Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 649
Filtrar
1.
ACS Biomater Sci Eng ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835795

RESUMO

Regenerated silk nanofibers are interesting as protein-based material building blocks due to their unique structure and biological origin. Here, a new strategy based on control of supramolecular assembly was developed to regulate interactions among silk nanofibers by changing the solvent, achieving tough mechanical features for silk films. Formic acid was used to replace water related to charge repulsion of silk nanofibers in solution, inducing interactions among the nanofibers. The films formed under these conditions had an elastic modulus of 3.4 ± 0.3 GPa, an ultimate tensile strength of 76.9 ± 1.6 MPa, and an elongation at break of 3.5 ± 0.1%, while the materials formed from aqueous solutions remained fragile. The mechanical performance of the formic acid-derived nanofiber films was further improved through post-stretching or via the addition of graphene. In addition, the silk nanofiber films could be functionalized with various bioactive ingredients such as curcumin. These new silk nanofiber films with a unique combination of mechanical properties and functions provide new biomaterials achieved using traditional solvents and processes through insight and control of their assembly mechanisms in solution.

2.
Cell Death Dis ; 12(4): 352, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824285

RESUMO

Transcription factor AP-2α (TFAP2A) was previously regarded as a critical regulator during embryonic development, and its mediation in carcinogenesis has received intensive attention recently. However, its role in lung adenocarcinoma (LUAD) has not been fully elucidated. Here, we tried to investigate TFAP2A expression profiling, clinical significance, biological function and molecular underpinnings in LUAD. We proved LUAD possessed universal TFAP2A high expression, indicating a pervasively poorer prognosis in multiple independent datasets. Then we found TFAP2A was not indispensable for LUAD proliferation, and exogenous overexpression even caused repression. However, we found TFAP2A could potently promote LUAD metastasis possibly by triggering epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated TFAP2A could transactivate Pregnancy-specific glycoprotein 9 (PSG9) to enhance transforming growth factor ß (TGF-ß)-triggering EMT in LUAD. Meanwhile, we discovered suppressed post-transcriptional silencing of miR-16 family upon TFAP2A partly contributed to TFAP2A upregulation in LUAD. In clinical specimens, we also validated cancer-regulating effect of miR-16 family/TFAP2A/PSG9 axis, especially for lymph node metastasis of LUAD. In conclusion, we demonstrated that TFAP2A could pivotally facilitate LUAD progression, possibly through a novel pro-metastasis signaling pathway (miR-16 family/TFAP2A/PSG9/ TGF-ß).

3.
BMC Gastroenterol ; 21(1): 142, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789567

RESUMO

BACKGROUND: The preoperative prediction of post hepatectomy liver failure (PHLF) is essential, but there is no gold standard for the prediction at present, and the efficacy of different methods for the prediction has not been compared systematically. In this study, we aimed to compare the efficacy of preoperative two-dimensional shear wave elastography (2D-SWE), indocyanine green (ICG) clearance test and biomarkers for PHLF prediction in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively studied 215 patients with HCC, who had undergone major liver resection in our hospital. Preoperative data of each patient, including liver stiffness value (LSV) of underlying hepatic parenchyma measured by 2D-SWE, ICG retention rate at 15 min (ICG-R15) measured by ICG clearance test, albumin-bilirubin (ALBI) scores, aspartate aminotransferase-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) were collected for analysis. Post hepatectomy outcomes of study patients were also recorded for assessment of PHLF. The study patients were divided into development cohort (133 patients without PHLF, and 17 patients with PHLF) and validation cohort (59 patients without PHLF, and 6 patients with PHLF) randomly. RESULTS: In the development cohort, LSV, ICG-R15 and ALBI scores were significantly different between patients with and without PHLF, while no significant difference of APRI and FIB-4 scores was found. LSV had higher AUC (the area under the receiver operating characteristic curve) (AUC = 0.795) for PHLF prediction than ICG-R15 (AUC = 0.619) and ALBI scores (AUC = 0.686) (p < 0.05 for all comparisons). In the validation cohort, the cutoff value of LSV obtained from the development cohort, 10.35 kPa,  revealed higher specificity (76.3%) for PHLF prediction than ICG-R15 (specificity: 66.1%) and ALBI scores (specificity: 69.5%) (p < 0.0001). CONCLUSIONS: Compared with ICG-R15, ALBI scores, APRI and FIB-4, LSV measured by 2D-SWE may demonstrate better efficacy for preoperative PHLF prediction in patients with HCC.

4.
J Orthop Translat ; 27: 132-138, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33786320

RESUMO

Background: Osteonecrosis of the femoral head (ONFH) is a refractory disease due to its unclear pathomechanism. Neither conservative treatment nor surgical treatment during the early stage of ONFH achieves satisfactory results. Therefore, this study aims to explore the available evidence on the effect of zoledronic acid on early-stage ONFH. Methods: For groups were established:the Normal group, model group, Normal saline group(NS group) and zoledronic acid-treated group. The blood supply to the femoral head of animals in the model group and zoledronic acid-treated group was interrupted via a surgical procedure, and zoledronic acid was then locally administered to the femoral head. Four weeks after surgery, all the hips were harvested and evaluated by micro-CT and histopathology(H&E staining, TRAP staining, Toluidine blue staining and masson staining). Results: The values of BMD, BS/BV and Tb.Th in the Normal group and zoledronic acid-treated group were significantly higher than those in the model group and NS group (p â€‹< â€‹0.05). The outcome of H&E staining, Toluidine blue staining and masson staining were consistent with that of micro-CT. Conclusion: The local administration of zoledronic acid in the femoral head had positive effects on the bone structure of the femoral head in a modified rat model of traumatic ONFH and offered a promising therapeutic strategy during the early stage of ONFH. The Translational potential of this article: This article could provide a choice for treating patients who have osteonecrosis of femora head and can be the basic research for advanced development over this disease.

5.
Medicine (Baltimore) ; 100(13): e25178, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787597

RESUMO

RATIONAL: Fungal liver infection mostly occurs in immunocompromised patients, and is often associated with delayed diagnosis and high mortality rates. Dynamic contrast enhanced imaging is crucial for the diagnosis of fungal liver infection and has been reported having variable manifestations. PATIENT CONCERNS: A 38-year-old Chinese man, with a history of diabetes and chronic hepatitis B, was admitted to our hospital due to prolonged fever of unknown cause. He had a medical history of receiving broad-spectrum antibiotic treatment for pulmonary inflammation at the local hospital. The blood test results showed that the white cell count (14.0 × 109/L) and neutrophil count ratio (77.0%) were subtly elevated. C-reactive protein (92.0 mg/l) and cancer antigen (CA)-125 (904.50 U/ml) were elevated. Non-small cell lung cancer antigen was within the normal limit. Hepatitis B virus DNA load was 3.28 × 103 IU/ml. Sputum and blood cultures were normal. Abdominal ultrasonography (US) found a large heterogeneous mass, with diffused echogenic foci without infiltrating the surrounding vascular, which exhibiting "rapid wash in and out" on contrast-enhanced ultrasound (CEUS). DIAGNOSIS: The diagnosis of liver fungal infection was confirmed pathologically via ultrasound-guided biopsy. INTERVENTIONS: Antibiotic and antifungal therapy with imipenem and voriconazole. OUTCOMES: The patient's body temperature had been controlled and the huge mass disappeared on follow-up ultrasound 1-year later. LESSONS: This case highlights the unusual imaging features of fungal liver infection, presenting as huge heterogeneous mass with diffusive echogenic foci without infiltrating the surrounding vascular on grayscale US and the enhancement pattern of "rapid wash in and out" on CEUS. Additionally, ultrasound-guided biopsy is necessary for the correct diagnosis of suspected liver lesions.

6.
Chemosphere ; 275: 130057, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33667766

RESUMO

Selenium (Se) species can deposit in selective catalytic reduction (SCR) system during the denitrification process, which is harmful to the catalyst. To improve the Se-poisoning resistance of SCR catalysts, the influence mechanism of Se species on vanadium-titanium-based catalysts should be elucidated from an atomic scale. In this paper, theoretical calculations were conducted to reveal the adsorption and interaction mechanism of Se species on V2O5-WO3(MoO3)/TiO2 surface based on the first-principles. The impact of Se species on the electronic structure of the catalyst was investigated from electron transfer, bond formation, and VO site activity. The results show that the adsorption of elementary Se (Se0) belongs to chemisorption, while SeO2 can undergo both physisorption and chemisorption. For the chemisorption of Se species, obvious charge transfer with the catalyst is observed and Se-O bond is formed, which enhances the oxidation activity of the catalyst, triggers the reaction of Se0 and SeO2 with the catalyst components to generate SeVOx and SeW(Mo)Ox. The active sites are thereby damaged and the SCR performance is reduced. The above conclusions are mutually confirmed with the previous experimental research. By studying the correlation with the adsorption energies of Se species, descriptors manifesting the Se species adsorption were initially investigated to unveil the relationship between the electronic structure and the adsorption energy. Finally, the influence of temperature on Se adsorption was investigated. The adsorption can only proceed spontaneously below 500 K and is inhibited at high temperatures.

7.
FASEB J ; 35(5): e21420, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33774855

RESUMO

Although an aberrant reduction in pancreatic ß-cell mass contributes to the pathogenesis of diabetes, the mechanism underlying the regulation of ß-cell mass is poorly understood. Here, we show that diacylglycerol kinase δ (DGKδ) is a key enzyme in the regulation of ß-cell mass. DGKδ expression was detected in the nucleus of ß-cells. We developed ß-cell-specific DGKδ knockout (ßDGKδ KO) mice, which showed lower blood glucose, higher plasma insulin levels, and better glucose tolerance compared to control mice. Moreover, an increased number of small islets and Ki-67-positive islet cells, as well as elevated cyclin B1 expression in the islets, were detected in the pancreas of ßDGKδ KO mice. DGKδ knockdown in the ß-cell line MIN6 induced significant increases in bromodeoxyuridine (BrdU) incorporation and cyclin B1 expression. Finally, we confirmed that streptozotocin-induced hyperglycemia and ß-cell loss were alleviated in ßDGKδ KO mice. Thus, suppressing the expression or enzymatic activity of DGKδ that functions as a suppressor of ß-cell proliferation could be a novel therapeutic approach to increase ß-cell mass for the treatment of diabetes.

8.
ACS Biomater Sci Eng ; 7(3): 1147-1158, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33522800

RESUMO

Dysangiogenesis and chronic inflammation are two critical reasons for diabetic foot ulcers. Desferrioxamine (DFO) was used clinically in the treatment of diabetic foot ulcers by repeated injections because of its capacity to induce vascularization. Biocompatible carriers that release DFO slowly and facilitate healing simultaneously are preferable options to accelerate the healing of diabetic wounds. Here, DFO-laden silk nanofiber hydrogels that provided a sustained release of DFO for more than 40 days were used to treat diabetic wounds. The DFO-laden hydrogels stimulated the healing of diabetic wounds. In vitro cell studies revealed that the DFO-laden hydrogels modulated the migration and gene expression of endothelial cells, and they also tuned the inflammation behavior of macrophages. These results were confirmed in an in vivo diabetic wound model. The DFO-laden hydrogels alleviated dysangiogenesis and chronic inflammation in the diabetic wounds, resulting in a more rapid wound healing and increased collagen deposition. Both in vitro and in vivo studies suggested potential clinical applications of these DFO-laden hydrogels in the treatment of diabetic ulcers.

9.
Medicine (Baltimore) ; 100(3): e24243, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546044

RESUMO

RATIONALE: Hepatic splenosis or heterotopic auto-transplantation of spleen in the liver usually occurs after either spleen trauma or surgery. It is of great importance for the differential diagnosis of hepatic splenosis and other liver tumors because surgery is usually not needed if a diagnosis of splenosis is confirmed. PATIENT CONCERNS: Multiple hepatic masses were revealed by grayscale ultrasound in a 55-year-old man complaining of persistent colic in the upper abdomen after greasy food. DIAGNOSIS: Benign neoplasm with enlarged lymph node in the gastro-hepatic ligament was suspected by contrast enhanced US. The nature of the hepatic mass was undetermined by CECT. INTERVENTIONS: The lesions were surgically removed. OUTCOMES: Multiple splenic tissue implants in the liver and peritoneum were confirmed by pathology after surgery. The patient recovered well and was followed up for more than 1 year without recurrence. LESSONS: Splenosis should be included in the differential diagnosis of focal liver lesion in patients with a history of spleen trauma or surgery. In spite of nonspecific findings on pre-contrast ultrasound, splenosis shows characteristic homogeneous hyperenhancement in arterial and portal phases, as well as prolonged hyperenhancement in the late phase for more than 5 minutes. Furthermore, the confidence of the diagnosis of splenosis may be enhanced by identifying multiple masses with similar enhancing patterns in other regions of the abdominal cavity.


Assuntos
Coristoma/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Baço , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos , Hexafluoreto de Enxofre , Ultrassonografia
11.
J Nurs Manag ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33605474

RESUMO

AIM: This study explores the influence of team mindfulness on nurses' presenteeism. The mediation effect of perceived empathic concern and perceived insider status and the moderating effect of organisational formalization are assessed. BACKGROUND: Nurses are prone to presenteeism. Few studies have explored the influence of the organisational environment on nurses' presenteeism. Studies that consider organisational, work-related and person-related factors on the decision-making process influencing nurses' presenteeism are scarce. METHODS: Using a cross-sectional survey, data from 396 nurses were gathered from three time points and multiple regression analyses were used to test each hypothesis. RESULTS: (a) Team mindfulness reduces nurses' presenteeism. (b) Both perceived empathic concern and perceived insider status mediate the relationship between team mindfulness and nurses' presenteeism. (c) Organisational formalization exerts a positive moderating effect on the relationship between team mindfulness and perceived empathic concern. CONCLUSIONS: Team mindfulness reduces nurses' presenteeism through affective (perceived empathic concern) and cognitive (perceived insider status) sensemaking paths. Organisational formalization is a situational factor to improve the effectiveness of team mindfulness. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers need to devote themselves to cultivating team mindfulness, building an atmosphere to promote perceived empathic concern and perceived insider status, and promoting a formal organisational structure.

12.
Neurol Sci ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462635

RESUMO

OBJECTIVES: Diagnosis of hyperkinetic movement disorders with an unknown cause is usually challenging. The objective of this study is to learn about video electroencephalogram (VEEG) combined with electromyography (EMG) in the diagnosis of hyperkinetic movement disorders with an unknown cause. METHODS: We performed an observational cohort study by recruiting consecutive patients with hyperkinetic movements as the main manifestation with an unknown cause for VEEG combined with EMG evaluations. RESULTS: A total of 77 consecutive patients were enrolled for VEEG-EMG examination. Among them, 57 patients changed their diagnosis after VEEG-EMG assessment, with a mean final diagnosis age of 35.4 ± 20.3 years (range, 4-74 years). The mean duration between initial and final diagnosis was 54.8 ± 71.3 months (range 0.5-300 months). The most common misdiagnosed hyperkinetic movement disorders were myoclonus (40.4%), followed by tremors (24.6%), dystonia (15.8%), psychogenic movement disorders (10.5%), and periodic leg movement syndrome (PLMS) (7.0%). Outcomes of therapy were significantly improved after VEEG-EMG examination (p = 0.000). CONCLUSIONS: Simultaneous VEEG and EMG are important in the diagnosis of hyperkinetic movement disorders with an unknown cause.

13.
Mol Plant ; 14(4): 571-587, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33515768

RESUMO

The biological functions of the epitranscriptomic modification N6-methyladenosine (m6A) in plants are not fully understood. CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPSF30-S and an m6A-binding YTH domain. Little is known about the biological roles of CPSF30-L and the molecular mechanism underlying its m6A-binding function in alternative polyadenylation. Here, we characterized CPSF30-L as an Arabidopsis m6A reader whose m6A-binding function is required for the floral transition and abscisic acid (ABA) response. We found that the m6A-binding activity of CPSF30-L enhances the formation of liquid-like nuclear bodies, where CPSF30-L mainly recognizes m6A-modified far-upstream elements to control polyadenylation site choice. Deficiency of CPSF30-L lengthens the 3' untranslated region of three phenotypes-related transcripts, thereby accelerating their mRNA degradation and leading to late flowering and ABA hypersensitivity. Collectively, this study uncovers a new molecular mechanism for m6A-driven phase separation and polyadenylation in plants.

14.
Gynecol Endocrinol ; 37(4): 328-331, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33487087

RESUMO

AIMS: To investigate the correlation between hypertriglyceridemic waist circumference (HTWC) phenotype and gestational diabetes mellitus (GDM). METHODS: A total of 1083 patients with gestational age ≤8 weeks were divided into four groups: normal triglyceride and waist circumference group (group A, n = 575), simple abdominal obesity group (group B, n = 317), simple high triglyceride group (group C, n = 125), and HTWC group (group D, n = 66). General information and serum biochemical indicators were measured and recorded. Analysis of variance (ANOVA) and logistic regression analysis were used to evaluate the relationship between HTWC with GDM. RESULTS: The prevalence of GDM in the HTWC group was significantly greater than in the other three groups. After adjustment by multivariate logistic regression analysis, the proportion of GDM in the HTWC group was 1.753 times higher than in group A. CONCLUSION: These findings suggest that there is a significant correlation between HTWC phenotype and GDM, indicating that the HTWC phenotype could be applied as a simple marker for identifying GDM risk factors.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33513034

RESUMO

Objectives: The presence of varices affects the survival of patients with primary biliary cholangitis (PBC). The aim of this study is to assess the criteria based on liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) and platelet count (PLT), and recently published noninvasive models for triaging PBC patients. Methods: 231 patients with PBC who underwent EGD and 2D-SWE examination were enrolled. Areas under the receiver-operating characteristic curve (AUROC) were used to assess the performance of 2D-SWE for predicting all-size varices and high-risk varices. All-size varices and high-risk varices miss rate < 10% and <5%, respectively, were acceptable for screening varices. Results: The AUROCs of LS for predicting all-size varices and high-risk varices were 0.87 (95%CI: 0.82-0.91) and 0.84 (95%CI: 0.74-0.86), respectively. LS <25 kPa and PLT >110 × 109/L spared 46.3% EGD screening, with 3.7% high-risk varices miss rate and 8.4% all-size varices miss rate. One hundred and sixteen (50.2%) patients met the Newcastle varices in PBC score (cutoff, 0.5), with 4.3% high-risk varices miss rate and 11.2% all-size varices miss rate. Conclusion: The criteria based on LS and PLT are useful for triaging PBC patients. LS <25 kPa and PLT >110 × 109/L could be the optimal criteria for screening varices.

16.
Eur Radiol ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492470

RESUMO

OBJECTIVES: To evaluate the relationship between contrast-enhanced (CE) ultrasound Liver Reporting and Data System (LI-RADS) classification of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and their histopathological component predominance, and to determine if the CEUS LI-RADS category can be used to predict the patient's survival after surgical resection. METHODS: Between January 2011 and December 2018, medical records and CEUS of patients with pathologically proven cHCC-CCA were studied. The predominance of hepatocellular carcinoma (HCC)/intrahepatic cholangiocarcinoma (ICC) component of cHCC-CCA was analyzed by histopathology. The proportion of HCC-predominant cHCC-CCA in different LI-RADS category was compared by using Fisher's exact test. Factors affecting tumor recurrence were analyzed by Cox proportional hazard model. Disease-free survival (DFS) was estimated by using Kaplan-Meier survival curve and compared by log-rank test. RESULTS: The study included 37 cHCC-CCA patients (33 men, 4 women; average age, 50.4 ± 11.0 years) and 37 nodules (mean diameter, 6.1 ± 3.9 cm). According to CEUS LI-RADS, 62.2% (23/37), 18.9% (7/37), and 18.9% (7/37) of cHCC-CCA were classified as LR-M, LR-5, and LR-TIV, respectively. The ratio of HCC predominance in LR-5 was 100% (10/10) vs 81.5% (22/27) in the LR-M group (p = 0.591). In our population, LR-5 patients had longer DFS than LR-M and LR-TIV patients combined (median DFS: 18.0 vs 6.4 months, p = 0.016). Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS. CONCLUSION: cHCC-CCA characterized as LR-5 on CEUS tend to represent HCC-predominant tumors with significantly longer disease-free survival compared to cHCC-CCA categorized as LR-M and LR-TIV. KEY POINTS: • By using the American College of Radiology contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), majority (30/37, 81.1%) of cHCC-CCA tumors were classified as LR-M or LR-TIV and only 18.9% (7/30) of cHCC-CCA were categorized as LR-5. • Patients with CEUS LR-5 cHCC-CCA had statistically significant longer disease-free time than those with LR-M and TIV cHCC-CCA (median DFS: 18.0 vs 6.4 months, p = 0.016). • Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS.

17.
J Clin Pharmacol ; 61(5): 714-724, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33314148

RESUMO

We evaluated interleukin-6 (IL-6) receptor-α subunit (IL-6Rα) signaling inhibition with sarilumab and tocilizumab, the association between IL-6Rα receptor occupancy (RO) and C-reactive protein (CRP), and the potential clinical relevance of any differences. For this, we measured IL-6Rα binding and signaling inhibition with sarilumab and tocilizumab in vitro, simulated soluble IL-6Rα RO over time for approved sarilumab subcutaneous (SC) and tocilizumab intravenous (IV) and SC doses, and assessed associations between calculated RO and CRP reduction, 28-joint Disease Activity Score based on CRP, and 20%/50%/70% improvement in American College of Rheumatology responses from clinical data. Sarilumab binds IL-6Rα in vitro with 15- to 22-fold higher affinity than tocilizumab, and inhibits IL-6-mediated classical and trans signaling via membrane-bound and soluble IL-6Rα. Sarilumab 200 and 150 mg SC every 2 weeks achieved >90% RO after first and second doses, respectively, maintained throughout the treatment period. At steady-state trough, RO was greater with sarilumab 200 mg (98%) and 150 mg SC every 2 weeks (94%), and tocilizumab 162 mg SC weekly (>99%) and 8 mg/kg IV every 4 weeks (99%), vs tocilizumab 162 mg SC every 2 weeks (84%) and 4 mg/kg IV every 4 weeks (60%). Higher RO was associated with greater CRP reduction and 28-joint Disease Activity Score based on CRP reduction, and more sarilumab patients achieving 20%/50%/70% improvement in American College of Rheumatology responses. The greatest reduction in CRP levels was observed with sarilumab (both doses) and tocilizumab 8 mg/kg IV every 4 weeks (reductions proportionally smaller with 4 mg/kg IV every 4 weeks). Higher IL-6Rα binding affinity translated into higher RO with sarilumab vs tocilizumab 4 mg/kg every 4 weeks or 162 mg every 2 weeks; tocilizumab required the higher dose or increased frequency to maintain the same degree of RO and CRP reduction. Higher RO was associated with clinical parameter improvements.

18.
Waste Manag ; 120: 59-67, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285374

RESUMO

Heavy metal pollutants generated from municipal solid waste (MSW) incineration are mainly concentrated in the fly ash, among which lead species have received considerable attention due to their high content and biotoxicity. CaO is an active component in fly ash to adsorb heavy metal species. In this study, based on density functional theory (DFT) calculations, the migration and transformation mechanisms of lead species over the CaO (100) surface were investigated by calculating the adsorption configurations, energies, and electronic structures, etc. The results indicate that the adsorption of lead species over the CaO (100) surface is dominated by chemisorption, and PbCl2 molecule exhibits a stronger affinity to the CaO surface than Pb0. The dissociation of HCl molecule on the CaO (100) surface facilitates the adsorption and chemical reactivity of lead species. The chlorination of Pb0 to PbCl2 is a two-stage route. In the first stage, two HCl molecules are exothermically adsorbed on the surface without an energy barrier, and Pb0 is directly bonded to the active Cl atom, which is controlled by the Eley-Rideal mechanism. In the second stage, PbCl intermediate bonds with another Cl atom over the surface to form the PbCl2 molecule, following the Langmuir-Hinshelwood mechanism, which is also the rate-determining step. Compared with the homogeneous chlorination, CaO catalyzes the heterogeneous process to greatly reduce the oxidation energy barrier and promotes the formation of PbCl2. Consequently, CaO is able to accelerate the lead enrichment in fly ash, which is favorable for lead species purification.

19.
Am J Cancer Res ; 10(11): 4005-4015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294282

RESUMO

A growing number of progression on Osimertinib among EGFR-mutated lung cancers represents a great challenge clinically. Our study aims to gain insights into novel mechanisms of acquired resistance to Osimertinib. We performed genomic studies on 2 large independent cohorts of lung cancer patients with progressed diseases on different tyrosine kinase inhibitors (TKIs). In silico modeling was used to study the structural mechanism of selected EGFR mutations. Compared with the 1st-TKIs-resistant group, EGFR mutations C797S/G, L718Q/V, L792F/H were significantly more enriched in the Osimertinib-resistant cohort, whose sensitivities to Osimertinib were successfully predicted. Importantly, a total of 14 low-frequency EGFR mutations were exclusively or significantly observed in the Osimertinib-resistant group, 7 were predicted to dramatically reduce the binding affinity of EGFR to Osimertinib (G796S, V802F, T725M, Q791L/H, P794S/R). Analysis of pre-Osimertinib treatment samples of two patients supported that EGFR V802F and G796S were acquired during the treatment. In addition, EGFR G796S was predicted to be susceptible to gefitinib. This study represented the largest real-world data so far investigating Osimertinib resistance in EGFR-mutated lung cancer. We identified a collection of coexistent EGFR rare mutations and provided possible guidance for those patients who progressed on the first-line treatment of Osimertinib.

20.
Ultraschall Med ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33307595

RESUMO

OBJECTIVES: The American College of Radiology (ACR) contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS), which includes diagnostic criteria for hepatocellular carcinoma (HCC) and other hepatic malignancies (OM), is increasingly used in clinical practice. This study performed a meta-analysis to assess the diagnostic accuracy of CEUS LI-RADS for differentiating between HCC and OM in high-risk patients. METHODS: PubMed, Embase (Ovid), and Cochrane (CENTRAL) were searched for relevant studies. All studies that reported the percentage of HCC and OM in the LI-RADS categories were included. Random-effects models were used to calculate the pooled sensitivity and specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve. RESULTS: Eight studies involving 4215 focal liver lesions were included in the final analysis. The pooled sensitivity and specificity of the LR-5 criteria for HCC were 0.71 (95 % CI, 0.69-0.72) and 0.88 (0.85-0.91), respectively, the DOR was 18.36 (7.41-45.52), and the area under the SROC curve (AUC) was 0.8128. The pooled sensitivity and specificity of the LR-M criteria for OMs were 0.85 (0.81-0.88) and 0.86 (0.85-0.87), the DOR was 27.82 (11.83-65.40), respectively, and the SROC AUC was 0.9098. CONCLUSION: The CEUS LI-RADS can effectively distinguish HCC from other hepatic malignancy in high-risk patients based on LR-5 criteria and LR-M criteria. However, further studies are needed for validation due to the limited number of included studies and the potential heterogeneity among the included studies.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...