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1.
Chemosphere ; 286(Pt 2): 131747, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34358893

RESUMO

Pyrimidine and purine bases (adenine, cytosine, guanine and thymine) are important precursors of organic chloramines (OC) and disinfection by-products (DBPs) during chlor(am)ination. In this study, OC and DBP formation derived from pyrimidine and purine bases during chlor(am)ination, post-chlor(am)ination after pretreated by UV alone and UV/chlorination were systematically investigated with ultraviolet light-emitting diodes (UV-LEDs, 265 and 275 nm) and low pressure mercury lamp (LPUV, 254 nm). The results revealed that higher OC formation was observed during chlorination than that during chloramination of pyrimidine and purine bases. The degradation of pyrimidine and purine bases followed the pseudo-first-order kinetics. Both solution pH and UV wavelength played vital influence on the degradation of pyrimidine and purine bases. In terms of fluence-based rate constants (kobs), the degradation rates of pyrimidine and purine bases decreased in the order of 275 nm > 265 nm > 254 nm in alkaline conditions. The synergistic effects of kobs, chlorine,kobs, •OH and kobs, RCS contributed to the differences of pyrimidine and purine bases degradation at different pH values and UV wavelengths. A vital suppression of OC formation was observed during post-chlorination after pretreated by 275 nm UV-LED/chlorination. In addition, compared with LPUV (254 nm), less DBP formation was observed at UV-LED (275 nm), especially during the UV/chlorine process. The phenomena obtained in this study indicated that 275 nm UV-LED combined with chlorine could be a preferred method to promote pyrimidine and purine bases degradation and control OC and DBP formation in practical water treatment.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Cloraminas , Cloro , Desinfecção , Halogenação , Purinas , Pirimidinas , Poluentes Químicos da Água/análise
2.
Artigo em Inglês | MEDLINE | ID: mdl-34811946

RESUMO

BACKGROUND: Gut health plays a vital role in the overall health and disease control of human and animals. Intestinal oxidative stress is a critical player in the induction and progression of cachexia which is conventionally diagnosed and classified by weight loss. Therefore, reduction of intestinal oxidative injury is a common and highly effective strategy for the maintenance of human and animal health. Here we identify intestinal myeloid differentiation primary response gene 88 (MyD88) as a novel target for intestinal oxidative stress using canonical oxidative stress model induced by paraquat (PQ) in vitro and in vivo. METHODS: Intestinal oxidative stress was induced by administration of PQ in intestinal epithelial cells (IECs) and mouse model. Cell proliferation, apoptosis, DNA damage, mitochondrial function, oxidative status, and autophagy process were measured in wild-type and MyD88-deficient IECs during PQ exposure. Autophagy inhibitor (3-methyladenine) and activator (rapamycin) were employed to assess the role of autophagy in MyD88-deficient IECs during PQ exposure. MyD88 specific inhibitor, ST2825, was used to verify function of MyD88 during PQ exposure in mouse model. RESULTS: MyD88 protein levels and apoptotic rate of IECs are increased in response to PQ exposure (P < 0.001). Intestinal deletion of MyD88 blocks PQ-induced apoptosis (~42% reduction) and DNA damage (~86% reduction), and improves mitochondrial fission (~37% reduction) and function including mitochondrial membrane potential (~23% increment) and respiratory metabolism capacity (~26% increment) (P < 0.01). Notably, there is a marked decrease in reactive oxygen species in MyD88-deficient IECs during PQ exposure (~70% reduction), which are consistent with high activity of antioxidative enzymes (~83% increment) (P < 0.001). Intestinal ablation of MyD88 inhibits mTOR signalling, and further phosphorylates p53 proteins during PQ exposure, which eventually promotes intestinal autophagy (~74% increment) (P < 0.01). Activation of autophagy (rapamycin) promotes IECs growth as compared with 3-methyladenine-treatment during PQ exposure (~173% increment), while inhibition of autophagy (3-methyladenine) exacerbates oxidative stress in MyD88-deficient IECs (P < 0.001). In mouse model, inhibition of MyD88 using specific inhibitor ST2825 followed by PQ treatment effectively ameliorates weight loss (~4% increment), decreased food intake (~92% increment), gastrocnemius and soleus loss (~24% and ~20% increment, respectively), and intestinal oxidative stress in an autophagy dependent manner (P < 0.01). CONCLUSIONS: MyD88 modulates intestinal oxidative stress in an autophagy-dependent mechanism, which suggests that reducing MyD88 level may constitute a putative therapeutic target for intestinal oxidative injury-induced weight loss.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34806347

RESUMO

BACKGROUND: Unintentional weight loss (cachexia) has been associated with poor outcomes in chronic heart failure (CHF). Meteorin-like (Metrnl) is a novel myokine with protective effects on cardiovascular diseases. However, the change of Metrnl concentrations and its role in elderly patients with CHF remains unclear. The aim of this study was to evaluate the association of serum Metrnl with weight loss and outcomes in elderly patients with CHF. METHODS: A total of 931 consecutive elderly patients (aged 60 years and older) with CHF and 135 age-matched and sex-matched control subjects were enrolled. Serum Metrnl concentration was measured by enzyme-linked immunosorbent assay. Body weight was measured at baseline and 12 months. RESULTS: Median of serum Metrnl levels was lower in CHF patients when compared with controls [201.31 (184.95-261.16) pg/mL vs. 168.68 (103.15-197.54) pg/mL, P < 0.001]. Patients with the lowest levels of Metrnl had higher N-terminal pro brain natriuretic peptide (NT-proBNP) levels but lower left ventricular eject fraction (LVEF) and estimated glomerular filtration rate (P < 0.001). Lower serum Metrnl was associated with a higher risk of >5% weight loss from baseline to 12 months [odds ratio = 6.13, 95% confidence interval (CI) = 2.57-14.62 per log decrease; P < 0.001]. Serum Metrnl levels were decreased as LVEF decreased (P < 0.001) and were positively correlated with LVEF (r = 0.267, P < 0.001) but negatively correlated with NT-proBNP levels (r = -0.257, P < 0.001). Cox regression analysis suggested that lower serum Metrnl was associated with higher cardiovascular mortality [hazard ratio (HR) = 6.71, 95% CI = 3.41-13.18 per log decrease; P < 0.001], CHF rehospitalization (HR = 3.07, 95% CI = 1.82-5.17 per log decrease; P < 0.001), and the combined major adverse cardiac event(s) (MACEs) (HR = 5.38, 95% CI = 3.51-8.25 per log decrease; P < 0.001). The Kaplan-Meier survival curves showed that low concentration of Metrnl was a prognostic indicator of MACEs in patients with CHF. CONCLUSIONS: Our study suggests that lower serum Metrnl level is correlated with weight loss and the severity of cardiac dysfunction in elderly patients with CHF.

4.
Entropy (Basel) ; 23(11)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34828217

RESUMO

Detecting multipartite quantum coherence usually requires quantum state reconstruction, which is quite inefficient for large-scale quantum systems. Along this line of research, several efficient procedures have been proposed to detect multipartite quantum coherence without quantum state reconstruction, among which the spectrum-estimation-based method is suitable for various coherence measures. Here, we first generalize the spectrum-estimation-based method for the geometric measure of coherence. Then, we investigate the tightness of the estimated lower bound of various coherence measures, including the geometric measure of coherence, the l1-norm of coherence, the robustness of coherence, and some convex roof quantifiers of coherence multiqubit GHZ states and linear cluster states. Finally, we demonstrate the spectrum-estimation-based method as well as the other two efficient methods. We observe that the spectrum-estimation-based method outperforms other methods in various coherence measures, which significantly enhances the accuracy of estimation.

5.
Inquiry ; 58: 469580211055636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34789038

RESUMO

BACKGROUND: Brain metastasis is an important cause of breast cancer-related death. AIM: We evaluated the relationships between breast cancer subtype and prognosis among patients with brain metastasis at the initial diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was searched to identify patients with brain metastasis from breast cancer between 2010 and 2015. Multivariable Cox proportional hazard models were used to identify factors that were associated with survival among patients with initial brain metastases. The Kaplan-Meier method was used to compare survival outcomes according to breast cancer subtype. RESULTS: Among 752 breast cancer patients with brain metastasis at diagnosis, 140 patients (18.6%) underwent primary surgery and 612 patients (81.4%) did not undergo surgery, while 460 patients (61.2%) received chemotherapy and 292 patients (38.8%) did not receive chemotherapy. Multivariable analysis revealed that, relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with significantly poorer overall survival (hazard ratio: 2.52, 95% confidence interval: 1.99-3.21), independent of age, sex, race, marital status, insurance status, grade, liver involvement, lung involvement, primary surgery, radiotherapy, and chemotherapy. The median overall survival intervals were 12 months for HR+/HER2-, 19 months for HR+/HER2+, 11 months for HR-/HER2+, and 6 months for HR-/HER2- (P < .0001). Relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with a significantly higher risk of mortality among patients, and the association was stronger among patients who received chemotherapy (p for interaction = .005). CONCLUSIONS: Breast cancer subtype significantly predicted overall survival among patients with brain metastasis at diagnosis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34831753

RESUMO

Economic development in the "new era" will require green innovation. To encourage the growth of green technology innovation, it has become fashionable to strengthen environmental regulation. However, the impact of environmental regulation on green technology innovation, as well as the role of government subsidies, needs to be examined. Utilizing fixed-effect models and 2SLS models to explore the impact of environmental regulation on green technology innovation in China from 2003 to 2017, this research sought to examine whether environmental regulations impact green technology innovation, as well as the role of government subsidies in the above-mentioned influence path. The findings support the Porter Hypothesis by demonstrating an inverted "U" relationship between environmental regulation and green technology innovation. The impact of environmental regulation on green technology innovation varies by region. To be specific, there is an inverted "U" relationship between environmental regulation and green technology innovation in China's central and central coast regions. In comparison, the north area, southern coast, and southwest region exhibit a "U" relationship between the two. The relationship is not significant in the Beijing-Tianjin region. Additionally, government subsidies act as an intermediate in this process, positively influencing firms to pursue green technology innovation during the earliest stages of environmental regulation strengthening. However, government subsidies above a certain level are unproductive and should be used appropriately and phased off in due course.

7.
Environ Pollut ; 293: 118572, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838710

RESUMO

Paraquat, a widely used herbicide, causes environmental pollution, and liver injury in humans and animals. As a natural compound in fruits, ellagic acid (EA) shows anti-inflammatory and antioxidant effects. This study examines the beneficial effects of dietary EA against the paraquat-induced hepatic injury and further explores the underlying molecular mechanisms using a piglet model. Post-weaning piglets are fed basal diet supplemented with 50 mg/kg, 100 mg/kg, or 200 mg/kg EA for 3 weeks. At week 2, hepatic injury is induced by 4 mg/kg paraquat followed by 7 days recovery. EA supplementation significantly mitigates paraquat-induced hepatic fibrosis, steatosis, and high apoptotic rate. In agreement, EA supplementation reduces serum pro-inflammatory levels, ameliorates inflammatory cells infiltration into hepatic tissue, which are associated with suppressed NF-κB signaling during paraquat exposure. In addition, EA supplementation significantly improves activities of antioxidative enzymes which were correlated with activated Nrf2/Keap 1 signaling during paraquat exposure. Furthermore, EA supplementation restores cecal microbial community during paraquat exposure. The protective effect of EA is strongly linked with increased relative abundance of Lactobacillus reuteri and Lactobacillus amylovorus. Taken together, EA supplementation effectively reduced the occurrence of hepatic oxidative damage and inflammation induced by paraquat through modulating cecal microbial communities, which provides a novel nutritional therapeutic strategy for hepatic injury.

8.
J Food Biochem ; : e13995, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730855

RESUMO

Tyrosinase (polyphenol oxidase) is the key enzyme of enzymatic browning in fruits and vegetables. In this research, the impact of ascorbic acid on tyrosinase and its anti-browning effect on fresh-cut Fuji apple were investigated. Ascorbic acid had a dual effect on tyrosinase with a half inhibitory concentration (IC50 ) of 13.40 ± 0.05 µM. Fluorescence assay demonstrated that ascorbic acid interacted with tyrosinase in a dynamic contaction caused by Förster's resonance energy transfer (FRET) and induced a conformational change of the enzyme. Thermodynamic analysis, copper interaction, and molecular docking further confirmed that ascorbic acid could chelate the copper ions located in active center and interact with amino acid residues of tyrosinase via hydrophobic interaction. In addition, ascorbic acid prevented the browning of fresh-cut apples by increasing APX activity and inhibiting PPO and POD activities which reduce the oxidation of total phenolics and flavonoids. PRACTICAL APPLICATIONS: The present study demonstrated that ascorbic acid had a strong inhibitory activity against tyrosinase (IC50 = 13.40 ± 0.05 µM) and anti-browning activity against fresh-cut Fuji apple. It could delay the browning degree of apple juice, increase APX activity, inhibit PPO and POD activities, and reduce the oxidation of total phenolics and flavonoids. These findings provided a basis for the feasible application of ascorbic acid on the preservation of fruits.

9.
Am J Transl Res ; 13(10): 11987-11992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786132

RESUMO

OBJECTIVE: To investigate the expression levels and significance of T lymphocyte subsets, RANTES (regulated on activation, normal T cell expressed and secreted), and inflammatory factors in serum of patients with abdominal aortic aneurysm (AAA). METHODS: 32 patients each with large (large AAA) and small (small AAA) groups were selected, and 32 normal subjects were selected as control group. Serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), RANTES and CD4+ T cells, CD8+ T cells and CD4+/CD8+ expressions in peripheral blood were compared among the three groups. RESULTS: Compared with control group, CRP, TNF-α, IL-6, RANTES and CD8+ T cells levels were higher in large and small AAA groups, while CD4+ T cells and CD4+/CD8+ levels were lower (P<0.05). Compared with small AAA group, CRP, TNF-α, IL-6, RANTES and CD8+ T cells levels in large AAA group were higher, while CD4+ T cells and CD4+/CD8+ levels were lower (P<0.05). The abdominal aorta diameter was positively correlated with CRP, TNF-α, IL-6, RANTES and CD8+ T cells levels, while negatively correlated with CD4+ T cells and CD4+/CD8+ levels (P<0.001). Receiver operating characteristic curve results showed that the areas under the curve of CRP, TNF-α, IL-6 and RANTES in the diagnosis of AAA were all more than 0.800 (P<0.001). CONCLUSION: The serum of patients with AAA was in a state of inflammatory activation, and the expression of T lymphocytes was abnormal. The levels of T lymphocyte subsets, RANTES and inflammatory factors were closely related to abdominal aorta diameter. CRP, TNF-α, IL-6 and RANTES levels could be used as auxiliary indicators for the diagnosis of AAA.

10.
Ann Vasc Surg ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34644628

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

11.
Nanoscale Res Lett ; 16(1): 151, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622366

RESUMO

The electron multipliers gain is closely related to the secondary electron emission coefficient (SEE) of the emission layer materials. The SEE is closely related to the thickness of the emission layer. If the emission layer is thin, the low SEE causes the low gain of electron multipliers. If the emission layer is thick, the conductive layer can't timely supplement charge to the emission layer, the electronic amplifier gain is low too. The electron multipliers usually choose Al2O3 and MgO film as the emission layer because of the high SEE level. MgO easy deliquescence into Mg(OH)2 Mg2(OH)2CO3 and MgCO3 resulting in the lower SEE level. The SEE level of Al2O3 is lower than MgO, but Al2O3 is stable. We designed a spherical system for testing the SEE level of materials, and proposed to use low-energy secondary electrons instead of low-energy electron beam for neutralization to measuring the SEE level of Al2O3, MgO, MgO/Al2O3, Al2O3/MgO, and precisely control the film thickness by using atomic layer deposition. We propose to compare the SEE under the adjacent incident electrons energy to partition the SEE value of the material, and obtain four empirical formulas for the relationship between SEE and thickness. Since the main materials that cause the decrease in SEE are Mg2(OH)2CO3 and MgCO3, we use the C element atomic concentration measured by XPS to study the deliquescent depth of the material. We propose to use the concept of transition layer for SEE interpretation of multilayer materials. Through experiments and calculations, we put forward a new emission layer for electron multipliers, including 2-3 nm Al2O3 buffer layer, 5-9 nm MgO main-body layer, 1 nm Al2O3 protective layer or 0.3 nm Al2O3 enhancement layer. We prepared this emission layer to microchannel plate (MCP), which significantly improved the gain of MCP. We can also apply this new emission layer to channel electron multiplier and separate electron multiplier.

12.
Appl Opt ; 60(27): 8349-8359, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34612932

RESUMO

In this paper, a compact fluorescence hyperspectral imaging system based on a prism-grating-prism (PGP) structure is designed. Its spectrometer spectral range is 400-1000 nm with a spectral resolution of 2.5 nm, and its weight is less than 1.7 kg. The PGP imaging spectrometer combines the technical advantages of prism and grating, by not only using six lenses for imaging and collimation to realize the dual telecentres of object and image but also having a "straight cylinder" structure, which makes the installation and adjustment simple, compact, and stable. By the push-broom method, we obtained the three-dimensional cubic data of different oil products. By normalization processing, minimum noise separation transformation processing, visualization processing, and support vector machine classification processing of different oil fluorescence hyperspectral data, we demonstrate that the fluorescence hyperspectral imaging system can identify different kinds of oil and recognize the oil film thickness. The fluorescence hyperspectral imaging system can be used in oil spill detection, resource exploration, natural disaster monitoring, environmental pollution assessment, and many other fields.

13.
Asian J Androl ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34596600

RESUMO

To reduce treatment-related side effects in low-risk prostate cancer (PCa), both focal therapy and deferred treatments, including active surveillance (AS) and watchful waiting (WW), are worth considering over radical prostatectomy (RP). Therefore, this study aimed to compare long-term survival outcomes between focal therapy and AS/WW. Data were obtained and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included. Focal therapy included cryotherapy and laser ablation. Multivariate Cox proportional hazards models were used to compare overall mortality (OM) and cancer-specific mortality (CSM) between AS/WW and focal therapy, and propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. A total of 19 292 patients with low-risk PCa were included in this study. In multivariate Cox proportional hazards model analysis, the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW (hazard ratio [HR] = 1.35, 95% confidence interval [CI]: 1.02-1.79, P = 0.037), whereas no significant difference was found in CSM (HR = 0.98, 95% CI: 0.23-4.11, P = 0.977). After PSM, the OM and CSM of focal therapy and AS/WW showed no significant differences (HR = 1.26, 95% CI: 0.92-1.74, P = 0.149; and HR = 1.26, 95% CI: 0.24-6.51, P = 0.782, respectively). For patients with low-risk PCa, focal therapy was no match for AS/WW in decreasing OM, suggesting that AS/WW could bring more overall survival benefits.

14.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(5): 503-506, 2021 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-34628761

RESUMO

OBJECTIVE: To develop a self deep breathing training device which can improve lung function compliance and blood oxygen saturation. METHODS: The device consists of four parts:flow tube, measuring cylinder, mobile phone holder and meridian guidance audio-visual synthesis training software. The flow tube measures the flow rate of inhaled gas, the metering cylinder measures the total amount of inhaled gas, and the mobile phone rack is equipped with a mobile phone storing the meridian guidance audio-visual synthesis training software. RESULTS: The device is reasonable in structure and flexible in operation, which can meet the requirements of self deep inspiration training under the guidance of training module. CONCLUSIONS: Deep inspiration training under the guidance of guidance training module can form "deep and slow" abdominal breathing, and then improve lung function.


Assuntos
Telefone Celular , Meridianos , Pulmão , Software
15.
Front Nutr ; 8: 738281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692749

RESUMO

This study aimed to investigate the beneficial effect of baicalin-zinc complex (BZN) on intestinal microorganisms in deoxynivalenol (DON)-challenged piglets and the association between intestinal microorganisms and host immunity and hormone secretion. Forty weaned piglets were randomly divided into four treatments with 10 piglets in each treatment: (1) control (Con) group (pigs fed basal diet); (2) DON group (pigs fed 4 mg DON/kg basal diet); (3) BZN group (pigs fed 0.5% BZN basal diet); and (4) DBZN group (pigs fed 4 mg DON/kg and 0.5% BZN basal diet). The experiment lasted for 14 days. The BZN supplementation in DON-contaminated diets changed the intestinal microbiota composition and increased intestinal microbial richness and diversity of piglets. The BZN supplementation in DON-contaminated diets also alleviated the inflammatory responses of piglets and modulated the secretion of hormones related to the growth axis. Moreover, microbiota composition was associated with inflammatory and hormone secretion. In conclusion, BZN alleviated inflammatory response and hormone secretion in piglets, which is associated with the intestinal microbiome.

16.
J Ovarian Res ; 14(1): 143, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711234

RESUMO

BACKGROUND: FOXL2 mutations in human cause Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). While type II BPES solely features eyelid abnormality, type I BPES involves not only eyelid but also ovary, leading to primary ovarian insufficiency (POI) and female infertility. Current mainstream reproductive option for type I BPES is embryo or oocyte donation. Attempts on assisted reproductive technology (ART) aiming biological parenthood in this population were sparse and mostly unsuccessful. CASE PRESENTATION: Two Chinese type I BPES patients with low anti-müllerian hormone (AMH) and elevated follicle stimulating hormone (FSH) presented with primary infertility in their early 30s. Genetic studies confirmed two heterozygous duplication mutations that were never reported previously in East Asian populations. They received in vitro fertilization (IVF) treatment and both exhibited resistance to gonadotropin and difficulty in retrieving oocytes in repeated cycles. Doubled to quadrupled total gonadotropin doses were required to awaken follicular response. Patient 1 delivered a baby girl with the same eyelid phenotype and patient 2 had ongoing live intrauterine pregnancy at the time of manuscript submission. CONCLUSIONS: This is the second reported live birth of biological offspring in type I BPES patients, and first success using IVF techniques. It confirmed that ART is difficult but feasible in type I BPES. It further alerts clinicians and genetic counsellors to type female BPES patients with caution in view of the precious and potentially narrowed reproductive window.

17.
Front Cell Dev Biol ; 9: 719351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631707

RESUMO

Chronic catecholamine stress (CCS) induces the occurrence of cardiomyopathy-pathological cardiac hypertrophy (PCH), which is characterized by left ventricular systolic dysfunction (LVSD). Recently, mounting evidence has implicated myocardial inflammation in the exacerbation of pathological cardiac remodeling. However, there are currently no well-defined treatment interventions or regimes targeted at both the attenuation of maladaptive myocardial hypertrophy and inflammation during CCS to prevent PCH. G protein-coupled receptor kinase 5 (GRK5) and adenylyl cyclases (ACs)-cAMP mediates both cardiac and inflammatory responses. Also, GRK5 and ACs are implicated in stress-induced LVSD. Herein, we aimed at preventing PCH during CCS via modulating adaptive cardiac and inflammatory responses by inhibiting GRK5 and/or stimulating ACs. Isoproterenol-induced cardiomyopathy (ICM) was modeled using 0.5 mg/100 g/day isoproterenol injections for 40 days. Alterations in cardiac and inflammatory responses were assessed from the myocardia. Similarities in the immunogenicity of cardiac troponin I (cTnI) and lipopolysaccharide under CCS were assessed, and Amlexanox (35 µM/ml) and/or Forskolin (10 µM/ml) were then employed in vitro to modulate adaptive inflammatory responses by inhibiting GRK5 or activating ACs-cAMP, respectively. Subsequently, Amlexanox (2.5 mg/100 g/day) and/or Forskolin (0.5 mg/100 g/day) were then translated into in vivo during CCS to modulate adaptive cardiac and inflammatory responses. The effects of Amlexanox and Forskolin on regulating myocardial systolic functions and inflammatory responses during CCS were ascertained afterward. PCH mice had excessive myocardial hypertrophy, fibrosis, and aggravated LVSD, which were accompanied by massive CD68+ inflammatory cell infiltrations. In vitro, Forskolin-AC/cAMP was effective than Amlexanox-GRK5 at downregulating proinflammatory responses during stress; nonetheless, Amlexanox and Forskolin combination demonstrated the most efficacy in modulating adaptive inflammatory responses. Individually, the translated Amlexanox and Forskolin treatment interventions were ineffective at subduing the pathological remodeling and sustaining cardiac function during CCS. However, their combination was potent at preventing LVSD during CCS by attenuating maladaptive myocardial hypertrophy, fibrosis, and inflammatory responses. The treatment intervention attained its potency mainly via Forskolin-ACs/cAMP-mediated modulation of cardiac and inflammatory responses, coupled with Amlexanox inhibition of GRK5 mediated maladaptive cascades. Taken together, our findings highlight the Amlexanox and Forskolin combination as a potential therapeutic intervention for preventing the occurrence of pathological cardiac hypertrophy during chronic stress.

18.
Artigo em Chinês | MEDLINE | ID: mdl-34628817

RESUMO

Objective:To investigate the correlation of conventional ultrasound features and related factors with BRAFV600E gene mutation in papillary thyroid carcinoma(PTC). Methods:A total of 266 nodules in 208 patients with PTC confirmed by operation and pathology in First Affiliated Hospital of Jinzhou Medical University from October 2019 to March 2021 were selected. BRAFV600E gene was detected by real-time fluorescence PCR quantitative technique after operation. According to the results of gene detection, the patients were divided into gene mutation positive group and gene mutation negative group. The routine ultrasound features and clinical data of the patients were collected, and the correlation with BRAFV600E gene mutation was analyzed. Results:Among the 266 samples, 188 cases(70.7%) had gene mutation. Univariate analysis showed that there were significant differences in age, nodular edge, capsule boundary, microcalcification and abnormal cervical lymph nodes between the two groups(P<0.05). The results of Logistic multivariate regression analysis showed that age, nodular margin and abnormal cervical lymph nodes were independent influencing factors of BRAFV600E gene mutation in patients with PTC. ROC curve showed that when the age was 46.5 years old, the Youden index was the highest. Conclusion:BRAFV600E gene mutation is associated with age≤46.5 years old, uneven edge of nodules and abnormal lymph nodes in neck in patients with PTC. The above characteristics can be used to evaluate BRAFV600E gene mutation and have certain guiding significance for clinical diagnosis, treatment and prognosis.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética , Ultrassonografia
19.
Int J Nanomedicine ; 16: 5755-5776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471351

RESUMO

Background: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration. Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly. Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and -15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect. Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.


Assuntos
Neoplasias Encefálicas , Glioma , Animais , Barreira Hematoencefálica , Encéfalo , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Colesterol , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Lipossomos/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/uso terapêutico
20.
Shanghai Kou Qiang Yi Xue ; 30(3): 302-305, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476450

RESUMO

PURPOSE: To evaluate the safety and efficacy of sedation and analgesia using dexmedetomidine combined with flurbiprofen axetil in multiple complex teeth extraction under local anesthesia. METHODS: According to the inclusion and exclusion criteria of the study, 40 patients scheduled for multiple complex teeth (4-6) extraction were randomly divided into 2 groups: experimental group (sedation and analgesia using dexmedetomidine combined with flurbiprofen axetil in addition to local anesthesia, n=20) and control group (local anesthesia, n=20). The mean arterial pressure(MAP), heart rate(HR), Ramsay sedation score, VAS pain score of each patient at T0(basis value), T1 (during local anesthesia), T2(during extraction), T3(10 minutes after extraction) and the follow-up results were recorded. SAS 8.0 software was used for statistical analysis. RESULTS: Compared to T0 and control group at the same time, the experimental group revealed more stable mood and hemodynamic manifestation and better analgesic effect (P<0.05), from T1 to T3, patients in the control group showed increased blood pressure, heart rate, emotional fluctuation, bodily and facial pain(P<0.05). The follow-up results showed 5 and 0 patients taking painkillers in the control and experimental group, respectively(P<0.05). CONCLUSIONS: Sedation and analgesia using dexmedetomidine combined with flurbiprofen axetil in addition to local anesthesia is a safe and effective approach in multiple complex teeth extraction.


Assuntos
Dexmedetomidina , Flurbiprofeno , Anestesia Local , Dexmedetomidina/uso terapêutico , Flurbiprofeno/análogos & derivados , Flurbiprofeno/uso terapêutico , Humanos , Manejo da Dor
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