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1.
Neuroradiology ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32363484

RESUMO

PURPOSE: Silent new ischemic cerebral lesions (sNICL) detected by diffusion-weighted imaging (DWI) are common after carotid artery stenting (CAS). As part of the Revascularization of Extracranial Carotid Artery Stenosis (RECAS) study, this work aimed to determine predictors of sNICL detected by DWI following CAS. METHODS: A total of 694 patients eligible for the RECAS study treated in Xuanwu Hospital, Capital Medical University, with complete imaging data were included in this retrospective study. The patients were asymptomatic after CAS, and those with stroke, transient ischemic attack (TIA), or death were excluded. The RECAS protocol specified that DWI was completed 1-7 days before the procedure and within 3 days after CAS. Several parameters were assessed for associations with sNICL occurrence after CAS in univariate analysis. Finally, multivariate analysis was performed to determine risk factors for sNICL. RESULTS: The rate of post-procedural sNICL in CAS was 51.3% (356/694 patients with sNICL). All patients underwent stenting with embolic protection devices. Univariate analysis showed that diabetes mellitus (P = 0.008), ipsilateral calcified plaques (P = 0.036), ipsilateral ulcerated plaques (P = 0.026), pre-dilatation (P = 0.003), and open-cell stent use (P < 0.001) were significantly associated with sNICL occurrence in CAS. Multivariate analysis revealed that diabetes mellitus (P = 0.006), ipsilateral calcified plaques (P = 0.024), ipsilateral ulcerated plaques (P = 0.021), and open-cell stent use (P < 0.001) were independent risk factors for sNICL. CONCLUSIONS: Patients with diabetes, calcified or ulcerated plaques who undergo CAS with open-cell stent application, are at high risk of sNICL. Large-scale prospective randomized controlled trials are needed to confirm these findings.

2.
Clin Infect Dis ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32271376

RESUMO

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from two hospitals outside Wuhan. RESULTS: The median duration of SARS-CoV-2 RNA detection was 17 days (Interquartile Range [IQR], 13-22 days) as measured from illness onset. When comparing patients with early (<15 days) and late viral RNA clearance (≥15 days after illness onset), prolonged SARS-CoV-2 RNA shedding was associated with male sex (p=0.009), old age (p=0.033), concomitated with hypertension (p=0.009), delayed admission to hospital after illness onset (p=0.001), severe illness at admission (p=0.049), invasive mechanical ventilation (p=0.006), and corticosteroid treatment (p=0.025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (p<0.001) and focal absorption on radiograph images (p<0.001) than patients with early SARS-CoV-2 RNA clearance. Male sex (odds ratio [OR], 3.24 [95% CI, 1.31-8.02]), delayed hospital admission (OR, 1.30 [95% CI, 1.10-1.54]), and invasive mechanical ventilation (OR, 9.88 [95% CI, 1.11-88.02]) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

3.
Zhongguo Zhen Jiu ; 40(3): 247-50, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32270635

RESUMO

OBJECTIVE: To compare the clinical effect between Stiletto needle combined with massotherapy and articular injection of sodium hyaluronate for pain in patients with knee osteoarthritis (KOA). METHODS: A total of 156 patients with KOA were randomly divided into an observation group and a control group, 78 cases in each group. The patients in the observation group were treated with Stiletto needle (once a week) combined with massotherapy (twice a week); the patients in the control group were treated with articular injection of sodium hyaluronate (once a week). The treatment period were 5 weeks in total. The visual analogue scale (VAS) score, local tenderness value, knee joint activity and Lysholm knee joint score were recorded before treatment, 3 weeks and 5 weeks of treatment. RESULTS: Compared before treatment, the VAS score, local tenderness value, knee joint activity and Lysholm knee joint score in the two groups were improved 5 weeks of treatment (P<0.05). After 5 weeks of treatment, The local tenderness value and Lysholm knee joint score in the observation group were significantly improved compared with the control group (P<0.05), but the knee joint activity in the control group was superior to that in the observation group (P<0.05). CONCLUSION: The Stiletto needle combined with massotherapy are superior to articular injection of sodium hyaluronate in relieving pain and improving knee joint function in patients with early-to-moderate KOA, but its effect on joint activity is inferior to sodium hyaluronate.

4.
Gut ; 69(6): 1002-1009, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32213556

RESUMO

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus , Trato Gastrointestinal , Pandemias , Pneumonia Viral , Adulto , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Feminino , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Fatores de Risco
5.
World Neurosurg ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32112939

RESUMO

BACKGROUND: The safety of carotid artery stenting (CAS) in elderly patients is controversial. The aims of this study were to evaluate 30-day outcomes after CAS in elderly patients (≥70 years old) and to investigate risk factors for postoperative incidence of major adverse clinical events (MACE) to improve CAS safety based on clinical evidence in this specific subgroup of patients. METHODS: The data set included patients who underwent CAS between 2001 and 2017 at Xuanwu Hospital, Capital Medical University. The primary outcome variable was 30-day postoperative incidence of the following MACE: death, myocardial infarction, and ipsilateral stroke. Univariate and multivariate analyses were performed to identify high-risk patients and procedural characteristics associated with MACE. RESULTS: A total of 1029 elderly patients who underwent CAS for carotid artery stenosis were identified and analyzed. The incidence of postoperative MACE was 3.01% (n = 31 cases [5 deaths, 24 strokes, and 2 myocardial infarctions]). After multivariate analysis, independent predictors of MACE included a family history of stroke (odds ratio [OR] = 3.817; 95% confidence interval [CI], 1.227-11.876; P = 0.021), symptomatic status (OR = 2.650; 95% CI, 1.210-5.806; P = 0.015), and modified Rankin Scale score ≥3 (OR = 4.594; 95% CI, 1.708-12.352; P = 0.003). Hyperlipidemia was not an independent risk factor (OR = 1.597; 95% CI, 0.745-3.425; P = 0.229). CONCLUSIONS: At our center, CAS was safely performed in elderly patients. A family history of stroke, symptomatic status, and modified Rankin Scale score ≥3 indicating a neurologic deficit increased the risk of 30-day postoperative MACE.

6.
Bioorg Med Chem ; 28(7): 115358, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32081628

RESUMO

PET imaging of α-synuclein (α-syn) deposition in the brain will be an effective tool for earlier diagnosis of Parkinson's disease (PD) due to α-syn aggregation is the widely accepted biomarker for PD. However, the necessary PET radiotracer for imaging is clinically unavailable until now. The lead compound discovery is the first key step for the study. Herein, we initially established an efficient biologically evaluation system well in highthroughput based on SPR technology, and identified a novel class of N, N-dibenzylcinnamamide (DBC) compounds as α-syn ligands through the assay. These compounds were proved to have high affinities against α-syn aggregates (KD < 10 nM), which well met the requirement of binding activity for the PET probe. These DBC compounds were firstly reported as α-syn ligands herein and the preliminary obtained structure has been further modified into F-labeled ones. Among them, a high-affinity tracer (5-41) with 1.03 nM (KD) has been acquired, indicating its potential as a new lead compound for developing PET radiotracer.

7.
Clin Neurophysiol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32089450

RESUMO

OBJECTIVES: This study aimed to determine vestibular involvement in patients with auditory neuropathy (AN) using ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), caloric tests, video Head Impulse Tests (vHIT), and Suppression Head Impulse Paradigm (SHIMP) tests. METHODS: Twenty-two patients with AN (study group) and 50 age-and-gender-matched healthy subjects (control group) were enrolled. All patients underwent air-conducted sound oVEMP and cVEMP tests. In the study group, 20 patients underwent a caloric test, 10 patients underwent a video Head Impulse Test (vHIT), and nine patients underwent the Suppression Head Impulse Paradigm (SHIMP) test. RESULTS: Significant differences in VEMP abnormalities were found between the two groups. Most AN patients showed no VEMP response, while only a few patients showed VEMP responses with normal parameters. Some AN patients presented abnormal VEMP parameters, including thresholds, latencies, and amplitudes. The abnormal rate (including no response and abnormal parameters) was 91% in the cVEMP test and 86% in the oVEMP test. No significant difference was found between oVEMP and cVEMP abnormalities. AN patients exhibited a 70% abnormal rate in the caloric test. Most AN patients showed normal VOR gains. Most patients showed no overt corrective saccades in vHIT, and exhibited normal anticompensatory saccades in the SHIMP test. CONCLUSION: Many AN patients experience vestibular dysfunction, which may be detected by using a vestibular functional test battery. SIGNIFICANCE: VEMP abnormalities might reflect the status and degree of vestibular involvement in AN.

8.
J Coll Physicians Surg Pak ; 30(2): 134-138, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32036818

RESUMO

OBJECTIVE: To determine the diagnostic value of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) for patients with non-B, non-C hepatocellular carcinoma (NBNC HCC). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from June 2016 to June 2019. METHODOLOGY: Patients with NBNC HCC diagnosed by histology were inducted after curative resection. Serum levels of AFP and DCP were determined. Their receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve (AUC) calculated. In subgroup analyses involving patients with hepatitis B core antibody (HBcAb) testing, the AUC of AFP and DCP were also calculated and compared. RESULTS: Serum levels of AFP and DCP were clearly increased in the NBNC HCC group relative to controls (p = 0.000 for both). The AUC for AFP, DCP and their combination (AFP+DCP) were 0.763 (95%CI: 0.712-0.814), 0.853 (95%CI: 0.811-0.894), and 0.867 (95%CI: 0.829-0.906), respectively. For HBcAb-positivity, the AUC of AFP and DCP were 0.7517 (95%CI: 0.6917-0.8116) and 0.8469 (95% CI: 0.7985-0.8963), respectively. For HBcAb-negativity, the AUC of AFP and DCP were 0.8083 (95%CI: 0.6993-0.9174) and 0.8740 (95%CI: 0.7901-0.9580), respectively. CONCLUSION: A combination of AFP and DCP is useful for assisting the diagnosis of NBNC HCC before surgery. AFP and DCP showed better diagnostic accuracy for HBcAb-negativity compared with HBcAb-positivity in NBNC HCC patients.

9.
J Virol ; 94(6)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31896600

RESUMO

Differentiating infected from vaccinated animals (DIVA) strategies have been central enabling techniques in several successful viral disease elimination programs. However, owing to their long and uncertain development process, no DIVA-compatible vaccines are available for many important diseases. We report herein a new DIVA strategy based on hybrid protein-peptide microarrays which can theoretically work with any vaccine. Leading from our findings from peste des petits ruminants (PPR) virus, we found 4 epitope-containing short peptides (ECSPs) which have distinct IgG serodynamics: anti-ECSP IgGs only exist for 10 to 60 days postvaccination (dpv), while anti-protein IgGs remained at high levels for >1,000 dpv. These data enabled the design of a DIVA diagnostic microarray containing 4 ECSPs and 3 proteins, which, unlike competitive enzyme-linked immunosorbent assay (cELISA) and virus neutralization tests (VNTs), enables ongoing monitoring of serological differences between vaccinated individuals and individuals exposed to the pathogen. For 25 goats after 60 dpv, 13 were detected with positive anti-ECSP IgGs, indicating recent infections in vaccinated goat herds. These DIVA diagnostic microarrays will almost certainly facilitate eradication programs for (re)emerging pathogens and zoonoses.IMPORTANCE Outbreaks of infectious diseases caused by viruses, such as pseudorabies (PR), foot-and-mouth disease (FMD), and PPR viruses, led to economic losses reaching billions of dollars. Both PR and FMD were eliminated in several countries via large-scale vaccination programs using DIVA-compatible vaccines, which lack the gE protein and nonstructural proteins, respectively. However, there are still extensive challenges facing the development and deployment of DIVA-compatible vaccines because they are time-consuming and full of uncertainty. Further, the negative marker strategy used for DIVA-compatible vaccines is no longer functional for live-attenuated vaccines. To avoid these disadvantageous scenarios, a new strategy is desired. Here, we made the exciting discovery that different IgG serodynamics can be monitored when using protein-based assays versus arrays comprising ECSPs. This DIVA microarray strategy should, in theory, work for any vaccine.

10.
Cancer Prev Res (Phila) ; 13(1): 15-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31818852

RESUMO

There is limited understanding of how walnut consumption inhibits the development of colorectal cancer. A possible mechanism may involve alterations to the gut microbiota. In this study, the effects of walnut on gut microbiota were tested in a mouse tumor bioassay using the colonotropic carcinogen, azoxymethane (AOM) added to the total Western diet (TWD). 16S rRNA pyrosequencing identified three enterotype-like clusters (E1, E2, and E3) in this murine model. E1, E2, and E3 are associated with AOM exposure, walnut consumption, and TWD diet, respectively. E2 and E3 showed distinct taxonomic and functional characteristics, while E1 represented an intermediate state. At the family level, E1 and E3 were both enriched with Bacteroidaceae, but driven by two different operational taxonomic units (OTU; OTU-2 for E1, OTU-4 for E3). E2 was overrepresented with Porphyromonadaceae and Lachnospiraceae, with OTU-3 (family Porphyromonadaceae) as the "driver" OTU for this cluster. Functionally, E3 is overrepresented with genes of glycan biosynthesis and metabolism, xenobiotic metabolism, and lipid metabolism. E2 is enriched with genes associated with cell motility, replication and repair, and amino acid metabolism. Longitudinally, E2 represents the gut microbial status of early life in these mice. In comparison with E1 and E3, E2 is associated with a moderate lower tumor burden (P = 0.12). Our results suggest that walnuts may reduce the risk of colorectal cancer within a Western diet by altering the gut microbiota. Our findings provide further evidence that colorectal cancer risk is potentially modifiable by diet via alterations to the microbiota.

11.
Virus Res ; 277: 197844, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866422

RESUMO

Peste des petits ruminants virus (PPRV) is a highly contagious disease that affects sheep and goats. To better understand PPRV replication and virulence, cyclophilin A (CypA), a multifunctional goat host protein, was selected for further studies. CypA has been reported to inhibit or facilitate viral replication. However, the precise roles of CypA during PPRV infection remain unclear. Our data show for the first time that CypA suppressed PPRV replication by its PPIase activity, and PPRV infection decreased CypA protein levels. Detailed analysis revealed that PPRV H protein was responsible for the reduction of CypA, which was dependent on the lysosome pathway. No interaction was identified between H and CypA. Furthermore, the 35-58 region of H was essential for the reduction of CypA. In conclusion, our findings identify the antiviral role of CypA against PPRV and provide key insights into how PPRV H protein antagonizes host antiviral response.

12.
Oncol Lett ; 18(6): 6697-6703, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31814851

RESUMO

Abnormal expression of Holliday junction recognition protein (HJURP) in several types of tumor cells plays a vital role in the formation and progression of tumors. Few studies have investigated the role of HJURP in prostate cancer (PCa). The aim of this study was to analyze the expression levels of HJURP in PCa and to establish the association with clinicopathological data. Reverse transcription quantitative polymerase chain reaction and immunohistochemical analysis were used to detect the expression levels of HJURP in benign and PCa prostate tissues. The Taylor dataset was statistically analyzed to determine if HJURP expression levels were associated with PCa clinicopathological data. HJURP was overexpressed in PCa tissues compared with benign prostate tissues. Statistical analysis of the Taylor dataset indicated that upregulation of HJURP was significantly associated with positive prostate-specific antigen (PSA) levels (P=0.004), high Gleason score (P=0.005), advanced pathological stage (P=0.007), metastasis (P<0.001) and PSA failure (P<0.001). Higher HJURP mRNA expression levels were significantly associated with shorter biochemical recurrence (BCR)-free survival (P<0.001). To the best of our knowledge, this study is the first report of HJURP upregulation in PCa tissues. Upregulation of HJURP may predict BCR-free survival and HJURP may be an oncogene that impacts the prognosis of patients with PCa.

13.
Life Sci ; 239: 116871, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521692

RESUMO

Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) closely associated with cancer progression. In this paper, we focus on exploring the functional role of circ-LDLRAD3 in pancreatic cancer. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. Cell count kit-8 and 5-ethynyl-2'-deoxyuridine assay were applied to evaluate the proliferation of PANC-1 and SW1990 cells. The migration and invasion of PANC-1 and SW1990 cells were assessed using wound healing assay and transwell invasion assay. Luciferase reporter assay was performed for target validation. The results showed that circ-LDLRAD3 was overexpressed in pancreatic cancer tissues and cell lines. Increased expression of circ-LDLRAD3 was indicative of a poor prognosis in patients with pancreatic cancer. Knockdown of circ-LDLRAD3 repressed the growth of pancreatic cancer in vitro and in vivo. miR-137-3p was identified as a direct target of circ-LDLRAD3. More importantly, upregulation of circ-LDLRAD3 could mitigate the inhibitory effect of miR-137-3p on the proliferation, migration and invasion of pancreatic cancer cells. Besides, circ-LDLRAD3 could regulate the expression of pleiotrophin (PTN) through miR-137-3p. Taken together, knockdown of circ-LDLRAD3 repressed the proliferation, migration and invasion of pancreatic cancer cells through miR-137-3p/PTN axis, providing a new mechanism for pancreatic cancer progression.


Assuntos
Neoplasias Pancreáticas/genética , Receptores de LDL/genética , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Citocinas/metabolismo , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Pâncreas/metabolismo , RNA/metabolismo , Receptores de LDL/metabolismo
14.
BMJ Open ; 9(8): e030025, 2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31446417

RESUMO

INTRODUCTION: New ischaemic cerebral lesions (NICL) detected by diffusion-weighted imaging MRI are common after carotid artery stenting (CAS), with an occurrence rate ranging from 18% to 57%. Many studies reported occurrence of NICL could increase risk of future cerebrovascular events and cognitive impairment. However, controversies about determinants for occurrence of NICL after CAS exist among studies, and one risk factor embodied in an article may not be in another. Aim of this study is to introduce a protocol for a systematic review and meta-analysis to identify risk factors associated with occurrence of NICL after CAS. METHODS AND ANALYSIS: All relevant literature referring to risk factors for occurrence of NICL after CAS will be searched on the major databases, such as PubMed, Embase, Web of Science and the Cochrane Library until 31 December 2018. Literature, which must be randomised controlled trials, case-control studies or cohort studies, will be included in accordance with the prespecified eligibility criteria. The risk of bias will be assessed using the Cochrane Collaboration criteria and the quality of evidence will be assessed with the corresponding scale. Data will be extracted with a form prepared before and analysed using RevMan V.5.3 analyses software. Heterogeneity will be assessed using I2 statistic. Our systematic review will be performed according to the guidance from the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. ETHICS AND DISSEMINATION: There is no need for ethical approval because primary data will not be attained. The systematic review will be presented at international conferences and published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42019121129.

15.
Cancer Manag Res ; 11: 6995-7006, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440088

RESUMO

Background: Transforming growth factor-beta-induced (TGFBI) is an exocrine protein, which has been found to be able to promote the development of nasopharyngeal carcinoma, glioma, pancreatic cancer, and other tumors. However, there is currently no report concerning the relationship between TGFBI and invasive progression of bladder cancer (BCa). Methods: IHC staining, qRT-PCR and Western blot were used to analyze TGFBI and EMT markers levels. In vivo tumorigenesis was performed by xenograft tumor model. Results: In this study, we found that both mRNA and protein levels of TGFBI were significantly up-regulated in muscle invasive bladder cancer (MIBC) tissues compared with non-muscle-invasive bladder cancer (NMIBC) tissues. The high expression level of TGFBI was positively correlated with high histological grade and advanced clinical stage, and BCa patients with high TGFBI levels exhibited poor prognoses. We further confirmed that high expression level of TGFBI can promote proliferation, invasive progression, and epithelial-to-mesenchymal transition (EMT) of BCa cells in vitro, as well as promote tumor growth and EMT in vivo, while silencing of TGFBI inhibited these malignant phenotypes. TGFBI was involved in the up-regulation of EMT by inducing the expression level of Slug, Vimentin, Snail, MMP2, and MMP9 genes, while it down-regulated the expression level of E-cadherin. Moreover, Western blot analysis was carried out to demonstrate that BCa cell lines stably transfected with expression of TGFBI, a secreted protein. Furthermore, conditional medium containing TGFBI protein also resulted in enhanced EMT and malignant phenotype of BCa cells. Conclusion: Our results indicate that high expression level of TGFBI promotes EMT, proliferation, and invasive progression of BCa cells, and TGFBI is a potential therapeutic target and prognostic marker for BCa.

16.
Medicine (Baltimore) ; 98(29): e16460, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335704

RESUMO

BACKGROUND: Lumbar fusion is considered to the gold standard for treatment of spinal degenerative diseases but results in adjacent segment degeneration and acquired spinal instability. Total disc replacement is a relatively new alternative avoiding the occurrence of the above complications. The systematic review and meta-analysis was designed to evaluate whether total disc replacement exhibited better outcomes and safety. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure Database(CNKI), Wangfang database, and VIP database were searched for RCTs comparing total disc replacement with lumbar fusion. All statistical analyses were carried out using the RevMan5.3 and STATA12.0 software. RESULTS: Of 1116 citations identified by our search strategy, 14 RCTs met the inclusion criteria. Compared to lumbar fusion, total disc replacement significantly improved ODI, VAS, SF-36, patient satisfaction, overall success, reoperation rate, ODI successful, reduced operation time, shortened duration of hospitalization, decreased postsurgical complications. However, total disc replacement did not show a significant difference regarding blood loss, consumption of analgesics, neurologic success and device success with lumbar fusion. And charges were significantly lower for total disc replacement compared with lumbar fusion in the 1-level patient group, while charges were similar in the 2-level group. CONCLUSION: Total disc replacement is recommended to alleviate the pain of degenerative lumbar diseases, improve the state of lumbar function and the quality of life of patients, provide a high level of security, have better health economics benefits for 1-level patients.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/patologia , Fusão Vertebral , Substituição Total de Disco , Humanos , Degeneração do Disco Intervertebral/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Substituição Total de Disco/efeitos adversos , Substituição Total de Disco/métodos , Resultado do Tratamento
17.
J Sep Sci ; 42(16): 2650-2659, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197944

RESUMO

Mycophenolate mofetil is an antiproliferative immunosuppressive agent. Since its clinical efficacy and safety highly depend on the quality, the stability, and impurity profiles of mycophenolate mofetil are paid ever-increasing attention. However, there are few published studies reporting the complete characterization of both the process-related substances and degradation products in mycophenolate mofetil. In the present study, a highly specific and efficient liquid chromatography coupled with quadrupole-time of flight mass spectrometry method was developed for the separation and identification of all the potential impurities in mycophenolate mofetil. According to the ICH Q1A (R2) guideline, the forced degradation studies were conducted to elucidate the stability and degradation pathways of mycophenolate mofetil. A total of 15 related substances, including the process-related substances and stress degradation products were characterized by the established hyphenated method, 11 of them have not been reported before. In view of the synthetic route and degradation pathways of mycophenolate mofetil, the origins and formation mechanisms of these related substances were discussed. Based on the obtained stability and impurity profiles, key points of the manufacturing process were proposed to deliver mycophenolate mofetil with high purity.


Assuntos
Ácido Micofenólico/isolamento & purificação , Cromatografia Líquida , Espectrometria de Massas , Estrutura Molecular , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/química , Fatores de Tempo
18.
Clin Rheumatol ; 38(10): 2865-2871, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31165340

RESUMO

OBJECTIVE: Gout is a common inflammatory disease, and the prevalence of gout in men is significantly higher than in women. Catechol-O-methyltransferase (COMT) regulates dopamine activity and metabolism, thereby participating in the uric acid metabolism, which in turn affects the occurrence of gout. Our study aimed to investigate the association between COMT methylation and gout in men. METHODS: This study involved 57 male gout patients and 103 age-matched healthy men. We used quantitative methylation-specific polymerase chain reaction (qMSP) to determine DNA methylation levels in the blood. The COMT methylation level was represented by the percentage of methylation reference (PMR). RESULTS: Our results showed that COMT methylation levels were significantly lower in gout patients than in the control group (median PMR 9.50 vs 31.34, p = 3E-5). The area under the curve (AUC) was 0.701 (95% CI 0.611-0.790, p = 2.7E-5) with a sensitivity of 68% and a specificity of 68.4%. CONCLUSION: Our study found that there was a significant correlation between COMT hypomethylation and the risk of gout in males, and this provides an epigenetic mechanism of COMT in gout. COMT hypomethylation might be used as a potential diagnostic biomarker for gout in the future.

19.
Materials (Basel) ; 12(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067798

RESUMO

The influences of process annealing temperature during cold rolling on microstructure and mechanical properties of Ti-3.5Al-5Mo-6V-3Cr-2Sn-0.5Fe near ß high strength titanium alloy sheets have been investigated. Results showed that the alloy mainly included the deformation induced dislocation structures after cold rolling but no obvious band structure, twin crystal or martensite were observed in this work. The texture components, which were affected by process annealing, are mainly γ-fiber, α-fiber and weak Goss texture. The γ-fiber of alloy when process annealed at 780 °C (α/ß phase field) is stronger than at 830 °C (ß phase field), where the Goss texture of alloy with process annealing temperature of 830 °C is more obvious. Results of annealing heat treatments showed that the recrystallization of the cold rolled was basically completed in a relatively short time of 2 min at 750 °C for 2 min. The refinement of grain size led to a significant increase of plasticity compared to rolled alloy. Results of tensile testing of aged alloy display the excellent combination of strength and plasticity, and the cold rolled alloy with process annealed at α/ß phase field exhibits the better mechanical properties than at ß phase field.

20.
Molecules ; 24(10)2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31130654

RESUMO

This study aimed to investigate whether the anti-tumor effect of gemcitabine (GEM) in non-small-cell lung cancer (NSCLC) treatment was affected by Danggui Buxue decoction (DBD), and explore the potential mechanisms. The combined use of GEM and DBD showed an enhanced tumor growth inhibition effect in a murine Lewis lung carcinoma (LLC) model. LC-MS/MS results showed that the pharmacokinetic behaviors of a GEM active metabolite, gemcitabine triphosphate (dFdCTP), were found to be altered remarkably in the peripheral blood mononuclear cells (PBMC) of DBD co-administration rats. In addition, after co-administration of DBD with GEM, Western Blot and qPCR results confirmed that the expression of deoxycytidine kinase (dCK) in tumor tissues of LLC-bearing mice were markedly increased. DBD co-administration also reversed the upregulation of P-glycoprotein (P-gp) in tumor tissues induced by GEM. Moreover, DBD could notably up-regulate the IL-12p70 and GM-CSF expression in mice serum, suggesting potential immunomodulatory activities in tumor-bearing mice. Meanwhile, DBD inhibited the P-gp efflux activity in A549 cells. Therefore, the regulation of dCK and P-gp played important roles in the alternation of GEM pharmacokinetics and the enhancement of the anti-tumor effect of GEM. DBD being a potential dCK promoter could work as an adjuvant agent to boost the anticancer effect of GEM.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Desoxicitidina Quinase/metabolismo , Desoxicitidina/análogos & derivados , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Animais , Desoxicitidina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos
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