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1.
Medicine (Baltimore) ; 100(35): e26918, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477122

RESUMO

BACKGROUND: Radical pancreaticoduodenectomy is the only possible cure for pancreatic head adenocarcinoma, and although several RCT studies have suggested the extent of lymph node dissection, this issue remains controversial. This article wanted to evaluate the survival benefit of different lymph node dissection extent for radical surgical treatment of pancreatic head adenocarcinoma. METHODS: A total of 240 patients were assessed for eligibility in the study, 212 of whom were randomly divided into standard lymphadenectomy group (SG) or extended lymphadenectomy group (EG), there were 97 patients in SG and 95 patients in EG receiving the radical pancreaticoduodenectomy. RESULT: The demography, histopathology and clinical characteristics were similar between the 2 groups. The 2-year overall survival rate in the SG was higher than the EG (39.5% vs 25.3%; P = .034). The 2-year overall survival rate in the SG who received postoperative adjuvant chemotherapy was higher than the EG (60.7% vs 37.1%; P = .021). There was no significant difference in the overall incidence of complications between the 2 groups (P = .502). The overall recurrence rate in the SG and EG (70.7% vs 77.5%; P = .349), and the patterns of recurrence between 2 groups were no significant differences. CONCLUSION: In multimodality therapy system, the efficacy of chemotherapy should be based on the appropriate lymphadenectomy extent, and the standard extent of lymphadenectomy is optimal for resectable pancreatic head adenocarcinoma. The postoperative slowing of peripheral blood lymphocyte recovery might be 1 of the reasons why extended lymphadenectomy did not result in survival benefits. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT02928081) in October 7, 2016. https://clinicaltrials.gov/.


Assuntos
Adenoma/cirurgia , Excisão de Linfonodo/normas , Neoplasias Pancreáticas/cirurgia , Adenoma/epidemiologia , Adenoma/mortalidade , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/normas , Pancreaticoduodenectomia/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Método Simples-Cego
2.
Emerg Microbes Infect ; 10(1): 1890-1895, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34487488

RESUMO

Vibrio vulnificus is a pathogenic marine bacteria associated with high mortality. Changes in climate and the global seafood trade have increased the prevalence of marine and freshwater systems affected by V. vulnificus. As a result, the incidence of land animals, plants, and insects contacting V. vulnificus and acting as disease vectors is on the rise. We report the case of a 53-year-old male who was infected with V. vulnificus as the result of a bee sting. The patient had no history of contact with the sea or fresh water or aquatic organisms or products. Due to bacterial pathogenicity and the patient's underlying diseases, his condition deteriorated rapidly and eventually resulted in death. Here, we review the pathogenic mechanisms and treatment of V. vulnificus. We determined that V. vulnificus has spread from seawater to freshwater and that individuals may become infected from insects, even in the absence of direct contact with infected water. This case report will inform clinicians about the possible sources of V. vulnificus infection and indicates the possibility that more insects may transmit V. vulnificus in the future.

3.
J Hazard Mater ; 416: 125924, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492856

RESUMO

The chitosan-stabilized biochar supported S-nZVI (CS@BC/S-nZVI) composite with low aggregation and superior antioxidation were successfully synthesized by liquid-phase reduction method for the outstanding removal of Cr(VI) from wastewater and characterized by SEM, BET, FTIR, XRD, and XPS. The optimized synthesis parameters of CS@BC/S-nZVI were determined as a 0.14 molar ratio of S/Fe and a 0.25 mass ratio of BC/Fe. The CS@BC/S-nZVI possessed a specific surface area of 199.246 m2/g and an average pore size and pore volume of 1.186 nm and 0.272 cc/g. The CS@BC/S-nZVI could remain reductive activity after Cr(VI) removal and present a remarkable tolerance to the coexisting ions during Cr(VI) removal. The adsorption data were fitted well by the pseudo-second order model and the Langmuir model. The removal of Cr(VI) by CS@BC/S-nZVI was an exothermic process with prominent Cr(VI) removal capacities of 244.07 mg/g at 120 min and 221.84 mg/g at 15 min at 25 â„ƒ. Further mechanism analysis proved that the binding of Cr(VI) to CS@BC/S-nZVI was mainly a synergistic effect of reduction and electrostatic attraction. Overall, these findings shed new light on the research of a novel S-nZVI compound and revealed the potential practical application of CS@BC/S-nZVI in the future heavy metal removal from wastewater.


Assuntos
Ferro , Poluentes Químicos da Água , Adsorção , Cromo , Poluentes Químicos da Água/análise
4.
J Affect Disord ; 296: 41-48, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34587548

RESUMO

BACKGROUND: Despite growing adoption of digital technologies, the gap between users and non-users (aka digital divide) persists. It is imperative to determine whether and how such a gap can lead to disparities in mental health outcomes among populations. However, few empirical studies have explored the effect of smartphone non-use on psychological well-being. METHODS: A large-scale cross-sectional survey was conducted among 26,951 college students in Shaanxi Province, China. Levels of depression and loneliness were first compared between smartphone non-users and their user counterparts. Based on the Conservation of Resources theory, structural equation modeling was then used to test the mediating roles of social support, quality of peer relationship, and self-esteem. RESULTS: Around 56.8% of smartphone non-users had probable depression and they reported significantly higher depressive symptoms (Cohen's d = 0.52) and loneliness (Cohen's d = 0.30) than users. The hypothesized mediation model was well supported with good model fit. Lower levels of social support, quality of peer relationship, and self-esteem fully mediated the total effect of smartphone non-use status on loneliness and explained 69.4% of the total effect on depression. LIMITATIONS: Findings might be subject to self-reporting bias and limitations due to a cross-sectional design. CONCLUSIONS: The study adds new evidence that the minority group of smartphone non-users exhibited disproportionately greater psychological distress than users resulting from lower supportive social relationships and positive sense of self. The findings inform the future investigation into digital divide in smartphone use/access and its negative impact on population's psychological well-being.

5.
Mol Med Rep ; 24(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34435648

RESUMO

The present study aimed to investigate the protective effect of carvacrol on liver injury in mice with type 2 diabetes mellitus (T2DM) and to assess its potential molecular mechanism. Mice were divided into three groups (n=15/group): Non­diabetic db/m+ mice group, db/db mice group and db/db mice + carvacrol group. In the db/db mice + carvacrol group, db/db mice were administered 10 mg/kg carvacrol daily by gavage for 6 weeks. Fasting blood glucose and insulin levels were separately examined. Pathological changes were observed using hematoxylin and eosin, Masson's trichrome, periodic acid Schiff and reticular fiber staining. In addition, immunohistochemistry, immunofluorescence and western blotting were used to examine the expression levels of Toll­like receptor 4 (TLR4), NF­κB, NALP3, AKT1, phosphorylated (p)­AKT1, insulin receptor (INSR), p­INSR, mTOR, p­mTOR, insulin receptor substrate 1 (IRS1) and p­IRS1 in the liver tissues. The results revealed that carvacrol improved blood glucose and insulin resistance of T2DM db/db mice. After treatment with carvacrol for 6 weeks, the serum levels of TC, TG and LDL­C were markedly reduced, whereas HDL­C levels were significantly increased in db/db mice. Furthermore, carvacrol administration significantly decreased serum ALT and AST levels in db/db mice. Serum BUN, Cre and UA levels were markedly higher in db/db mice compared with those in the control group; however, carvacrol treatment markedly reduced their serum levels in db/db mice. Furthermore, histological examinations confirmed that carvacrol could protect the liver of db/db mice. Carvacrol could ameliorate liver injury induced by T2DM via mediating insulin, TLR4/NF­κB and AKT1/mTOR signaling pathways. The present findings suggested that carvacrol exerted protective effects on the liver in T2DM db/db mice, which could be related to insulin, TLR4/NF­κB and AKT1/mTOR signaling pathways.

6.
Ann Clin Transl Neurol ; 8(9): 1917-1934, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34310081

RESUMO

The aim of this meta-analysis was to review systematically and to identify the relationship between the severity and location of white matter hyperintensities (WMHs) and the degree of cognitive decline in patients with Parkinson's disease (PD). We searched the PubMed, EMBASE, Web of Science, Ovid, and Cochrane Library databases for clinical trials of the severity and location of WMHs on the degree of cognitive impairment in PD through October 2020. We conducted the survey to compare the association of WMH burden in patients with PD with mild cognitive impairment (PD-MCI) versus those with normal cognition (PD-NC) and in patients with PD with dementia (PDD) versus those with PD without dementia (PD-ND). Nine studies with PD-MCI versus PD-NC and 10 studies with PDD versus PD-ND comparisons were included. The WMH burden in PD-MCI patients was significantly different compared to that in PD-NC patients (standard mean difference, SMD = 0.39, 95% CI: 0.12 to 0.66, p = 0.005), while there was no correlation shown in the age-matched subgroup of the comparison. In addition, PDD patients had a significantly higher burden of WMHs (SMD = 0.8, 95% CI: 0.44 to 1.71, p < 0.0001), especially deep white matter hyperintensities (SMD = 0.54, 95% CI: 0.36 to 0.73, p < 0.00001) and periventricular hyperintensities (SMD = 0.70, 95% CI: 0.36 to 1.04, p < 0.0001), than PD-NC patients, regardless of the adjustment of age. WMHs might be imaging markers for cognitive impairment in PDD but not in PD-MCI, regardless of age, vascular risk factors, or race. Further prospective studies are needed to validate the conclusions.

8.
J Environ Manage ; 294: 113029, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34126537

RESUMO

Phytoremediation is an essential technique for mines' ecological restoration. Modifiers addition can alleviate the stress of heavy metals to plants and enhanced remediation efficiency. Herein, spent mushroom compost (SMC) and calcium carbonate (CaCO3) were added to lead-zinc mine tailings to reveal the mechanism of Macleaya cordata adaptive to heavy metals stress. Pot experiments were conducted in 100% tailing (T), 90% tailing + 5% SMC + 5% CaCO3 (T+), and 100% natural soil (NS). The results indicate that SMC and CaCO3 amendments could improve the structure and fertility of tailings, and promote the growth of M. cordata, increase the content of heavy metals accumulated in plants, enhance the synthesis of chlorophyll and increas the content of soluble protein in leaves; enhance the activities of antioxidase, that can protectcelluar components from oxidative damage. Moreover, most of Pb, Zn, and Cd existed in the cell wall and soluble components, adding SMC and CaCO3 could promote the conversion of Pb, Zn, and Cd to chemical forms with less toxicity and migratory capability. The results of transmission electron microscopy (TEM) and Fourier transform infrared spectrometer (FTIR) showed that SMC and CaCO3 could protect the structural integrity of cells and increase the contents of -OH, -COOH functional groups that can bind to heavy metals in cells. The addition of SMC and CaCO3 can alleviate the stress of heavy metals on M. cordata, enhancing its adaptability to heavy metals and phytoremediation capacity.


Assuntos
Agaricales , Compostagem , Metais Pesados , Poluentes do Solo , Biodegradação Ambiental , Carbonato de Cálcio , Metais Pesados/análise , Solo , Poluentes do Solo/análise , Zinco
9.
Small ; : e2101107, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34018683

RESUMO

The poor stability, in particular with respect to temperature, moisture, and light exposure, remains a ubiquitous impediment virtually for metal halide perovskite materials and devices in their future practical application. Herein, from the perspective of precursor solution chemistry, ionic liquid solvent methylammonium acetate (MAAc) is introduced to prepare high-quality MAPbBr3 perovskite thin films in a one-step air-processing process without anti-solvent treatment. Due to formation of pinhole-free, uniform, and compact MAPbBr3 perovskite film, excellent amplified spontaneous emission (ASE) with high emission efficiency and low threshold is obtained under nanosecond laser. Furthermore, the prepared MAPbBr3 perovskite exhibits excellent two-photon induced ASE with a low threshold of 100 µJ cm-2 under 800 nm femtosecond laser excitation. More importantly, in comparison with the traditional MAPbBr3 films prepared with N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO), the MAPbBr3 film prepared with MAAc shows excellent optical stability: no signs of degradation under more than 2 h pulsed laser excitation, stable ASE emission spectra under the humidity of 95% and ASE spectra can be stimulated when films are kept in air for more than 6000 h without encapsulation.

10.
Small ; : e2100560, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33817963

RESUMO

Ruddlesden-Popper (RP) metal halide perovskites are considered as promising optoelectronic materials due to their good environmental stability and desirable optoelectronic properties. However, the phase composition and ordering in the deposited film, with a fixed ratio of large organic spacer cation in the precursor solution, are hard to be further tailored for specific optoelectronic applications. Herein, it is shown that even with a fixed spacer cation ratio, the phase composition and ordering can still be largely regulated by utilizing different crystallization kinetics of various cations with the inorganic octahedral lead halide. By using two different short cations to compete with the large spacer cation, the phase composition can be continuously tailored from thin multiple quantum wells (MQWs) dominated to 3D perovskite dominated. The phase ordering can be reversed from small n phases' prior to large n phases' prior near the substrate. Finally, with the same amount of large spacer cation protection, the perovskite can be tailored for both high-performance electroluminescence and photovoltaics with favorable energetic landscape for the corresponding desired first-order excitonic recombination and second-order free electron-hole recombination, respectively. This exploration substantially contributes to the understanding of precise phase engineering in RP perovskite and may provide a new insight into the design of multiple functional devices.

11.
Infect Genet Evol ; 91: 104804, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33684569

RESUMO

OBJECTIVES: To explore if SOCS1 is regulated by plasma HDL and its subcomponents HDL2b and HDL3 to affect inflammatory reaction then to influence the severity degree and prognosis of sepsis. METHODS: One hundred sepsis patients in ICU and 85 normal control persons from October 2018 to October 2019 in our hospital were enrolled. Adult male C57BL/6 mice were used to establish sepsis model by CLP method. HDL, CRP, and WBC count of human were measured using an auto-analyzer. Plasma HDL, IL-1ß, and TNF-α proteins levels of mice were measured with ELISA. Microfluidic chip was used for plasma HDL2b and HDL3 detections. SOCS1 in liver and spleen of mice were measured by qRT-PCR. The relationship between plasma HDL//HDL2b and inflammatory indices/SOCS1 in liver/spleen was analyzed with spearman correlation coefficient method. The sepsis patients/mice were divided into non-survival and survival groups. The sepsis patients were divided into severe and mild sepsis patients based on the SOFA score or divided into high and low score groups according to the APACHE II score. The sepsis mice were divided into high and low score group based on the modified sepsis severity score criterion. RESULTS: Plasma HDL and HDL2b levels were significantly declined (P < 0.01), while HDL3 was normal in both sepsis patients and mice (P > 0.05). Plasma HDL and HDL2b were negatively associated with the serum CRP concentration and positively correlated with the prognosis and severity in sepsis patients (P < 0.05). Moreover, the downregulated plasma HDL but not HDL2b was negatively related to increased SOCS1 mRNA levels in liver and spleen of mice, which were positively connected with TNF-α and IL-1ß protein levels (P < 0.05). CONCLUSIONS: Plasma HDL is downregulated in sepsis, which may facilitate inflammatory reaction then activate the SOCS1 signaling to regulate the severity and affect prognosis of sepsis. The decline of plasma HDL2b content could aggravate the severity and poor prognosis of sepsis through facilitating inflammatory reaction. The plasma HDL3 is not involved in sepsis. The more and further explorations may be needed.

12.
Science ; 371(6536): 1359-1364, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33766883

RESUMO

The stabilization of black-phase formamidinium lead iodide (α-FAPbI3) perovskite under various environmental conditions is considered necessary for solar cells. However, challenges remain regarding the temperature sensitivity of α-FAPbI3 and the requirements for strict humidity control in its processing. Here we report the synthesis of stable α-FAPbI3, regardless of humidity and temperature, based on a vertically aligned lead iodide thin film grown from an ionic liquid, methylamine formate. The vertically grown structure has numerous nanometer-scale ion channels that facilitate the permeation of formamidinium iodide into the lead iodide thin films for fast and robust transformation to α-FAPbI3 A solar cell with a power-conversion efficiency of 24.1% was achieved. The unencapsulated cells retain 80 and 90% of their initial efficiencies for 500 hours at 85°C and continuous light stress, respectively.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33783198

RESUMO

Surface passivation has demonstrated to be an effective strategy to improve the power conversion efficiency (PCE) and long-term stability of perovskite solar cells (PSCs). Passivation treatment can effectively reduce the density of defect states at the surface and grain boundaries of perovskite films. Herein, a passivation agent of 2-amino-5-(trifluoromethyl)pyridine (5-TFMAP) with bidentate groups is applied to passivate perovskite CH3NH3PbI3 films for the first time. Two types of electron-rich nitrogen atoms from both the pyridine ring and the amino group provide strong interaction with the under-coordinated Pb2+. Additionally, the trifluoromethyl group offers a hydrophobic property and improves moisture stability of the as-fabricated PSCs. It is found that the 5-TFMAP passivation layer can effectively reduce the defect states, promote better carrier transport, and suppress non-radiation recombination of the perovskite films. The best PCE of carbon-based PSCs passivated by the 5-TFMAP agent achieves a high efficiency of 14.96% compared with that of 11.90% for the control PSCs. Moreover, the long-term stability of PSCs with the 5-TFMAP passivation treatment is greatly improved, and its PCE can maintain 80% of its original PCE after being stored for 1200 h with a relative humidity of around 35% at room temperature.

14.
Adv Mater ; 33(14): e2005410, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33656209

RESUMO

Solar cells based on emerging organic-inorganic hybrid perovskite materials have reached certified power conversion efficiency as high as 25.5%, showing great potential in the next generation of photovoltaics toward large-scale industrialization. The most competitive feature of perovskite solar cells (PSCs) is that the perovskite light absorber can be fabricated by a low-cost solution method. For the solution method, the characteristics of the solvent play a key role in determining the crystallization kinetics, growth orientation, and optoelectronic properties of the perovskite film. Although significant progress has been made in the field of solvent engineering in PSCs, it is still challenging for the solution method to sustainably produce industrial-scale PSCs for future commercialization applications. Herein, the advanced progress of solvent engineering of precursor solution in terms of coordination regulation and toxicity reduction is highlighted. The physical and chemical characteristics of different solvents in reducing the toxicity of the solvent system, regulating the coordination property of the precursor solution, controlling the film-forming process of the perovskite film, and adjusting the photovoltaic performance of the PSC are systematically discussed. Lastly, important perspectives on solvent engineering of the perovskite precursor solution toward future industrial production of high-performance PSCs are provided.

15.
Adv Mater ; 33(12): e2003615, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33586290

RESUMO

While halide perovskites (HPs) have achieved enormous success in the field of optoelectronic applications, much attention has been recently drawn to the unique polarization sensitivity of HPs, either intrinsic or extrinsic, which makes HPs a potential candidate for innovative applications in directly polarized luminescence and detection. Herein, the research status in the field of polarization-sensitive HPs, including linear polarization and circular polarization, is comprehensively summarized. To evaluate the effectiveness of HPs in generating and detecting linearly or circularly polarized light, the principles and characterization methods of polarized luminescence and detection are introduced. Sequentially, the state-of-the-art development of the strategies that induce the linear or circular polarization characteristics of HPs is systematically reviewed, based on which the application of polarization-sensitive HPs in the field of polarization luminescence and detection are summarized. Moreover, the current challenges and opportunities are discussed, and prospects of the future development in this promising field are outlined.

16.
Oncol Rep ; 45(2): 786, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416180

RESUMO

Subsequently to the publication of the above paper, the authors have drawn to our attention that, owing to errors made in the compilation of the images in Fig. 6, the images shown in Fig. 6A­C in the article were selected incorrectly (essentially, the images shown in Fig. 6A and B were alterative presentations of the same data shown in Fig. 6C). The authors were able to re­examine the original data files and retrieve the correct data panels. The revised version of Fig. 6, featuring the corrected data panels for Fig. 6A­C, is shown opposite. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 36: 2017-2024, 2016; DOI: 10.3892/or.2016.4995].

17.
Soft Robot ; 8(1): 71-84, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32320346

RESUMO

Fluid actuated soft robots, or fluidic elastomer actuators, have shown great potential in robotic applications where large compliance and safe interaction are dominant concerns. They have been widely studied in wearable robotics, prosthetics, and rehabilitations in recent years. However, such soft robots and actuators are tethered to a bulky pump and controlled by various valves, limiting their applications to a small confined space. In this study, we report a new and effective approach to fluidic power actuation that is untethered, easy to design, fabricate, control, and allows various modes of actuation. In the proposed approach, a sealed elastic tube filled with fluid (gas or liquid) is segmented by adaptors. When twisting a segment, two major effects could be observed: (1) the twisted segment exhibits a contraction force and (2) other segments inflate or deform according to their constraint patterns. Utilizing such effects, various actuation modes could be realized. In this research, four modes of actuation are illustrated: (1) soft actuator and pump actuation, (2) serial actuation, (3) parallel actuation, and (4) agonist and antagonist actuation. Theoretic analysis and experimental studies for the basic actuation principle have been conducted. A case study on an anthropomorphic forearm based on the proposed twisting tube actuation has been developed to showcase the effectiveness of the actuation modes. The studies suggest that the proposed approach has a great potential in both soft and compliant robotics.

18.
Soft Robot ; 8(1): 97-108, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32522089

RESUMO

Given that mobile soft robots are adaptable to the environment, they are always tethered with slow locomotion speed. Compared with other types of mobile robots, mobile soft robots may be more suitable for rescuing tasks, accompanying elderly people, and being used as a safe toy for children. However, the infinite freedom of soft robots increases the difficulty of precision control. In addition, the large volume and long tube of the conventional soft actuator structure limit the range of motion of current mobile soft robots. In this article, a newly designed innovative untethered-bioinspired quadrupedal robot based on double-chamber pre-charged pneumatic (DCPCP) soft actuators with highly flexible trunk is proposed. Asymmetrical cross-tendons actuated by servo motors are used to drive the DCPCP soft legs so that buckling can be avoided and mimic the gait of quadruped animals with the simplest drive and control strategy. In addition, the proposed design greatly improves energy efficiency and exhibits superior performance of variable stiffness. The bioinspired highly flexible trunk is designed with the supporting spine structure and tendon driven muscle to deform, which can constantly adjust to the contact situation between the foot and the ground to adjust the center of gravity of the soft quadruped robot and increase stability when walking and turning. The proposed soft quadruped robot does not require any air compressors, valves, and hoses. The characteristics of untethered, high-energy efficiency, linear control, and stability make the soft quadruped robot suitable for many applications.

19.
Diabetes Metab Res Rev ; 37(1): e3366, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32543027

RESUMO

Immune checkpoint inhibitors (ICIs) are widely used in oncology for their favourable antitumor efficacy. ICI therapy is associated with a unique toxicity profile known as immune-related adverse events (irAEs). One such irAE is ICI-related diabetes mellitus (DM), which is relatively uncommon but can become extremely severe, leading to irreversible impairment of ß-cells, and even lead to death if not promptly recognised and properly managed. The precise mechanisms of ICI-related DM are not well understood. In this review, we summarise the clinical characteristics, pathophysiology, and management of this adverse effect caused by ICI therapy. Deeper investigation of ICI-related DM may contribute to elucidate the molecular mechanisms of classical type 1 DM.

20.
J Cancer ; 11(24): 7312-7319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193895

RESUMO

Background: It has been reported that local anesthetics are toxic to various types of cells. Furthermore, several local anesthetics have been confirmed to exert demethylation effects and regulate the proliferation of human cancer cells. Our previous findings suggest that lidocaine may exert potential antitumor activity and enhance the sensitivity of cisplatin to hepatocellular carcinoma in vitro and in vivo. A recent study proved that lidocaine sensitizes breast cancer cells to cisplatin via upregulation of RASSF1A, a promotor of tumor suppressive gene (TSG) demethylation. We sought to determine whether amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine) exert growth-inhibitory effects on human hepatoma cells and to determine whether amide-type local anesthetics sensitize human hepatoma cells to cisplatin-mediated cytotoxicity via upregulation of RASSF1A expression. Methods: Human hepatoma cell lines HepG2 and BEL-7402 were incubated with lidocaine, ropivacaine and bupivacaine. The viability of local anesthetic-treated cells with or without cisplatin was investigated. Further, we evaluated RASSF1A expression after treatment of HepG2 and BEL-7402 cells with three local anesthetics and determined the influence of RASSF1A expression on the toxicity of cisplatin to these cells. Results: The viability of HepG2 and BEL-7402 cells was significantly decreased by treatment with amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine). In these cells, the combination treatment with cisplatin and local anesthetics exhibited a stronger reduction in viability. Lidocaine, ropivacaine and bupivacaine promoted a significant increase in RASSF1A expression and a decrease in RASSF1A methylation. The combined treatment with both local anesthetics and cisplatin resulted in a significantly lower level of HepG2 and BEL-7402 cell viability than that with singular local anesthetics or cisplatin treatment. Moreover, local anesthetics enhanced the cytotoxicity of cisplatin against HepG2 and BEL-7402 cells, accompanied by an increase in RASSF1A expression. Conclusions: These data indicated that amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine) have growth-inhibitory and demethylation effects in human hepatoma cells. We also found that these amide local anesthetics may enhance the cytotoxicity of cisplatin in human hepatocellular carcinoma cells possibly via upregulation of RASSF1A expression and demethylation.

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