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BACKGROUND: The etiology of allergic rhinitis (AR) is not fully understood. Studies have shown that the maturation of children's immune systems is closely related to microecology. However, few studies have focused simultaneously on changes in respiratory and gut microbiota in AR and their correlation between microecological changes and Th1/Th2/Treg. OBJECTIVE: The aim is to investigate the pathogenesis of AR based on respiratory microecology, gut microecology, and Th1/Th2/Treg levels by applying microbiome techniques and correlation analysis. METHODS: Standardized OVA-induced AR mice were established. Serum OVA-sIgE, IL-4, IFN-γ, IL-10 were measured by ELISA, Tregs in lymph nodes were determined by flow cytometry, and the histological characteristics of nasal tissues were evaluated by Hematoxylin & Eosin (H&E). Nasal symptoms were observed to determine the reliability of the AR mouse model. Nasal lavage fluid (NALF) and fecal samples were collected after the last OVA challenge. The composition of respiratory microbiota in NALF and gut microbial in feces samples via 16S rRNA gene sequencing between the two groups, further explored the relationship between microbiota and Th1/Th2/Treg levels. RESULTS: In the AR group, the incidence of nose rubbing and sneezing in each mouse was significantly increased compared with the control group (all P < 0.001) and the inflammatory cell infiltration of NALF shows a significant increase in eosinophilic and neutrophilic infiltrates upon the AR group; H&E showed that the nasal mucosa of AR mice infiltration of massive eosinophils cells and neutrophils cells. OVA-sIgE and IL-4 in the AR group were increased (P < 0.01, P < 0.05) and IFN-γ, IL-10 were significantly decreased (P < 0.01, P < 0.05). Tregs showed a downward trend in the AR group, but there was no statistical difference. Compared with the control group, the respiratory microbiota of AR mice did not change significantly, while the gut microbiota changed significantly. In gut microbiota, compared to the control group, Shannon index in the AR group revealed a significant decrease at the genus level (P < 0.01), and Simpson index was significantly increased at all levels (all P < 0.05). PCoA also showed significant differences in beta diversity between the two groups (all P < 0.05). Compared to the control group, Deferribacteres at phylum level, Roseburia, Ruminiclostridium, Anaerotruncus at genus level were significantly decreased in the AR group (all P < 0.05). Spearman's rank correlation showed that OVA-sIgE was positively correlated with Bacteroidetes, Muribaculaceae and Erysipelotrichaceae (all P < 0.05); IL-4 was significantly negatively correlated with Epsilonbacteraeota and Deferribacteres (all P < 0.05). Treg was significantly positively correlated with Patescibacteria, Lachnospiraceae, and Saccharimonadaceae in gut microecology. CONCLUSION: Our results showed that the respiratory microbiota of AR mice was not significantly altered, but the gut microbiota varied significantly and there was a correlation between gut microbiota and Th1/Th2/Treg.
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Modelos Animais de Doenças , Microbioma Gastrointestinal , Ovalbumina , RNA Ribossômico 16S , Sistema Respiratório , Rinite Alérgica , Linfócitos T Reguladores , Células Th1 , Células Th2 , Animais , Camundongos , Microbioma Gastrointestinal/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Rinite Alérgica/imunologia , Rinite Alérgica/microbiologia , Células Th1/imunologia , Ovalbumina/imunologia , RNA Ribossômico 16S/genética , Sistema Respiratório/microbiologia , Sistema Respiratório/imunologia , Feminino , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Interleucina-10/genética , Imunoglobulina E/sangue , Fezes/microbiologia , Líquido da Lavagem Nasal/imunologia , Líquido da Lavagem Nasal/microbiologia , Interferon gama/genética , Interleucina-4RESUMO
The pathological basis of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is severe coronary stenosis, unstable plaque erosion, and rupture, resulting in coronary blood flow reduction and myocardial ischemia, leading to acute thrombosis cardiovascular disease events. This subject intends to study the treatment of NSTE-ACS patients with blood stasis and toxin syndrome by Qingre Jiedu Huoxue Huayu Decoction, observe its clinical efficacy, and explore the effects of serum lipoprotein phospholipase A2 (Lp-PLA2) and tumor necrosis factor- α (TNF- α), the effect of placental growth factor (PIGF) expression. In this study, 100 patients with blood stasis and toxin syndrome of NSTE-ACS treated in the cardiovascular department of Enshi National Hospital from August 2020 to August 2021 were selected as the research object. They were randomly divided into traditional Chinese medicine comprehensive treatment groups and conventional western medicine control groups, with 50 cases. The conventional western medicine control group was treated with hydroclopidogrel tablets orally, and the comprehensive treatment group of traditional Chinese medicine combined with Qingre Jiedu Huoxue Huayu formula orally. The patients in both groups were treated for four weeks. The results showed that after treatment, the practical clinical rate of the comprehensive treatment group was significantly higher than that of the conventional western medicine control group. After treatment, the TCM syndrome score, angina pectoris attack duration, and angina pectoris attack frequency, myocardial zymogram index level, serum Lp-PLA2 and TNF of the two groups were measured- α. The levels of PIGF were significantly lower than those before treatment. The decline of the above indexes in the comprehensive treatment group of traditional Chinese medicine was significantly better than that in the control group of conventional Western Medicine (P<0.05). The incidence of MACE events in the TCM Comprehensive treatment group was significantly lower than that in the conventional western medicine control group (P <0.05).
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Síndrome Coronariana Aguda , 1-Alquil-2-acetilglicerofosfocolina Esterase , Síndrome Coronariana Aguda/tratamento farmacológico , Angina Pectoris , Feminino , Humanos , Lipoproteínas , Fator de Crescimento Placentário , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Anoikis is a form of apoptosis, which inhibits metastatic cascade and deprives cancer cells with invasive capacity. Epidermal growth factor-like domain-containing protein 7 (EGFL7) is overexpressed in colorectal cancer (CRC) and is a potential biomarker for malignancy. The present study aimed was to investigate the effect and underlying mechanism of EGFL7 on CRC cell function. METHODS: EGFL7 expression in mutable human CRC cell lines and normal intestinal epithelial cell line HIEC were measured by qRT-PCR. To investigate the biological functions of EGFL7, loss-of-function experiments were performed by transfecting EGFL7 siRNA into SW620 and LoVo cells. Western blot analysis, MTT, invasion and anoikis assay were used to explore the underlying mechanism of EGFL7. RESULTS: EGFL7 was upregulated in several CRC cell lines as compared with normal intestinal epithelial cell line HIEC. Transfection of EGFL7 siRNA significantly decreased cell proliferation and invasion capacity of SW620 and LoVo cells. Additionally, EGFL7 inhibition markedly elevated anoikis through modulating anoikis marker proteins as reflected by increasing of cleaved-caspase-3 and cleaved-PAPR expression. Moreover, downregulation of EGFL7 inhibited PI3K and P-AKT expression. Furthermore, re-expression of PI3K remarkably reversed the effects of EGFL7 on SW620 cells. CONCLUSION: Overall, our findings suggested that EGFL7 acts as an oncogene, regulated CRC invasion and anoikis through PI3K/AKT signaling, which provided a theoretical basis for EGFL7 as a potential therapeutic target of CRC treatment.
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BACKGROUND: Pancreatic acinar cell carcinoma (ACC) is a rare tumor that constitutes 1% of all pancreatic neoplasms. Pancreatic ACC has unique characteristics in terms of biological behavior, imaging and prognosis. CASE PRESENTATION: The present study reported two cases of pancreatic ACC confirmed by postoperative pathology and both cases exhibited several different imaging features and laboratory test results. Both cases had approximately 4 cm mass located in uncinate process of pancreas. Dilated intra- and extra-hepatic bile ducts was observed in one case, along with calcification. Heterogeneous enhancement of the tumor was exhibited in both patients with different intensities. Obstructive jaundice, elevated α-fetoprotein and CA 19-9 was found in one case, while the other case had normal liver function and tumor markers. CONCLUSIONS: It was difficult to accurately diagnose pancreatic ACC before the operation despite its unique characteristics. Radical resection was the best treatment modality for resectable pancreatic ACC.
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Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Idoso , Biomarcadores Tumorais , Biópsia , Terapia Combinada , Gerenciamento Clínico , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Probiotic bacteria can induce immune regulation or immune tolerance in patients with allergic diseases, but the underlying mechanisms are still unclear. There has been a growing interest in the use of beneficial bacteria for allergic diseases recently. This study aimed at exploring whether Clostridium butyricum CGMCC0313-1 (C. butyricum) can reduce ovalbumin (OVA)-induced allergic airway inflammation in a mouse model. METHODS: Mouse model of allergic airway inflammation induced via OVA was used in this study. C. butyricum was administered daily by the oral route during or after the sensitization. Airway function, pulmonary airway inflammation, mast cell degranulation, T helper (Th)-specific and anti-inflammatory cytokines, OVA-specific Ig, matrix metalloproteinase 9 (MMP-9) and histopathological alterations were examined. RESULTS: C. butyricum significantly reduced lung resistance in the asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, airway remodelling and the expression of OVA-specific IgE/G1 were suppressed by oral C. butyricum. It also reversed the imbalance of Th1/Th2 and increased the anti-inflammatory cytokine IL-10. CONCLUSION: C. butyricum reduces OVA-induced allergic airway inflammation in mice and might be an additional or supplementary therapy for allergic asthma.
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Asma/imunologia , Clostridium butyricum , Pulmão/imunologia , Probióticos , Hipersensibilidade Respiratória/imunologia , Administração Oral , Remodelação das Vias Aéreas/imunologia , Animais , Asma/induzido quimicamente , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas , Modelos Animais de Doenças , Inflamação , Interleucina-10/imunologia , Pulmão/fisiopatologia , Masculino , Metaloproteinase 9 da Matriz/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/fisiopatologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
BACKGROUND: Myocardial infarction (MI) is the major cause of death by disease in the world. Many studies have identified the associations between matrix metalloproteinase 9 (MMP9) C-1562T polymorphisms and MI. However, the results remain inconclusive. To clarify the role of MMP9 C-1562T polymorphism in MI risk, we conducted a systematic review and large-scale meta-analysis. METHODS: Studies published between January 2005 and March 2014 were obtained from the electronic databases PubMed, Medline, and Embase. The odds ratios (ORs) with 95% CIs were calculated for comparisons of the alleles and genotypes in the overall population and in ethnicity subgroups to measure the strength of genetic associations. RESULTS: A total of 7 related studies, including 3952 MI cases and 4977 healthy control subjects were included in our meta-analysis. Our results show a statistically significant association between T allele and MI in the overall population (OR = 1.23; 95% CI, 1.02-1.48; P = 0.03). The risk of MI was also significantly higher in patients carrying the T allele (TC + TT genotypes) than in those with the CC genotype (P < 0.05). In stratified analysis by ethnicity, we found the T allele was strongly associated with MI in white populations, whereas in Asian populations there appeared no significant association. CONCLUSIONS: Our data show that the MMP9 C-1562T polymorphism is a risk factor associated with increased MI susceptibility in the total population and white populations, although no significant association was observed in Asians populations. Further studies with larger sample sizes and assessing gene-gene and gene-environment interactions are required.
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BACKGROUND: Posterior fossa malformation (PFM) is a relatively uncommon prenatal brain malformation. Genetic diagnostic approaches, including chromosome karyotyping, copy number variant (CNV) testing, and whole-exome sequencing (WES), have been applied in several cases of fetal structural malformations. However, the clinical value of appropriate genetic diagnostic approaches for different types of PFMs has not been confirmed. Therefore, in this study, we aimed to analyze the value of different combined genetic diagnostic approaches for various types of fetal PFMs. METHODS: This retrospective study was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital. Fifty-one pregnant women diagnosed with fetal PFMs who underwent genetic testing in our hospital from January 1, 2017 to December 31, 2022 were enrolled; women with an isolated enlarged cisterna magna were excluded. All participants were categorized into two groups according to the presence of other abnormalities: isolated and non-isolated PFMs groups. Different combined approaches, including karyotype analysis, CNV testing, and trio-based WES, were used for genetic analysis. The detection rates of karyotype analysis, CNV testing, and WES were measured in the isolated and non-isolated groups. RESULTS: In isolated PFMs, pathogenic/likely pathogenic (P/LP) CNVs were detected in four cases (36.36%, 4/11), whereas G-banding karyotyping and WES showed negative results. In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); karyotyping revealed aneuploidies in five cases (16.67%, 5/30), CNV testing showed P/LP CNVs in five cases (16.13%, 5/31), and WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22). WES showed a detection rate of 83.33% (5/6) in fetuses with Joubert syndrome. Only six patients (five with Blake's pouch cyst and one with unilateral cerebellar hemisphere dysplasia) survived. CONCLUSIONS: We recommend CNV testing for fetuses with isolated PFMs. A sequential genetic approach (karyotyping, CNV testing, and WES) may be beneficial in fetuses with non-isolated PFMs. Particularly, we recommend WES as the first-line genetic diagnostic tool for Joubert syndrome.
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Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Cariotipagem , Diagnóstico Pré-Natal , Humanos , Feminino , Variações do Número de Cópias de DNA/genética , Gravidez , Cariotipagem/métodos , Sequenciamento do Exoma/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Estudos Retrospectivos , Testes Genéticos/métodos , Fossa Craniana Posterior/anormalidadesRESUMO
Purpose: This aims to investigate the efficacy and safety of intercostal nerve anastomosis among breast cancer patients who undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Methods: From 2022 to 2023, female patients between the ages of 20 and 60 diagnosed with stage I-IIIA breast cancer, who required and were willing to undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy, were screened and assigned to take the operation with (treatment group) or without (control group) intercostal nerve anastomosis (the nerves with appropriate length and thickness were selected from the 2nd-4th intercostal nerves, which were then dissociated and anastomosed to the posterior areola tissue). A radial incision at the surface projection of the tumor location was used. The patients' breast local sensation was assessed using Semmes-Weinstein monofilaments before the operation as well as at 10 days, 3 months, and 6 months postoperatively. Furthermore, the patients' quality of life was evaluated 6 months postoperatively using the EORTC QLQ-C30 questionnaire. Adverse events, operation duration, drainage volume, and the duration of drainage tube carrying time were also monitored and recorded. Results: Compared to the pre-operative period, a significant decrease in local sensation was observed 10 days after surgery in both groups. However, the control group showed a significant reduction in sensation at 3 and 6 months postoperatively, while the treatment group showed noticeable recovery. A statistically significant difference (P < 0.001) in local sensation between the pre-operative and post-operative periods was observed at the final follow-up in the two groups. By the time of 3 and 6 months postoperatively, a significant difference was seen in the local sensation between the two groups. Intercostal nerve anastomosis was found to significantly improve the patients' quality of life, including emotional (P = 0.01), physical (P = 0.04), and social functioning (P = 0.02) and pain (P = 0.04). There were no significant differences in general characteristics (such as age, BMI, and subtypes). Although intercostal nerve anastomosis increased the duration of operation by around 20 min (P < 0.001), it did not affect the volume or duration of postoperative drainage tube usage between the two groups. Conclusion: This study indicated that intercostal nerve anastomosis improved the local sensation and quality of life of patients who underwent immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=42487, identifier ChiCTR1900026340.
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Platinum-based antitumor drugs are broad-spectrum agents with unique mechanisms of action. Combination chemotherapy regimens based on platinum drugs are commonly used in cancer treatment. However, these drugs can cause various adverse reactions in the human body through different routes of administration, including reproductive toxicity, genetic toxicity, and embryonic developmental toxicity. Preventing adverse effects is crucial to enhance patients' quality of life and reduce healthcare costs. This article discusses the types and developmental history of antitumor active platinum compounds, their mechanisms of action, routes of administration, and their potential reproductive, genetic, and embryonic developmental toxicity. This text explores preventive measures based on animal experimental results. Its aim is to provide references for personalized treatment and occupational protection when using platinum drugs. The continuous progress of science and technology, along with the deepening of medical research, suggests that the application of platinum drugs will broaden. Therefore, the development of new platinum drugs will be an important direction for future research.
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Objective: Based on machine learning method, four types of early postoperative frailty risk prediction model of enterostomy patients were constructed to compare the performance of each model and provide the basis for preventing early postoperative frailty of elderly patients with enterostomy. Methods: The prospective convenience sampling method was conducted and 362 early postoperative enterostomy patients were selected in three hospitals from July 2020 to November 2023 in Shanghai, four different prediction models of Support Vector Machine (SVM), Bayes, XG Boost, and Logistic regression were used and compared the test effects of the four models (MCC, F1, AUC, and Brier index) to judge the classification performance of the four models in the data of this study. Results: A total of 21 variables were included in this study, and the predictors mainly covered demographic information, stoma-related information, quality of life, anxiety and depression, and frailty. The validated models on the test set are XGBoost, Logistic regression, SVM prediction model, and Bayes on the MCC and F1 scores; on the AUC, XGBoost, Logistic regression, Bayes, and SVM prediction model; on the Brier scores, Bayes, Logistic regression, and XGBoost. Conclusion: XGBoost based on machine learning method is better than SVM prediction model, Logistic regression model and Bayes in sensitivity and accuracy. Quality of life in the early postoperative period can help guide clinical patients to identify patients at high risk of frailty and reduce the incidence of early postoperative frailty in elderly patients with enterostomy.
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We describe the case of a patient who swallowed a small fish bone and felt it lodge in her pharynx, but failed to seek medical attention in a timely manner. One week later, no foreign body was found in the hypopharynx or larynx, but a small purulent cyst was present in the epiglottic vallecula. A computed tomography scan showed a high-density area on the lingual surface of the epiglottis, which was considered to represent an embedded fish bone. A week later, the patient's discomfort had subsided, and flexible videoendoscopy showed that the purulent cyst in the epiglottic vallecula had disappeared. We surmise that the purulent cyst had ruptured spontaneously and the foreign body had been discharged. This represents an example of how an impacted small foreign body may be spontaneously discharged from the body.
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Cistos , Corpos Estranhos , Laringe , Feminino , Animais , Faringe/diagnóstico por imagem , Epiglote/patologia , Hipofaringe/diagnóstico por imagem , Hipofaringe/cirurgia , Cistos/patologia , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgiaRESUMO
Temporomandibular joint osteoarthritis (TMJ OA) is a progressive degenerative disease of the temporomandibular joint (TMJ). The unclear etiology and mechanisms of TMJ OA bring great difficulties to early diagnosis and effective treatment, causing enormous burdens to patients' life and social economics. In this narrative review, we summarized the main pathological changes of TMJ OA, including inflammatory responses, degeneration of extracellular matrix (ECM), abnormal cell biological behaviors (apoptosis, autophagy, and differentiation) in TMJ tissue, and aberrant angiogenesis. All pathological features are closely linked to each other, forming a vicious cycle in the process of TMJ OA, which results in prolonged disease duration and makes it difficult to cure. Various molecules and signaling pathways are involved in TMJ OA pathogenesis, including nuclear factor kappa-B (NF-κB), mitogen-activated protein kinases (MAPKs), extracellular regulated protein kinases (ERKs) and transforming growth factor (TGF)-ß signaling pathways et al. One molecule or pathway can contribute to several pathological changes, and the crosstalk between different molecules and pathways can further lead to a complicated condition TMJ OA. TMJ OA has miscellaneous etiology, complex clinical status, depressed treatment results, and poor prognosis. Therefore, novel in-vivo and in-vitro models, novel medicine, materials, and approaches for therapeutic procedures might be helpful for further investigation of TMJ OA. Furthermore, the role of genetic factors in TMJ OA needs to be elucidated to establish more reasonable and effective clinical strategies for diagnosing and treating TMJ OA.
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[This corrects the article DOI: 10.3389/fnut.2021.762929.].
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This study aimed to explore nitrogen fertilizer management measures to synergistically improve wheat yields and water and nitrogen use efficiency under supplemental irrigation based on soil moisture in the Huang Huai winter wheat area. Wheat variety "Yannong 1212" was used as the test material. There were three nitrogen application levels, 150 kg·hm-2 (N1), 210 kg·hm-2 (N2), and 270 kg·hm-2 (the conventional nitrogen application rate in the Huang Huai winter wheat area, N3), with the relative soil water content of 0-40 cm of each treatment was supplemented to 70% at the jointing and flowering stages. We investigated the effects of nitrogen rates on photosynthetic characteristics of flag leaves after flowering, 13C assimilate accumulation and transport, and water and nitrogen use efficiency after flowering of wheat. The results showed that photosynthetic capacity of flag leaves in the N2 and N3 was significantly higher than that in N1 14-35 days after flowering, and that there was no significant diffe-rence between N2 and N3 treatments. The 13C isotope tracing results showed that the translocation amount of 13C assimilates in vegetative organs in N2 was 12.1% and 7.1% higher than that in N1 and N3, respectively. The distribution amount of 13C assimilates in grains at maturity was 10.1% and 5.3% higher than that of N1 and N3, respectively. The amount of nitrogen fertilizer affected water consumption, water consumption proportion, and total water consumption in different growth stages of wheat. Water consumption during the whole growth period showed no difference between N2 and N3 treatments, but both were significantly higher than that for N1. Water consumption and water consumption proportion of N2 were higher from the jointing to maturity stages, water use efficiency of N2 was 7.5% and 4.8%, and grain yield was 4.7% and 10.9% higher than that of N3 and N1 treatments, respectively. The partial productivity of nitrogen fertilizer was 34.6% higher in the N2 than that of N3. Considering wheat grain yield and water and nitrogen use efficiency, 210 kg·hm-2 nitrogen application was the best rate under water-saving condition of supplementary irrigation after soil moisture measurement in the study area.
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Irrigação Agrícola , Solo , Triticum , Nitrogênio , Água , Fertilizantes , Biomassa , Grão ComestívelRESUMO
Aims: To investigate the correlation and predictive value of left atrial diameter and blood uric acid levels with the occurrence of left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate CHA2DS2-VASc scores. Methods and results: A total of 849 inpatients diagnosed with atrial fibrillation who had low to moderate CHA2DS2-VASc scores and complete transesophageal echocardiography were included in this study. Among them, 66 patients had left atrial thrombus or dense spontaneous echo contrast. When different models were used to correct other known risk factors, acid levels and abnormal left atrial diameter were identified as additional risk factors for left atrial thrombus or dense spontaneous echo contrast. The incidence of left atrial thrombus or dense spontaneous echo contrast was higher in patients with abnormal serum uric acid levels than in the control group (12.4% vs. 5.6%, p < 0.05), and this difference persisted after correcting the baseline data with propensity score matching (10.6% vs. 4.1%, p < 0.05). Abnormal left atrial diameter was another risk factor suggested by regression analysis, with an increased incidence of left atrial thrombus or dense spontaneous echo contrast in the abnormal left atrial diameter group compared to the control group, both before (18.0% vs. 3.5%, p < 0.05) and after (15.5% vs. 5.2%, p < 0.05) propensity score matching. The best predictive value was obtained by adding both abnormal serum uric acid levels and abnormal left atrial diameter. Conclusion: Left atrial enlargement and high uric acid levels increase the risk of left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate CHA2DS2-VASc scores.
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Hepatitis B surface antigen (HBsAg) loss and seroconversion are considered as an end point of a functional cure. Therefore, it is crucial to find new agents which could efficiently decrease HBsAg. Traditional herbal plants have been considered as an important source of new hepatitis B drugs development for their extensive use in antimicrobial and anti-inflammation. In this study, Peristrophe japonica, which could remarkably reduce HBsAg in the supernatant of HepG2.2.15 cells, was screened out for further extraction. Here, an active ethyl acetate fraction of Peristrophe japonica containing 34 sub-fractions was extracted. Subsequently, the monomeric compound Ciliatoside A was isolated and identified as a potential antiviral reagent with low cytotoxicity from Fraction 30. Ciliatoside A exhibited strong inhibition on intracellular and circulating HBsAg and HBV RNAs in HBV-infected cells and an HBV recombinant-cccDNA mouse model. The mechanistic study revealed that Ciliatoside A exhibited a potent anti-HBV effect through inducing autophagy-lysosomal pathway to autophagic degradation of HBc by activating AMPK-ULK1 axis and inhibiting mTOR activation. In summary, we have identified a novel antiviral compound Ciliatoside A isolated from Peristrophe japonica. This study may provide important direction and new ideas for the discovery of hepatitis B cure drugs.
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Hepatite B Crônica , Hepatite B , Animais , Camundongos , Antivirais/farmacologia , Antivirais/uso terapêutico , Autofagia , DNA Viral/genética , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/tratamento farmacológico , HumanosRESUMO
OBJECTIVE: Reduced left ventricular ejection fraction (LVEF) is common in hemodialysis (HD) patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered an important determinant of cardiovascular events. The aim of the study was to evaluate the relationship between Lp-PLA2 and LVEF in HD patients. METHODS: Fifty-seven HD patients with coronary heart disease were enrolled. Predialysis and postdialysis venous whole blood samples were collected. The patients were divided into preserved and reduced LVEF groups. The relationship between Lp-PLA2 and LVEF was assessed. RESULTS: A significant difference in C-reactive protein (CRP) and Lp-PLA2 was observed, with higher levels noted in patients with reduced LVEF (P ≤ .001). Both Lp-PLA2 and CRP were negatively correlated with LVEF in the HD patients. Only Lp-PLA2 remained associated with LVEF in multiple regression analysis. CONCLUSION: Lipoprotein-associated phospholipase A2 levels are associated with LVEF and could potentially be used to evaluate chronic heart failure with reduced LVEF in HD patients for risk stratification management.
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1-Alquil-2-acetilglicerofosfocolina Esterase , Ventrículos do Coração , Humanos , Biomarcadores , Proteína C-Reativa , Ventrículos do Coração/química , Diálise Renal , Fatores de Risco , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Objective: The aim of this study is to evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of elderly patients with papillary thyroid microcarcinoma (PTMC). Methods: From September 2015 to April 2017, 38 elderly patients with PTMC confirmed through fine-needle aspiration biopsy (FNAB) were treated with PLA. Before the treatment, the location and volume of the nodule together with the patients' symptoms were evaluated. Twenty-four hours after the treatment, contrast-enhanced ultrasound (CEUS) was performed to evaluate the completeness of the ablation. To evaluate the volume of the ablation area and recurrence or metastasis, ultrasound examination was performed at 1, 3, 6, and 12 months after the treatment and every 6 months thereafter. FNAB was performed for any suspicious recurrence or metastasis lesions. Result: The ablation of all the 38 patients was all achieved completely as confirmed by CEUS. No obvious complications were found. The success rate of single ablation was 100%. The average follow-up time was 64.58 ± 5.29 months (60-78 months). By the time of the last follow-up, 31 (81.58%) ablation lesions disappeared completely and seven (18.42%) ablation lesions showed scar-like changes. The volume of nodules was 40.69 ± 16.45 mm3 before operation, which decreased to 0.22 ± 0.76 mm3 by the end of 42 months, and all nodules disappeared 4 years after ablation (P < 0.01). At 6, 12, 18, 24, 30, 36, and 42 months after ablation, the average volume reduction rates (VRRs) were 12.09%, 31.21%, 50.9%, 72.06%, 84.79%, 95.65%, and 100%, respectively. Of all the patients enrolled, one patient (2.6%) had local recurrence and was treated with PLA again. No regrowth of treated nodule or lymph node metastasis and distant metastases was detected. Conclusion: Ultrasound-guided PLA is effective and safe for the treatment of elderly patients with PTMC who are ineligible for surgery.
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Terapia a Laser , Humanos , Idoso , Seguimentos , Estudos Retrospectivos , China/epidemiologia , Ultrassonografia de Intervenção , PoliésteresRESUMO
Pulmonary hypertension secondary to heart failure (HF-PH) combined with pulmonary vascular remodeling has a high mortality rate. Apolipoprotein A1 (ApoA1) has been shown to adversely affect outcomes in patients with HF. A prospective follow-up study was performed on 239 consecutive patients with HF-PH who underwent right heart catheterization. Proteomics technology was used to analyze different proteins in plasma between post- and precapillary pulmonary hypertension (CpcPH) and isolated postcapillary pulmonary hypertension (IpcPH) filtered by propensity score matching. Ultimately, 175 patients were enrolled and followed for an average of 4.4 years. Lipoprotein components in plasma were measured, and the following clinical events were tracked. Proteomics data showed that lipid metabolism and inflammation were different between CpcPH and IpcPH. ApoA1 levels in HF-PH patients with CpcPH were lower than those in HF-PH patients with IpcPH. The patients with lower ApoA1 levels (≤1.025 g/L) were in a higher New York Heart Association class and had high levels of NT-proBNP, mean pulmonary artery pressure, PVR, and diastolic pressure gradient. Besides, HF-PH patients with lower ApoA1 levels had a 2.836-fold higher relative risk of comorbid CpcPH compared with patients with higher ApoA1 levels. Moreover, patients with lower ApoA1 levels had a lower survival rate after adjusting for CpcPH. In conclusion, ApoA1 levels were negatively correlated with PVR levels. Lower ApoA1 levels were an independent risk factor for pulmonary vascular remodeling in HF-PH patients. The survival of HF-PH patients with lower ApoA1 levels was reduced.
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BACKGROUND: Chemotherapy-related cognitive impairment (CRCI) is highly prevalent in patients with cancer and is associated with poor outcomes and quality of life. To date, the management of CRCI remains a clinical challenge. Herein, we aim to determine the preventive effects of probiotics on CRCI development and underlying mechanisms. METHODS: We conducted a randomised, double-blind and placebo-controlled trial (ChiCTR-INQ-17014181) of 159 patients with breast cancer and further investigated the underlying mechanism in a pre-clinical setting. From 2018 to 2019, patients with breast cancer (Stage I-III) who needed adjuvant chemotherapy were screened, enrolled and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) during chemotherapy. Their cognition, anxiety and depression were assessed with well-established assays; their plasma biomarkers, metabolites and faecal microbiota compositions were measured. In addition, the systemic effects of the metabolites found in the clinical trial on long-term potentiation, synapse injury, oxidative stress and glial activation were assessed in rats. RESULTS: Probiotics supplement significantly decreased the incidence of CRCI, improved the allover cognitive functions, changed the gut microbial composition and modulated nine plasma metabolite changes. Among these metabolites, p-Mentha-1,8-dien-7-ol, Linoelaidyl carnitine and 1-aminocyclopropane-1-carboxylic acid were negatively correlated with the occurrence of CRCI. Furthermore, probiotics supplement increased plasma p-Mentha-1,8-dien-7-ol in rats. Administration of exogenous p-Mentha-1,8-dien-7-ol significantly alleviated chemotherapy-induced long-term potentiation impairment, synapse injury, oxidative stress and glial activation in the hippocampus of rats. CONCLUSION: Our data indicated that probiotics supplement prevents the occurrence of CRCI in patients with breast cancer via modulating plasma metabolites, including p-Mentha-1,8-dien-7-ol. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-INQ-17014181) [http://www.chictr.org.cn/showproj.aspx?proj=24294].