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1.
J Nanosci Nanotechnol ; 20(3): 1740-1748, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492338

RESUMO

Pure CuC2O4·xH2O and CuC2O4·xH2O/carbon nanotubes (CNTs) composites are synthesized by a low-temperature hydrothermal process. The structure and morphology of the products are analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TG) and Raman spectrum. The results demonstrate that the as-prepared CuC2O4·xH2O takes on a microsphere-like morphology, all CuC2O4·xH2O/CNTs nanocomposites are constructed by the intertwining of tabular CuC2O4·xH2O nanoparticles (NPs) and CNTs to form a tanglesome net. When evaluated as an anode materials for lithium ion batteries (LIBs), all CuC2O4·xH2O/CNTs electrodes possess higher reversible discharge capacities (more than 1000 mAh g-1) than the pure CuC2O4·xH2O, up to 200th cycle at a current density of 100 mA g-1. The results illustrate that the addition of CNTs can enhance the electrochemical performance of CuC2O4·xH2O. Overall, CuC2O4·xH2O/CNTs composite can be a promising candidate used as a promising anode for LIBs.

2.
Colloids Surf B Biointerfaces ; : 110604, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31727506

RESUMO

Protein adsorption plays a key role in bone repair and regeneration by affecting cell behavior. In this study, TiO2 nanofibers (TiO2 NFs) with different structures, including anatase TiO2 nanofibers (A-NFs), anatase TiO2 nanofibers with beads (B-NFs), anatase-rutile TiO2 nanofibers (AR-NFs) and rutile TiO2 nanofibers (R-NFs), were prepared by electrospinning method. Bovine serum albumin (BSA) and lysozyme (LYZ) were used to explore the adsorption behaviors of TiO2 NFs and then the effects of materials with protein on bone marrow mesenchymal stem cells (MSCs) were studied. Pure titanium metal (PT) was used as control. The results displayed that the adsorption amounts of BSA on samples were B-NFs > AR-NFs > A-NFs ≈ R-NFs > PT, and that for LYZ were B-NFs > AR-NFs > R-NFs > A-NFs > PT. The conformation of proteins changed remarkably when they were adsorbed on meterials. Soaking the TiO2 NFs with and without protein into SBF revealed that the BSA and LYZ on B-NFs, A-NFs and AR-NFs could accelerate the HA deposition on its surface, but it had no promoting effect on HA deposition on B-NFs. MTT and PCR tests showed that the BSA and LYZ adsorbed on materials could promote the proliferation and osteogenic differentiation of MSCs to different degrees due to their different adsorption amount and conformation changes on different TiO2 NFs. The current work demonstrated that the surface properties and crystal structure of TiO2 NFs could influence the adsorption behavior and conformational change of BSA and LYZ, and then further regulate MSCs biological behavior.

3.
Exp Cell Res ; 385(2): 111691, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678170

RESUMO

Rafoxanide is commonly used as anti-helminthic medicine in veterinary medicine, a main compound of salicylanilide. Previous studies have reported that rafoxanide, as an inhibitor of BRAF V600E mutant protein, inhibits the growth of colorectal cancer, multiple myeloma, and skin cancer. However, its therapeutic effect on gastric cancer (GC) and the potential mechanism has not been investigated. Here, we have found that rafoxanide inhibited the proliferation of GC cells in vitro, arrested the cell cycle in the G0/G1 phase, and promoted apoptosis and autophagy in GC cells. Treatment with specific autophagy inhibitor 3-methyladenine drastically inhibited the apoptotic cell death effect by suppressing the switch from autophagy to apoptosis. Mechanistically, we found that rafoxanide inhibited the growth of GC cells in vitro by inhibiting the activity of the PI3K/Akt/mTOR signaling pathway. This process induced autophagy, which essentially resulted in the apoptosis of GC cells. Results from subcutaneous implanted tumor models in nude mice also indicated that rafoxanide inhibited the growth of GC cells in vivo. Taken together, our findings revealed that rafoxanide inhibited the growth of GC cells both in vitro and vivo, indicating a potential drug candidate for the treatment of GC.

4.
HPB (Oxford) ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732465

RESUMO

BACKGROUND: The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC). METHODS: The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052). CONCLUSION: Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.

5.
BMC Pulm Med ; 19(1): 211, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711450

RESUMO

BACKGROUND: Anti-tuberculosis therapy requires at least six-month treatment with continuous administration of combined antibiotics, including isoniazid, rifampicin, pyrazinamide, and ethambutol. The long-term exposure to antibiotics could cause consequent changes in gut microbiota, which may alter the gastrointestinal function and drug absorption in patients, thereby affect the outcome of treatment. The study aims to characterize the longitudinal changes of gut microbiota among tuberculosis (TB) patients under standardized first-line treatment and provide an understanding of the association between alterations in gut microbiota composition and unfavorable clinical outcomes. METHODS: The study is a multicenter, observational prospective cohort study. Three study sites are purposively selected in the western (Sichuan Province) and eastern (Jiangsu Province and Shanghai) parts of China. Three-hundred patients with bacteriologically confirmed pulmonary TB are enrolled. All eligible patients should be investigated using structured questionnaires before treatment initiation; and be followed up during the treatment at Day-14, Month-2, Month-5, the end of treatment and the sixth month after ending therapy. Stool samples are to be collected at each visit, consisting of six stool samples from each patient. Additionally, 60 healthy volunteers from Sichuan province and Shanghai city will be recruited as healthy controls to form the baseline of patient gut microbiota in the Chinese population. The dynamic changes of gut microbiota in terms of alpha diversity, beta diversity, taxonomic composition are to be illustrated individually from the time at diagnosis until the sixth month after therapy is completed. Furthermore, the diversity and component of gut microbiota will be compared between the groups with and without unfavorable treatment outcome in terms of adverse effect and treatment failure. DISCUSSION: Studies on the clinical manifestations, adverse reactions, and gut microbiota alterations will provide scientifically-sound evidence on the impact of gut microbiota alterations on TB treatment outcomes. The study is not only useful for guiding personalized TB treatment but also sheds light on the effects of continuous antibiotics administration on gut microbiota. TRIAL REGISTRATION: Chinese Clinical Trial Registry, trial ID: ChiCTR1900023369, May 24, 2019. Retrospectively registered.

6.
Chemosphere ; 242: 125228, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31677507

RESUMO

The uptake and accumulation of three imidazolium ionic liquids with different alkyl chain lengths ([C2min]Br, [C4min]Br, [C8min]Br) in rice seedlings were investigated. All three different ILs were primarily accumulated in roots, while only a little amount of ILs were translocated and accumulated in stems and leaves. Accumulation and transportation of ILs in rice depend on the concentration and the alkyl chain length of ILs. ILs contents in the roots, stems and leaves decreased as ILs alkyl chain length increased. Growth inhibition results showed that the toxic effects of ILs on rice growth depends on the alkyl chain length: [C8min]Br >[C4min]Br >[C2min]Br. As markers of defense and phytotoxicity, the plant antioxidant enzymes and biochemical stress responses were also assessed. All different ILs significantly increased malondialdehyde (MDA), catalase (CAT), peroxidase (POD) and dismutase (SOD) activities in rice tissue. Compared to the control group, the contents of chlorophyll a reduced by 59.56%, 62.28% and 69.74% after addition of [C2min]Br, [C4min]Br, and [C8min]Br, respectively. This study provides important information for a better understanding on the uptake and accumulation of imidazolium ILs by agricultural plants.

7.
Gerontologist ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688909

RESUMO

BACKGROUND AND OBJECTIVES: Older African Americans are at high risk for becoming frail in later life. Interventions can reverse or delay frailty, yet African Americans have largely been excluded from such research. Many interventions are also time- and resource-intensive, and thus inaccessible to socially disadvantaged older African Americans. We evaluated the feasibility of a low-dose frailty prevention intervention integrated with primary care among 60 community-dwelling, prefrail older African Americans aged 55+ recruited from a primary care clinic. RESEARCH DESIGN AND METHODS: We conducted a 2-arm randomized control trial. Participants were assigned to a 4-session intervention (1 session per month), delivered by an occupational therapist, or enhanced usual care. Feasibility criteria were set a priori at 75% for participant retention (including attrition due to death/hospitalization), 80% for session engagement, 2 participants/week for mean participant accrual, and 90% for program satisfaction. RESULTS: Participants were 65% female with an average age of 76.6 years, 51.7% lived alone and 39.1% reported <$10,000 in yearly income. Feasibility metrics were met. The study recruited, a mean of, 2.5 participants per week and retained 75% of participants who attended 95% of scheduled sessions. The mean satisfaction score was 29.75 (range = 0-32; SD .25). Changes in physical activity and dietary habit formation as well as changes in secondary outcomes were largely in the expected direction. DISCUSSION AND IMPLICATIONS: The intervention was feasible to deliver. Qualitative findings from exit interviews suggested changes to the program dose, structure, and content that could improve it for future use.

8.
Chem Commun (Camb) ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746851

RESUMO

Mitochondrial targeting of drugs largely relies on delocalized lipophilic cations. Nevertheless, mitochondrial membrane potentials in cancer cells are inconstant, which could compromise stable mitochondrial targeting. Herein, we further validated a mitochondrial temperature-dependent drug delivery strategy in vivo. Thermoresponsive drug delivery to mitochondria may represent a promising strategy for cancer therapy.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31774640

RESUMO

Li-metal anode attracts great focus owing to its ultrahigh specific capacity and the lowest redox potential. However, uncontrolled growth of Li dendrite leads to severe safety hazards with limited cycle life. Herein, Al2O3 loading mesoporous carbon (Al2O3@MOF-C) derived from Al-based metal-organic frameworks (Al-MOFs) was investigated as the stable host matrix for Li metal, in which, Al2O3 was served as nano-seeds for the Li deposition and decrease the Li nucleation overpotential. Except that, the high specific surface area and wide pore distribution can also buffer the volume changes of Li and fasten electron transfer, hence a dendrite-free morphology was observed even after 50 cycles at 2 mA cm-2. High Li coulombic efficiency of 97.9% after 100 cycles at 1 mA cm-2, 1 mAh cm-2 and 97.6% after 50 cycles with increased capacity to 6 mAh cm-2 were observed for Al2O3@MOF-C electrodes. Good performances were also obtained for full cells: Li-S, and LiFePO4 batteries. The performances of Al2O3@MOF-C were compared with Li foil and Cu@Li in full cell configurations. The electrochemical tests of full cells based on Al2O3@MOF-C indicated that this Al-based functional host matrix can enhance the Li-utilization and lead to significant improvement of the cycling performance of Li anodes.

10.
Biomed Pharmacother ; 121: 109280, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715373

RESUMO

Coronary microvascular dysfunction (CMD) is the pathological basis and pathogenesis of diabetic cardiomyopathy (DCM). Propylene glycol alginate sodium sulfate (PSS) as heparinoid drug has many biological activities. Here, a novel PSS-loaded nanoparticle (PSS-NP) was prepared to study its effect on the CMD of DCM. We used diabetes mellitus rat induced by STZ to establish the CMD model of DCM, and the study was detected by echocardiography, histological analysis, transmission electron microscopy, immunofluorescence staining, enzyme-linked immunosorbent assay, real time-PCR analysis, liquid-chip analysis, western blot analysis and so on. The experimental results suggested that PSS-NP could improve the survival state of rats, cardiac function, myocardial morphology and coronary microcirculation structure disorders, and increase the number of microvessels. In addition, we demonstrated that PSS-NP could alleviate the CMD by improving endothelial function, anticoagulation and antioxidative stress. The outcomes of this study provided new treatment thoughts for the therapy of coronary microcirculation dysfunction in DCM.

11.
Mol Biol Evol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750915

RESUMO

Each influenza pandemic was caused at least partly by avian- and/or swine-origin influenza A viruses (IAVs). The timing of and the potential IAVs involved in the next pandemic are currently unpredictable. We aim to build machine learning (ML) models to predict human-adaptative IAV nucleotide composition. 217,549 IAV full-length coding sequences of the PB2 (Polymerase basic protein-2), PB1, PA (Polymerase acidic protein), HA (Hemagglutinin), NP (Nucleoprotein), NA (Neuraminidase) segments were decomposed for their codon position-based mononucleotides (12 nts) and dinucleotides (48 dnts). 68,742 human sequences and 68,739 avian sequences (1:1) were resampled to characterize the human adaptation-associated (d)nts with principal component analysis (PCA) and other ML models. Then, the human adaptation of IAV sequences was predicted based on the characterized (d)nts. Respectively, 9, 12, 11, 13 and 10 human-adaptive (d)nts were optimized for the six segments. PCA and hierarchical clustering analysis revealed the linear separability of the optimized (d)nts between the human-adaptive and avian-adaptive sets. The results of the confusion matrix and the area under the receiver operating characteristic (ROC) curve (AUC) indicated a high performance of the ML models to predict human adaptation of IAVs. Our model performed well in predicting the human adaptation of the swine/avian IAVs before and after the 2009 H1N1 pandemic. In conclusion, we identified the human adaptation-associated genomic composition of IAV segments. ML models for IAV human adaptation prediction using large IAV genomic datasets can facilitate the identification of key viral factors that affect virus transmission/pathogenicity. Most importantly, it allows the prediction of pandemic influenza.

13.
OTJR (Thorofare N J) ; : 1539449219876877, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642394

RESUMO

Intervening to change clients' habits in the course of their everyday occupations could improve health. Habit formation interventions are an emerging area of science, however, and there is a need to better understand the current state of habit intervention research. The objective of this study is to examine the evidence related to habit formation interventions to modify health habits among adults. We performed a scoping review of peer-review articles published since January 1, 2008. The majority of the 18 studies included in the review were randomized control trials using one of two measures to assess habit change. Studies targeted a range of habits. Trial results were mixed but supportive of habit formation approaches. Through habit formation interventions, a range of everyday behaviors can become a habit. Occupational therapy professionals can use data and results generated from this review to inform the development of occupation-based habit formation treatments.

14.
Environ Int ; 133(Pt B): 105249, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31665676

RESUMO

Nanoscale zero-valent iron (NZVI) has been engineered as an attractive tool for in-situ groundwater remediation. However, the poor mobility and aqueous corrosion of NZVI in the porous subsurface have hindered its practical applications. In this research, the NZVI surface was coated with a novel Mg(OH)2 shell (NZVI@Mg(OH)2) to improve the feasibility of NZVI for remediation. In the column tests for continuous removal of Cr(VI) from the flowing water, the Mg(OH)2 shell greatly improved the delivery of NZVI into the sand columns. Coating NZVI with Mg(OH)2 shell also showed considerably greater chemical stability than bare NZVI and thus greater resistance to aqueous corrosion. In addition, the dissolution of Mg(OH)2 allowed the reactivity to be gradually recovered along the sand column for Cr(VI) reduction. As a result, compared to bare NZVI in the columns, NZVI@Mg(OH)2 significantly prolonged the breakthrough period of Cr(VI) and hence increased the columns' Cr(VI) removal capacity. Moreover, the Cr(III) produced was effectively immobilized by NZVI@Mg(OH)2, even under an acidic condition (pH 4.0). The results show that Mg(OH)2 coating is a promising technique to improve the longevity and capacity of NZVI for full-scale in-situ soil and groundwater remediation.

15.
Orthop Surg ; 11(5): 914-920, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663276

RESUMO

Three-dimensional (3D) printing technology, virtual reality, and augmented reality technology have been used to help surgeons to complete complex total hip arthroplasty, while their respective shortcomings limit their further application. With the development of technology, mixed reality (MR) technology has been applied to improve the success rate of complicated hip arthroplasty because of its unique advantages. We presented a case of a 59-year-old man with an intertrochanteric fracture in the left femur, who had received a prior left hip fusion. After admission to our hospital, a left total hip arthroplasty was performed on the patient using a combination of MR technology and 3D printing technology. Before surgery, 3D reconstruction of a certain bony landmark exposed in the surgical area was first performed. Then a veneer part was designed according to the bony landmark and connected to a reference registration landmark outside the body through a connecting rod. After that, the series of parts were made into a holistic reference registration instrument using 3D printing technology, and the patient's data for bone and surrounding tissue, along with digital 3D information of the reference registration instrument, were imported into the head-mounted display (HMD). During the operation, the disinfected reference registration instrument was installed on the selected bony landmark, and then the automatic real-time registration was realized by HMD through recognizing the registration landmark on the reference registration instrument, whereby the patient's virtual bone and other anatomical structures were quickly and accurately superimposed on the real body of the patient. To the best of our knowledge, this is the first report to use MR combined with 3D printing technology in total hip arthroplasty.

16.
ACS Appl Mater Interfaces ; 11(46): 43116-43121, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31663324

RESUMO

The sol-gel (SG) method has been well-documented as one useful way to produce ZnO films as an excellent electron transport material (ETM) for efficient perovskite solar cells (PSCs). Generally, the precursor films containing zinc acetate dihydrate and a stabilizing ligand monoethanolamine (EA) were annealed to obtain ZnO films. A noteworthy issue is the commonly reported annealing temperature (Ta) in a wide range of 150-600 °C. In this work, we investigated the effect of the annealing temperature on the film composition and first confirmed the co-existence of acetate and EA species when Ta is below 380 °C. EA still survived within the ZnO films when Ta was between 380 and 450 °C. When Ta was over 450 °C, pure ZnO films can be obtained. The presence of ligands also remarkably altered the work function of the corresponding ZnO samples, thereby resulting in the remarkably different effects on the efficiency and stability of PSCs with the ZnO samples as ETMs. This work affords a clearer understanding of ZnO films prepared by the SG method at molecular insights, promoting their application in photoelectric fields.

17.
Lancet Respir Med ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31628085

RESUMO

BACKGROUND: Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. We aimed to assess the efficacy and safety of ensartinib in ALK-positive patients with non-small-cell lung cancer (NSCLC), in whom crizotinib therapy was unsuccessful. The associations between ensartinib efficacy and crizotinib-resistant mutations were also explored. METHODS: We did a single-arm, open-label, phase 2 study at 27 centres in China. Patients were aged 18 years or older, had stage IIIb or stage IV ALK-positive NSCLC that had progressed while they were on crizotinib therapy, an Eastern Cooperative Oncology Group performance status of 2 or less, had measurable disease, and had received fewer than three previous treatments. Patients with CNS metastases were included if these metastases were asymptomatic and did not require steroid therapy. All patients received 225 mg ensartinib orally once daily on a continuous dosing schedule. The primary outcome was the proportion of patients with an objective response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), as assessed by an independent review committee in all patients who received at least one dose of ensartinib with no major violations of the inclusion criteria (ie, the full analysis set). Safety was assessed in all enrolled patients who received at least one dose of ensartinib. This trial was registered with ClinicalTrials.gov, NCT03215693. FINDINGS: Between Sept 28, 2017, and April 11, 2018, 160 patients were enrolled and had at least one dose of ensartinib (safety analysis set). Four patients had inclusion violations and were excluded from the efficacy analysis, which thus included 156 patients (full analysis set). 97 (62%) patients in the full analysis set had brain metastases. 76 (52% [95% CI 43-60]) of 147 patients in the full analysis set, with responses that could be assessed by the independent review committee, had an objective response. 28 (70% [53-83]) of 40 patients with measurable brain metastases as assessed by the independent review committee had an intracranial objective response. 145 (91%) of 160 patients had at least one treatment-related adverse event, which were mostly grade 1 or 2. The most common treatment-related adverse events were rash (89 [56%]), increased alanine aminotransferase concentrations (74 [46%]), and increased aspartate aminotransferase concentrations (65 [41%]). INTERPRETATION: Ensartinib has activity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including those with brain metastases. The role of ensartinib in patients in whom other second-generation ALK inhibitors have been unsuccessful warrants further studies. FUNDING: Betta Pharmaceuticals.

18.
J Cell Mol Med ; 23(11): 7796-7809, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31503410

RESUMO

Sepsis-induced cardiac dysfunction represents a main cause of death in intensive care units. Previous studies have indicated that GSK-3ß is involved in the modulation of sepsis. However, the signalling details of GSK-3ß regulation in endotoxin lipopolysaccharide (LPS)-induced septic myocardial dysfunction are still unclear. Here, based on the rat septic myocardial injury model, we found that LPS could induce GSK-3ß phosphorylation at its active site (Y216) and up-regulate FOXO3A level in primary cardiomyocytes. The FOXO3A expression was significantly reduced by GSK-3ß inhibitors and further reversed through ß-catenin knock-down. This pharmacological inhibition of GSK-3ß attenuated the LPS-induced cell injury via mediating ß-catenin signalling, which could be abolished by FOXO3A activation. In vivo, GSK-3ß suppression consistently improved cardiac function and relieved heart injury induced by LPS. In addition, the increase in inflammatory cytokines in LPS-induced model was also blocked by inhibition of GSK-3ß, which curbed both ERK and NF-κB pathways, and suppressed cardiomyocyte apoptosis via activating the AMP-activated protein kinase (AMPK). Our results demonstrate that GSK-3ß inhibition attenuates myocardial injury induced by endotoxin that mediates the activation of FOXO3A, which suggests a potential target for the therapy of septic cardiac dysfunction.

19.
Cancer Immunol Immunother ; 68(9): 1527-1535, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31535160

RESUMO

BACKGROUND: Evidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory. METHODS: Chinese BTC patients receiving a PD-1 inhibitor with chemotherapy, PD-1 inhibitor monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcomes were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T cell costimulation or immune checkpoints were excluded. RESULTS: The study included 77 patients (a PD-1 inhibitor plus chemotherapy, n = 38; PD-1 inhibitor monotherapy, n = 20; chemotherapy alone, n = 19). The median OS was 14.9 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 4.1 months with PD-1 inhibitor monotherapy (HR 0.37, 95% CI 0.17-0.80, P = 0.001) and the 6.0 months with chemotherapy alone (HR 0.63, 95% CI 0.42-0.94, P = 0.011). The median PFS was 5.1 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 2.2 months with PD-1 inhibitor monotherapy (HR 0.59, 95% CI 0.31-1.10, P = 0.014) and the 2.4 months with chemotherapy alone (HR 0.61, 95% CI 0.45-0.83, P = 0.003). Grade 3 or 4 treatment-related adverse events were similar between the anti-PD-1 combination group and the chemotherapy alone group (34.2% and 36.8%, respectively). CONCLUSIONS: Anti-PD-1 therapy plus chemotherapy is an effective and tolerable approach for advanced BTC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/terapia , Imunoterapia/métodos , Idoso , Neoplasias do Sistema Biliar/mortalidade , China , Terapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
J Am Chem Soc ; 141(40): 16014-16023, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31509391

RESUMO

To explore a new supramolecular interaction as the main driving force to induce hierarchical self-assembly (HSA) is of great importance in supramolecular chemistry. Herein, we present a radical-induced HSA process through the construction of well-defined rhomboidal metallacycles containing triphenylamine (TPA) moieties. The light-induced radical generation of the TPA-based metallacycle has been demonstrated, which was found to subsequently drive hierarchical self-assembly of metallacycles in both solution and solid states. The morphologies of nanovesicle structures and nanospheres resulting from hierarchical self-assembly have been well-illustrated by using TEM and high-angle annular dark-field STEM (HAADF-STEM) micrographs. The mechanism of HSA is supposed to be associated with the TPA radical interaction and metallacycle stacking interaction, which has been supported by the coarse-grained molecular dynamics simulations. This study provides important information to understand the fundamental TPA radical interaction, which thus injects new energy into the hierarchical self-assembly of supramolecular coordination complexes (SCCs). More interestingly, the stability of TPA radical cations was significantly increased in these metallacycles during the hierarchical self-assembly process, thereby opening a new way to develop stable organic radical cations in the future.

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