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1.
Int Ophthalmol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802371

RESUMO

PURPOSE: To analyze the protective effect of PARP inhibitors on light-damaged retina and explore its possible mechanism from the perspective of ciliopathy. METHODS: A systematic review of the literature was performed to investigate the protection of PARP inhibition on light-damaged cilia. PubMed database was retrieved to find the relevant studies and 119 literatures were involved in the review. RESULTS: In retina, the outer segment of photoreceptor is regarded as a special type of primary cilium, so various retinal diseases actually belong to a type of ciliopathy. The retina is the only central nervous tissue exposed to light, but poly (ADP-ribose) polymerase (PARP), as a nuclear enzyme repairing DNA breaks, is overactivated during the light-induced DNA damage, and is involved in the cell death cascade. Studies show that both ATR and phosphorylated Akt colocalize with cilium and play an important role in regulating ciliary function. PARP may function at ATR or PI3K/Akt signal to exert protective effect on cilia. CONCLUSION: PARP inhibitors may protect the cilia/OS of photoreceptor during light-induced damage, which the possible mechanism may be involved in the activation of ATR and PI3K/Akt signal.

2.
Math Biosci Eng ; 16(6): 7921-7933, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31698647

RESUMO

Background: An increasing number of patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and develop progressive disease after receiving conventional treatments. In recent years, several novel therapies have been approved for later lines of therapy of previously treated NSCLC. Erlotinib, an EGFR tyrosine kinase inhibitor, was recommended as the second-line therapy for pre-treated patients. However, the use of erlotinib has been reported to represent different clinical effects and adverse effects. Objectives: The current study was aim to investigate the efficacy and safety of erlotinib versus chemotherapy in pre-treated patients with advanced NSCLC. Methods: Electronic databases were searched for eligible literatures updated on June 2018. Randomized-controlled trials assessing the efficacy and safety of erlotinib in pre-treated NSCLC were included, of which the main outcomes were ORR (objective response rate), PFS (progression-free survival), OS (overall survival) and AEs (adverse events). All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated. Results: A total of 11 randomized controlled trials were included in this analysis. The group of erlotinib did not achieved benefit in progression-free survival (OR = 0.61, 95%CI = 0.33-1.12, P = 0.11), overall survival (OR = 0.98, 95%CI = 0.84-1.15, P = 0.81) as well with the objective response rate (OR = 0.77, 95%CI = 0.36-1.63, P = 0.49), respectively. In the results of subgroup analysis among the patients with EGFR wild-type, there is also no significant differences in overall survival with erlotinib (OR = 0.90, 95%CI = 0.78-1.04, P = 0.15) and progression-free survival (OR = 0.33, 95%CI = 0.09-1.18, P = 0.09). The most common treatment-related adverse events in the erlotinib group is rash (OR = 5.79, 95%CI = 2.12-15.77, P = 0.0006), and neutropenia (OR = 0.02, 95%CI = 0.01-0.10, P ≤ 0.00001) is more found in the control group. In addition, fatigue (P = 0.09) and diarrhea (P = 0.52), the difference between the two groups had no statistical significance. Conclusions: There was no significant difference noted with regard to efficacy and safety between erlotinib vs. chemotherapy as the later-line therapy for previously treated patients with NSCLC, even with subgroup patients who have wild-type EGFR tumors. While, erlotinib might increase the risk of rash, and decrease the risk of neutropenia, compared with the chemotherapy. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31669280

RESUMO

NK-lysins, a type of broad-spectrum antimicrobial peptide (AMP), act as an essential effector of innate defense against microbial attack in higher vertebrates and so in fish. The present study delineates the structural and functional characterization of NK-lysin from yellow catfish (Pelteobagrus fulvidrac) (Pelteobagrus fulvidraco). PfNK-lysin encodes a 153-residue peptide, which displays the hallmark features of other known NK-lysins with the ordered array of six well-conserved cysteine residues and five-exon/four-intron structure. It was found to be ubiquitous in tissues, being detected most abundantly in gill and head kidney. In vivo exposure to stimuli (LPS, PolyI:C, and Edwardsiella ictaluri) induced PfNK-lysin expression in head kidney and spleen. Synthetic PfNK-lysin-derived peptide exhibited in vitro bactericidal potency against both Gram-positive and Gram-negative bacteria, with the highest inhibitory effect on pathogen Edwardsiella ictaluri. Fluorescence microscopy and scanning electron microscopy further confirmed its capacity to cause damage to the bacterial plasma membrane. Taken together, these data suggest that PfNK-lysin might participate in antimicrobial defense of yellow catfish by membrane-disruptive action.

4.
ACS Appl Mater Interfaces ; 11(47): 43820-43834, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31687796

RESUMO

End-tagging with a single hydrophobic residue contributes to improve the cell selectivity of antimicrobial peptides (AMPs), but systematic studies have been lacking. Thus, this study aimed to systematically investigate how end-tagging with hydrophobic residues at the C-terminus and Gly capped at the N-terminus of W4 (RWRWWWRWR) affects the bioactivity of W4 variants. Among all the hydrophobic residues, only Ala end-tagging improved the antibacterial activity of W4. Meanwhile, Gly capped at the N-terminus could promote the helical propensity of the end-tagged peptides in dodecylphosphocholine micelles, increasing their antimicrobial activities. Of these peptides, GW4A (GRWRWWWRWRA) showed the best antibacterial activity against the 19 species of bacteria tested (GMMIC = 1.86 µM) with low toxicity, thus possessing the highest cell selectivity (TIall = 137.63). It also had rapid sterilization, good salt and serum resistance, and LPS-neutralizing activity. Antibacterial mechanism studies showed that the short peptide GW4A killed bacteria by destroying cell membrane integrity and causing cytoplasmic leakage. Overall, these findings suggested that systematic studies on terminal modifications promoted the development of peptide design theory and provided a potential method for optimization of effective AMPs.

5.
Oxid Med Cell Longev ; 2019: 7021428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737172

RESUMO

Background: Skin photodamage is associated with ultraviolet- (UV-) induced reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (Nrf2) inactivation. In our previous study, skin-derived precursors (SKPs) were shown to ameliorate a UV-induced damage in mice, probably through Nrf2 activation and ROS scavenging. Objective: To clarify the mechanism underlying the photoprotective effect of SKPs against UV-induced damage in a three-dimensional (3D) skin model. Methods: The Nrf2 gene in SKPs was modified using lentiviral infection, and 3D skin models were reconstructed with keratinocytes and fibroblasts on the basis of type I collagen. Subsequently, these models were divided into the following six groups: normal, model, overexpressed, control, silenced, and negative control groups. Prior to irradiation, respective SKPs were injected into the last four groups. Next, all groups except the normal group were exposed to UVA+UVB. Lastly, the pathological and molecular-biological techniques were employed to determine the parameters. Additionally, LY294002, a PI3K inhibitor, was used to investigate the roles of PI3K/Akt and Nrf2/hemeoxygenase-1 (HO-1) in SKP photoprotection. Results: Normal 3D skin models appeared as milky-white analogs with a clear, well-arranged histological structure. After the skin was exposed to irradiation, it exhibited cell swelling and a disorganized structure and developed nuclear condensation with numerous apoptotic cells. The expressions of cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins remarkably decreased, which were accompanied by increased oxidative stress and decreased antioxidants (P < 0.05). However, these phenomena were reversed by nrf2-overexpressing SKPs. The 3D skin in the overexpressed group showed mild swelling, neatly arranged cells, and few apoptotic cells. Cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins were highly expressed, and the oxidative biomarkers were remarkably ameliorated (P < 0.05). Nevertheless, the expression of these proteins decreased after LY294002 pretreatment regardless of SKP treatment or not. Meanwhile, there were increases in both UV-induced apoptotic cells and ROS level accompanied with SOD and GPX decrease in the presence of LY294002. Conclusions: Evidence from the 3D skin model demonstrates that the protection of SKPs against UV-mediated damage is primarily via the PI3K/Akt-mediated activation of the Nrf2/HO-1 pathway, indicating that SKPs may be a promising candidate for the treatment of photodermatoses.

6.
Int J Biometeorol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754771

RESUMO

Limited evidence was seen as the association between fine particulate matter (PM2.5) and physician visits for allergic rhinitis (AR), especially in countries with extreme air pollution exposure. This paper addressed the issues about the association between PM2.5 and daily outpatient visits for AR among individuals residing in Beijing, China. Data on daily outpatient visits for AR obtained from Beijing Medical Claim Data for Employees and daily PM2.5 concentrations available from US embassy reports were linked by date from January 1, 2010, to June 30, 2012. A time-series analysis was conducted with a generalized additive Poisson model to assess the association between PM2.5 and AR, adjusting for daily average temperature, relative humidity, day of the week, calendar time, and public holiday. Totally, 229,685 outpatient visits for AR were included in the analysis. The daily mean (SD) concentration of PM2.5 was 99.5 (75.3) µg/m3 during the study period. We found that a 10-µg/m3 increase in PM2.5 content was associated with a 0.47% (95% CI: 0.39% to 0.55%) increase in the number of outpatient visits on the same day. Furthermore, results from subgroup analyses suggested that the association was consistently significant among the groups of different ages (< 65 years and ≥ 65 years) and gender. However, this study failed to find a statistically significant association in the autumn season but found significant positive associations during the spring and summer seasons (P for interaction < 0.001). This study indicated a possible association between PM2.5 and AR outpatients, which may benefit further researches in studying PM2.5 and its influence on diseases in a real and seriously air-polluted context.

7.
Aging (Albany NY) ; 11(22): 10316-10337, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31743108

RESUMO

Identification of novel clinical biomarker in clear cell renal carcinoma (ccRCC) is warranted. Integrating transcriptome (n=1669), DNA methylation (n=577) and copy number data (n=832), we developed a method to identify driver biomarkers by analyzing the omics-level dynamics of Epithelial-Mesenchymal Transition (EMT)-related genes in ccRCC. We first identified 504 expression dynamic changed genes involved in ccRCC-associated key pathways such as EMT, cell cycle, EGFR and PI3K/AKT signaling. Further analysis identified 229 (90 gene promoters) aberrant expression quantitative trait methylation (eQTM) and 256 genes with expression quantitative trait copy number (eQTCN) alterations. Among them, FOXM1 was affected by both eQTM and eQTCN. FOXM1 copy number amplification (115/500, 23% of patients), occurred in an amplified peak in chromosome 12q13.3, was enriched in late-stage ccRCC samples and was associated with worse survival. FOXM1-overexpressed pT3 patients with distant metastasis showed ~25% shorter overall survival in both training (log-rank P=0.006) and validation (log-rank P=0.018) cohorts. The eQTM-gene hybrid signature (cg00044170 and FOXM1), superior to either gene expression or DNA methylation alone, showed great potential in diagnosing localized ccRCC in training (area under curve = 0.958) and validation datasets. FOXM1 could be a novel prognostic biomarker and shed light for early diagnosis at molecular level in ccRCC.

8.
Medicine (Baltimore) ; 98(40): e17411, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577753

RESUMO

Evidence on the prescription patterns of antihypertensive drug use in children and adolescents in China is scarce. A descriptive analysis of the Beijing Medical Claim Data, which covered over 95% of the urban residents, was conducted to investigate antihypertensive prescribing patterns and trends in children and adolescents aged under 18 from 2009 to 2014 in Beijing, China. An additional meta-analysis of trends in hypertension prevalence was conducted to compare trends with antihypertensive medications.A total of 11,882 patients received at least 1 prescription for antihypertensive drugs from 2009 to 2014. The number of annual antihypertensive users increased from 2009 to 2012, then declined steadily until 2014, which was consistent with the trend of the hypertension prevalence estimated from the meta-analysis. ß-receptor blockers, thiazide diuretics, and angiotensin-converting enzyme inhibitors were the 3 most commonly prescribed antihypertensive drugs. More boys took the antihypertensive drugs than girls. For users aged under 3 years, thiazide diuretics, α-receptor blockers, and angiotensin-converting enzyme inhibitors were the most prescribed drugs, while ß-receptor blockers, thiazide diuretics were the most used drugs for users above 3 years.In conclusion, antihypertensive drug prescribing for children and adolescents increased from 2009 to 2014, with different characteristics in different subgroups.


Assuntos
Anti-Hipertensivos/classificação , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Fatores Etários , Pequim , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/epidemiologia , Lactente , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Fatores Sexuais , População Urbana/estatística & dados numéricos
9.
Oxid Med Cell Longev ; 2019: 8127362, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31636809

RESUMO

Strategies to battle malignant tumors have always been a dynamic research endeavour. Although various vehicles (e.g., chemotherapeutic therapy, radiotherapy, surgical resection, etc.) are used for skin cancer management, they mostly remain unsatisfactory due to the complex mechanism of carcinogenesis. Increasing evidence indicates that redox imbalance and aberrant reactive oxygen species (ROS) are closely implicated in the oncogenesis of skin cancer. When ROS production goes beyond their clearance, excessive or accumulated ROS could disrupt redox balance, induce oxidative stress, and activate the altered ROS signals. These would damage cellular DNA, proteins, and lipids, further leading to gene mutation, cell hyperproliferation, and fatal lesions in cells that contribute to carcinogenesis in the skin. It has been known that ROS-mediated skin carcinogenesis involves multiple ways, including modulating related signaling pathways, changing cell metabolism, and causing the instability of the genome and epigenome. Nevertheless, the exact role of ROS in skin cancer has not been thoroughly elucidated. In spite of ROS inducing skin carcinogenesis, toxic-dose ROS could trigger cell death/apoptosis and, therefore, may be an efficient therapeutic tool to battle skin cancer. Considering the dual role of ROS in the carcinogenesis and treatment of skin cancer, it would be essential to clarify the relationship between ROS and skin cancer. Thus, in this review, we get the related data together to seek the connection between ROS and skin carcinogenesis. Besides, strategies basing on ROS to fight skin cancer are discussed.

10.
J Cell Biochem ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646666

RESUMO

BACKGROUND: Breast cancer (BC) is a common malignant tumor and its incidence and mortality rates are ranked first among female cancers. So far, there has been no effective biomarkers for BC prognosis. METHODS: The DNA methylation data of BC was downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and Functional ANnoTation of The Mammalian Genome databases. The RNA-Seq data and clinical information of patients were downloaded from TCGA. R packages edgeR and minfi were used for differentially methylated genes (DMGs) screening. Then, the DMGs were collected for gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis by the online tool database for annotation, visualization and integrated discovery (DAVID) and Reactome. Cox regression analysis was used to screen candidate differentially methylated sites (DMSs) for BC prognosis. Logrank test was used to explore the correlation between DMSs and survival time. Correlation analysis was used to investigate the correlation between DNA methylation and gene expression. RESULTS: We identified 276 DMGs which contained 1454 DMSs in those three datasets. Also, six DMGs that contained seven DMSs were identified by Cox regression analysis. Interestingly, their expression levels were negatively correlated with the DNA methylation level and not affected by age, subtypes, or tumor stages. CONCLUSIONS: We proposed that these seven differentially DNA methylation sites can be used as a novel prognostic biomarker for BC area under curve (AUC) = 0.74), which may facilitate research and benefit the clinical treatment of BC.

11.
Ann Rheum Dis ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31662318

RESUMO

OBJECTIVES: Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome. METHODS: The stools from a case-control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray. RESULTS: Previous reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients. CONCLUSION: These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

12.
Cell Signal ; 66: 109436, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654716

RESUMO

BACKGROUND: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown obvious protective effect on SAP. However, little is known about the underlying mechanism. The objective of this study is to unravel the role and regulatory mechanism of miR-181a-5p in BMSCs-mediated pancreatic repair. METHODS: BMSCs were isolated from Sprague-Dawley rats and characterized by flow cytometry and Oil Red O staining. Sodium taurocholate- and caerulein-induced models were used as SAP models in vivo and in vitro, respectively. Pancreatic injury were evaluated by H&E and histopathological analysis, as well as by measuring levels of amylase, lipase and cytokines. qRT-PCR and western blotting were performed to detect the level of miR-181a-5p and the protein levels of PTEN/Akt, respectively. ELISA was conducted to detect the levels of TNF-α, IL-1ß, IL-6, angiopoietin, IL-4, IL-10 and TGF-ß1. The apoptotic rate of AR42J cells was quantitated by concurrent staining with Annexin-V-FITC and PI. RESULTS: BMSCs significantly attenuated pancreatic injury in SAP rats by reducing inflammatory infiltration and necrosis, and this effect was abolished by CXCR4 agonist AMD3100. ADM3100 exhibited more severe pancreatic injury and decreased miR-181a-5p levels in the pancreas and serum compared to SAP group. Overexpression of miR-181a-5p in BMSCs (BMSCs-miR-181a-5p) markedly potentiated the protective effect of BMSCs by reducing histological damage and levels of amylase and lipase. Moreover, BMSCs-miR-181a-5p dramatically reduced levels of angiopoietin, TNF-α, IL-1ß and IL-6, but induced the levels of IL-4 and IL-10. In caerulein-treated AR42J cells, co-culturing of BMSCs-miR-181a-5p alleviated caerulein-induced increase of amylase and lipase, and apoptosis via PTEN/Akt/TGF-ß1 signaling. CONCLUSION: BMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-ß1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP.

13.
J Glaucoma ; 28(11): 974-978, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31567910

RESUMO

PRECIS: Chinese Glaucoma Study Consortium (CGSC) as the first nationwide glaucoma registry in China, we describe its design, rationale, the geographic distribution of the hospitals, and baseline patient characteristics. AIM: As a leading cause of blindness in China, glaucoma affects 2% to 4% of adults over the age of 40 and will become increasingly prevalent as the population ages. At the national level, there are few reports on the current medical practice for glaucoma patients. CGSC will be considered as the first nationwide glaucoma registry in China. Here we describe its design, rationale, the geographic distribution of the hospitals, and baseline patient characteristics. METHODS: From December 21, 2015 to September 9, 2018, CGSC recruited patients with the diagnoses of primary angle-closure suspect, primary angle-closure, primary angle-closure glaucoma, acute primary angle closure, primary open-angle glaucoma (POAG), pigmentary glaucoma (PG), and pseudoexfoliative glaucoma (PXG) from 111 hospitals covering 67 cities from 22 provinces, 4 municipalities, and 5 autonomous regions in mainland China. Clinical data were collected using an Electronic Data Capture System designed by Tongren hospital and Gauss informed Ltd. Blood samples were collected from every patient for further genetic analysis. RESULTS: Medical records of 10,892 patients were collected, of which 5762 patients have complete information. The average age of those with complete information (n=5762) was 62.05±11.26 years old, and 35.25% were males. Primary angle-closure disease, including primary angle-closure suspect/primary angle-closure/primary angle-closure glaucoma/acute primary angle closure, was predominant (4588, 79.63%), and the distribution for others is as follows: POAG (1116, 19.37%), PXG (41, 0.71%) and PG (17, 0.30%). A total of 16,684 blood samples were collected, of which 9917 (82.68%) were primary angle-closure disease, 1987 (16.57%) were POAG, 69 (0.58%) were PXG, 22 (0.18%) were PG, and 4689 were normal controls. CONCLUSIONS: The CGSC is the first national-level glaucoma registry study in China. Clinical data and blood samples will provide the opportunity to study the epidemiology of glaucoma in Chinese hospitals, to evaluate the level of medical diagnosis and treatment of glaucoma in China, and to identify the susceptibility loci for glaucoma.

14.
MBio ; 10(5)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481383

RESUMO

Eukaryotic cells share a basic scheme of internal organization featuring membrane-based organelles. The use of fluorescent proteins (FPs) greatly facilitated live-cell imaging of organelle dynamics and protein trafficking. One major limitation of this approach is that the fusion of an FP to a target protein can and often does compromise the function of the target protein and alter its subcellular localization. The optimization process to obtain a desirable fusion construct can be time-consuming or even unsuccessful. In this work, we set out to provide a validated set of FP-based markers for major organelles in the budding yeast (Saccharomyces cerevisiae). Out of over 160 plasmids constructed, we present a final set of 42 plasmids, the recommendations for which are backed up by meticulous evaluations. The tool set includes three colors (green, red, and blue) and covers the endoplasmic reticulum (ER), nucleus, Golgi apparatus, endosomes, vacuoles, mitochondria, peroxisomes, and lipid droplets. The fidelity of the markers was established by systematic cross-comparison and quantification. Functional assays were performed to examine the impact of marker expression on the secretory pathway, endocytic pathway, and metabolic activities of mitochondria and peroxisomes. Concomitantly, our work constitutes a reassessment of organelle identities in this model organism. Our data support the recognition that "late Golgi" and "early endosomes," two seemingly distinct terms, denote the same compartment in yeast. Conversely, all other organelles can be visually separated from each other at the resolution of conventional light microscopy, and quantification results justify their classification as distinct entities.IMPORTANCE Cells contain elaborate internal structures. For eukaryotic cells, like those in our bodies, the internal space is compartmentalized into membrane-bound organelles, each tasked with specialized functions. Oftentimes, one needs to visualize organelles to understand a complex cellular process. Here, we provide a validated set of fluorescent protein-based markers for major organelles in budding yeast. Yeast is a commonly used model when investigating basic mechanisms shared among eukaryotes. Fluorescent proteins are produced by cells themselves, avoiding the need for expensive chemical dyes. Through extensive cross-comparison, we make sure that each of our markers labels and only labels the intended organelle. We also carefully examined if the presence of our markers has any negative impact on the functionality of the cells and found none. Our work also helps answer a related question: are the structures we see really what we think they are?

16.
World J Surg Oncol ; 17(1): 141, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409355

RESUMO

BACKGROUND: To evaluate the clinical significance of low-frequency electrical stimulation in preventing urinary retention after radical hysterectomy. METHODS: A total of 91 women with stage IA2-IB2 cervical cancer, who were treated with radical hysterectomy and lymphadenectomy from January 2009 to December 2012, were enrolled into this study and were randomly divided into two groups: trail group (48 cases) and control group (43 cases). Traditional bladder function training and low-frequency electrical stimulation were conducted in the trail group, while patients in the control group were only treated by traditional bladder training. The general condition, rate of urinary retention, and muscle strength grades of pelvic floor muscle in the perioperative period were compared between these two groups. RESULTS: The incidence of postoperative urinary retention in the electrical stimulation group was 10.41%, significantly lower than that in the control group (44.18%), and the difference was statistically significant (P < 0.01). The duration of postoperative fever and use of antibiotics were almost the same between these two groups. Eleven days after surgery, the difference in grades of the pelvic floor muscle between these two groups was not statistically significant. However, 14 days after the operation, grades of the pelvic floor muscle were significantly higher in the trail group than in the control group, and the difference was statistically significant (P < 0.01). In addition, although there was no significant difference between the two groups with different parameters (P = 0.782), the incidence of urinary retention was lower in the endorphins analgesia program group than in the neuromuscular repair program group (9.09% < 11.54%). CONCLUSION: Low-frequency electrical stimulation is more effective than conventional intervention in preventing urinary retention after radical hysterectomy. It also intensifies the recovery of pelvic muscle strength.

17.
BMC Womens Health ; 19(1): 109, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405377

RESUMO

BACKGROUND: This study aims to investigate the difference in vaginal microecology, local immunity and HPV infection among childbearing-age women with different degrees of cervical lesions. METHODS: A total of 432 patients were included in this study. Among these patients, 136 patients had LSIL, 263 patients had HSIL and 33 patients had CSCC. These patients were assigned as the research groups. In addition, 100 healthy females were enrolled and assigned as the control group. RESULTS: The microbiological indexes of vaginal secretions were evaluated. Furthermore, the concentrations of SIgA, IgG, IL-2 and IL-10 in vaginal lavage fluid, as well as the presence of HPV, mycoplasma and Chlamydia in cervical secretions, were detected. The results is that: (1) Differences in evaluation indexes of vaginal microecology among all research groups and the control group were statistically significant (P < 0.0001). As the degree of cervical lesions increased, the number of Lactobacillus decreased, and there was an increase in prevalence of bacterial imbalance, and the diversity, density and normal proportion of bacteria was reduced. Furthermore, the incidence of HPV, trichomonads, clue cell and Chlamydia infection increased. Moreover, the positive rate of H2O2 decreased, while the positive rates of SNa and GADP increased. (2) Differences in the ratio of IL-2 and IL-10 in the female genital tract among all research groups and the control group were statistically significant (P < 0.0001). CONCLUSIONS: As the degree of cervical lesions increased, IL-2 decreased, IL-10 increased and IL-2/IL-10 decreased, while SIgA and IgG were elevated. The reduction of dominant Lactobacillus in the vagina, impairment of H2O2 function, flora ratio imbalance, pathogen infections, reduction in IL-2/IL-10 ratio, and changes in SIgA and IgG levels could all be potential factors that influenced the pathogenicity of HPV infection and the occurrence and development of cervical lesions.


Assuntos
Infecções por Chlamydia/epidemiologia , Infecções por Papillomavirus/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Vagina/imunologia , Vagina/microbiologia , Adulto , Líquidos Corporais/metabolismo , China/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Coagulase/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Mycoplasma/isolamento & purificação , Neuraminidase/metabolismo , Papillomaviridae/isolamento & purificação , Esfregaço Vaginal , Adulto Jovem
18.
Libyan J Med ; 14(1): 1652058, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31405338

RESUMO

Objective: To investigate the effect of the duration of gonadotropin releasing hormone agonist (GnRH-a) use on the outcome of in vitro fertilization and embryo transfer (IVF-ET) during the short-acting long-term hyperstimulation cycle. Methodology: Clinical data from 776 patients receiving controlled ovarian stimulation (COS) after short-term regimen downregulation were retrospectively analyzed. According to the duration of GnRH-a, the patients were divided into 3 groups: Group A, 14 days for GnRH-a; Group B, 15-17 days for GnRH-a; and Group C, >18 days for GnRH-a. The clinical data, treatment and clinical outcomes were compared among the groups. Results: There were no significant differences in fertilization rate, implantation rate, clinical pregnancy rate, abortion rate, ovarian hyperstimulation syndrome (OHSS) rate(P > 0.05). The total costs in group A were significantly less than those in group B and C(P < 0.001). The number of eggs and quality embryos generated in group A was significantly higher than that in groups B and C (P = 0.014, P = 0.005). Conclusions: In the short-acting GnRH agonist long protocol, satisfactory IVF-ET pregnancy outcome was obtained with the use of GnRH-a for 14 days under the premise of lowering the receptor-regulating standard. Excessive application of GnRH-a will affect the number of eggs and embryos and increase the cost of medical treatment.

19.
BMC Pregnancy Childbirth ; 19(1): 294, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409379

RESUMO

BACKGROUND: The risk of venous thromboembolism (VTE) during pregnancy and puerperal periods is significantly higher than during the non-pregnant period and is one of the major causes of maternal mortality. Developed countries have promulgated guidelines for risk assessment and prevention of maternal VTE, and standardized management has led to a significant reduction in maternal mortality. However, there is a paucity of relevant research related to pregnancy and puerperal VTE in China. METHODS/DESIGN: We will perform a prospective cohort study and recruit 13,000 pregnant women from 2018 to 2020 in Beijing, China. VTE risk assessment will be conducted using the Royal College of Obstetricians and Gynaecologists (RCOG) pregnancy and puerperal VTE risk-assessment-scoring tool during early and late pregnancy, as well as during the puerperal period. Venous ultrasonography of lower extremities, routine blood tests, and coagulation parameters will be examined. These VTE risk assessments will be performed again if patients have VTE-related symptoms during their pregnancies, or if any of the following occur: (1) patients are hospitalized over 7 days due to any pregnancy complications; (2) patients are placed under strict bed rest for ≥ 3 days to prevent miscarriage. For patients with a confirmed diagnosis of VTE, treatment and follow-up plans will be decided jointly by the obstetricians, vascular surgeons, and pulmonologists. All patients in the study will be followed up by dedicated healthcare providers for up to 42 days postpartum. Statistical analyses will be performed to test the feasibility of the RCOG scoring tool for the Chinese population. The RCOG scoring tool will then be revised based upon the characteristics of the Chinese population, and the revised assessment scoring tool will then be tested in the cohort to evaluate its efficacy. Finally, a pregnancy and puerperal VTE risk-assessment tool will be proposed based on our study results. DISCUSSION: This study will establish a preliminary VTE risk-assessment tool that is applicable to pregnant and puerperal women in China and provide guidelines for further thrombophylactic interventions. Furthermore, we wish to draw increased attention to pregnancy-associated VTE to reduce VTE-related mortality. TRIAL REGISTRATION: Chi CTR1800015848 (04/24/2018).

20.
Sci Total Environ ; 696: 133764, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31454603

RESUMO

Frequent and intensive urban flooding requires an extensive adoption of low-impact development (LID) to supplement traditional drainage infrastructures. Our study conceptualizes the resilient infrastructure framework with a particular reference to adaptation, an adjustment capacity in the social-ecological system to withstand various natural hazards and absorb negative impacts. We argue that adaption is an indicator for measuring LID effectiveness. A methodological framework is adopted using a time-dependent technique with a hydrodynamic inundation model to evaluate LID effectiveness. Results of a case study in Gongming, Shenzhen, China, show that LID projects can effectively reinforce adaptation capacity. However, spatial inequality and accumulation of different levels of adaptation are evident. This outcome is due to a relatively low absorption capacity because most areas will have a relatively high recovery capacity but retain a low absorption capacity with the construction of LID projects. A relatively mild increase in absorption capacity is due to the quality of man-made infrastructural development is conflicting across different areas of Gongming, for example some infrastructures are constructed by the government, whereas others by developers and villagers. In addition, the topographical factor makes some areas in Gongming lower-lying than others and is therefore increasingly vulnerable to urban flooding during rainstorms given the difficulty of discharging the surface runoff, thereby limiting the effectiveness of LID projects. Furthermore, the spatial inequality of adaptation improvement where LID projects cannot be evenly distributed within the research area leads to the unequal distribution of adaptation. These findings can confirm that the government can practically use adaptation as an indicator in evaluating LID effectiveness and identifying the problematic stages of drainage resilience in urban flooding risk mitigation.

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