A/sangue , Vacinas contra Hepatite A/administração & dosagem , Hepatite A/imunologia , Imunidade Ativa , Vacinação , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Modelos Estatísticos , Vacinação/estatística & dados numéricos
15.
Am Heart J ; 227: 47-55, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32679281

RESUMO

Acute ST-segment elevation myocardial infarction (STEMI) remains a serious life-threatening event. Despite coronary revascularization, patients might still suffer from poor outcomes caused by myocardial no-reflow and ischemic/reperfusion injury. Tongxinluo (TXL), a traditional Chinese medicine, has been preliminarily demonstrated to reduce myocardial no-reflow and ischemic/reperfusion injury. We further hypothesize that TXL treatment is also effective in reducing clinical end points for the patients with STEMI. METHODS AND RESULTS: The CTS-AMI trial is a prospective, randomized, double-blind, placebo-controlled, multicenter clinical study in China. An estimated 3,796 eligible patients with STEMI from about 120 centers are randomized 1:1 ratio to TXL or placebo groups. All enrolled patients are orally administrated a loading dose of 8 capsules of TXL or placebo together with dual antiplatelet agents on admission followed by 4 capsules 3 times a day until 12 months. The primary end point is 30-day major adverse cardiovascular and cerebrovascular events, a composite of cardiac death, myocardial reinfarction, emergency coronary revascularization, and stroke. Secondary end points include each component of the primary end point, 1-year major adverse cardiovascular and cerebrovascular events, and other efficacy and safety parameters. CONCLUSIONS: Results of CTS-AMI trial will determine the clinical efficacy and safety of traditional Chinese medicine TXL capsule in the treatment of STEMI patients in the reperfusion era.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , China , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos
16.
Medicine (Baltimore) ; 99(23): e20473, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501994

RESUMO

BACKGROUND: In China, heat-clearing and detoxifying Chinese medicines combined with conventional therapy are commonly applied to treat the mild hand, foot, and mouth disease (HFMD). However, there is lack of solid evidence on the efficacy and safety of such therapies. METHODS: We conducted a pooled analysis with individual patient data from 5 strictly randomized controlled clinical trials to assess the efficacy and safety of this combination therapy for mild HFMD. An intention-to-treat analysis was performed. A 2-stage meta-analysis method was adopted to analyze the pooled effect size. RESULTS: In total, 947 patients were included. Compared with conventional therapy, the combination therapy significantly reduced the progression rate of HFMD from mild to severe (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.22 to 0.83, P = .01). Meanwhile, the healing time of skin rash and oral ulcer in the combination therapy group was significantly shorter than that of conventional therapy. The overall hazard ratio (HR) of healing time of the skin rash or oral ulcer was 1.22 (95%CI: 1.04 to 1.43; P = .02). However, except Jinlianqingre effervescent tablets, the combination therapy cannot shorten the time to fever resolution (HR 1.12, 95%CI: 0.97 to 1.29, P = .14). Because of the heterogeneity, Jinlianqingre effervescent tablets were analyzed separately and the HRs of the time to fever resolution and the healing time of skin rash or oral ulcer were 3.88 (95%CI: 3.19 to 4.72; P < .0001) and 3.79 (95%CI: 2.81 to 5.11; P < .0001), respectively. There were 30 adverse events reported in total; 2 cases were related to Chinese medicines. CONCLUSION: In conclusion, the heat-clearing and detoxifying Chinese medicines on top of conventional therapy can effectively reduce the progressive rate of mild HFMD and improve healing of skin and oral mucosal lesions. More studies are needed for the time to fever resolution.


Assuntos
Quimioterapia Combinada/normas , Medicamentos de Ervas Chinesas/normas , Febre/tratamento farmacológico , Doença de Mão, Pé e Boca/tratamento farmacológico , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Inativação Metabólica , Razão de Chances
17.
Theranostics ; 10(15): 6758-6773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32550902

RESUMO

Photodynamic therapy (PDT), which involves the generation of reactive oxygen species (ROS) through interactions of a photosensitizer (PS) with light and oxygen, has been applied in oncology. Over the years, PDT techniques have been developed for the treatment of deep-seated cancers. However, (1) the tissue penetration limitation of excitation photon, (2) suppressed efficiency of PS due to multiple energy transfers, and (3) insufficient oxygen source in hypoxic tumor microenvironment still constitute major challenges facing the clinical application of PDT for achieving effective treatment. We present herein a PS-independent, ionizing radiation-induced PDT agent composed of yttrium oxide nanoscintillators core and silica shell (Y2O3:Eu@SiO2) with an annealing process. Our results revealed that annealed Y2O3:Eu@SiO2 could directly induce comprehensive photodynamic effects under X-ray irradiation without the presence of PS molecules. The crystallinity of Y2O3:Eu@SiO2 was demonstrated to enable the generation of electron-hole (e--h+) pairs in Y2O3 under ionizing irradiation, giving rise to the formation of ROS including superoxide, hydroxyl radical and singlet oxygen. In particular, combining Y2O3:Eu@SiO2 with fractionated radiation therapy increased radio-resistant tumor cell damage. Furthermore, photoacoustic imaging of tumors showed re-distribution of oxygen saturation (SO2) and reoxygenation of the hypoxia region. The results of this study support applicability of the integration of fractionated radiation therapy with Y2O3:Eu@SiO2, achieving synchronously in-depth and oxygen-insensitive X-ray PDT. Furthermore, we demonstrate Y2O3:Eu@SiO2 exhibited radioluminescence (RL) under X-ray irradiation and observed the virtually linear correlation between X-ray-induced radioluminescence (X-RL) and the Y2O3:Eu@SiO2 concentration in vivo. With the pronounced X-RL for in-vivo imaging and dosimetry, it possesses significant potential for utilization as a precision theranostics producing highly efficient X-ray PDT for deep-seated tumors.

18.
Curr Med Res Opin ; : 1-5, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: covidwho-305917

RESUMO

Objective: The aim of this study was to provide recommendations for improving the design of subsequent studies through analysis of the registered coronavirus disease 2019 (COVID-19) clinical trials.Methods: A retrospective analysis of 189 trial retrievals achieved on 20 February 2020.Results: A total of 189 trials are included in the study. There were 69.3% interventional studies, 21.7% observational studies, 5.3% diagnostic tests and 3.7% other studies. The following statistics are provided only for the interventional studies. Severity of disease: 5.3% light and common type, 17.6% severe and critically ill and 59.6% with no restricted classification. Medication use: 51.1% Western medicine, 32.1% Chinese medicine, 10.7% blood related product and 6.1% non-drug therapy. The median and inner quantile range of the sample sizes included in these studies: 104 (IQR: 60, 200). Primary outcome type most used: 45.8% with clinical characteristics and 21.4% with virological. Study design characteristics: 71% of all studies were randomized, 5% of all studies were blinded, 18% of all studies were multicenter and 76% of all studies were single center.Conclusion: Although many COVID-19 studies include randomization in their design, the lack of additional double-blind and placebo-controlled elements in their designs result in a less robust evaluation of intervention safety and efficacy. Furthermore, similar or repeated research and small sample studies that have less promise in gains of new information have possibly led to a shortage of recruitable patients and become a barrier to the completion of large multicenter clinical trial studies.

20.
Medicine (Baltimore) ; 99(20): e20215, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443350

RESUMO

Hip preserving procedures are still a challenge in late-stage osteonecrosis of femoral head (ONFH) patients. We aimed to compare the clinical outcomes of surgical dislocation and impaction bone graft and surgical dislocation and rotational osteotomy for treatment of ONFH in Association Research Circulation Osseous (ARCO) stage III patients.We retrospectively reviewed 30 ARCO stage III patients (33 hips) who had surgical dislocation and impaction bone graft or surgical dislocation and rotational osteotomy in our center from June 2012 to December 2017. Baseline characteristics, clinical evaluation using Harris score and radiologic evaluation up to 12 months after surgery were recorded and compared.Fifteen patients (17 hips) were in the surgical dislocation and impaction bone graft group and 15 patients (16 hips) were in the surgical dislocation and rotational osteotomy group. No significant differences in age, gender, etiology, ARCO stage, duration of illness, operation time, and length of hospitalization were observed between the 2 groups. Compared to preoperation Harris score, the Harris score of 6 months postoperation and 12 months postoperation significantly improved. At 12 months postoperation, the excellent and good rate was 76.5% in the impaction bone graft group and 87.5% in the rotational osteotomy group. No significant difference in Harris scores was detected in the 2 groups.Surgical dislocation and impaction bone graft and surgical dislocation and rotational osteotomy had satisfactory 1-year efficacy for ARCO III ONFH patients. Surgical dislocation and rotational osteotomy had better short-term efficacy than surgical dislocation and impaction bone graft.


Assuntos
Necrose da Cabeça do Fêmur/cirurgia , Fratura-Luxação/cirurgia , Osteotomia/efeitos adversos , Adulto , Transplante Ósseo/métodos , Feminino , Cabeça do Fêmur/lesões , Cabeça do Fêmur/fisiopatologia , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/métodos , Estudos Retrospectivos , Resultado do Tratamento
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