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1.
Int J Biol Sci ; 16(11): 2001-2013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32398966

RESUMO

Nicotine is proved to be an important factor for cardiac hypertrophy. Autophagy is important cell recycling system involved in the regulation of cardiac hypertrophy. Cilostazol, which is often used in the management of peripheral vascular disease. However, the effects of cilostazol on nicotine induced autophagy and cardiac hypertrophy are unclear. Here, we aim to determine the role and molecular mechanism of cilostazol in alleviating nicotine-induced cardiomyocytes hypertrophy through modulating autophagy and the underlying mechanisms. Our results clarified that nicotine stimulation caused cardiomyocytes hypertrophy and autophagy flux impairment significantly in neonatal rat ventricular myocytes (NRVMs), which were evidenced by augments of LC3-II and p62 levels, and impaired autophagosomes clearance. Interestingly, cathepsin B (CTSB) activity decreased dramatically after stimulation with nicotine in NRVMs, which was crucial for substrate degradation in the late stage of autophagy process, and cilostazol could reverse this effect dramatically. Intracellular ROS levels were increased significantly after nicotine exposure. Meanwhile, p38MAPK and JNK were activated after nicotine treatment. By using ROS scavenger N-acetyl-cysteine (NAC) could reverse the effects of nicotine by down-regulation the phosphorylation of p38MAPK and JNK pathways, and pretreatment of specific inhibitors of p38MAPK and JNK could restore the autophagy impairment and cardiomyocytes hypertrophy induced by nicotine. Moreover, CTSB activity of lysosome regained after the treatment with cilostazol. Cilostazol also inhibited the ROS accumulation and the activation of p38MAPK and JNK, which providing novel connection between lysosome CTSB and ROS/p38MAPK/JNK related oxidative stress pathway. This is the first demonstration that cilostazol could alleviate nicotine induced cardiomyocytes hypertrophy through restoration of autophagy flux by activation of CTSB and inhibiting ROS/p38/JNK pathway, exhibiting a feedback loop on regulation of autophagy and cardiomyocytes hypertrophy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32427404

RESUMO

In this work, we demonstrated a simple random ternary copolymerization strategy to synthesize a series of polymer acceptors PTPBT-ET x by polymerizing a small molecule acceptor unit modified from Y6 with thiophene connecting unit and controlled amount of 3-ethylesterthiophene (ET) unit. Compared PTPBT of only Y6-like units and thiophene units, PTPBT-ET x (where x represents the molar ratio of ET unit) with incorporating ET unit in the ternary copolymers show up-shifted LUMO energy level, increased electron mobility and improved blend morphology in the blend film with polymer donor PBDB-T. And the all-PSC based on PBDB-T:PTPBT-ET 0.3 achieved high power conversion efficiency (PCE) over 12.5%. In addition, the PTPBT-ET 0.3 based all-PSC device also exhibits long-term photostability over 300 hours. These results demonstrate that the random ternary copolymerization of a small molecule acceptor unit with a third functional unit is a simple but effective strategy to develop efficient polymer acceptors for all-PSCs.

3.
Dig Dis Sci ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32405981

RESUMO

BACKGROUND: Direct-acting antivirals (DAAs) are current standard of HCV treatment (Rx). However, data remain lacking on real-world safety, patterns of biochemical, virologic responses, and sustained virologic response (SVR12) rate in geriatric patients. AIMS: The present study assessed clinical presentation, safety, SVR12 rate, dynamic changes in HCV RNA, ALT, and AFP in geriatric patients (age ≥ 65 year old, G1) versus non-geriatric patients (G2) with chronic hepatitis C and received DAA treatment. METHODS: This was a single-center, retrospective study on 183 patients with DAA Rx and 12-week post-Rx follow-up. RESULTS: There were no significant differences in patterns of biochemical and virologic responses between the two groups. Undetectable HCV RNA rates were 67.2% versus 75.7% (p = 0.22) and 77.3% versus 84.3% (p = 0.24) at Rx week 2 and Rx week 4, respectively. The SVR12 rate was comparable in 2 groups, 94.1% (G1) versus 95.7% (G2, p = 0.64). ALT normalization rates were 91.2% versus 91.3% (p = 0.98), 92.6% versus 93.9% (p = 0.74), and 97.1% versus 97.4% (p = 0.89) at Rx week 2, post-Rx week12, and post-Rx week 24, respectively. AFP normalization was lower in G1 with 89.7% versus 95.7% (p = 0.12), 77.9% versus 87.8% (p = 0.08), and 79.4% versus 92.2% (p = 0.01), at Rx week 2, and post-Rx week 12, and post-Rx week 24, respectively. Both groups showed similar side effects profile including fatigue 11.8% versus 12.2% (p = 0.93) and headache 11.8% versus 13.9% (p = 0.68). CONCLUSION: Based on our real-world data, geriatric patients had excellent and comparable treatment outcomes with non-geriatric patients in safety and SVR12 rates to different DAA regimens.

4.
Phytomedicine ; : 153242, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32425361

RESUMO

Background: Coronavirus disease 2019 (Covid-19) has resulted in a global outbreak. Few existing targeted medications are available. Lianhuaqingwen (LH) capsule, a repurposed marketed Chinese herb product, has been proven effective for influenza. Purpose: To determine the safety and efficacy of LH capsule in patients with Covid-19. Methods: We did a prospective multicenter open-label randomized controlled trial on LH capsule in confirmed cases with Covid-19. Patients were randomized to receive usual treatment alone or in combination with LH capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the rate of symptom (fever, fatigue, coughing) recovery. Results: We included 284 patients (142 each in treatment and control group) in the full-analysis set. The recovery rate was significantly higher in treatment group as compared with control group (91.5% vs. 82.4%, P=0.022). The median time to symptom recovery was markedly shorter in treatment group (median: 7 vs. 10 days, P<0.001). Time to recovery of fever (2 vs. 3 days), fatigue (3 vs. 6 days) and coughing (7 vs. 10 days) was also significantly shorter in treatment group (all P<0.001). The rate of improvement in chest computed tomographic manifestations (83.8% vs. 64.1%, P<0.001) and clinical cure (78.9% vs. 66.2%, P=0.017) was also higher in treatment group. However, both groups did not differ in the rate of conversion to severe cases or viral assay findings (both P>0.05). No serious adverse events were reported. Conclusion: In light of the safety and effectiveness profiles, LH capsules could be considered to ameliorate clinical symptoms of Covid-19.

5.
J Infect Dis ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32437567

RESUMO

BACKGROUND AND AIMS: Long-term nucleos(t)ide analogues (NAs) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an anti-fibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs. METHODS: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5mg per day) plus BR (2g three times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥1 point by the Ishak Fibrosis Stage (IFS). RESULTS: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 week treatment was significantly higher in ETV+BR group (40% versus 31.8%, P=0.0069). Among 388 patients with cirrhosis (i.e., IFS ≥5) at baseline, the rate of cirrhosis reversal (i.e., IFS ≤4) was significantly higher in ETV+BR group (41.5% versus 30.7%, P=0.0103). CONCLUSIONS: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression.

6.
Medicine (Baltimore) ; 99(19): e20081, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384478

RESUMO

INTRODUCTION: S-1, a new oral fluorouracil chemotherapeutical drug, has been increasingly used in clinical maintenance after first-line chemotherapy for stage III or IV gastric carcinoma (GC) and colorectal carcinoma (CRC) for its own advantages. XiangshaLiujunzi Decoction (XSLJZD), a classic traditional Chinese medicine (TCM) formula with effects of alleviating the adverse reactions of chemotherapy and improving the quality of life of cancer patients has been gradually confirmed, with no more reports about the maintenance therapy mode of combination of chemotherapeutic drugs and TCM. We designed the study of XSLJZD combined with S-1 in the maintenance therapy of Stage III or IV GC and CRC, and hoped that this research program will go further and comprehensively evaluate its efficacy and safety. OBJECTIVES: The aim of this study was to determine the efficacy and safety of XSLJZD combined with S-1 in the maintenance therapy of stage III or IV GC and CRC. METHODS: This study is an open, single-center, randomized study. Patients with stage III or stage IV GC and CRC will be randomized (1:1) into S-1group, S-1 combined with XSLJZD group for 5 years of maintenance therapy. The primary endpoint was progression-free survival, and secondary end point was overall survival and Quality of Life Assessment (QOLA), which include an improvement in symptoms before and after treatment, Karnofsky Performance Status, and adverse events assessment. DISCUSSION: This study will provide meaningful clinical information about the combination of chemotherapeutic drugs S-1 with TCM in the maintenance therapy of stage III or IV GC and CRC. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-INR-16008575.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Quimioterapia de Manutenção , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Humanos , Estadiamento de Neoplasias , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/patologia , Resultado do Tratamento
8.
J Med Virol ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32437014

RESUMO

Currently, coronavirus disease 2019 (COVID-19) is a global pandemic disease with significant morbidity and mortality. Ozone may exert its antiviral actions and ozone therapy has been demonstrated therapeutically usefulness in influenza and novel viruses. In this letter, two severe cases with COVID-19 received ozone therapy were described. The results showed that ozone therapy may promote recovery of clinical condition and improvement of chest CT images, shorten the duration of viral shedding and length of hospital stay. This article is protected by copyright. All rights reserved.

9.
Sleep Breath ; 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32335852

RESUMO

PURPOSE: Inadequate sleep duration affects asthma and weight. The associations among sleep duration, asthma, and different weight statuses in the Chinese population need to be further determined. METHODS: The study included 32,776 Chinese adults from the China Health and Nutrition Survey during 2009-2015. Self-reported sleep duration was classified into three groups: ≤ 6 h (short), 7 to 8 h (optimal), and ≥ 9 h (long). Age, sex, smoking, drinking alcohol, and residence location were adjusted as potential confounding factors in a generalized estimating equations model. RESULTS: The prevalence of asthma in the Chinese population was approximately 1.17% (383/32,776). Asthmatics were associated with shorter sleep duration and higher indices of central obesity (mean waist circumference, waist to height ratio, and conicity index) than the population without asthma. After adjusting for potential confounding factors, odds ratios (ORs) indicated positive associations between sleep duration and asthma (short vs optimal, adjusted OR = 1.74, 95%CI 1.33, 2.26; and long vs optimal, adjusted OR = 1.51, 95%CI 1.18, 1.93). When stratified by weight status, the participants with central obesity showed highest prevalence of asthma among the three sleep duration groups. With the adjustment of confounding factors, underweight and obesity grouped by waist to height ratio and conicity index remained associated with higher risk of asthma among short and long sleepers than in optimal sleepers. CONCLUSIONS: Short and long sleepers with central obesity and underweight status were associated with significantly higher prevalence of asthma than optimal sleepers in Chinese adults.

10.
J Clin Lab Anal ; : e23346, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32342557

RESUMO

OBJECTIVE: This study aimed to investigate the abilities of long non-coding RNA PVT1 (lnc-PVT1) and microRNA-146a (miR-146a) in predicting chronic obstructive pulmonary disease (COPD) susceptibility and acute exacerbation risk, moreover, to explore the association of lnc-PVT1 with disease severity, inflammation, and miR-146a in patients with COPD. METHODS: A total of 80 acute exacerbation of COPD (AECOPD) patients, 80 stable COPD patients, and 80 healthy controls (HCs) were consecutively recruited. Peripheral blood samples of all participants were collected to isolate peripheral blood mononuclear cells (PBMCs), and serum: PBMCs were used to detect lnc-PVT1 and miR-146a by RT-qPCR; serum was used to detect inflammatory cytokines by ELISA. Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage of COPD was assessed. RESULTS: Lnc-PVT1 expression was highest in AECOPD patients, followed by stable COPD patients and HCs. Receiver operating characteristic curves disclosed that lnc-PVT1 distinguished AECOPD patients and stable COPD patients from HCs, also distinguished AECOPD patients from stable COPD patients. In AECOPD patients and stable COPD patients, lnc-PVT1 expression positively correlated with GOLD stage and levels of TNF-α, IL-6, IL-8, and IL-17. Moreover, lnc-PVT1 was negatively correlated with miR-146a. For miR-146a, its expression was lowest in AECOPD patients, followed by stable COPD patients and HCs, and it predicted reduced COPD susceptibility and decreased acute exacerbation risk; meanwhile, it negatively correlated with GOLD stage and inflammatory cytokine levels in AECOPD patients and stable COPD patients. CONCLUSION: Lnc-PVT1 assists the disease management and acute exacerbation risk monitoring of COPD via interaction with miR-146a.

11.
J Vet Intern Med ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255541

RESUMO

BACKGROUND: Determination of plasma adrenocotrophic hormone (ACTH) concentration (endogenous or thyrotropin-releasing hormone [TRH] stimulation test) is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID) in horses. Because ACTH is unstable, samples often are frozen to be shipped to laboratories or to allow for batch analysis of research samples. However, the effect of multiple freeze-thaw cycles on equine ACTH is unknown. OBJECTIVE: To determine the effects of multiple freeze-thaw cycles on immunoreactive ACTH concentration. ANIMALS: Twenty-eight horses ranging from 10 to 27 years of age were used. METHODS: Prospective study. Horses were divided into 4 groups: group 1, PPID-negative, without TRH stimulation; group 2, PPID-negative, with TRH stimulation; group 3, PPID-positive, without TRH stimulation; and group 4, PPID-positive, with TRH stimulation. Whole blood was collected from each horse at baseline or 30 minutes after TRH stimulation. Immunoreactive plasma ACTH concentration was determined using a chemiluminescence assay. Plasma samples then were frozen at -80°C >24 hours, thawed at 4°C and reanalyzed for 5 freeze-thaw cycles. Changes in plasma ACTH concentration were analyzed using a linear mixed-effect model. RESULTS: Significant effects of freeze-thaw cycles (P = .001) and PPID status (P = .04) on plasma ACTH concentration were observed, but no significant effect of TRH stimulation was identified. CONCLUSIONS AND CLINICAL IMPORTANCE: The plasma ACTH concentration is altered by freeze-thaw cycles, and the effect is observed sooner in horses with PPID. To diagnose PPID, multiple freeze-thaw cycles should be avoided when measuring plasma ACTH concentration.

12.
PLoS One ; 15(3): e0227244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196490

RESUMO

Community detection in complex networks is an important issue in network science. Several statistical measures have been proposed and widely applied to detecting the communities in various complex networks. However, due to the lack of flexibility resolution, some of them have to encounter the resolution limit and thus are not compatible with multi-scale structures of complex networks. In this paper, we investigated a statistical measure of interest for community detection, Significance [Sci. Rep. 3 (2013) 2930], and analyzed its critical behaviors based on the theoretical derivation of critical number of communities and the phase diagram in community-partition transition. It was revealed that Significance exhibits far higher resolution than the traditional Modularity when the intra- and inter-link densities of communities are obviously different. Following the critical analysis, we developed a multi-resolution version of Significance for identifying communities in the multi-scale networks. Experimental tests in several typical networks have been performed and confirmed that the generalized Significance can be competent for the multi-scale communities detection. Moreover, it can effectively relax the first- and second-type resolution limits. Finally, we displayed an important potential application of the multi-scale Significance in computational biology: disease-gene identification, showing that extracting information from the perspective of multi-scale module mining is helpful for disease gene prediction.

13.
BMC Mol Cell Biol ; 21(1): 8, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111164

RESUMO

BACKGROUND: TgDCX is a doublecortin-domain protein associated with the conoid fibers, a set of strongly curved non-tubular tubulin-polymers in Toxoplasma. TgDCX deletion impairs conoid structure and parasite invasion. TgDCX contains two tubulin-binding domains: a partial P25α and the DCX/doublecortin domain. Orthologues are found in apicomplexans and their free-living relatives Chromera and Vitrella. RESULTS: We report that isolated TgDCX-containing conoid fibers retain their pronounced curvature, but loss of TgDCX destabilizes the fibers. We crystallized and determined the 3D-structure of the DCX-domain, which is similar to those of human doublecortin and well-conserved among TgDCX orthologues. However, the orthologues vary widely in targeting to the conoid in Toxoplasma and in modulating microtubule organization in Xenopus cells. Several orthologues bind to microtubules in Xenopus cells, but only TgDCX generates short, strongly curved microtubule arcs. EM analysis shows microtubules decorated with TgDCX bundled into rafts, often bordered on one edge by a "C"-shaped incomplete tube. A Chromera orthologue closely mimics TgDCX targeting in Toxoplasma and binds to microtubules in Xenopus cells, but does not generate arcs or "C"-shaped tubes, and fails to rescue the defects of the TgDCX-knockout parasite. CONCLUSIONS: These observations suggest that species-specific features of TgDCX enable it to generate strongly curved tubulin-polymers to support efficient host-cell invasion.

14.
Cancer Lett ; 478: 45-55, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32160976

RESUMO

Multiple myeloma (MM) is an incurable hematological malignancy, for which novel effective therapies are urgently needed. We synthesized a novel phosphoramide compound, DCZ0847, showing a potent anti-myeloma activity both in vitro and in vivo. DCZ0847 showed high cytotoxicity towards primary MM cells but had no effect on normal cells and was well tolerated in vivo. The anti-myeloma activity of DCZ0847 was associated with inhibition of cell proliferation; promotion of cell apoptosis via mitochondrial transmembrane potential collapse and caspase-mediated extrinsic or intrinsic apoptotic pathways; and the induction of G2/M phase arrest via downregulation of CDC25C, CDK1, and cyclin B1. In particular, DCZ0847 induced DNA damage and triggered a DNA-damage response by enhancing the levels of γ-H2A.X, phosphorylated (p)-ATM, p-ATR, p-Chk1, and p-Chk2. Additionally, DCZ0847 was able to overcome the bone marrow stromal cells-induced proliferation of MM cells and blocked JAK2/STAT3 signaling. Importantly, DCZ0847 acted synergistically with bortezomib, with the combination exerting greater cytotoxic effects in vitro and in vivo. Together, our results indicate that DCZ0847, alone or in combination with bortezomib, may represent a potential new therapy for patients with MM.

15.
Zhongguo Fei Ai Za Zhi ; 23(3): 136-141, 2020 03 20.
Artigo em Chinês | MEDLINE | ID: mdl-32077441

RESUMO

Since late December 2019, an outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. With the spread of COVID-19, the routine clinical diagnosis and treatment for lung cancer patients has been disturbed. Due to the systemic immunosuppressive of lung cancer patients caused by the malignancy and anticancer treatments, lung cancer patients are more susceptible to infection than healthy individuals. Furthermore, patients with cancer had poorer prognosis from infection. Lung cancer patients should be the priority group for COVID-19 prevention. The protection provisions and control measures aiming to protect lung cancer patients from COVID-19 have been increasingly concerned. During the COVID-19 outbreak period, it should be carefully differentiated for fever and respiratory symptoms for lung cancer patients receiving anti-tumor treatment, in order to evaluate the risk of COVID-19. Moreover, it is necessary to carry out meticulous and individualized clinical management for lung cancer patients to effectively protect the patients from COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Surtos de Doenças , Hospedeiro Imunocomprometido , Neoplasias Pulmonares , Pneumonia Viral , Betacoronavirus/patogenicidade , China , Infecções por Coronavirus/epidemiologia , Suscetibilidade a Doenças , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Planejamento de Assistência ao Paciente , Pneumonia Viral/epidemiologia , Risco
16.
Artigo em Inglês | MEDLINE | ID: mdl-32012837

RESUMO

Understanding the sources of volatile organic compounds (VOCs) is essential in the implementation of abatement measures of ground-level ozone and secondary organic aerosols. In this study, we conducted offline VOC measurements at residential, industrial, and background sites in Wuhan City from July 2016 to June 2017. Ambient samples were simultaneously collected at each site and were analyzed using a gas chromatography-mass spectrometry/flame ionization detection system. The highest mixing ratio of total VOCs was measured at the industrial site, followed by the residential, and background sites. Alkanes constituted the largest percentage (>35%) in the mixing ratios of quantified VOCs at the industrial and residential sites, followed by oxy-organics and alkenes (15-25%).The values of aromatics and halohydrocarbons were less than 15%. By contrast, the highest values of oxy-organics accounted for more than 30%. The model of positive matrix factorization was applied to identify the VOC sources and quantify the relative contributions of various sources. Gasoline-related emission (the combination of gasoline exhaust and gas vapor) was the most important VOC-source in the industrial and residential areas, with a relative contribution of 32.1% and 40.4%, respectively. Industrial process was the second most important source with a relative contribution ranging from 30.0% to 40.7%. The relative contribution of solvent usage was 6.5-22.3%. Meanwhile, the relative contribution of biogenic emission was only within the range of 2.0-5.0%. These findings implied the importance of controlling gasoline-related and industrial VOC emissions in reducing the VOC emissions in Wuhan.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32024116

RESUMO

Life expectancy (LE) is a comprehensive and important index for measuring population health. Research on LE and its influencing factors is helpful for health improvement. Previous studies have neither considered the spatial stratified heterogeneity of LE nor explored the interactions between its influencing factors. Our study was based on the latest available LE and social and environmental factors data of 31 provinces in 2010 in China. Descriptive and spatial autocorrelation analyses were performed to explore the spatial characteristics of LE. Furthermore, the Geographical Detector (GeoDetector) technique was used to reveal the impact of social and environmental factors and their interactions on LE as well as their optimal range for the maximum LE level. The results show that there existed obvious spatial stratified heterogeneity of LE, and LE mainly presented two clustering types (high-high and low-low) with positive autocorrelation. The results of GeoDetector showed that the number of college students per 100,000 persons (NOCS) could mainly explained the spatial stratified heterogeneity of LE (Power of Determinant (PD) = 0.89, p < 0.001). With the discretization of social and environmental factors, we found that LE reached the highest level with birth rate, total dependency ratio, number of residents per household and water resource per capita at their minimum range; conversely, LE reached the highest level with consumption level, GDP per capita, number of college students per 100,000 persons, medical care expenditure and urbanization rate at their maximum range. In addition, the interaction of any two factors on LE was stronger than the effect of a single factor. Our study suggests that there existed obvious spatial stratified heterogeneity of LE in China, which could mainly be explained by NOCS.

19.
Sci Rep ; 10(1): 362, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941966

RESUMO

This retrospective study was designed to investigate the heterogeneity of patients with cervical cancer in stage IIIC1 (the 2018 International Federation of Gynecology and Obstetrics staging system, FIGO) and conduct a risk stratification for this group of patients. We reviewed clinical records of 325 patients with stage IIIC1 treated with definitive concurrent chemoradiotherapy in our institute between January 2008 and December 2014. The median follow-up duration was 28.4 months (range: 1.9-114.2 months). The 3-year DFS for the 325 eligible patients was 66.3%. Tumor size of ≥4 cm and number of pelvic lymph node metastasis ≥2 were identified as adverse prognostic factors for disease free survival (DFS) in cervical cancer patients with stage IIIC1 (2018). A risk stratification based on the number of identified prognostic factors for DFS was performed. The 3-year DFS for patients in low-risk (without prognostic factor), intermediate-risk (with one prognostic factor) and high-risk group (with two prognostic factors) was 92.1%, 70.0%, and 51.1%, respectively (P < 0.001). Our study confirms the heterogeneity of patients with cervical cancer in FIGO stage IIIC1 (the 2018 FIGO staging system). Tumor size and number of pelvic lymph node metastasis (PLNM) are significant prognostic factors for DFS in patients with FIGO stage IIIC1. The next revision of FIGO staging system for cervical cancer, especially for stage IIIC1, should focus on tumor size and number of pelvic lymph node metastasis.

20.
Theranostics ; 10(2): 462-483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903132

RESUMO

Drug delivery for tumor theranostics involves the extensive use of the enhanced permeability and retention (EPR) effect. Previously, various types of nanomedicines have been demonstrated to accumulate in solid tumors via the EPR effect. However, EPR is a highly variable phenomenon because of tumor heterogeneity, resulting in low drug delivery efficacy in clinical trials. Because ultrasonication using micro/nanobubbles as contrast agents can disrupt blood vessels and enhance the specific delivery of drugs, it is an effective approach to improve the EPR effect for the passive targeting of tumors. In this review, the basic thermal effect, acoustic streaming, and cavitation mechanisms of ultrasound, which are characteristics that can be utilized to enhance the EPR effect, are briefly introduced. Second, micro/nanobubble-enhanced ultrasound imaging is discussed to understand the validity and variability of the EPR effect. Third, because the tumor microenvironment is complicated owing to elevated interstitial fluid pressure and the deregulated extracellular matrix components, which may be unfavorable for the EPR effect, few new trends in smart bubble drug delivery systems, which may improve the accuracy of EPR-mediated passive drug targeting, are summarized. Finally, the challenging and major concerns that should be considered in the next generation of micro/nanobubble-contrast-enhanced ultrasound theranostics for EPR-mediated passive drug targeting are also discussed.

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