Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 438
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33162028

RESUMO

Glioma is the most typical malignant brain tumor, and the chemotherapy to glioma is limited by poor permeability for crossing blood-brain-barrier (BBB) and insufficient availability. In this study, angiopep-2 modified lipid-coated mesoporous silica nanoparticle loading paclitaxel (ANG-LP-MSN-PTX) was developed to transport paclitaxel (PTX) across BBB mediated by low-density lipoprotein receptor-related protein 1 (LRP1), which is over-expressed on both BBB and glioma cells. ANG-LP-MSN-PTX was characterized with homogeneous hydrodynamic size, high drug loading capacity (11.08%) and a sustained release. In vitro experiments demonstrated that the targeting efficiency of PTX was enhanced by ANG-LP-MSN-PTX with higher penetration ability (10.74%) and causing more C6 cell apoptosis. ANG-LP-MSN-PTX (20.6%) revealed higher targeting efficiency compared with LP-MSN-PTX (10.6%) via blood and intracerebral microdialysis method in the pharmacokinetic study. The therapy of intracranial C6 glioma bearing rats was increasingly efficient, and ANG-LP-MSN-PTX could prolong the survival time of model rats. Taken together, ANG-LP-MSN-PTX might hold great promise as a targeting delivery system for glioma treatment.

2.
Cereb Cortex ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037819

RESUMO

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.

3.
Obes Surg ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047288

RESUMO

Abnormal anatomic findings are a major concern before performing bariatric surgery, while pathological changes are considered less often. The present study aimed to investigate the incidences of gastric lesions warranting follow-up in patients undergoing bariatric surgery. Meta-analyses were conducted to calculate the pooled incidences of gastric lesions in patients undergoing bariatric surgery. Fifty-nine studies including 32,789 patients were included: 26 on endoscopic biopsy, 26 on pathological findings of the excised specimen, five on the intraoperative exploration results, and two on both preoperative endoscopy and postoperative specimen. Generally, atrophic gastritis (3.05% (95% CI (confidence interval) 1.53-6.09)), intestinal metaplasia (2.44% (95% CI 1.76-3.25)), and GIST (gastrointestinal stromal tumor) (0.45% (95% CI 0.31-0.60)) were not rarely found. Routine preoperative endoscopy was applied in 16 studies, and the pooled incidences of atrophic gastritis and intestinal metaplasia were 2.64% (95% CI 0.78-8.9) and 2.70% (95% CI 0.9-5.42), respectively. Hp. (Helicobacter pylori) screening and eradication were routinely performed in 10 studies, and that was related to a reduced incidence of atrophic gastritis (0.94% (95% CI 0.03-2.92)) vs. 4.31% (95% CI 2.01-9.23). GIST was more likely to be found by intraoperative exploration than by preoperative endoscopy (0.68% (95% CI 0.50-0.93) vs. 0.23% (95% CI 0.11-0.52)). Patients undergoing bariatric surgery demonstrated non-negligible incidences of gastric pathologies warranting follow-up. Preoperative endoscopy and careful intraoperative exploration should be routinely performed, and Hp. screening and eradication are suggested before endoscopy. In condition that such findings are detected, sleeve gastrectomy may be preferred over Roux-en-Y gastric bypass.

4.
Bioengineered ; 11(1): 1197-1207, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33108235

RESUMO

In recent years, more and more studies have shown that antiparasitic drugs can affect a variety of biological processes of tumor cells and exhibit a potential anti-tumor activity. Although artesunate (ART), a strong bioactive derivative of artemisinin and widely used clinically against malaria, was found to have an inhibitory effect on tumor cells, it is still unclear whether ART could regulate the tumor malignancy of non-small-cell lung cancer (NSCLC) cells. In this study, we aimed to investigate the effect of ART on migration capacities in NSCLC cell lines of A549 and H1975. Cell migration capacity was remarkably inhibited by ART treatment. The expression of epithelial marker E-cadherin was upregulated, while mesenchymal markers (N-cadherin, vimentin and FN1) were inhibited by ART in both protein and mRNA levels in A549 and H1975 cells, indicating ART could suppress the epidermal interstitial transformation (EMT) of NSCLC cells. Meanwhile, BTBD7 was found highly expressed in tumor tissues of NSCLC patient and associated with poor prognosis. The anti-migration activity of ART was found to be mediated by the inhibition of BTBD7 mRNA expression and was reversed when the cells were transiently transfected with the BTBD7 overexpression plasmid. Our study demonstrated the potent anti-migratory activity of ART, thereby presenting it as a new candidate for clinical therapy in NSCLC.

5.
Addict Biol ; : e12974, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084195

RESUMO

Obese individuals exhibit brain functional abnormalities in multiple regions implicated in reward/motivation, emotion/memory, homeostatic regulation, and executive control when exposed to food cues and during rest. However, it remains unclear whether abnormal brain responses to food cues might account for or relate to their abnormal activity in resting state. This information would be useful for understanding the neural mechanisms behind hyperactive responses to food cues, a critical marker of obesity. Resting-state functional magnetic resonance imaging (RS-fMRI) and a cue-reactivity fMRI task with high- (HiCal) and low-caloric (LoCal) food cues were employed to investigate brain baseline activity and food cue-induced activation differences in 44 obese participants (OB), in 37 overweight participants (OW), and in 37 normal weight (NW) controls. One-way analyses of variance showed there was a group difference in the left hippocampus/amygdala activity during resting state and during food-cue stimulation (pFWE < 0.05); post-hoc tests showed the OB group had both greater basal activity and greater food cue-induced activation than the OW and NW groups; OW had higher activity in the hippocampus/amygdala than the NW group, which was only significant during resting state. In the OB group, resting-state activity in the left hippocampus/amygdala was positively correlated with activation induced by HiCal food cues, and both of these measures correlated with body mass index (BMI). Mediation analysis showed that the relationship between BMI and hippocampus/amygdala response to HiCal food cues was mediated by their resting-state activity. These findings suggest a close association between obesity and brain functional abnormality in the hippocampus/amygdala. They also indicate that resting-state activity in the hippocampus/amygdala may impact these regions' responses to food cues.

6.
Cancer Med ; 9(22): 8722-8732, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32937009

RESUMO

BACKGROUND: Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non-high-incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. METHODS: We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40-74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. RESULTS: Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C-index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high-risk and low-risk group divided based on score from the nomogram predicted a significantly distinct detection rate. CONCLUSION: The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non-high-risk areas, thus reducing the incidence of UGC by improving the UGPL detection.

7.
Theranostics ; 10(21): 9865-9887, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863964

RESUMO

Background: Glutathione (GSH), the primary antioxidant in cells, could fight against oxidative stress. Tumor cells display a higher GSH level than normal cells for coping with the hyperoxidative state, which meets the requirements of enhanced metabolism and vicious proliferation. Therefore, the consumption of GSH will lead to cell redox imbalance and impede life activities. Herein, targeted sorafenib (SFB) loaded manganese doped silica nanoparticle (FaPEG-MnMSN@SFB) was constructed, which could destroy the intracellular redox homeostasis by consuming GSH. Methods: In this study, MnMSN was prepared by an optimized one-pot Stober's method for loading SFB, and FaPEG chain was modified on the surface of MnMSN to achieve long circulation and targeted delivery. The anticancer efficacy and mechanism of the designed FaPEG-MnMSN@SFB were assessed both in vitro and in vivo. Results: FaPEG-MnMSN@SFB exhibited efficient antitumor activity by dual depleting intracellular GSH (the degradation of MnMSN would consume intracellular GSH and the SFB would inhibit the effect of Xc - transport system to inhibit GSH synthesis). Moreover, disruption of redox balance would lead to apoptosis and reactive oxygen species (ROS)-dependent ferroptosis of tumor cells. Conclusion: Such a GSH-starvation therapeutic strategy would cause multi-path programmed cell death and could be a promising strategy for cancer therapy.

8.
Int J Syst Evol Microbiol ; 70(10): 5467-5472, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32894210

RESUMO

A Gram-stain-positive, facultatively anaerobic, endospore-forming bacterium, designated strain TD8T, was isolated from surface-sterilized rice seeds (Oryza sativa L.). Phylogenetic analysis of the 16S rRNA gene indicated that strain TD8T should be placed within the genus Gracilibacillus (95.2-99.0 % sequence similarity); it exhibited highest similarities to Gracilibacillus ureilyticus CGMCC 1.7727T (99.0 %), 'Gracilibacillus xinjiangensis' CGMCC 1.12449T (98.9 %) and Gracilibacillus dipsosauri CGMCC 1.3642T (97.5 %). Chemotaxonomic analysis showed that menaquinone-7 (MK-7) was the major isoprenoid quinone. Diphosphatidylglycerol, phosphatidylglycerol and one unidentified phospholipid were the major cellular polar lipids, and the major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0, iso-C15 : 0, C16 : 0 and iso-C16 : 0, which supported the allocation of the strain to the genus Gracilibacillus. The digital DNA-DNA hybridization value between strain TD8T and Gracilibacillus ureilyticus CGMCC 1.7727T was lower than 70 % (22.60 %), and the average nucleotide identity score was 79.54±5.09 %, suggesting that strain TD8T represented a novel species in the genus Gracilibacillus. The genomic DNA G+C content was 37.5 %. Based on physiological and biochemical characteristics and genotypic data, strain TD8T represents a novel species of the genus Gracilibacillus, for which the name Gracilibacillus oryzae sp. nov. is proposed. The type strain is TD8T (=ACCC 61556T=CICC 24889T=JCM 33537T).


Assuntos
Bacillaceae/classificação , Oryza/microbiologia , Filogenia , Sementes/microbiologia , Bacillaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
9.
Acta Radiol ; : 284185120958412, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32985224

RESUMO

BACKGROUND: The ability of 68Ga-DOTA-SSTR to detect the primary sites of neuroendocrine tumors (NETs) remains undetermined, and the clinical benefit of this imaging agent is not clear. PURPOSE: To evaluate the diagnostic accuracy of 68Ga-DOTA-SSTR for carcinoma unknown primary (CUP) neuroendocrine tumors and to further analyze the detection rate of 68Ga-DOTA-SSTR for primary and metastatic sites. MATERIAL AND METHODS: A comprehensive literature search of PubMed/MEDLINE and ScienceDirect was performed in October 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used to evaluate the quality of the methodology of the included studies. RESULTS: A total of 10 studies (484 patients, mean age = 56.6 ± 4.3 years) were included in the study. The pooled sensitivity and specificity of 68Ga-DOTA-SSTR in identifying CUP-NETs were 82% and 55%, respectively. The area under the receiver operating characteristic curve was 69%. Regarding metastasis sites, 68Ga-DOTA-SSTR found the most metastases in the liver (57.9%), followed by the lymph nodes (22.8%), bones (12.8%), lung (2.8%), and others (1.7%). The pooled detection rate of 68Ga-DOTA-SSTR for CUP-NETs was 61%. CONCLUSION: The present study demonstrated the high diagnostic sensitivity of 68Ga-DOTA-SSTR for CUP-NETs. 68Ga-DOTA-SSTR PET/CT was highly effective in locating the primary and metastatic sites of CUP-NETs.

10.
J Orthop Res ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915488

RESUMO

Administration of bisphosphonates following total joint arthroplasty might be beneficial to reduce aseptic loosening. However, their effects on peri-implant bone formation and bone-implant interface strength have not been investigated yet. We used a physiologically loaded mouse implant model to investigate the short-term effects of postoperative systemic alendronate on osseointegration. A titanium implant with a rough surface was inserted in the proximal tibiae of 17-week-old female C57BL/6 mice (n = 44). Postimplantation mice were given alendronate (73 µg/kg/days, n = 22) or vehicle (n = 22) 5 days/week. At 7- and 14-day postimplantation, histology and histomorphometry were conducted. At 28 days, microcomputed tomography and biomechanical testing were performed (n = 10/group). Postoperative alendronate treatment enhanced osseointegration, increasing maximum pullout load by 45% (p < .001) from 19.1 ± 4.5 N in the control mice to 27.6 ± 4.9 N in the treated mice, at day 28 postimplantation. Alendronate treatment increased the bone volume fraction by 139% (p < .001) in the region distal to the implant and 60% (p < .05) in the peri-implant region. At 14-day postimplantation, alendronate treatment decreased the number of osteoclasts per bone perimeter (p < .05) and increased bone volume fraction (p < .01) when compared with the control group. Postimplantation, short-term alendronate treatment enhanced osseointegration as demonstrated by increased bone mass, trabecular bone thickness, and maximum pullout load. Alendronate decreased peri-implant osteoclasts while preserving peri-implant osteoblasts and endothelial cells, in turn, increasing bone volume fraction. This data supports the postoperative clinical use of bisphosphonates, especially in patients with high risks of aseptic loosening.

11.
Zhongguo Zhen Jiu ; 40(9): 976-82, 2020 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-32959594

RESUMO

OBJECTIVE: To explore the mechanism of moxibustion on the treatment of rheumatoid arthritis (RA) in the perspective of programmed cell death-1 and its ligand 1 (PD-1/PD-L1). METHODS: A total of 30 Japanese big ear white rabbits were randomly divided into a control group, a model group and a moxibustion group, 10 rabbits in each one. In the model group and the moxibustion group, RA model was prepared by the injection of Freund's complete adjuvant (FCA) into the hind knee joint cavities of each rabbit. In the control group, 0.9% sodium chloride solution of the same dose was injected. On the 8th day of experiment, in the moxibustion group, moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36), 5 cones at each acupoint, on the bilateral sides alternatively, once a day, 6 treatments as one course, with an interval of 1 days between the treatment courses. Totally, 3 courses of treatment were required. On the 1st, 7th, 14th, 21st and 28th days of experiment, successively, the circumference of the bilateral knee joints was measured with the tape. On the 28th day of experiment, H.E. staining was adopted to observe the histopathological morphology and to evaluate the score of knee synovial tissue. ELISA was used to determined the concentrations of soluble PD-1 (sPD-1) and its ligand 1 (sPD-L1), the interleukin 2 (IL-2) and IL-17 in knee synovial fluid and the concentrations of sPD-1 and sPD-L1 in serum. The histochemistry method was used to determine the expressions of membrane PD-1 (mPD-1) and its ligand 1 (mPD-L1) in spleen tissue. RESULTS: On the 14th, 21st and 28th days of experiment, the circumference of both knee joints was increased in each of the rabbits in the model group as compared with the control group (P<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (P<0.01). Compared with the control group, the hyperplasia of synovial tissue and fibrous tissue, as well as inflammatory cell infiltration were increased obviously in the model group (P<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (P<0.01, P<0.05). Compared with the control group, the concentrations of IL-2 and IL-17 in knee synovial fluid were increased in the rabbits of the model group (P<0.01). Compared with the model group, after the intervention with moxibustion, the concentrations of IL-2 and IL-17 in knee synovial fluid were reduced in the rabbits of the moxibustion group (P<0.05). Compared with the control group, the concentrations of sPD-1 and sPD-L1 in knee synovial fluid and serum in the rabbits of the model group were all increased (P<0.05). Compared with the model group, the concentration of sPD-1 in the knee synovial fluid and serum were reduced in the rabbits of moxibustion group (P<0.05). Compared with the control group, the expressions of mPD-1 and mPD-L1 in spleen tissue were increased obviously in the rabbits of the model group (P<0.05). Compared with the model group, the expression of mPD-L1 in spleen tissue was up-regulated in the rabbits of the moxibustion group (P<0.05). CONCLUSION: Moxibustion could inhibit the over-activation of T cells by enhancing the negative regulation of PD-1/PD-L1 signaling pathway so as to play its effect in treatment of RA.

12.
J Virol ; 94(24)2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967959

RESUMO

Selective autophagy regulates the degradation of cytoplasmic cargos, such as damaged organelles, invading pathogens, and aggregated proteins. Furthermore, autophagy is capable of degrading avibirnavirus, but the mechanism responsible for this process is unclear. Here, we show that autophagy cargo receptor p62 regulates the degradation of the avibirnavirus capsid protein VP2. Binding of p62 to VP2 enhances autophagic induction and promotes autophagic degradation of viral protein VP2. Further study showed that the interaction of p62 with viral protein VP2 is dependent on ubiquitination at the K411 site of VP2 and the ubiquitin-associated domain of p62. Mutation analysis showed that the K411R mutation of viral protein VP2 prohibits its p62-mediated degradation. Consistent with this finding, p62 lacking the ubiquitin-associated domain or the LC3-interacting region no longer promoted the degradation of VP2. Virus production revealed that the knockout of p62 but not the overexpression of p62 promotes the replication of avibirnavirus. Collectively, our findings suggest that p62 mediates selective autophagic degradation of avibirnavirus protein VP2 in a ubiquitin-dependent manner and is an inhibitor of avibirnavirus replication.IMPORTANCE Avibirnavirus causes severe immunosuppression and mortality in young chickens. VP2, the capsid protein of avibirnavirus, is responsible for virus assembly, maturation, and replication. Previous study showed that avibirnavirus particles could be engulfed into the autophagosome and degradation of virus particles took apart. Selective autophagy is a highly specific and regulated degradation pathway for the clearance of damaged or unwanted cytosolic components and superfluous organelles as well as invading microbes. However, whether and how selective autophagy removes avibirnavirus capsids is largely unknown. Here, we have shown that selective autophagy specifically clears ubiquitinated avibirnavirus protein VP2 by p62 recognition and that p62 is an inhibitor of avibirnavirus replication, highlighting the role of p62 as a potential drug target for mediating the removal of ubiquitinated virus components from cells.

13.
Prog Biophys Mol Biol ; 156: 3-13, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32758492

RESUMO

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.

14.
J Mol Diagn ; 22(9): 1139-1150, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32610162

RESUMO

The accurate identification of tissue origin in patients with metastatic cancer is critical for effective treatment selection but remains a challenge. The aim of this study is to develop a gene expression assay for tumor molecular classification and integrate it with clinicopathologic evaluations to identify the tissue origin for cancer of uncertain primary (CUP). A 90-gene expression signature, covering 21 tumor types, was identified and validated with an overall accuracy of 89.8% (95% CI, 0.87-0.92) in 609 tumor samples. More specifically, the classification accuracy reached 90.4% (95% CI, 0.87-0.93) for 323 primary tumors and 89.2% (95% CI, 0.85-0.92) for 286 metastatic tumors, with no statistically significant difference (P = 0.71). Furthermore, in a real-life cohort of 141 CUP patients, predictions by the 90-gene expression signature were consistent or compatible with the clinicopathologic features in 71.6% of patients (101/141). Findings suggest that this novel gene expression assay could efficiently predict the primary origin for a broad spectrum of tumor types and support its diagnostic utility of molecular classification in difficult-to-diagnose metastatic cancer. Additional studies are ongoing to further evaluate the clinical utility of this novel gene expression assay in predicting primary site and directing therapy for CUP patients.

15.
Medicine (Baltimore) ; 99(27): e20964, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629705

RESUMO

Intraoperative radiotherapy (IORT) has been used to treat different residual solid tumors after tumor removal and has shown many advantages over other treatment methods. However, the use of IORT for invasive thymoma has not been reported. Therefore, in this study, we tried to determine the safety and efficacy of INTRABEAM IORT for the treatment of invasive thymoma.Among the patients admitted to our hospital from September to December 2016 who were diagnosed with invasive thymoma, 14 were selected as study subjects. With medical histories taken beforehand, 8 of these patients were diagnosed with Masaoka stage IIA and 6 with Masaoka stage IIB; furthermore, 5 of the patients were diagnosed with myasthenia gravis (MG). INTRABEAM radiation (8-10 Gy, low energy) was delivered to the postoperative tumor bed of each patient during surgery. The intra- and postoperative complications were observed and evaluated, and the improvement in symptoms was assessed. An additional 23 patients with stage II thymoma undergoing radical surgery from April to August 2016 were chosen as the control group.One month after the operation, only 1 patient in the IORT group had cough, increased levels of leucocytes and neutrophils, and pulmonary inflammation on chest computed tomography. Reactive inflammation and pleural effusion in the 2 groups were similar (P > .05). There was no significant difference between the 2 groups in the improvement of myasthenia gravis (P > .05). Postoperative chest computed tomography and routine blood examination at 3 and 12 months showed that all the patients recovered, with normal hemogram levels and no pulmonary fibrosis around the radiation field. In addition, ultrasonic cardiography and electrocardiography demonstrated no significant difference before or after surgery within the IORT group. At the end of the follow-up, all the patients were alive, no relapse or remote metastasis was observed in the IORT group, and 2 inpatients in the control group had experienced relapse at 24 and 26 months. There was a significant difference in disease-free survival between the 2 groups (P = .00).It is safe to administer low-energy INTRABEAM IORT at a dose of approximately 10 Gy in patients with stage II invasive thymoma. INTRABEAM IORT does not significantly increase operation- or radiation-related complications and has no significant effect on vital organs such as the lungs and heart. Its long-term efficacy is worth expecting.


Assuntos
Timoma/radioterapia , Neoplasias do Timo/radioterapia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Dosagem Radioterapêutica , Radioterapia Adjuvante/instrumentação , Radioterapia Adjuvante/métodos , Cirurgia Torácica Vídeoassistida/métodos , Timoma/complicações , Timoma/patologia , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia
16.
Acta Pharmacol Sin ; 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699265

RESUMO

Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy, two essential aspects of ferroptosis. Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in HCC treatment. The combined treatment can be easily translated into clinical applications.

17.
Water Res ; 185: 116218, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32726715

RESUMO

Fungal contamination of drinking water sources is increasingly threatening the environment and human health. In this study, the inactivation of three genera of dominant fungi in drinking water sources using ozone was first reported. The inactivation of the fungal spores by ozone could be divided into two distinct stages: first a rapid reduction in survival, and then the inactivation at a slower rate. The secondary stage inactivation fitted the Chick-Watson model well, and there was no significant difference in the second-order inactivation rate constants of the three fungal spores (0.199-0.209 L mg-1 min-1). The inactivation rate constants of fungal spores by molecular ozone were much lower than those of viruses, which were equivalent to that of Cryptosporidium. The increase in pH and temperature showed a positive effect on the inactivation rate. Damage to cell membranes, leakage of intracellular compounds, and changes of reactive oxygen species and esterase activity in the spores were detected after inactivation. The results indicated that ozone inactivated fungal spores by firstly destroying cell walls and membranes and then causing the release of intracellular compounds. The fungicidal efficiency of ozone was superior to those of chlorine and chlorine dioxide. In addition, the inactivation efficiency of ozone on fungal spores in real water matrices was reduced to 50.7-91.2% of the efficiency in phosphate buffer. In conclusion, ozone showed high efficiency in the inactivation of fungal spores and could be used as an alternative disinfectant for fungal contamination in drinking water sources.


Assuntos
Criptosporidiose , Cryptosporidium , Ozônio , Purificação da Água , Animais , Desinfecção , Cinética , Esporos Fúngicos , Água
18.
BMJ Open ; 10(6): e034685, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32499264

RESUMO

INTRODUCTION: Anlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy in some solid tumours. However, evidence on the safety and feasibility of anlotinib in patients with stage IV gastric cancer is scarce. METHODS AND ANALYSIS: This study is a single-armed and single-centred clinical study being designed to include 150 patients of stage IV gastric cancer. The patients' demographics, pathological characteristics, test results of blood, biochemistry and tumour markers before and after medication, disease-free survival and overall survival will be collected and analysed. The primary and main efficacy outcomes are objective response rate, progression-free survival, disease control rate and overall survival. The secondary efficacy outcome is safety indicator including the incidence of adverse drug reactions and adverse events after administration. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20192111-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1900026291 (registration date: 29 September 2019).

19.
Nature ; 582(7813): 501-505, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32541968

RESUMO

Quantum key distribution (QKD)1-3 is a theoretically secure way of sharing secret keys between remote users. It has been demonstrated in a laboratory over a coiled optical fibre up to 404 kilometres long4-7. In the field, point-to-point QKD has been achieved from a satellite to a ground station up to 1,200 kilometres away8-10. However, real-world QKD-based cryptography targets physically separated users on the Earth, for which the maximum distance has been about 100 kilometres11,12. The use of trusted relays can extend these distances from across a typical metropolitan area13-16 to intercity17 and even intercontinental distances18. However, relays pose security risks, which can be avoided by using entanglement-based QKD, which has inherent source-independent security19,20. Long-distance entanglement distribution can be realized using quantum repeaters21, but the related technology is still immature for practical implementations22. The obvious alternative for extending the range of quantum communication without compromising its security is satellite-based QKD, but so far satellite-based entanglement distribution has not been efficient23 enough to support QKD. Here we demonstrate entanglement-based QKD between two ground stations separated by 1,120 kilometres at a finite secret-key rate of 0.12 bits per second, without the need for trusted relays. Entangled photon pairs were distributed via two bidirectional downlinks from the Micius satellite to two ground observatories in Delingha and Nanshan in China. The development of a high-efficiency telescope and follow-up optics crucially improved the link efficiency. The generated keys are secure for realistic devices, because our ground receivers were carefully designed to guarantee fair sampling and immunity to all known side channels24,25. Our method not only increases the secure distance on the ground tenfold but also increases the practical security of QKD to an unprecedented level.

20.
Int J Syst Evol Microbiol ; 70(7): 4171-4178, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32552985

RESUMO

A novel Gram-stain-negative strain, designated ZYY5T, was isolated from rice roots. Results of 16S rRNA gene analysis indicated that strain ZYY5T was a member of the genus Dickeya, with a highest similarity to Dickeya zeae DSM 18068T (98.5%). The major fatty acids were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). Multi-locus sequence analysis using five concatenated genes (16S rRNA, atpD, infB, recA and gyrB) and phylogenomic analysis based on 2940 core gene sequences showed that strain ZYY5T formed a robust cluster with strains EC1, ZJU1202, DZ2Q, NCPPB 3531 and CSL RW192, while separated from the other strains of D. zeae. The orthologous average nucleotide identity (ANI) and digital DNA-DNAhybridization (dDDH) values among these six strains ranged from 96.8-99.9% and 73.7-99.8%, which supported that they were belonged to the same species. However, strain ZYY5T shared 58.4 of dDDH and 94.5% of ANI values with type strain D. zeae DSM 18068T, which were lower than the proposed species boundary cut-off for dDDH and ANI. The genomic analysis revealed that strain ZYY5T contained virulence-associated genes, which is same as the phylogenetic-related strains of the genus Dickeya. Based on the results of the polyphasic approaches, we propose that strain ZYY5T represents a novel species in the genus Dickeya, for which the name Dickeya oryzae sp. nov. (=JCM 33020 T=ACCC 61554 T) is proposed. Strains EC1, ZJU1202, DZ2Q, NCPPB 3531 and CSL RW192 should also be classified in the same genomospecies of D. oryzae same as ZYY5T.


Assuntos
Enterobacteriaceae/classificação , Oryza/microbiologia , Filogenia , Raízes de Plantas/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Enterobacteriaceae/isolamento & purificação , Ácidos Graxos/química , Genes Bacterianos , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA