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Polymerization confined to the pore was first adapted for the nanoscale structure adjustment of adsorption resin. The self-cross-linked polymer (P-1) formed in the pore of hyper-cross-linked resin (HR) by the Friedel-Crafts reaction of p-dichloroxylene (p-DCX), occupying the macropore of the HR resin and bringing about an external micropore. Compared with the raw HR resin, the volume of the micropore of HR@P-1 in 0.4 < D < 1 nm increased but the volume of the macropore has obviously decreased. After the loading of P-1 in the nanopore of HR, HR@P-1 has better gas adsorption performance. At 298 and 100 KPa, the adsorption capacity of CO2 is almost 30% higher than that of HR, reaching 35.7 cm3/g, due to the increase in the smaller micropore volume. Moreover, HR@P-1 has also been found to be the first C2H6-selective adsorption resin. The uptake of C2H6 is up to 56 cm3/g, and the IAST selectivity of C2H6/CH4 reaches 15.3. HR@P-1 can also separate syngas efficiently at ambient temperature and be regenerated by simple vacuum operation.
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Introduction: Palmoplantar pustulosis (PPP) is a complex inflammatory skin disease. Currently, no standardized treatments exist, and traditional systemic therapies often display limited effectiveness and substantial adverse effects. Biologics, however, have shown potential for enhanced clinical outcomes in psoriasis patients, thereby prompting this investigation into their applicability in PPP treatment. Aim: This study constitutes the first comprehensive review to assess the effectiveness and underlying mechanisms of biologics for PPP. Material and methods: We conducted a PubMed search to identify studies on biologics for PPP from 1992 onward. The review focused on assessing the efficacy of biologics targeting cytokines like IL-1, IL-8, IL-17, IL-12/23, IL-36, and TNF-α. Results: Biologics for PPP are generally less effective than for psoriasis. Secukinumab and guselkumab, IL-17 and IL-23 inhibitors respectively, have shown better results compared to other biologics in trials. However, the effectiveness of other biologics remains uncertain due to limited data. Conclusions: More research is needed to find effective treatments for PPP, and selecting the right biologic for each patient is challenging.
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PURPOSE: Recent research has shown that hypomagnesemia is associated with increased all-cause mortality in hemodialysis patients. However, the relationship between the long-term prognosis of peritoneal dialysis (PD) and the study is not yet clear. This study will analyze the effects of hypomagnesemia on all-cause, cardiovascular diseases (CVD), and non-CVD mortality in PD patients. METHOD: In a retrospective cohort study, 1,004 samples were selected from 7 PD centers in China. Based on the baseline blood magnesium level at the beginning of stable dialysis, all patients were classified into blood magnesium <0.7 mmol/L group, 0.7-1.2 mmol/L group, and >1.2 mmol/L group (the end event was death). The Kaplan-Meier method was used to calculate the difference in cumulative survival rate; the Cox proportional hazard model was used to analyze the risk factors of all-cause, CVD, and non-CVD death causes. RESULTS: Cox multiple regression analysis results (reference comparison of 0.7-1.2 mmol/L group): patients with serum magnesium <0.7 mmol/L have a higher risk ratio of all-cause mortality (HR = 1.580, 95% CI: 1.222-2.042, p = 0.001), and it is also obvious after correction by multiple models (HR = 1.578, 95% CI: 1.196-2.083, p = 0.001). Subgroup analysis of the causes of death was as follows: CVD risk (HR = 1.628, 95% CI: 1.114-2.379, p = 0.012) and non-CVD risk (HR = 1.521, 95% CI: 1.011-2.288, p = 0.044). Further analysis of the causes of infection-related death in non-CVD is also significant (HR = 1.919, 95% CI: 1.131-3.1257, p = 0.016). On the other hand, the serum magnesium>1.2 mmol/L group had lower all-cause mortality after correction (HR = 0.687, 95% CI: 0.480-0.985, p = 0.041), and subgroup analysis of the cause of death had no statistical significance (p > 0.05). CONCLUSIONS: Hypomagnesemia (serum magnesium <0.7 mmol/L) during stable dialysis in PD patients is a risk factor for CVD- and non-CVD-related mortality, especially infection-related death causes.
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Doenças Cardiovasculares/sangue , Magnésio/sangue , Diálise Peritoneal , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To analyze the effect of factors relevant to blastocyst transfer on the pregnancy outcome of in vitro fertilization-embryo transfer (IVF-ET). METHODS: The clinical data of 790 pregnant women who underwent IVF-ET in our hospital from July 2015 to July 2020 were retrospectively analyzed. The pregnancy outcome of blastocysts transferred on day 5 (D5, n=705) and those transferred on day 6 (D6, n=85) were compared. According to the pregnancy outcome, the cases were divided into a live birth group ( n=322) and a non-live birth group ( n=468), and multivariate logistic regression was conducted to study the effect of factors relevant to blastocyst transfer on the live birth outcome of IVF-ET. RESULTS: In the D5 group, the biochemical pregnancy rate, clinical pregnancy rate and live birth rate of blastocyst transfer were 69.93%, 64.96%, and 41.84%, respectively, which were significantly higher than those of the D6 group at 50.59%, 45.88%, and 30.59%, respectively. The difference was statistically significant ( P<0.05). There was no statistically significant difference in the miscarriage rate between the D5 group and the D6 group ( P>0.05). Multivariate logistic analysis revealed that age>35 years, years of infertility>5 years, endometrium thickness<9 mm on the day of blastocyst transfer, trophoblast cell rating of C, blastocyst transfer performed on D6, and multiparity were all risk factors for non-live birth outcome of IVF-ET ( P<0.05). CONCLUSION: The adverse pregnancy outcomes of IVF-ET were found to be associated with age, duration of infertility, endometrial thickness on the day of to blastocyst transfer, trophoblast cell rating, and blastocyst transfer performed after how many days of embryo development, and multiparity, which should be closely monitored, and effective measures should be adopted accordingly to prevent adverse outcomes of pregnancy.
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Transferência Embrionária , Resultado da Gravidez , Adulto , Blastocisto , Feminino , Fertilização in vitro , Humanos , Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
We report a composite extreme phenotype design using distribution of white matter hyperintensities and brain infarcts in a population-based cohort of older persons for gene-mapping of cerebral small vessel disease. We demonstrate its application in the 3C-Dijon whole exome sequencing (WES) study (n = 1924, nWESextremes = 512), with both single variant and gene-based association tests. We used other population-based cohort studies participating in the CHARGE consortium for replication, using whole exome sequencing (nWES = 2,868, nWESextremes = 956) and genome-wide genotypes (nGW = 9924, nGWextremes = 3308). We restricted our study to candidate genes known to harbour mutations for Mendelian small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2 and TREX1. We identified significant associations of a common intronic variant in HTRA1, rs2293871 using single variant association testing (Pdiscovery = 8.21 × 10-5, Preplication = 5.25 × 10-3, Pcombined = 4.72 × 10-5) and of NOTCH3 using gene-based tests (Pdiscovery = 1.61 × 10-2, Preplication = 3.99 × 10-2, Pcombined = 5.31 × 10-3). Follow-up analysis identified significant association of rs2293871 with small vessel ischaemic stroke, and two blood expression quantitative trait loci of HTRA1 in linkage disequilibrium. Additionally, we identified two participants in the 3C-Dijon cohort (0.4%) carrying heterozygote genotypes at known pathogenic variants for familial small vessel disease within NOTCH3 and HTRA1. In conclusion, our proof-of-concept study provides strong evidence that using a novel composite MRI-derived phenotype for extremes of small vessel disease can facilitate the identification of genetic variants underlying small vessel disease, both common variants and those with rare and low frequency. The findings demonstrate shared mechanisms and a continuum between genes underlying Mendelian small vessel disease and those contributing to the common, multifactorial form of the disease.
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Doenças de Pequenos Vasos Cerebrais/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Receptor Notch3/genética , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/genética , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/metabolismo , Estudos de Coortes , Feminino , Heterozigoto , Serina Peptidase 1 de Requerimento de Alta Temperatura A/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único , Receptor Notch3/metabolismo , Receptor Notch3/fisiologia , Acidente Vascular Cerebral/genética , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Sequenciamento do Exoma/métodosRESUMO
BACKGROUND: To evaluate associations between diabetes mellitus (DM) coexisting with hyperlipidemia and mortality in peritoneal dialysis (PD) patients. METHODS: This was a retrospective cohort study with 2939 incident PD patients in China from January 2005 to December 2018. Associations between the DM coexisting with hyperlipidemia and mortality were evaluated using the Cox regression. RESULTS: Of 2939 patients, with a median age of 50.0 years, 519 (17.7%) died during the median of 35.1 months. DM coexisting with hyperlipidemia, DM, and hyperlipidemia were associated with 1.93 (95% CI 1.45 to 2.56), 1.86 (95% CI 1.49 to 2.32), and 0.90 (95% CI 0.66 to 1.24)-time higher risk of all-cause mortality, compared with without DM and hyperlipidemia, respectively (P for trend < 0.001). Subgroup analyses showed a similar pattern. Among DM patients, hyperlipidemia was as a high risk of mortality as non-hyperlipidemia (hazard ratio 1.02, 95%CI 0.73 to 1.43) during the overall follow-up period, but from 48-month follow-up onwards, hyperlipidemia patients had 3.60 (95%CI 1.62 to 8.01)-fold higher risk of all-cause mortality than those non-hyperlipidemia (P interaction = 1.000). CONCLUSIONS: PD patients with DM coexisting with hyperlipidemia were at the highest risk of all-cause mortality, followed by DM patients and hyperlipidemia patients, and hyperlipidemia may have an adverse effect on long-term survival in DM patients.
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Complicações do Diabetes/mortalidade , Diabetes Mellitus/mortalidade , Hiperlipidemias/mortalidade , Diálise Peritoneal/mortalidade , Adulto , Idoso , China/epidemiologia , Complicações do Diabetes/patologia , Diabetes Mellitus/patologia , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention. METHODS: A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model. RESULTS: Of eligible 1579 patients with a mean age of 49.3 ± 14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P = 0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR) = 1.50, 95% confidence index (CI) 1.09-2.07, P = 0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR = 1.43, 95%CI 1.08-2.41, P = 0.002). CONCLUSIONS: PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.
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Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Diálise Peritoneal , Adulto , Área Sob a Curva , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Curva ROC , Insuficiência Renal Crônica/terapia , Estudos RetrospectivosRESUMO
The fitness effects of mutations can depend on the genetic backgrounds in which they occur and thereby influence future opportunities for evolving populations. In particular, mutations that fix in a population might change the selective benefit of subsequent mutations, giving rise to historical contingency. We examine these effects by focusing on mutations in a key metabolic gene, pykF, that arose independently early in the history of 12 Escherichia coli populations during a long-term evolution experiment. Eight different evolved nonsynonymous mutations conferred similar fitness benefits of â¼10% when transferred into the ancestor, and these benefits were greater than the one conferred by a deletion mutation. In contrast, the same mutations had highly variable fitness effects, ranging from â¼0% to 25%, in evolved clones isolated from the populations at 20,000 generations. Two mutations that were moved into these evolved clones conferred similar fitness effects in a given clone, but different effects between the clones, indicating epistatic interactions between the evolved pykF alleles and the other mutations that had accumulated in each evolved clone. We also measured the fitness effects of six evolved pykF alleles in the same populations in which they had fixed, but at seven time points between 0 and 50,000 generations. Variation in fitness effects was high at intermediate time points, and declined to a low level at 50,000 generations, when the mean fitness effect was lowest. Our results demonstrate the importance of genetic context in determining the fitness effects of different beneficial mutations even within the same gene.
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Adaptação Fisiológica/genética , Escherichia coli/genética , Aptidão Genética/genética , Bactérias/genética , Evolução Biológica , Epistasia Genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Evolução Molecular , Genética Populacional/métodos , Mutação/genética , Piruvato Quinase/genética , Piruvato Quinase/metabolismoRESUMO
OBJECTIVE: Surfactant and noninvasive ventilation are two major strategies for the treatment of neonates with respiratory distress syndrome (RDS). However, the optimal time for surfactant administering is yet controversial. This study compared the early and rescue Calsurf administration in preterm infants with RDS. STUDY DESIGN: Preterm infants born between 260/7 and 326/7 weeks of gestation and needed nasal continuous positive airway pressure (nCPAP) immediately after birth were randomly assigned to the early or rescue Calsurf treatment group. In the early treatment group, neonates were intubated, administered surfactant with bag-mask ventilation, and extubated to nCPAP (INSURE [intubation-surfactant-extubation]). In the rescue treatment group, InSurE was given until the clinical manifestation and chest X-ray displayed RDS. The primary outcome was to compare the reintubation rate within 72 hour age between the two groups. RESULTS: Among 305 neonates randomized to the early (n = 154) and rescue (n = 151) groups, the reintubation rate within 72 hours of age in these two groups did not differ significantly (p > 0.05). The incidence of oxygen dependence until 36 weeks' corrected age was similar in both groups. CONCLUSION: No differences were observed between early and rescue Calsurf treatment groups with respect to the reintubation rate within 72 hours of age and the incidence of bronchopulmonary dysplasia.
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Produtos Biológicos/administração & dosagem , Recém-Nascido Prematuro , Fosfolipídeos/administração & dosagem , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Displasia Broncopulmonar/epidemiologia , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Recém-Nascido , Intubação Intratraqueal , Masculino , Oxigenoterapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Tempo para o TratamentoRESUMO
OBJECTIVE: To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China. METHODS: A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia. RESULTS: Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05). CONCLUSIONS: The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.
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Asfixia Neonatal , Asfixia Neonatal/epidemiologia , China , Humanos , Incidência , Recém-Nascido , Estudos RetrospectivosRESUMO
Pyruvate kinase catalyzes the final step in glycolysis and is allosterically regulated to control flux through the pathway. Two models are proposed to explain how Escherichia coli pyruvate kinase type 1 is allosterically regulated: the "domain rotation model" suggests that both the domains within the monomer and the monomers within the tetramer reorient with respect to one another; the "rigid body reorientation model" proposes only a reorientation of the monomers within the tetramer causing rigidification of the active site. To test these hypotheses and elucidate the conformational and dynamic changes that drive allostery, we performed time-resolved electrospray ionization mass spectrometry coupled to hydrogen-deuterium exchange studies followed by mutagenic analysis to test the activation mechanism. Global exchange experiments, supported by thermostability studies, demonstrate that fructose 1,6-bisphosphate binding to the allosteric domain causes a shift toward a globally more dynamic ensemble of conformations. Mapping deuterium exchange to peptides within the enzyme highlight site-specific regions with altered conformational dynamics, many of which increase in conformational flexibility. Based upon these and mutagenic studies, we propose an allosteric mechanism whereby the binding of fructose 1,6-bisphosphate destabilizes an α-helix that bridges the allosteric and active site domains within the monomeric unit. This destabilizes the ß-strands within the (ß/α)8-barrel domain and the linked active site loops that are responsible for substrate binding. Our data are consistent with the domain rotation model but inconsistent with the rigid body reorientation model given the increased flexibility at the interdomain interface, and we can for the first time explain how fructose 1,6-bisphosphate affects the active site.
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Proteínas de Escherichia coli/química , Escherichia coli/enzimologia , Modelos Moleculares , Piruvato Quinase/química , Regulação Alostérica/fisiologia , Medição da Troca de Deutério , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Piruvato Quinase/genéticaRESUMO
Extraction of high-value products from agricultural wastes is an important component for sustainable bioeconomy development. In this study, wax extraction from sugarcane bagasse was performed and the beneficial effect of dewaxing pretreatment on the enzymatic hydrolysis was investigated. About 1.2% (w/w) of crude sugarcane wax was obtained from the sugarcane bagasse using the mixture of petroleum ether and ethanol (mass ratio of 1:1) as the extraction agent. Results of Fourier-transform infrared characterization and gas chromatography-mass spectrometry qualitative analysis showed that the crude sugarcane wax consisted of fatty fractions (fatty acids, fatty aldehydes, hydrocarbons, and esters) and small amount of lignin derivatives. In addition, the effect of dewaxing pretreatment on the enzymatic hydrolysis of sugarcane bagasse was also investigated. The digestibilities of cellulose and xylan in dewaxed sugarcane bagasse were 18.7 and 10.3%, respectively, compared with those of 13.1 and 8.9% obtained from native sugarcane bagasse. The dewaxed sugarcane bagasse became more accessible to enzyme due to the disruption of the outermost layer of the waxy materials.
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Celulose/química , Saccharum/química , Ceras/química , Biotecnologia , Celulose/ultraestrutura , Etanol/química , Cromatografia Gasosa-Espectrometria de Massas , Hidrólise , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
[This corrects the article DOI: 10.1155/2016/1405924.].
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The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.
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Compostos de Bifenilo/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Tetrazóis/uso terapêutico , Animais , Anti-Hipertensivos/uso terapêutico , Western Blotting , Diabetes Mellitus Tipo 2/metabolismo , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Irbesartana , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de TransmissãoRESUMO
Peritoneal dialysis effluent (PDE) potentially carries an archive of peptides relevant to pathological processes in abdominal and surrounding tissues. Magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is one such approach that offers a unique tool for profiling of peptides, but this approach has not been used in the PDE analysis. In this study, we developed a strategy for screening PDE proteins <15 kDa and applied this technique to identify potential biomarkers for peritonitis. We examined four kinds of magnetic beads, including a carbon series (C3, C8), weak cation exchange (WCX) and immobilized metal-affinity chromatography (IMAC-Cu) beads. Samples processed with IMAC-Cu magnetic beads consistently showed more MS signals across all beads within the measured mass range. Moreover, there was no difference in the number and morphology of MS signals between concentrated and unconcentrated samples. The PDE peptidome pattern, based on a panel of 15 peaks, accurately recognized peritonitis PD patients from peritonitis-free patients with sensitivity of 90.5% and specificity of 94.7% respectively. Therefore, IMAC-Cu magnetic beads and unconcentrated samples can be used as a fast and cost-effective approach for sample preparation prior to more in-depth discovery of predictive biomarkers of disease in patients on dialysis.
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Líquido Ascítico/química , Separação Imunomagnética/métodos , Diálise Peritoneal/métodos , Proteoma/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Humanos , Sensibilidade e EspecificidadeRESUMO
Adventitia is the outer part of the arterial wall where the inflammatory response often occurs. Urotensin II (UII) is a potent vasoconstrictive peptide that also promotes the inflammatory process in patients with cardiovascular disease. Leukotriene C4 (LTC4), a lipid mediator, was recently found to play a role in the inflammatory process in the artery. We hypothesized that the adventitia is one of the resources of LTC4 and that UII may promote LTC4 production through the 5-LO (5-lipoxygenase) pathway in adventitial fibroblasts. Rat adventitial fibroblasts were isolated and incubated in serum-free medium with either UII alone or in combination with inhibitors of p38 MAPK, ERK, and UII receptors. The expression of 5-LO was detected using real-time polymerase chain reaction and Western blot. The translocation and binding activity of nuclear factor (NF)-κB were measured using immunofluorescence and electrophoretic mobility shift assay, respectively. The production of LTC4 was measured by enzyme-linked immunosorbent assay. The results indicated that: (1) adventitial fibroblasts were a source of LTC4 production; (2) UII increased the expression of the 5-LO mRNA and the protein by NF-κB activation through p38 MAPK and ERK pathways; and (3) UII promoted the LTC4 release in fibroblasts through the 5-LO pathway by p38 MAPK and ERK activations. The 5-LO pathway mediates LTC4 production, which may be a new mechanism in the pathogenesis of the vascular adventitial inflammation caused by UII.
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Túnica Adventícia/efeitos dos fármacos , Aorta/efeitos dos fármacos , Araquidonato 5-Lipoxigenase/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Leucotrieno C4/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Urotensinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Transporte Ativo do Núcleo Celular , Túnica Adventícia/citologia , Túnica Adventícia/enzimologia , Animais , Aorta/citologia , Aorta/enzimologia , Araquidonato 5-Lipoxigenase/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Fibroblastos/enzimologia , Masculino , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Tempo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
Background: Postherpetic neuralgia (PHN), which represents the most common chronic complication of herpes zoster, is characterized by intense pain and is difficult to treat. In fact, no treatments are currently available that can effectively reduce the pain associated with PHN. Recent evidence has been presented indicating that Botulinum toxin (BoNT-A) can serve as an effective and safe treatment for peripheral neuropathic pain. Objective: The effects of intradermal BoNT-A injections on herpes zoster related neuralgia were investigated in this study. Methods: Patients diagnosed with herpes zoster related acute neuralgia (N=13 - acute group) and those diagnosed with postherpetic neuralgia (N=17 - PHN group) were enrolled in this study. The two groups were treated with intradermal injections of BoNT-A at the site of their affected pain areas and were then assessed at 1 day, 1 week, 2 weeks, 1 month, 2 months and 3 months after their BoNT-A treatments. Results: When compared with pre-treatment values, Visual Analogue Scores (VAS) in all patients were all significantly decreased at all times tested following BoNT-A injection. Before treatment, PHN patients had significantly higher VAS than those in the acute group. However, after 1 day of treatment, there was no difference in VAS between the two groups. None of the patients in the acute phase treated with BoNT-A developed PHN. Conclusion: BoNT-A injections significantly reduced herpetic-related pain and proved to be a more effective treatment for the PHN versus acute pain group. Moreover, an early application of BoNT-A can alleviate the probability of developing PHN.
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Background: Herpes zoster (HZ) is an acute herpetic skin disease resulting from the varicella-zoster virus. Typically, this condition is treated with a one-week administration of antiviral drugs, including famciclovir, which can effectively control the symptoms during the acute phase and prevent the occurrence of postherpetic neuralgia (PHN). Objective: To investigate whether a longer, two-week, regimen would enhance the capacity for famciclovir to reduce pain and prevent the occurrence of postherpetic neuralgia. Methods: HZ patients were randomly divided into two groups who were treated with famciclovir for either a one- or two-week period. Following their respective famciclovir treatments, patients were assessed for potential differences in pain intensity as evaluated at 1, 2, 4, 8 and 12 weeks post-treatment. In addition, the occurrence of postherpetic neuralgia at three months after treatment was compared between the two groups. Results: Of the 86 patients initially enrolled, 80 completed the study with N=40 randomly assigned to each of the two groups. Pain scores decreased significantly at 1, 2, 4, 8 and 12 weeks after famciclovir treatments. There were no significant differences in pain scores, and the incidence of postherpetic neuralgia occurrence between the two groups. There were no statistically significant differences in reducing pain intensity or frequency of postherpetic neuralgia between the one-week and two-week treatment protocols. Conclusion: It suggests that longer administration of famciclovir has no further benefit in the treatment of herpes zoster in our study.
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There are many reports on clinical pregnancy outcomes in polycystic ovary syndrome (PCOS) patients receiving vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), but little research about abortion has been done and there is a debate on whether the abortion risk increases in PCOS patients receiving IVF/ICSI. Therefore, the aim of this study was to investigated the abortion in PCOS patients. Clinical data of 12055 IVF/ICSI fresh cycles performed in our hospital from January 2015 to December 2020 were collected. Based on the Rotterdam diagnostic criteria of PCOS and after propensity score matching (PSM) for baseline data of clinical pregnancy cycles, matched 599 PCOS (PCOS group) and Non-PCOS (non-PCOS group) cycles were obtained. Abortion and abortion-related outcomes were compared between the two groups. Risk factors for late abortion in twins were analyzed using binary Logistics regression. Post-PSM data showed that the late abortion rate was significantly higher in the PCOS group than in the non-PCOS group only in twin pregnancy (9.50% vs. 3.96%, OR: 2.55, 95%CI 1.10-5.89). There were no statistical differences in other pregnancy outcomes. The etiological distribution for late abortion were not statistically different between the two groups in both singletons and twins. Logistics regression indicated that PCOS and obesity [pregnancy-assisted body mass index (BMI) ≥ 28] were risk factors for late abortion in twin pregnancy. In twin pregnancy, PCOS and obese patients are more likely to have late abortion. In twin pregnancy, the late abortion risk significantly increased in the PCOS patients as compared with non-PCOS patients (OR: 2.59, 95%CI 1.11-6.03, P < 0.05), as well as in the patients with obesity (BMI ≥ 28) as compared with the patients with normal BMI (OR: 4.17, 95%CI 1.59-10.90, P < 0.05). PCOS does not significantly affect early and overall late abortion rates after IVF/ICSI fresh cycle pregnancy.