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1.
Nat Commun ; 11(1): 2070, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332765

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2.


Assuntos
Betacoronavirus/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/química , Imunoglobulina G/química , Testes de Neutralização , Peptidil Dipeptidase A/química , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Animais , Betacoronavirus/metabolismo , Ligação Competitiva/efeitos dos fármacos , Reações Cruzadas , Desenho de Fármacos , Humanos , Fragmentos Fc das Imunoglobulinas/metabolismo , Fragmentos Fc das Imunoglobulinas/farmacologia , Imunoglobulina G/metabolismo , Imunoglobulina G/farmacologia , Técnicas In Vitro , Concentração Inibidora 50 , Fusão de Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/farmacocinética , Peptidil Dipeptidase A/farmacologia , Domínios Proteicos/genética , Estabilidade Proteica , Receptores Virais/antagonistas & inibidores , Receptores Virais/química , Receptores Virais/genética , Receptores Virais/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacocinética , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
2.
Pol Arch Intern Med ; 130(5): 390-399, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32329978

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID­19) caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection spread worldwide. OBJECTIVES: The aim of the study was to identify the clinical characteristics and risk factors associated with severe incidence of SARS ­CoV­2 infection. PATIENTS AND METHODS: All adult patients (median [IQR] age, 52 [37-58] years) consecutively admitted to the Dabieshan Medical Center from January 30, 2020 to February 11, 2020 were collected and reviewed. Only patients diagnosed with COVID­19  according to the World Health Organization interim guidance were included in this retrospective cohort study. RESULTS: A total of 108 patients with COVID­19 were retrospectively analyzed. Twenty­five patients (23.1%) developed severe disease, and of those 12 patients (48%) died. Advanced age, comorbidities (most commonly hypertension), higher blood leukocyte count, neutrophil count, higher C­reactive protein level, D­dimer level, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score were associated with greater risk of COVID­19, and so were lower lymphocyte count and albumin level. Multivariable regress ion showed increasing odds of severe COVID­19 associated with higher SOFA score (odds ratio [OR], 2.45; 95% CI, 1.302-4.608; P = 0.005), and lymphocyte count less than 0.8 × 109/l (OR, 9.017; 95% CI, 2.808-28.857; P <0.001) on admission. Higher SOFA score (OR, 2.402; 95% CI, 1.313-4.395; P = 0.004) on admission was identified as risk factor for in­hospital death. CONCLUSIONS: Lymphocytopenia and a higher SOFA score on admission could help clinicians to identify patients at high risk for developing severe COVID­19. More related studies are needed in the future.

3.
Sci Total Environ ; 723: 138128, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32222513

RESUMO

To understand the adaptation of Litopenaeus vannamei to high environmental ammonia-N, RNA interference was used to investigate the function of crustacean hyperglycemic hormone (CHH) in the physiological process of neuroendocrine signaling transduction, and ammonia excretion and metabolism. The shrimp were exposed to 25 mg/L NH4Cl and injected with 20 µg/shrimp CHH dsRNA for 72 h. The results showed that hemolymph ammonia content increased under ammonia-N stress and further increased after CHH knockdown, suggesting that CHH can promote ammonia excretion. Moreover, after CHH knockdown, the levels of CHH, DA, and Wnts decreased significantly, the expression of receptor GC, DA1R, Frizzled and LRP 5/6 also decreased, while DA4R increased remarkably. Moreover, PKA and PKG decreased, while PKC markedly increased, and nuclear transcription factors (CREB and TCF) as well as effector proteins (ß-catenin, FXYD2, and 14-3-3) were significantly downregulated. Furthermore, ammonia transporters Na+/K+-ATPase (NKA), K+channel, Rh protein, AQP, V-ATPase, and VAMP decreased significantly, while Na+/H+ exchangers (NHE) and Na+/K+/2Cl- cotransporter (NKCC) increased significantly. These results suggest that CHH regulates ammonia excretion in three ways: 1) by mainly regulating ion channels via PKA, PKC, and PKG signaling pathways; 2) by activating related proteins primarily through Wnt signaling pathway; and 3) by exocytosis, mostly induced by the PKA signaling pathway. In addition, the levels of Gln, uric acid, and urea increased in accordance with the activities of GDH/GS, XDH, and arginase, respectively, suggesting that ammonia excretion was inhibited but ammonia metabolism was slightly enhanced. This study deepens our understanding of the mechanism by which crustaceans respond to high environmental ammonia-N.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32102388

RESUMO

To explore the joint toxicity and bio-accumulation of multi-heavy metals and potential chemoprevention strategies, Male Sprague Dawley (SD) rats (n = 30) were treated orally once a week for six months with 500mg/kg•bw of eight heavy metals which were commonly identified in aquatic products in the Ningbo area including chromium, manganese, nickel, copper, zinc, cadmium, mercury, and lead. At the same time, 200mg/kg•bw of epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD) or glutathione (GSH) were administered to evaluate their antagonistic effects against adverse effects of multi-heavy metal mixture. The Morris water maze test was used to evaluate spatial learning and memory in the treated rats. Then the rats were anesthetized by pentobarbital sodium (40 mg/kg•bw) to obtain blood samples for biochemical analysis and organs (heart, liver, spleen, lungs, kidneys, brain, testis) to be conducted for biopsy and organ coefficients. Inductively coupled plasma mass spectrometer (ICP-MS) was used to analyze the concentrations of heavy metals. Results indicated that six months of exposure to a multi-heavy metal mixture under this experimental dosage resulted in accumulation in organs and adverse effects on the blood, reproductive system, and liver function. EGCG, TCD or GSH all showed certain chemoprevention effects against the joint toxicity induced by the multi-heavy metal mixture and indicated alleviation and the potential mechanism that also included the promotion of excretion of metals to which animals were exposed.

5.
Sci Total Environ ; 718: 137304, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32087588

RESUMO

Fertilizer-replacement programs by the ministry of agriculture and rural affairs are extraordinary actions for environment protection and sustainable agriculture in China. A national-level survey was performed to acquire consensuses of bio-physiochemical properties for composts. A total of 116 compost samples collected from 16 provinces in China were analyzed by high throughput sequencing of bacterial 16S rRNA gene amplicons. The germination index and bacterial alpha-diversity were lower in composts from poultry manure than others. This large-scale survey revealed that bacterial communities were distinct among different composts and slightly explained by pH, moisture and total nitrogen, but not by raw material or composting process. Nevertheless, 26 OTUs affiliated with Firmicutes (Cerasibacillus, Atopostipes and Bacillus) and Actinobacteria (Thermobifida, Actinomadura and Nocardiopsis) were present in most (>90%) composts and majority of these bacterial species were possibly associated with the biodegradation of organic materials. Surprisingly, 629 potential human or animal bacterial pathogens accounting an average of 1.21% of total 16S rRNA gene were detected and these bacteria were mainly affiliated with Helicobacter, Staphylococcus, Acinotobacter, Streptococcus, Mycobacterium and Enterococcus. In summary, this study provides baseline data for the diversity and abundance of core microbiome and potential pathogens in composts.

6.
BMC Oral Health ; 20(1): 9, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914978

RESUMO

BACKGROUND: This study sought to evaluate dental utilization among 3-,4-, and 5-year-old children in China and to use Andersen's behavioural model to explore influencing factors, thereby providing a reference for future policy making. METHODS: This study is a cross-sectional study. Data of 40,305 children aged 3-5 years were extracted from the Fourth National Oral Health Survey, which was performed from August 2015 to December 2016. Patient data were collected using a questionnaire, which was answered by the child's parents, and clinical data were collected during a clinical examination. Stratification and survey weighting were incorporated into the complex survey design. Descriptive statistics, bivariate correlations and hierarchical logistic regression results were then analysed to find the factors associated with oral health service utilization. RESULTS: The oral health service utilization prevalence during the prior 12 months were 9.5% (95%CI: 8.1-11.1%) among 3-year-old children, 12.1% (95%CI: 10.8-13.5%) among 4-year-old children, and 17.5% (95%CI: 15.6-19.4%) among 5-year-old children. "No dental diseases" (71.3%) and "dental disease was not severe" (12.4%) were the principal reasons why children had not attended a dental visit in the past 12 months. The children whose parents had a bachelor's degree or higher (OR: 2.29, 95%CI: 1.97-2.67, p < 0.001), a better oral health attitude ranging from 5 to 8(OR: 1.64, 95%CI: 1.43-1.89, p < 0.001), annual per capital income more than 25,000 CNY (OR: 1.40, 95%CI: 1.18-1.65, p < 0.001),think their child have worse or bad oral health (OR: 3.54, 95%CI: 2.84-4.40, p < 0.001), and children who often have toothaches (OR: 9.72, 95%CI: 7.81-12.09, p < 0.001) were more likely to go to the dentist in the past year. CONCLUSION: The prevalence of dental service utilization was relatively low among preschool children. It is necessary to strengthen oral health education for parents and children, thereby improving oral health knowledge as well as attitude, and promoting dental utilization.

7.
J Reprod Immunol ; 137: 102856, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31809964

RESUMO

Human chorionic gonadotropin (hCG) can attract regulatory T cells (Tregs) into the fetal-maternal interface regulating maternal immune tolerance in pregnancy. The objective of this study was to investigate whether hCG recruits the Tregs into endometrium by inducing chemokines. The number of Tregs in the endometrium was analyzed by immunohistochemistry. The expression of CCL2 was analyzed in vivo and in vitro with hCG stimulation. CD4+CD25+ Tregs were isolated from peripheral blood for Tregs migration assay with hCG, CCL2 siRNA and CCR2 antagonist stimulation. Our results showed that the number of endometrial Tregs in RIF patients was significantly decreased (9.4 ±â€¯5.3 vs. 23.1 ±â€¯3.1, P < 0.01), while intrauterine infusion of 2000 IU hCG increased the endometrial Tregs (18.6 ±â€¯9.8 vs. 9.4 ±â€¯5.3, P < 0.05) and CCL2 expression (0.21 ±â€¯0.01 vs. 0.17 ±â€¯0.01, P < 0.01). Horn injecting with 10 IU hCG also increased the endometrial Tregs in pseudopregnant mice (46 ±â€¯16.8 vs. 7 ±â€¯4.3, P < 0.01). Furthermore, the CCL2 protein and mRNA levels were significantly increased in human endometrial stromal cells (hESCs) with the stimulation of hCG. Migration assays showed that hESCs with hCG stimulation promoted Tregs migration (2597 ±â€¯833.2 vs. 1115 ±â€¯670.7, P < 0.05), while the number of migrated Tregs significantly decreased with CCL2 siRNA (1061 ±â€¯105.4 vs. 2598 ±â€¯294.7, P < 0.05) or CCR2 antagonist (356.7 ±â€¯138.8 vs. 2597 ±â€¯833.2, P < 0.05) treatment. In conclusion, intrauterine perfusion of hCG might promote the recruitment of Tregs into endometrium by inducing chemokine CCL2.

8.
Community Dent Oral Epidemiol ; 48(1): 32-41, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31621099

RESUMO

OBJECTIVES: To explore the factors associated with utilization of oral health services among Chinese adults and older adults according to the Andersen Behavior Model. METHODS: Data from the 4th National Oral Health Survey (2015-2016) in China were used. A total of 7206 people (3669 adults aged 35-44 years and 3537 older adults aged 65-74 years) were included in our analysis. Oral health service utilization in the past 12 months was the outcome variable. Explanatory variables were selected according to the Andersen Behavior Model. Descriptive statistics and bivariate associations (chi-square tests) were analysed, followed by hierarchical Poisson regression models, which were conducted to determine the factors associated with oral health service utilization. RESULTS: In total, 21.4% (95% CI: 19.4%-23.7%) of adults (35-44 years old) and 20.7% (95% CI: 18.6%-22.9%) of older adults (65-74 years old) utilized oral health services in the past 12 months. Nearly 80% of adults (78.7%, 95% CI: 74.0%-82.7%) and more than 90% of older adults (93.7%, 95% CI: 91.0%-95.6%) visited a dentist for treatment. Adults aged 35-44 years old who were female (IRR: 1.15, 95% CI: 1.00-1.33, P = .047), had good oral health knowledge and attitudes (IRR: 1.30, 95% CI: 1.06-1.59, P = .011), perceived their oral health status as fair (IRR:1.51, 95% CI:1.24-1.85, P < .001) or poor/very poor (IRR:2.52, 95% CI:2.01-3.18, P < .001) and had a decayed, missing and filled teeth (DMFT) index >0 (IRR: 1.52, 95% CI: 1.11-2.09, P = .009) were more likely to report dental visits in the past 12 months. Older adults who utilized oral health services tended to be female (IRR: 1.32, 95% CI: 1.09-1.59, P = .004); to be covered by Urban Resident Basic Medical Insurance (URBMI) (IRR: 1.56, 95% CI: 1.18-2.05, P = .002), Urban Employee Basic Medical Insurance (UEBMI) (IRR: 1.69, 95% CI: 1.32-2.16, P < .001) or government medical insurance (GMI) (IRR: 1.03, 95% CI:1.01-2.16, P = .044); to have a high education level (IRR: 1.37, 95% CI: 1.08-1.74, P = .010); to have an income level in the 2nd tertile (IRR: 1.44, 95% CI: 1.13-1.84, P = .003) or 3rd tertile (IRR:1.52, 95% CI:1.18-1.95, P = .001); and to perceive their oral health status as poor or very poor (IRR: 1.53, 95% CI: 1.21-1.95, P = .001). CONCLUSIONS: Sex and self-perceived oral health status were associated with oral health utilization among Chinese population. Additionally, for older adults, education level, household income and insurance coverage were determinants of dental service use. These findings can aid in creating more targeted policies to increase the use of dental services by Chinese adults.

9.
Anal Chem ; 91(24): 16002-16009, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31746200

RESUMO

Multiblock DNA probe attracted a large amount of scientific attention, for the development of multitarget biosensor and improved specificity/sensitivity. However, the development of multiblock DNA probes highly relied on the chemical synthesis of organic linkers or nanomaterials, which limited their practicability and biological compatibility. In this work, we developed a label-free assembling strategy using a triblock DNA capture probe, which connects two DNA probes with its intrinsic polyA fragment (probe-PolyA-probe, PAP). The middle polyA segment has a high affinity to the gold electrode surface, leading to excellent reproducibility, stability, and regeneration of our biosensor. Two flanking capture probes were tandemly co-assembled on the electrode surface with consistent spatial relationship and exactly the same amount. When combined with the target DNA, the hybridization stability was improved, because of the strong base stacking effect of two capture probes. The sensitivity of our biosensor was proved to be 10 fM, with a wide analysis range between 10 fM to 1 nM. Our PAP-based biosensor showed excellent specificity when facing mismatched DNA sequences. Even single nucleotide polymorphisms can be distinguished by each probe. The excellent practicability of our biosensor was demonstrated by analyzing genomic DNA both with and without PCR amplification.

10.
BMC Public Health ; 19(1): 1288, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615472

RESUMO

BACKGROUND: Human activity and the interaction between health conditions and activity is a critical part of understanding the overall function of individuals. The World Health Organization's International Classification of Functioning, Disability and Health (ICF) models function as all aspects of an individual's interaction with the world, including organismal concepts such as individual body structures, functions, and pathologies, as well as the outcomes of the individual's interaction with their environment, referred to as activity and participation. Function, particularly activity and participation outcomes, is an important indicator of health at both the level of an individual and the population level, as it is highly correlated with quality of life and a critical component of identifying resource needs. Since it reflects the cumulative impact of health conditions on individuals and is not disease specific, its use as a health indicator helps to address major barriers to holistic, patient-centered care that result from multiple, and often competing, disease specific interventions. While the need for better information on function has been widely endorsed, this has not translated into its routine incorporation into modern health systems. PURPOSE: We present the importance of capturing information on activity as a core component of modern health systems and identify specific steps and analytic methods that can be used to make it more available to utilize in improving patient care. We identify challenges in the use of activity and participation information, such as a lack of consistent documentation and diversity of data specificity and representation across providers, health systems, and national surveys. We describe how activity and participation information can be more effectively captured, and how health informatics methodologies, including natural language processing (NLP), can enable automatically locating, extracting, and organizing this information on a large scale, supporting standardization and utilization with minimal additional provider burden. We examine the analytic requirements and potential challenges of capturing this information with informatics, and describe how data-driven techniques can combine with common standards and documentation practices to make activity and participation information standardized and accessible for improving patient care. RECOMMENDATIONS: We recommend four specific actions to improve the capture and analysis of activity and participation information throughout the continuum of care: (1) make activity and participation annotation standards and datasets available to the broader research community; (2) define common research problems in automatically processing activity and participation information; (3) develop robust, machine-readable ontologies for function that describe the components of activity and participation information and their relationships; and (4) establish standards for how and when to document activity and participation status during clinical encounters. We further provide specific short-term goals to make significant progress in each of these areas within a reasonable time frame.


Assuntos
Coleta de Dados , Informática Médica , Humanos
11.
Nat Commun ; 10(1): 4355, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554797

RESUMO

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms. Here, we report that CAR-T cells release extracellular vesicles, mostly in the form of exosomes that carry CAR on their surface. The CAR-containing exosomes express a high level of cytotoxic molecules and inhibit tumour growth. Compared with CAR-T cells, CAR exosomes do not express Programmed cell Death protein 1 (PD1), and their antitumour effect cannot be weakened by recombinant PD-L1 treatment. In a preclinical in vivo model of cytokine release syndrome, the administration of CAR exosomes is relatively safe compared with CAR-T therapy. This study supports the use of exosomes as biomimetic nanovesicles that may be useful in future therapeutic approaches against tumours.


Assuntos
Exossomos/imunologia , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Exossomos/metabolismo , Humanos , Ativação Linfocitária/imunologia , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Neoplasias/genética , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo
12.
Materials (Basel) ; 12(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561417

RESUMO

The dynamic loads acting on concrete-filled steel tubular members under axial impacts by rigid bodies were studied herein by FEM. The whole impact process was simulated and the time history of the impact load was obtained. The effects of eight factors on the axial impact load were studied; these factors were the impact speed, mass ratio, axial pressure ratio, steel ratio, slenderness ratio, concrete strength, impact position, and boundary conditions. Besides this, the effects of concrete creep on the impact load were also considered by changing the material parameters of the concrete. The results show that axial impact load changes with time as a triangle. The peak value of impact load increases and the impact resistance improves with the growth of the axial pressure ratio, steel ratio, slenderness ratio, and concrete strength after creep occurs. As the eccentricity of the axial impact acting on a concrete-filled steel tubular member increases, the peak value of the impact load decreases. The enhancement of constraints at both ends of the member can improve the impact resistance. The creep reduction coefficients for the peak axial impact load of a concrete-filled steel tubular member under axial compression and considering the creep effect over 6 months and 30 years are 0.60 and 0.55, respectively. A calculation formula for the peak value of impact load was suggested based on the existing formula, and its accuracy was proved by finite element calculation in this study.

13.
BMC Chem ; 13(1): 112, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31508598

RESUMO

Prostate cancer (PC) is the sixth most common cancer type in the world, which causes approximately 10% of total cancer fatalities. The detection of protein biomarkers in body fluids is the key topic for the diagnosis and prognosis of PC. Highly sensitive screening of PC is the most effective approach for reducing mortality. Thus, there are a growing number of literature that recognizes the importance of new technologies for early diagnosis of PC. Graphene is playing an important role in the biosensor field with remarkable physical, optical, electrochemical and magnetic properties. Many recent studies demonstrated the potential of graphene materials for sensitive detection of protein biomarkers. In this review, the graphene-based biosensors toward PC analysis are mainly discussed in two groups: Firstly, novel biosensor interfaces were constructed through the modification of graphene materials onto sensor surfaces. Secondly, ingenious signal amplification strategies were developed using graphene materials as catalysts or carriers. Graphene-based biosensors have exhibited remarkable performance with high sensitivities, wide detection ranges, and long-term stabilities.

14.
Brachytherapy ; 18(5): 733-739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31515049

RESUMO

INTRODUCTION: To evaluate the feasibility and safety of ultrasound-guided iodine-125 interstitial implants for high-risk hepatocellular carcinoma. METHODS: From October, 2016, to August, 2018, 49 patients suffering from a total of 66 hepatocellular carcinoma lesions were treated with ultrasound-guided iodine-125 interstitial implantation. Treatment planning system was applied to make preoperative plan. The response evaluation criteria in solid tumors were used to evaluate the curative effect. The evaluated outcomes included postoperative complications and complete disease control rate, 6-month disease-free survival, and 6-month overall survival. RESULTS: All 49 patients underwent iodine-125 seed implantation successfully. Patients were followed up for 5 to 27.5 months. No patients developed serious complications and only 2 (4.1%) patients had slight pain. The complete response was seen in 21 lesions (31.8%), partial response in 26 lesions (39.4%), stable disease in eight lesions (12.1%), and progressive disease in 11 lesions (16.7%). The overall disease control rate was reached to 83.3%. The 6-month disease-free survival rate was 46.4% with a median disease-free survival time of 5.0 months. The 6-month overall survival rate was 83.6% with a median overall survival time of 15.0 months. CONCLUSIONS: Iodine-125 interstitial implantation is a kind of safe and feasible treatment for high-risk hepatocellular carcinoma.

15.
Exp Ther Med ; 18(2): 1366-1374, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31363376

RESUMO

Percutaneous nephrolithotripsy (PCNL) is recommended as the first-line treatment for the management of kidney stones that are ≥2 cm in diameter. Retrograde intrarenal surgery (RIRS) has become increasingly preferred due to its high level of safety and repeatability, particularly in small stones. However, whether PCNL has superior efficacy and lower complication rates when compared with RIRS remains controversial. Therefore, the present meta-analysis was conducted to compare the clinical outcomes of patients treated with PCNL and RIRS as therapy for renal stones. Clinical trials published in PubMed, Web of Science, Excerpta Medica dataBASE (EMBASE), and the Chinese Biomedical Database (CBM) were systematically reviewed to evaluate the efficacy and safety profiles of patients with renal stones who were treated with PCNL or RIRS. Main outcomes measures included stone-free rate, operative time, hospital stay, and complication rate. Results were expressed as risk ratio (RR), or weighted mean difference (WMD) with 95% confidence intervals (CIs). Pooled estimates were calculated using a fixed-effects or random-effects model according to the heterogeneity among the studies. In total, 17 studies [4 randomized controlled trials (RCTs) and 13 cohort studies] involving 1,717 patients met the inclusion criteria, and were included in this meta-analysis. Pooled results showed that PCNL exhibited a significantly higher stone-free rate (RR=0.90, 95% CI: 0.86 to 0.95; P<0.001) but was associated with a longer hospital stay, when compared with RIRS (WMD=-2.72, 95% CI: -3.9 to -1.54; P<0.001). Operative time (WMD=7.86, 95% CI: -0.89 to 16.61; P=0.078) and complication rate (RR=0.71, 95% CI: 0.48 to 1.05; P=0.083) did not significantly differ between the groups. Subgroup analysis revealed that PCNL had a shorter operation time than RIRS in patients with stone sizes ≥2 cm (WMD=12.88, 95% CI: 4.77 to 20.99; P=0.002), and PCNL had a similar stone-free rate as RIRS when the estimates were pooled from RCTs (RR=0.88, 95% CI: 0.76 to 1.01; P=0.078). Compared with PCNL, RIRS had a significantly lower stone-free rate, shorter hospital stay, but a similar operation time and complication rate. Therefore, we propose that RIRS may be an alternative therapy to PCNL, with acceptable efficacy and complication rates for renal stones. Further large-scale, well-conducted RCTs are required to verify our findings.

16.
J Cancer Res Ther ; 15(4): 825-830, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436238

RESUMO

Aims: The study aimed to evaluate the safety and efficacy of navigated magnetic resonance imaging (MRI)-guided celiac plexus neurolysis (CPN) using a 0.4 T open magnetic resonance system. Materials and Methods: A retrospective analysis was performed on 23 patients with unresectable pancreatic cancer who underwent MRI-guided CPN between January 2013 and October 2017. Clinical outcomes were evaluated by recording the complications, the opioid intake, and questionnaire before the intervention and at the time point of 1 day, 1 month, and 3 months postprocedure using a numerical visual analog scale (VAS). Results: Navigated MRI guidance allowed the precise placement of needle in the targeted area and the visualization of the injected neurolysis agents for all cases. The VAS scores decreased from 8.8 ± 1.0 to 2.9 ± 0.9, 4.2 ± 1.7, and 4.7 ± 1.8 at 1 day, 1 month, and 3 months postprocedure (P < 0.05). This intervention reduced the dosage of opioid consumption 1 month after the procedure (52.3 ± 10.4 mg before the treatment vs. 28.2 ± 4.9 mg after the treatment; P < 0.001). Treatment-related side effects included hematoma in one patient, short episodes of diarrhea in three patients, and hypotension in four patients. Conclusions: With the assistance of the navigation system, MRI-guided CPN is a safe and effective treatment approach for managing the upper abdominal pain in patients with unresectable pancreatic cancer.


Assuntos
Dor Abdominal/prevenção & controle , Dor do Câncer/prevenção & controle , Plexo Celíaco/patologia , Imagem por Ressonância Magnética/métodos , Bloqueio Nervoso/métodos , Neoplasias Pancreáticas/complicações , Cirurgia Assistida por Computador/métodos , Dor Abdominal/etiologia , Dor Abdominal/patologia , Idoso , Analgésicos Opioides/uso terapêutico , Dor do Câncer/etiologia , Dor do Câncer/patologia , Plexo Celíaco/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos
17.
EMBO Mol Med ; 11(8): e10409, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31282614

RESUMO

Mitophagy can selectively remove damaged toxic mitochondria, protecting a cell from apoptosis. The molecular spatial-temporal mechanisms governing autophagosomal selection of reactive oxygen species (ROS)-damaged mitochondria, particularly in a platelet (no genomic DNA for transcriptional regulation), remain unclear. We now report that the mitochondrial matrix protein MsrB2 plays an important role in switching on mitophagy by reducing Parkin methionine oxidation (MetO), and transducing mitophagy through ubiquitination by Parkin and interacting with LC3. This biochemical signaling only occurs at damaged mitochondria where MsrB2 is released from the mitochondrial matrix. MsrB2 platelet-specific knockout and in vivo peptide inhibition of the MsrB2/LC3 interaction lead to reduced mitophagy and increased platelet apoptosis. Pathophysiological importance is highlighted in human subjects, where increased MsrB2 expression in diabetes mellitus leads to increased platelet mitophagy, and in platelets from Parkinson's disease patients, where reduced MsrB2 expression is associated with reduced mitophagy. Moreover, Parkin mutations at Met192 are associated with Parkinson's disease, highlighting the structural sensitivity at the Met192 position. Release of the enzyme MsrB2 from damaged mitochondria, initiating autophagosome formation, represents a novel regulatory mechanism for oxidative stress-induced mitophagy.

18.
Clin Chim Acta ; 497: 67-75, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31276634

RESUMO

BACKGROUND: Asymptomatic hypercholanemia of pregnancy (AHP) is a controversial hypercholanemia, which is difficult to distinguish from intrahepatic cholestasis of pregnancy (ICP). Our aim is to elucidate the characteristics of urinary bile acid (BA) profiling of women with AHP and to find potential biomarkers for the diagnosis and differential diagnosis of AHP. METHODS: We developed a pseudo-targeted approach to perform metabolomics analysis of bile acids (BAs) using ultra-high performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Urinary BAs profiles were compared among AHP women (n = 20), ICP patients (n = 33) and normal controls (n = 35). RESULTS: The profiling of urinary BAs was significantly different among the AHP, ICP and control groups. Compared to the control group, the AHP group had higher levels of four possible sulfated BAs and trihydroxy BAs, including the species of muricholic acid (MCA), cholic acid (CA) and six possible BAs, whereas, 20 possible sulfated BAs, taurochenodeoxycholic acid (TCDCA), tetrahydrocannabinolic acid (THCA), and seven possible BAs were significantly lower in the AHP group than those in the ICP group. Based on the receiver operating characteristic (ROC) analysis, glycocholic acid (GCA) combined with T-ω-MCA were found to be the potential combination biomarker for the diagnosis (area under the curve was 0.960) of AHP, and mono-S, Gtri-S-2 combined with TLCA-S were found to be the potential combination biomarker for the differential diagnosis (area under the curve was 0.990) of AHP and ICP. CONCLUSIONS: The metabolisms of urinary Bas were altered in the AHP group compared with the ICP group and the control group. Urinary BA profiling analysis can serve as an effective tool for the diagnosis of AHP and the differential diagnosis of AHP and ICP.


Assuntos
Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/urina , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/urina , Metabolômica , Complicações na Gravidez/metabolismo , Complicações na Gravidez/urina , Estudos de Casos e Controles , Colestase Intra-Hepática/diagnóstico , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Espectrometria de Massas , Análise Multivariada , Gravidez , Complicações na Gravidez/diagnóstico , Fatores de Tempo
19.
Cancer Lett ; 460: 128-138, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31207319

RESUMO

Alterations in circular RNA (circRNA) expression have a vital impact on the biological processes in cancer. Moreover, the expression pattern and roles of circRNAs in hepatocellular cancer (HCC) remain unclear. This study performed qRT-PCR to determine the regulated circRNAs in HCC tissues and cell lines. CCK8, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation, cell cycle assay, apoptotic assay, transwell, and wound healing assay were conducted to assess the function of hsa_circ_0091570 or miR-1307 on cell proliferation, apoptosis, and migration in vitro. Mouse xenograft models were used to measure the functions of hsa_circ_0091570 in vivo. The decreased expression of hsa_circ_0091570 was associated with the pathological staging of HCC patients. Furthermore, inhibition of hsa_circ_0091570 promoted cell proliferation and migration, blocked cell apoptosis in HCC cell lines, and promoted tumor growth in the mouse xenograft model. RNA immunoprecipitation assay verified the interaction of hsa_circ_0091570 and miR-1307. The miR-1307 inhibitor inhibited the function induced by hsa_circ_0091570 siRNA. Overall, hsa_circ_0091570 sponge miR-1307 as a ceRNA and regulate ISM1 expression by exerting functional roles in HCC.

20.
Int J Hyperthermia ; 36(1): 632-639, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244349

RESUMO

Purpose: Microwave ablation (MWA) has become increasingly popular as a minimally invasive treatment for benign and malignant liver tumors. However, few studies have demonstrated the benefits and disadvantages of MWA compared to surgical resection (SR) for large hepatic hemangiomas. This study aimed to evaluate the safety and effectiveness of MWA compared to SR for large (5-10 cm) hepatic hemangiomas. Methods and materials: This retrospective comparative study included 112 patients with large, symptomatic hepatic hemangiomas who had been treated with MWA (n = 44) or SR (n = 68) and followed up for a median of 44 months using enhanced computed tomography (CT) or magnetic resonance imaging (MRI). Intraoperative information, postoperative recovery time, postoperative discomfort and complications and treatment effectiveness between groups were compared using a chi-square test or an independent t-test. Results: The operative time was significantly shorter (31.3 ± 21.76 versus 148.1 ± 59.3 min, p < .001) and the blood loss (10.2 ± 60.6 versus 227.9 ± 182.9 mL, p < .0001) and rate of prophylactic abdominal drainage [1 (2.3%) versus 57 (83.8%), p < .001] were significantly lower in the MWA group than in the SR group. Postoperative recovery of the MWA group in regard to indwelling catheter time, normal diet time, incision cicatrization time and hospital stay (p < .001) was significantly better than the SR group. However, no statistically significant difference in effectiveness was noted between the groups (p = .58). Conclusions: MWA may be as effective as SR, and potentially safer for treating large, symptomatic hepatic hemangiomas. To confirm our findings, large-sample, multicentered, randomized controlled trials are needed.


Assuntos
Ablação por Cateter/métodos , Hemangioma/cirurgia , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Feminino , Hemangioma/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ultrassonografia
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