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1.
J Exp Clin Cancer Res ; 40(1): 25, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422093

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis. METHODS: The expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining. We mainly used pancreatic acinar cell 3-dimensional (3D) culture and a spontaneous pancreatic precancerous lesion mouse model called LSL-KrasG12D/+; Pdx1-Cre (KC) (and pancreatitis models derived from KC mice) to explore the pro-tumorigenesis mechanisms of the HSF1 in vitro and in vivo. Bioinformatics and molecular experiments were used to explore the underlying mechanisms between HSF1 and epidermal growth factor receptor (EGFR). RESULTS: In this study, we found that pharmacological inhibition of HSF1 slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion. Next, bioinformatics analysis revealed the closely linked between HSF1 and EGFR pathway and we also confirmed their parallel activation in pancreatic precancerous lesions. Besides, the pharmacological inhibition of EGFR suppressed the initiation of pancreatic cancer and the activation of HSF1 in vivo. Indeed, we demonstrated that the EGFR activation that mediated pancreatic cancer tumorigenesis was partly HSF1-dependent in vitro. CONCLUSION: Hence, we concluded that the EGFR-HSF1 axis promoted the initiation of pancreatic cancer.

2.
Nat Commun ; 12(1): 114, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414464

RESUMO

Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au24Cd1 clusterzymes exhibit 137 and 160 times higher antioxidant capacities than natural trolox, respectively. Meanwhile, the clusterzymes demonstrate preferential enzyme-mimicking catalytic activities, with Au25, Au24Cu1 and Au24Cd1 displaying compelling selectivity in glutathione peroxidase-like (GPx-like), catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities, respectively. Au24Cu1 decreases peroxide in injured brain via catalytic reactions, while Au24Cd1 preferentially uses superoxide and nitrogenous signal molecules as substrates, and significantly decreases inflammation factors, indicative of an important role in mitigating neuroinflammation.

3.
Mol Oncol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411982

RESUMO

Human Leucocyte Antigen (HLA) genotyping gains intensive attention due to its critical role in cancer immunotherapy. It is still a challenging issue to generate reliable HLA genotyping results through in silico tools. In addition, the survival impact of HLA alleles in tumor prognosis and immunotherapy remains controversial. In this study, the benchmarking of HLA genotyping on TCGA is performed and a "Gun-Bullet" model which helps to clarify the survival impact of HLA allele is presented. The performance of HLA class I genotyping is generally better than class II. POLYSOLVER, OptiType and xHLA perform generally better at HLA class I calling with an accuracy of 0.954, 0.949 and 0.937, respectively. HLA-HD obtained the highest accuracy of 0.904 on HLA class II alleles calling. Each HLA-genotyping tool displayed specific error patterns. The ensemble HLA calling from the top-3 tools is superior to any individual one. HLA alleles show distinct survival impact among cancers. Cytolytic activity (CYT) was proposed as the underlying mechanism to interpret the survival impact of HLA alleles in the "Gun-Bullet" model for fighting cancer. A strong HLA allele plus a high tumor mutation burden (TMB) could stimulate intensive immune CYT, leading to extended survival. We established an up-to-now most reliable TCGA HLA benchmark dataset, composing of concordance alleles generated from eight prevalently used HLA genotyping tools. Our findings indicate that reliable HLA genotyping should be performed based on concordance alleles integrating multiple tools and incorporating TMB background with HLA genotype, which helps to improve the survival prediction compared to HLA genotyping alone.

5.
Theranostics ; 11(2): 841-860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391508

RESUMO

Current endocrine therapy for prostate cancer (PCa) mainly inhibits androgen/androgen receptor (AR) signaling. However, due to increased intratumoural androgen synthesis and AR variation, PCa progresses to castration-resistant prostate cancer (CRPC), which ultimately becomes resistant to endocrine therapy. A search for new therapeutic perspectives is urgently needed. Methods: By screening lipid metabolism-related gene sets and bioinformatics analysis in prostate cancer database, we identified the key lipid metabolism-related genes in PCa. Bisulfite genomic Sequence Polymerase Chain Reaction (PCR) (BSP) and Methylation-Specific Polymerase Chain Reaction (PCR) (MSP) were preformed to detect the promoter methylation of ACSS3. Gene expression was analyzed by qRT-PCR, Western blotting, IHC and co-IP. The function of ACSS3 in PCa was measured by CCK-8, Transwell assays. LC/MS, Oil Red O assays and TG and cholesterol measurement assays were to detect the levels of TG and cholesterol in cells. Resistance to Enzalutamide in C4-2 ENZR cells was examined in a xenograft tumorigenesis model in vivo. Results: We found that acyl-CoA synthetase short chain family member 3 (ACSS3) was downregulated and predicted a poor prognosis in PCa. Loss of ACSS3 expression was due to gene promoter methylation. Restoration of ACSS3 expression in PCa cells significantly reduced LD deposits, thus promoting apoptosis by increasing endoplasmic reticulum (ER) stress, and decreasing de novo intratumoral androgen synthesis, inhibiting CRPC progression and reversing Enzalutamide resistance. Mechanistic investigations demonstrated that ACSS3 reduced LD deposits by regulating the stability of the LD coat protein perilipin 3 (PLIN3). Conclusions: Our study demonstrated that ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.

7.
Chin J Integr Med ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33420902

RESUMO

OBJECTIVE: To reveal the underlying relationships between Chinese medicine (CM) syndromes and ultrafiltration (UF) in the treatment of heart failure based on a metabonomic approach. METHODS: Seventeen acute decompensated heart failure (ADHF) patients were enrolled, and their CM syndromes before and after UF were collected. In addition, their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis. Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples. Partial least-squares to latent structure-discriminant analyses were used for data analysis. RESULTS: An obvious difference was observed pre- and post-treatment. A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine, 1-methylhistidine, phytosphingosine, O-decanoyl-R-carnitine, etc. were screened out, showing a significant change after UF. The major adjusted metabolic pathways were purine metabolism, histidine metabolism, leucine and isoleucine metabolism, arginine and proline metabolism, carnitine shuttle, sphingolipid metabolism and phospholipid metabolism. CONCLUSIONS: Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

8.
Biochem Biophys Res Commun ; 534: 966-972, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33121682

RESUMO

circRNAs have been shown to be involved in cancer progression. It is unclear whether circPGAM1 exerts its effect on laryngocarcinoma drug resistance. In this study, we employed colony formation and MTT assay to determine colony number and cell viability under cisplatin treatment. TUNEL experiment was used to evaluate apoptosis of laryngocarcinoma cells in the presence of cisplatin. Xenograft tumor experiment was performed to assess in vivo tumor growth of SNU46 cells. We found that circPGAM1 enhanced colony formation and viability of SNU46 and M4E cells. In contrast, circPGAM1 caused attenuated cell apoptosis. Furthermore, we also confirmed that circPGAM1 played a key role in tumor growth in animal model and clinical patients. miR-376a was identified and proved to act as key effector for circPGAM1-mediated drug resistance. Finally, autophagy-related gene ATG2A was shown to rescue miR-376a-modulated drug resistance of laryngocarcinoma cells. Herein, we illuminate the role of circPGAM1 in laryngocarcinoma drug resistance, thereby facilitating development of targeted therapy for treating laryngocarcinoma.

9.
Ann Vasc Surg ; 70: 449-458, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32634568

RESUMO

BACKGROUND: The aim of this study is to assess the incidence, clinical manifestations, management, and prognosis of graft infection after bypass surgery with prosthetic conduit for infectious femoral artery pseudoaneurysms (IFAPs) in patients with a history of intravenous drug use (IVDU). METHODS: A single-center retrospective chart review of IVDU presenting with graft infections after previously being treated with extra-anatomic prosthetic conduit bypass surgery for IFAPs between 2009 and 2019 was performed. Relevant clinical data and patient demographics were collected and analyzed. All patients underwent procedures consisting of graft removal with analysis of operative details and complications. RESULTS: Of all 122 patients who underwent IFAP resection with extra-anatomic prosthetic bypass, the incidence of graft infection was 38.5% (47 patients, 48 grafts) with an average age of 35.7 ± 7.3 years. The average interval between bypass surgery and infectious symptoms was 9.2 ± 2.5 months and average time from bypass to graft removal was 13.6 ± 3.4 months. The most common presentation was repeated or unhealable chronic ulcers with sinus formation or purulence either within the bypass area or along the graft conduit route (43, 89.6%). Occlusion of the infected bypass graft occurred in nearly all cases (46, 95.8%). Severe hemorrhage occurred in only 1 case (2.1%). After graft removal, the stumps were ligated in the majority of patients (33, 68.8%) with 15 patients (31.2%) not amenable to ligation due to a difficult dissection. The average time of operation was 35.4 ± 8.7 min with an average blood loss of 35.8 ± 6.7 mL. There were no significant complications such as infection reoccurrence, severe limb ischemia, amputation, or death observed postoperatively. CONCLUSIONS: Patients who receive bypass surgery with prosthetic conduit for IFAPs carry a high incidence of graft infection and subsequent occlusion. However, the presenting symptoms are generally mild, and the incidence of fatal complications is rare. This study suggests that a safe treatment option consists of direct graft removal without reconstruction. Additionally, the procedure proved to be relatively convenient and straightforward, which provides further support toward the strategy of treating IFAPs in IVDUs with pseudoaneurysm resection and prosthetic conduit bypass surgery.

10.
Toxicol Appl Pharmacol ; 410: 115355, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271250

RESUMO

Coenzyme Q10 (CoQ10), which is a key cofactor of the electron transport chain in the mitochondria has shown many beneficial effects on liver diseases. However, the mechanisms of CoQ10 protective role on the acetaminophen (APAP)-induced liver injury are elusive and unclear. In this study, we further investigated the CoQ10 therapeutic effects on APAP-overdose liver injury. C57BL/6 J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 1.5 h after APAP treatment. The results showed that hepatic CoQ10 levels were decreased during the APAP-induced hepatotoxicity and preceded serum ALT elevation. Treatment of CoQ10 significantly improved the liver injury induced by APAP. Moreover, CoQ10 treatment decreased the ROS levels and promoted the antioxidative related gene expression in APAP overdose mice. Importantly, results showed that even though CoQ10 had no effects on the mtDNA copy number and the expression of genes related to mitochondrial biogenesis, it significantly improved the mitochondrial complex I and V activities and promoted the mitophagy in APAP-overdose mice. To further authenticate mitophagy role in CoQ10-mediated improved liver injury in vivo, we administrated APAP-overdose mice with chloroquine 1 h prior to APAP treatment and found that chloroquine treatment functionally abrogated the CoQ10 protective role on APAP overdose mice. To conclude, this study provides evidence that CoQ10 activates mitophagy to protect against APAP-induced liver injury. Therefore, CoQ10 may represent a novel therapeutic option for the prevention and treatment of drug-induced liver injury.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Entorpecentes/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Mitofagia/efeitos dos fármacos , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitofagia/fisiologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Vitaminas/farmacologia
11.
Acta Biochim Biophys Sin (Shanghai) ; 53(1): 94-101, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33300557

RESUMO

Animal studies indicated that P1 promoter-driven hepatocyte nuclear factor 4 alpha (HFN4A) prevents carcinogenesis in colitis. But the function of total HNF4A protein has not been fully investigated, and it was assumed to be involved in the colitis-neoplastic sequence. The aim of this study was to determine the clinical value of total P1-/P2-driven HNF4A combined with ß-catenin in the colitis-neoplastic sequence. A total of 69 samples, including 4 normal colon tissues, 16 sporadic colorectal cancer (CRC) tissues, 35 inflammatory bowel disease (IBD) tissues, and 14 IBD-associated low-grade dysplasia tissues, were collected to assess P1-/P2-driven HNF4A and ß-catenin expressions by immunohistochemical assay. In addition, a colonic epithelial cell line Caco2 with stable P1-/P2-driven HNF4A knockdown was constructed. ß-Catenin expression and skeleton structure were determined in the transfected cells by western blot analysis and immunofluorescence assay respectively. Increased expression of nuclear P1-/P2-driven HNF4A was observed in the colitis-associated colorectal neoplasm and sporadic CRC samples, compared with that in colitis samples. The parallel alterations between cytoplasmic ß-catenin and nuclear P1-/P2-driven HNF4A were also verified. Silencing of P1-/P2-driven HNF4A expression in Caco2 cells decreased ß-catenin expression and F-actin formation. Our results confirmed the elevated expressions of nuclear P1-/P2-driven HNF4A and cytoplasmic ß-catenin in the colitis-neoplastic sequence, and both of them may be used as potential biomarkers to predict low-grade dysplasia.

12.
Food Chem ; 341(Pt 1): 128211, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33032248

RESUMO

The physicochemical mechanism of starch digestion is very complicated since it may be affected by the non-valence interactions of the amylase inhibitor with the substrate or the enzyme. The role of hydrophobic interaction in the process of starch digestion is not clear. In this study, pluronics (PLs) with different hydrophobicity were used as model amphiphilic compounds to study their inhibition on starch digestion using multi-spectroscopic methods. The results showed that the hydrophobic nature of PLs changed starch structure, but it had a greater effect on the structure of α-amylase by exposing more tryptophan residues and increasing α-helix and ß-sheet contents. Further investigation by using different chain-length fatty acids confirmed the results. The finding in this study is informative to design and fabricate α-amylase inhibitors for controlling starch digestion at the molecular level.


Assuntos
Poloxâmero/farmacologia , Amido/farmacocinética , alfa-Amilases/química , Digestão , Inibidores Enzimáticos/química , Interações Hidrofóbicas e Hidrofílicas , Poloxâmero/química , Domínios Proteicos , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/química , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo
13.
Steroids ; 165: 108740, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33137356

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. Cangfu Daotan Decoction (CFDTT) is one of the prescriptions in the stagnation of obesity-type PCOS. Our previous study showed that CFDTT treatment of obese PCOS was correlated with organic anion transporting polypeptides (OATPs). METHODS: Here, we studied the effects of CFDTT on obese PCOS and its underlying mechanism. We built an obese PCOS rat model and treated the rats with CFDTT. Then, we detected the serum levels of TCHO, TG, LDL-c, HDL-c, luteinizing hormone (LH), follicle stimulating growth hormone (FSH), testosterone (T), estradiol (E2), IL-1ß, IL-6, and TNF-α in each group and adopted RT-PCR, western blotting and immunohistochemical staining to investigate the effects of CFDTT treatment on the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. In addition, we compared the pregnancy outcomes of each group. RESULTS: We found that CFDTT decreased the serum levels of TCHO, TG, LDL-c, LH, T, IL-1ß, IL-6, and TNF-α and increased the levels of HDL-c, FSH and E2 in a dose-dependent manner. CFDTT could induce the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. Moreover, CFDTT could improve pregnancy outcomes. CONCLUSION: These data suggested that the therapeutic mechanism of Cangfu Daotan Decoction on PCOS may be correlated with regulating lipid metabolism, sex hormone secretion and the inflammatory response and increasing OATP2B1 and OATP3A1 expression. Cangfu Daotan Decoction can be developed as a PCOS treatment drug.

14.
Int J Nanomedicine ; 15: 10331-10347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376324

RESUMO

Background: Lung cancer is the leading cause of cancer patient death in the world. There are many treatment options for lung cancer, including surgery, radiation therapy, chemotherapy, targeted therapy, and combined therapy. Despite significant progress has been made in the diagnosis and treatment of lung cancer during the past few decades, the prognosis is still unsatisfactory. Purpose: To resolve the problem of chemotherapy failure, we developed a magnetite-based nanomedicine for chemotherapy acting synergistically with loco-regional hyperthermia. Methods: The targeting carrier consisted of a complex of superparamagnetic iron oxide (SPIO) and poly(sodium styrene sulfonate) (PSS) at the core and a layer-by-layer shell with cisplatin (CDDP), together with methotrexate - human serum albumin conjugate (MTX-HSA conjugate) for lung cancer-specific targeting, referred to hereafter as SPIO@PSS/CDDP/HSA-MTX nanoparticles (NPs). Results: SPIO@PSS/CDDP/HSA-MTX NPs had good biocompatibility and stability in physiological solutions. Furthermore, SPIO@PSS/CDDP/HSA-MTX NPs exhibited a higher temperature increase rate than SPIO nanoparticles under irradiation by a radiofrequency (RF) generator. Therefore, SPIO@PSS/CDDP/HSA-MTX NPs could be used as a hyperthermia inducer under RF exposure after nanoparticles preferentially targeted and then accumulated at tumor sites. In addition, SPIO@PSS/CDDP/HSA-MTX NPs were developed to be used during combined chemotherapy and hyperthermia therapy, exhibiting a synergistic anticancer effect better than the effect of monotherapy. Conclusion: Both in vitro and in vivo results suggest that the designed SPIO@PSS/CDDP/HSA-MTX NPs are a powerful candidate nanoplatform for future antitumor treatment strategies.


Assuntos
Óxido Ferroso-Férrico/química , Hipertermia Induzida , Neoplasias Pulmonares/terapia , Nanomedicina/métodos , Animais , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/uso terapêutico , Terapia Combinada , Portadores de Fármacos/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Metotrexato/química , Nanopartículas/química , Albumina Sérica/química
15.
IEEE Trans Cybern ; PP2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33382668

RESUMO

Feature selection (FS) is an important data preprocessing technique in data mining and machine learning, which aims to select a small subset of information features to increase the performance and reduce the dimensionality. Particle swarm optimization (PSO) has been successfully applied to FS due to being efficient and easy to implement. However, most of the existing PSO-based FS methods face the problems of trapping into local optima and computationally expensive high-dimensional data. Multifactorial optimization (MFO), as an effective evolutionary multitasking paradigm, has been widely used for solving complex problems through implicit knowledge transfer between related tasks. Inspired by MFO, this study proposes a novel PSO-based FS method to solve high-dimensional classification via information sharing between two related tasks generated from a dataset. To be specific, two related tasks about the target concept are established by evaluating the importance of features. A new crossover operator, called assortative mating, is applied to share information between these two related tasks. In addition, two mechanisms, which are variable-range strategy and subset updating mechanism, are also developed to reduce the search space and maintain the diversity of the population, respectively. The results show that the proposed FS method can achieve higher classification accuracy with a smaller feature subset in a reasonable time than the state-of-the-art FS methods on the examined high-dimensional classification problems.

16.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(12): 1816-1820, 2020 Dec 30.
Artigo em Chinês | MEDLINE | ID: mdl-33380391

RESUMO

OBJECTIVE: To investigate the role of autophagy in lipopolysaccharide (LPS)-induced apoptosis of murine odontoblasts. METHODS: Murine odontoblasts (mDPC-23 cells) were treated with 5 µg/mL LPS for 6, 12 and 24 h, and the changes in cell viability was examined using CCK8 kit and cell apoptosis was detected by TUNEL staining. The changes in the protein levels of LC3, Beclin1, Atg5, AKT, p-AKT, mTOR and p-mTOR were detected using Western blotting. The effect of 3-MA treatment for 24 h on LPS-induced apoptosis of mDPC-23 cells was evaluated by detecting the expressions of apoptosis-related proteins caspase-3 and Bax using Western blotting. RESULTS: Stimulation with LPS for 6 and 12 h did not cause significant changes in the proliferation or apoptosis of mDPC-23 cells, but LPS treatment for 24 h significantly suppressed cell proliferation (P < 0.05) and promoted cell apoptosis as shown by TUNEL assay (P < 0.05). Stimulation with LPS for 24 significantly increased the expression levels of LC3, Beclin1 and Atg5, decreased the expressions of p-AKT and p-mTOR (P < 0.05), and obviously upregulated the expressions of caspase-3 and Bax (P < 0.05). Treatment with 3-MA markedly lowered caspase-3 and Bax protein expressions in LPS-stimulated cells (P < 0.05). CONCLUSIONS: LPS stimulation induces autophagy to promote apoptosis of mDPC-23 cells, and suppression of autophagy attenuates LPS-induced apoptosis. Autophagy may play an important role in the injury of inflamed pulp tissues.

17.
Appl Opt ; 59(33): 10330-10338, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33361964

RESUMO

Crystalline silicon thin-film solar cells with period-mismatched sine dual-interface gratings are proposed. Several structural parameters of the front and rear gratings, such as heights, periods, and duty ratios, are optimized using the finite-difference time-domain method. The mechanisms of absorption enhancement are also illustrated by analyzing the optical and electrical performance in thin-film solar cells with different grating arrangements. Numerical results indicate that the period-mismatched sine dual-interface grating structure shows obvious improvement in absorption efficiency and is more suitable for grating structures with small period. The short-circuit current density of the period-mismatched dual-interface sine grating structure is improved to 18.89mA/cm2, an increase of 41.39% as compared with the planar structure. The research findings can be utilized to guide the design of grating structures for thin-film solar cells.

18.
Brain Behav ; : e02014, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33369267

RESUMO

INTRODUCTION: Occupational stress is considered to be a harmful physical and emotional response to an individual's psychological and/or physiological state in the work environment and is highly prevalent among medical staff. However, few epidemiological studies have investigated occupational stress in medical staff. Our study aims to explore the characteristics of occupational stress and its relationship with dyslipidemia in Chinese medical staff at tertiary hospitals and establish the basis for future preventive strategies. METHODS: A cross-sectional study was conducted in three tertiary public hospitals in Wenzhou City, Zhejiang Province, China. Data were collected using random sampling procedures to examine demographic characteristics and job-related data. The participants completed the Occupational Stress Inventory-Revised (OSI-R) questionnaires and serum lipids tests. Partial correlation analysis was conducted to explore the relationship between occupational stress and dyslipidemia. RESULTS: A total of 1,176 medical staff responses to questionnaires were obtained. The occupational stress levels of medical staff were higher than those of normative populations, while their coping resources were lower. Most of the subscales of occupational stress demonstrated higher results for doctors and males than for nurses and females with crude analyses. Each subscale of OSI-R was found to be associated with a different type of blood lipid level. CONCLUSIONS: The occupational stress level of medical staff in tertiary public hospitals in Wenzhou was high, and occupational stress may contribute to dyslipidemia. An investigation into occupational stress levels and their association with dyslipidemia in this population could draw more attention to medical staff in tertiary public hospitals.

19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(6): 1073-1079, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369347

RESUMO

Portal hypertension (PHT) is a common complication of liver cirrhosis, which could be measured by the means of portal vein pressure (PVP). However, there is no report about an effective and reliable way to achieve noninvasive assessment of PVP so far. In this study, firstly, we collected ultrasound images and echo signals of different ultrasound contrast agent (UCA) concentrations and different pressure ranges in a low-pressure environment based on an in vitro simulation device. Then, the amplitudes of the subharmonics in the echo signal were obtained by ultrasound grayscale image construction and fast Fourier transform (FFT). Finally, we analyzed the relationship between subharmonic amplitude (SA) and bionic portal vein pressure (BPVP) through linear regression. As a result, in the pressure range of 7.5-45 mm Hg and 8-20 mm Hg, the linear correlation coefficients (LCC) between SA and BPVP were 0.927 and 0.913 respectively when the UCA concentration was 1∶3 000, and LCC were 0.737 and 0.568 respectively when the UCA concentration was 1∶6 000. Particularly, LCC was increased to 0.968 and 0.916 respectively while the SAs of two UCA concentrations were used as the features of BPVP. Therefore, the results show a good performance on the linear relationship between SA and BPVP, and the LCC will be improved by using SAs obtained at different UCA concentrations as the features of BPVP. The proposed method provides reliable experimental verification for noninvasive evaluation of PVP through SA in clinical practice, which could be a guidance for improving the accuracy of PVP assessment.

20.
J Clin Oncol ; : JCO2001820, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33332190

RESUMO

PURPOSE: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively. CONCLUSION: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

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