Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.300
Filtrar
1.
Protein Expr Purif ; 165: 105482, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31470095

RESUMO

Trehalase catalyzes the conversion of one molecule of trehalose into two glucose molecules. The trehalase TreM from thermophilic fungus Myceliophthora sepedonium was expressed in Aspergillus niger via traditional homologous recombination with trehalase activity of 406.44 U/mL. The multi-copy knock-in expression strategy mediated by the CRISPR/Cas9 tool was used to improve the production of the TreM trehalase in Aspergillus niger, which was up to 1943.06 U/mL with a low-background of secreted proteins, 4.8-fold than the transformant obtained via the traditional method. The highest recombinant trehalase activity of the shake fermentation supernatant achieved 4268.29 U/mL when 1.5% glucose was added. Activity assaying showed that the recombinant TreM possessed a specific activity of 679.09 U/mg after gel filtration chromatography purification. The recombinant TreM displayed optimal activity at pH 5.6 and 60 °C and exhibited prominent stability under the conditions of 45-50 °C and pH 4.0-7.5. The activity of recombinant TreM was strongly enhanced by Co2+ (1, 5 mM), Cu2+ (1 mM), Mn2+ (1, 5 mM) and ATP (5 mM), and was greatly inhibited by Cu2+ (10 mM), EDTA (10 mM) and SDS (10 mM).

2.
Talanta ; 207: 120284, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594616

RESUMO

Magnetic carbon nanotubes (CNTs) with encapsulated Co nanoparticles (Co@CNTs), was synthesized by exploiting the one-step pyrolysis strategy using ZIF-67 as template. The as-synthesized Co@CNTs is provided with the nanopores, a large specific surface area, and strong magnetic response. The obtained Co@CNTs was used as magnetic solid-phase extraction adsorbents to extract two profens including flurbiprofen and ketoprofen. The parameters of extraction efficiency, involving extraction time, sample solution volume, ionic strength, pH and the conditions of desorption efficiency, were optimized in detail. After determined by high-performance liquid chromatography-ultraviolet (HPLC-UV), the results evinced that Co@CNTs showed a high extraction efficiency with high enrichment factors of 832 and 672. The good linear range of both flurbiprofen and ketoprofen were all 5.0-1000 ng L-1, with the limit of detection were 0.60 ng L-1 and 0.70 ng L-1, respectively. Furthermore, a valid method for the extraction of flurbiprofen and ketoprofen from human serum was established. The spiking recoveries of two profens were between 86.74% and 97.22%, and the relative standard deviation was less than 6.55%. Co@CNTs can be repeatedly used at least 10 times, indicating its excellent regeneration and reusability. The results demonstrated that the Co@CNTs materials exhibits high enrichment ability and extraction efficiency, playing great promise in MSPE.

3.
J Hazard Mater ; 382: 121018, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446354

RESUMO

The broad spectrum detection of veterinary drugs is very important for rapid and large-scale safe screen of animal-derived foods. Metal-organic frameworks (MOFs), as a kind of emerged functional porous materials are quite promising in the chemical sensing and molecular detection. In this work, we report the high-performance broad spectrum detection of 15 commonly-used veterinary drugs through the fluorescence quenching in a newly-designed chemically stable Al-based MOF, Al3(µ3-O)(OH)(H2O)2(PPTTA)3/2 (BUT-22). To the best of our knowledge, this is the first systematic investigation for the application of MOFs in the detection/sensing of veterinary drugs through fluorescence quenching method. The quenching efficiencies of the tested veterinary drugs on BUT-22 are all beyond 82%, and the limits of detection (LOD) are low at parts per billion (ppb) levels. Interestingly, BUT-22 also enables the selective detection of nicarbazin (NIC) through the clearly-observed red shift of its maximum fluorescence emission wavelength. Moreover, the fluorescence quenching mechanism was explored with the help of theoretical calculations. Our work indicates that MOFs are favorable materials for the detection of veterinary drugs, being potentially useful in monitoring drug residues of animal-derived foods.

4.
Biomaterials ; 227: 119573, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670080

RESUMO

Umbilical cord mesenchymal stem cells (UCMSCs) have shown great potentials in regenerative medicine for their extensive sources, multilineage differentiation potential, low immunogenicity and self-renewal ability. However, the clinical application of UCMSCs still confronts many challenges including the requirement of large quantity of cells, low survival ability in vivo and the loss of main original characteristics due to two-dimensional (2D) culture. The traditional three-dimensional (3D)-spheroid culture can mimic in vivo conditions, but still has limitations in clinical application due to large size of spheroid against direct injection and inner cell death. Based on self-renewal tenet, we produced single cell derived sphere (SCDS) of UCMSCs through combining single cell pattern on chip with 3D culture. Compared with the 2D and traditional 3D culture, SCDS culture has many advantages to meet clinical requirements, including small size, higher abilities of survival and migration, and stronger hypoxia resistance and stemness maintenance. Furthermore, SCDS culture promotes angiogenesis in UCMSCs-xenografts and displays greater therapeutic potential on acute liver failure (ALF) in vivo. Our results suggest that SCDS culture may serve as a simple and effective strategy for UCMSCs optimization to meet clinical demand.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31683470

RESUMO

OBJECTIVE: To evaluate the combined use of strain elastography (SE) and superb microvascular imaging (SMI) with grayscale ultrasound (US) according to the Breast Imaging Reporting and Data System (BI-RADS) classification for differentiating benign from malignant breast masses. METHODS: In total, 166 patients with 177 breast masses categorized as BI-RADS 3-5 were included in the study between April 2016 to September 2017. US, SMI and SE were performed to evaluate each mass. The following outcome measures were compared between US and the combinations of US, SMI, and SE: area under the receiver operating characteristic curve (AUC), sensitivity, specificity. RESULTS: The addition of SMI and SE to US increased the AUC from 0.816 to 0.948 (P < .001); and the specificity from 43.7% to 80.8% (P < .001), without a significant decrease in the sensitivity. Meanwhile, 66.1% (37 of 56) of the benign masses that were indicated for unnecessary biopsy were correctly changed to follow-up. CONCLUSIONS: The addition SMI and SE to US could improve the diagnostic performance in differentiating benign from malignant breast masses compared to US alone. When US was combined with SMI and SE, the specificity were increased, thus significantly reducing unnecessary biopsies.

6.
Int J Mol Sci ; 20(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683554

RESUMO

In our previous research, ten antioxidant pentapeptides including FYKWP, FTGMD, GFEPY, YLPYA, FPPYERRQ, GFYAA, FSGLR, FPYLRH, VPDDD, and GIEWA were identified from the hydrolysate of miiuy croaker (Miichthys miiuy) swim bladder. In this work, their protective function on H2O2-induced oxidative damage to human umbilical vein endothelial cells (HUVECs) was studied. Results indicated that there was no significant difference in the HUVEC viability between the normal group and the treated groups with the 10 pentapeptides at the concentration of 100 µM for 24 h (p < 0.05). Furthermore, FPYLRH of 100 µg/mL extremely significantly (p < 0.001) increased the viability (80.58% ± 5.01%) of HUVECs with H2O2-induced oxidative damage compared with that of the model group. The protective mechanism indicated that FPYLRH could extremely significantly (p < 0.001) increase the levels of superoxide dismutase (SOD) (211.36 ± 8.29 U/mg prot) and GSH-Px (53.06 ± 2.34 U/mg prot) and decrease the contents of reactive oxygen species (ROS) (139.1 ± 11.8% of control), malondialdehyde (MDA) (13.66 ± 0.71 nM/mg), and nitric oxide (NO) (4.36 ± 0.32 µM/L) at the concentration of 100 µM in HUVECs with H2O2-induced oxidative damage compared with those of the model group. In addition, FPYLRH dose-dependently protected DNA in oxidative damage HUVECs model. These results suggested that FPYLRH could significantly attenuate the H2O2-induced stress injury in HUVECs and might be used as a potential natural antioxidant in the functional food industries.

7.
Food Chem ; 309: 125608, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31678673

RESUMO

Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) can improve wound healing of potato tubers; however, how the chemical regulates reactive oxygen species (ROS) generation and scavenging during wound healing is not completely understood. BTH at 100 mg·L-1 regulated changes in ROS generation and scavenging in healing tissues of potato tubers. A higher H2O2 content was presented in healing tissues of potato tubers, while cell membrane permeability and malondialdehyde content declined due to BTH treatment. Additionally, the activities and transcript level of enzymes related with ROS generation, including NADPH oxidase, peroxidase and polyamine oxidase, as well as enzymes involved in ROS scavenging, such as superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, were significantly enhanced by BTH treatment. It is suggested that ROS metabolism might play a crucial role in wound healing of potato tubers mediated by BTH during postharvest.

8.
Diabetes ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712319

RESUMO

The whitening and loss of brown adipose tissue (BAT) during obesity and aging promote metabolic disorders and related diseases. The imbalance of Ca2+ homeostasis accounts for the dysfunction and clearance of mitochondria during BAT whitening. Capsaicin, a dietary factor activating TRPV1, can inhibit obesity induced by high-fat diet (HFD), but whether capsaicin inhibits BAT loss and the underlying mechanism remain unclear. In this study, we determined that the inhibitory effects capsaicin on HFD-induced obesity and BAT whitening were dependent on the participation of SIRT3, a critical mitochondrial deacetylase. SIRT3 also mediated all the beneficial effects of capsaicin on alleviating ROS generation, elevating mitochondrial activity and restricting mitochondrial calcium overload induced by HFD. Mechanistically, SIRT3 inhibits mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium overload by reducing the H3K27ac level on MCU promoter in an AMPK-dependent manner. In addition, HFD also inhibits AMPK activity to reduce SIRT3 expression, which could be reversed by capsaicin. Capsaicin intervention also inhibited aging-induced BAT whitening through this mechanism. In conclusion, this study emphasizes a critical role of AMPK/SIRT3 pathway in the maintenance of BAT morphology and function, and suggests that intervention in this pathway may be an effective target for preventing obesity or age-related metabolic diseases.

9.
Org Lett ; 21(22): 9179-9182, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31674788

RESUMO

Diastereoselective hydride transfer could be triggered by electrophilic halogenation (bromination or fluorination) of homoallylic alcohol O-Bn ethers. The resulting diastereomerically enriched haloalkyl alcohols underwent subsequent intramolecular nucleophilic substitution to afford the corresponding tetrahydrofurans.

10.
J Ovarian Res ; 12(1): 107, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703731

RESUMO

BACKGROUND: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate the synergistic effect of clarithromycin (CAM) with cisplatin to inhibit ovarian carcinoma cells growth in vitro and in vivo. RESULTS: We performed CCK-8 assay to detect apoptosis rates in response to CAM alone or in combination with cisplatin, which were further confirmed by Annexin V and PI staining methods and western blotting. Mechanistically, CAM could reduce endogenous antioxidant enzyme expression and increase the levels of reactive oxygen species (ROS) to augment the cytotoxic effect of cisplatin. Meanwhile, a tumor xenograft model in athymic BALB/c-nude mice demonstrated that CAM combined with cisplatin resulted in reduced tumor growth and weight compared with cisplatin alone. CONCLUSION: Collectively, our results indicate that CAM works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31696238

RESUMO

Objectives Shift work is associated with metabolic disorders as it disturbs circadian rhythms. However, the potential association of shift work with knee osteoarthritis (KOA), a metabolic-related disease, has not been confirmed. The objective of this study was to quantify the association of shift work with the risk of KOA. Methods This retrospective cohort study comprising 13 741 retired workers from the Dongfeng Motor Corporation. KOA was defined by knee pain and clinical X-ray radiographs. Occupational history, including job description and shift work, was collected from face-to-face interviews using questionnaires. Cox proportional hazards regression models were used to estimate exposure-response relationships. Results During the 590 085 person-years of follow-up, a total of 847 cases of KOA (incidence of KOA was 143.5 per 100 000 person-years) were identified. After adjusting for potential confounders, shift work was independently associated with an elevated risk of KOA [hazard ratio (HR) 1.19, 95% confidence interval 1.03-1.36]. Compared with daytime workers, the risk of KOA increased with prolonged periods of shift work; the HR of KOA for participants with 1-9 years, 10-19 years, and ≥20 years shift work were 1.03 (95% CI 0.84-1.26), 1.19 (95% CI 0.98-1.46), and 1.42 (95% CI 1.15-1.76), respectively. The HR for KOA associated with shift work gradually decreased as the period after finishing shift work increased. Conclusion Our results indicated that shift work could be an independent risk factor for KOA.

13.
BMC Pediatr ; 19(1): 405, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685004

RESUMO

BACKGROUND: An increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province. METHODS: A total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008-2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed. RESULTS: During 2008-2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival. CONCLUSIONS: Our study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.

14.
Mediators Inflamm ; 2019: 5869257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686983

RESUMO

Background: T-helper type 1 (Th1) cells and Th1-produced cytokines play essential roles in the immune response to foreign pathogens, such as Brucella spp. The aim of this study was to evaluate the dynamic changes of Th1 cells and Th1-produced cytokines in patients with acute brucellosis and their impact on clinical decision-making. Methods: Fifty-one individuals with acute brucellosis and 17 healthy subjects were enrolled in this study. The brucellosis patients were diagnosed based on clinical symptoms, laboratory tests, and clinical examination. The levels of serum gamma-interferon (IFN-γ) and tumor necrosis factor-alpha (TNF-α), along with the percentage of Th1 cells, were determined by flow cytometry bead arrays (CBA). Results: The frequency of Th1 cells, along with the levels of IFN-γ and TNF-α, was negatively correlated with the clinical parameters. The mean serum levels of IFN-γ and TNF-α and the frequency of Th1 cells were significantly higher in the brucellosis patients in comparison with the healthy subjects (p < 0.05). Besides, the cytokine levels were not significantly different between the positive and negative blood culture groups. IFN-γ levels significantly decreased from 6 months to 12 months post treatment (p < 0.05). However, the IFN-γ levels remained higher than those of the healthy subjects by 12 months post treatment (p < 0.05). The IFN-γ/TNF-α ratio was significantly higher in severe cases than in nonsevere cases (p < 0.05). Conclusions: The IFN-γ levels secreted by Th1 cells remain significantly higher than those of healthy subjects more than 12 months after treatment with antibiotics. This finding is different from similar studies. The IFN-γ/TNF-α ratio may be a feasible parameter for assessing clinical severity, yet further longitudinal studies of the immunization and inflammatory reaction of brucellosis are needed in larger patient populations.

15.
Comput Intell Neurosci ; 2019: 9027803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687008

RESUMO

BOLD-fMRI technology provides a good foundation for the research of human brain dynamic functional connectivity and brain state analysis. However, due to the complexity of brain function connectivity and the high dimensionality expression of brain dynamic attributions, more research studies are focusing on tracking the time-varying characteristics through the transition between different brain states. The transition process is considered to occur instantaneously at some special time point in the above research studies, whereas our work found the brain state transition may be completed in a time section gradually rather than instantaneously. In this paper, a brain state conversion rate model is constructed to observe the procedure of brain state transition trend at each time point, and the state change can be observed by the values of conversion rate. According to the results, the transition of status always lasts for a few time points, and a brain state network model with both steady state and transition state is presented. Network topological overlap coefficient is built to analyze the features of time-varying networks. With this method, some common regular patterns of time-varying characteristics can be observed strongly in healthy children but not in the autism children. This distinct can help us to distinguish children with autism from healthy children.

16.
Genes Dev ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699778

RESUMO

The establishment of polyubiquitin conjugates with distinct linkages play important roles in the DNA damage response. Much remains unknown about the regulation of linkage-specific ubiquitin signaling at sites of DNA damage. Here we reveal that Cezanne (also known as Otud7B) deubiquitinating enzyme promotes the recruitment of Rap80/BRCA1-A complex by binding to Lys63-polyubiquitin and targeting Lys11-polyubiquitin. Using a ubiquitin binding domain protein array screen, we identify that the UBA domains of Cezanne and Cezanne2 (also known as Otud7A) selectively bind to Lys63-linked polyubiquitin. Increased Lys11-linkage ubiquitination due to lack of Cezanne DUB activity compromises the recruitment of Rap80/BRCA1-A. Cezanne2 interacts with Cezanne, facilitating Cezanne in the recruitment of Rap80/BRCA1-A, Rad18, and 53BP1, in cellular resistance to ionizing radiation and DNA repair. Our work presents a model that Cezanne serves as a "reader" of the Lys63-linkage polyubiquitin at DNA damage sites and an "eraser" of the Lys11-linkage ubiquitination, indicating a crosstalk between linkage-specific ubiquitination at DNA damage sites.

17.
Clin Rheumatol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754886

RESUMO

OBJECTIVES: The impact of systemic lupus erythematosus (SLE) on preeclampsia is still obscure. This study was performed to systematically assess the association between preeclampsia and SLE. METHOD: According to the PRISMA statement, designed literature research was performed in PubMed, Web of Science, and Cochrane Library from inception to June 30, 2018. The pooled risk ratio (RR) of preeclampsia in pregnant SLE patients compared with health controls was synthesized by fixed effect model or random effects model depending on heterogeneity. RESULTS: Ten studies involving 6,389 SLE patients were included. Pregnant women with SLE have significantly increased risk of preeclampsia (RR = 2.99, 95% CI = 2.31 to 3.88; Z = 8.31, P < 0.001) compared with health controls. Subgroup analysis showed that the risk of preeclampsia was significant (Q = 7.64, P = 0.006) higher in prospective studies (RR = 6.94, 95% CI = 3.59 to 13.42) compared to retrospective studies (RR = 2.60, 95% CI = 2.08 to 3.25). CONCLUSIONS: The present study demonstrated that pregnant SLE patients have a high risk of preeclampsia, suggesting a pivotal role of SLE in the pathogenesis of preeclampsia. For rheumatologists and SLE patients, it is important to maintain inactive disease activity and prevent complications as LN, and the control of traditional risk factors of preeclampsia is also pivotal. Further study focus on the prevention of preeclampsia in SLE is also urgent.

18.
Cancer Med ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31733044

RESUMO

OBJECTIVE: To evaluate the association of human papilloma virus (HPV) infection with prognosis, specifically overall survival (OS) and disease-free survival (DFS), in laryngeal squamous cell carcinoma (LSCC) patients. METHOD: A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. LSCC was confirmed on the basis of histopathology, whereas HPV status was confirmed by polymerase chain reaction. RESULTS: A total of 6539 articles were initially searched from 8 databases, of which 11 studies were eligible for our review. A total of 1442 LSCC cases were included in this analysis. Eight studies examined 3-year OS for LSCC. The pooled hazard ratio (HR) from the 8 studies was 0.29 (95% CI: 0.25-0.33). There was a statistically significant difference in 3-year OS between the HPV-negative and -positive groups, with the latter having a better survival. There was no statistically significant differences in 5- and 10-year OS. Five studies examined 3- and 5-year DFS for LSCC, whereas only 3 studies examined 10-year DFS. There was no statistically significant difference in 3-, 5-, and 10-year DFS between the HPV groups. CONCLUSION: This study evaluated the survival impact of HPV infection in LSCC patients. The OS of the HPV-positive group was better than that of the HPV-negative group in terms of short-term survival. Compared with the HPV-negative group, the HPV-positive group had a better trend of DFS, suggesting that a larger sample size and further exploration of the pathology and local control of HPV-positive tumors are needed.

19.
J Cardiothorac Surg ; 14(1): 193, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711516

RESUMO

BACKGROUND: For low risk patients undergoing median sternotomies, no midterm follow-up studies involving sternal healing have been conducted. In this study we evaluated sternal healing in low risk patients by chest CT scan and the risk factors associated with poor healing were analyzed. METHODS: Patients who underwent sternal median incision heart surgery from September 2014 to March 2015 were recruited. The clinical information of these patients during hospitalization was collected, and the CT scan data were submitted to the two chief physicians of the Radiology Department for radiographical sternal healing score determination. Based on the method of wound closure, the patients were divided into sternum plate (Plates) and wire groups (Wires). RESULTS: Forty-four patients were recruited. The mean CT examination time was 17.27 ± 2.30 months postoperatively. Twenty-nine (65.9%) patients met the criteria for radiographic sternal healing. Three segments, including the aortopulmonary window, the main pulmonary artery, and the aortic root, had healed less in comparison to the manubrium segment. Compared to patients in whom 6-7 metal wires were used for sternal closure, healing of the lower sternum was worse in patients in whom five wires were used, but the difference in healing was not statistically significant. Univariate analysis of sternal healing showed that patient age was a risk factor for sternal non-healing. When the patient age was > 45 years, the predicted risk of radiographic sternal non-union was 1.833 (95% CI: 1.343-2.503). CONCLUSIONS: At the mid-term follow-up, 65.9% of patients undergoing median sternotomies demonstrated radiographic sternal healing. Age, but not closure device, was a risk factor for sternal non-healing in low risk patients. Use of more wires had a positive impact on sternal healing. TRIAL REGISTRATION: researchregistry4918, registered 28 May 2019, retrospectively registered.

20.
EBioMedicine ; 49: 247-257, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31680000

RESUMO

BACKGROUND: Chronic Hepatitis B (CHB) remains a major problem for global public health. Viral persistence and immune defects are the two major reasons for CHB, and it was hypothesized that based on a transient clearance of serum viral DNA and HBsAg "window stage", active immunization against hepatitis B virus (HBV) might initiate effective host immune responses versus HBV to achieve functional cure of CHB. METHODS: Two experimental mouse models that mice hydrodynamic injected HBV DNA or infected with recombinant AAV/HBV were used. The "sandwich" therapeutic effect by using a potent human anti-HBsAg neutralizing monoclonal antibody (G12) in combination with antiviral drug tenofovir disoproxil fumarate (TDF), followed by active immunization with HBsAg-HBsAb (mYIC) was evaluated. FINDINGS: A single G12 injection rapidly cleared serum HBsAg in HDI-HBV carrier mice, with a synergistic effect in decreasing viral DNA load when TDF was given orally. When both serum viral DNA and HBsAg load became low or undetectable, mYIC was administered. A more effective clearance of viral DNA and HBsAg was observed and serum HBsAb was developed only in these "sandwich"-treated mice. Efficient intrahepatic anti-HBV immune responses were also observed in these mice, including the formation of aggregates of myeloid cells with CD8+T cells and increased TNF-α, granzyme B production. INTERPRETATION: The "sandwich" combination therapy not only efficiently decreased HBsAg and HBV DNA levels but also induced effective cellular and humoral immunity, which may result in functional cure of CHB.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA