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Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
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Aged , Humans , Male , Middle Aged , Atrial Fibrillation/complications , Cross-Sectional Studies , Gastrointestinal Microbiome , Lipopolysaccharides , Prospective StudiesABSTRACT
ObjectiveTo study the inhibitory effect of Banxia Houputang （BHT） on lipopolysaccharide （LPS）-induced inflammation of microglia （BV2） cells and the neuroprotective effect on human neuroblastoma （SH-SY5Y） cells. MethodAfter the neuroinflammatory model was constructed by LPS inducing BV2 cells， model group （LPS 100 µg·L-1）， administration groups （LPS+1 g·L-1 BHT， LPS+2 g·L-1 BHT， LPS+5 g·L-1 BHT， LPS+10 g·L-1 BHT）， and blank group were given DEME medium at the same volume. In addition， neuronal apoptosis model was established by co-culture of LPS-induced BV2 cell inflammation medium and SH-SY5Y cells （LPS-DMEM） and was administrated according to the above grouping. Cell viability was detected by Cell Counting Kit-8 （CCK-8） assay. The content of nitric oxide （NO） and that of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by Griess aasay and enzyme-linked immunosorbent assay （ELISA）， respectively. The mRNA levels of TNF-α， IL-1β， interleukin-4 （IL-4）， nitric oxide synthase （iNOS）， and interleukin-10 （IL-10） were measured by real-time polymerase chain reaction （Real-rime PCR）. Western blot was used to detect the expression levels of signal transducer and activator of transcription 3 （STAT3）， Janus kinase 2 （JAK2） and nuclear factor kappa-B （NF-κB p65）， protein kinase B （Akt）， inhibitor of nuclear factor κB α （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax）. ResultCompared with blank group， LPS increased the NO release， levels of TNF-α， IL-1β， IL-6， and iNOS and protein expression of Akt， NF-κB p65， IκBα， JAK2 and STAT3， decreased the content of IL-4 and IL-10 in BV2 cells， and induced apoptosis of co-cultured SH-SY5Y cells （P<0.01）. Compared with model group， BHT reduced the content of NO， TNF-α， IL-1β， and iNOS （P<0.01） and protein expression of Akt， NF-κB p65， IκBα， JAK2 and STAT3 （P<0.01）， elevated the content of IL-4 and IL-10 （P<0.01）， and inhibited the apoptosis of SH-SY5Y cells induced by LPS-DMEM （P<0.01）. ConclusionThis experiment reveals that BHT inhibited LPS-induced inflammation in BV2 cells by regulating Akt/NF-κB/JAK2/STAT3 signaling pathway and showed neuroprotective effects on SH-SY5Y cells.
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This paper aimed to explore the mechanism of the split components of Phytolaccae Radix by means of network pharmaco-logy. Based on the theoretical hypothesis of the nature and taste of traditional Chinese medicine, the chemical components of the separated components of Phytolaccae Radix were selected by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and Traditional Chinese Medicines IntegratedDatabase(TCMID) databases in combination with related literatures. Relevant target analysis was carried out based on PubChem and SwissTargetPrediction databases. Targets corresponding to disease were excavated based on GeneCards for each split component, corresponding potential targets were obtained through mapping the target set of target compounds to disease targets. GO biological process analysis and KEGG pathway enrichment analysis were performed on the mapped targets with the help of DAVID database. Based on Cytoscape software and the corresponding efficacy, the network diagram of "medicinal material-split components-compound-target-pathway" was constructed to explore the mechanism of different efficacy of the separated components of Cytoscape. And the target purgation and diuretic mapping was used as the target of the traditional efficacy of smoothening secretion for the first time. The study explored esculentoside component, fatty oil component and phenolic acid component, a total of 30 target compounds and 301 corresponding targets, involving 44 potential targets for "anti-inflammatory", 50 potential targets for "immunoregulation", 52 potential targets for "smoothening secretion", 28 potential targets for "antibacterial activity", 28 potential targets for "antiviral effect", and 29 potential targets for "antitumor effect". Topological analysis revealed 14 key gene targets such as MAPK8, MAPK14, EGFR and PTGS2. A total of 684 GO entries and 235 KEGG pathways were obtained through bioinformatics enrichment analysis, mainly involving TNF signaling pathway, NF-kappaB signaling pathway and MAPK signaling pathway. This study revealed the multi-component, multi-target, and multi-channel action mechanism of the split components of Phytolaccae Radix, which provided certain basis for the next step to clarify the split components of Phytolaccae Radix through the method of system biology, and injected new content and significance into the study of properties and flavors theory.
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Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Signal Transduction , SoftwareABSTRACT
ObjectiveNeNewly onset atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI), which is considered to be related to cardiovascular adverse events. This paper aims to discuss the relationship between atrial fibrillation and long-term cardiovascular adverse events after acute myocardial infarction.MethodsA retrospective analysis of 483 STEMI patients with multivessel disease, who underwent emergency percutaneous coronary intervention (PCI) in Beijing Chaoyang Hospital from January 2014 to May 2017, was conducted. Patients were divided into two groups: AF group: n=52(10.8%) and non-AF group: n=431(89.2%) according to including criteria. The primary endpoint event was long-term major adverse cardiovascular events, including cardiovascular death, acute heart failure or ischemia stroke. The secondary endpoint event was defined as 30-day cardiovascular death. Multivariate logistic regression analysis and Cox proportional hazards mode were performed to analyze the relationship between newly onset atrial fibrillation and cardiovascular adverse events, such as cardiovascular death. ResultsCompared with non-AF group, AF group had older age, higher levels of C-reactive protein, erythrocyte sedimentation rate, creatinine, troponin, SYNTAX score and GRACE score and lower levels of total cholesterol, low density lipoproteins and ejection fraction (P<0.01). In the multivariate logistic regression analysis model, newly onset atrial fibrillation, age, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, admission creatinine level, fasting blood glucose, and coronary SYNTAX score were all independent risk factors associated with higher risks of 30-day cardiovascular death (OR=1.983, 95% CI=1.036-3.795, P=0.04). Using Cox proportional hazards mode, newly onset atrial fibrillation following primary PCI was associated with long-term clinical adverse cardiovascular event (HR=1.983, 95% CI=1.036-3.795, P=0.04) after adjusting all covariates. The area under the ROC curve for combined prediction mode with GRACE score and newly onset AF was comparable to the one for the model with GRACE score alone (0.788 vs 0.767，P=0.08).ConclusionNewly onset atrial fibrillation in STEMI patients with multivessel disease who underwent emergency PCI is associated with 30-day cardiovascular death and long-term clinical adverse cardiovascular events. However, newly onset atrial fibrillation does not increase the predictive value of GRACE score.
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BACKGROUND@#The potential benefit of arthroscopic surgery for osteoarthritic knee associated with medial meniscus tear is controversial. This study was conducted to determine the effect of pre-operative medial meniscus extrusion (MME) on arthroscopic surgery outcomes in the osteoarthritic knee associated with medial meniscus tear during a minimum 4-year follow-up.@*METHODS@#This was a retrospective review of a total of 131 patients diagnosed with osteoarthritic knee associated with medial symptomatic degenerative meniscus tear who underwent arthroscopic surgery from January 2012 to December 2014 and were observed for more than 4 years. Patients were classified into two groups: MME ≥3 mm (major MME group, n = 54) and MME <3 mm (non-major MME group, n = 77). Clinical assessments, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width (JSW), were evaluated pre-operatively and at final follow-up. The longitudinal changes of clinical and radiographic parameters (WOMAC and the medial JSW change, K-L grade progression) were compared between groups unadjusted and adjusted for age, sex, and body mass index. Four-year survival rates (without progression to knee replacement [KR]) were also evaluated using a log-rank test and Cox proportional hazard regression model.@*RESULTS@#Major MME was present in 41% of patients. After a minimum 4-year follow-up, the mean WOMAC total and pain scores improved significantly in both groups. However, the medial JSW and K-L grade worsened significantly. Patients with pre-operative major MME worsened more in WOMAC total (adjusted mean difference [MD] 3.800, 95% confidence interval [CI]: 0.900, 11.400; P = 0.037) and function (adjusted MD 3.100, 95% CI: 0.700, 6.300; P = 0.038) scores than patients with pre-operative non-major MME, and no significant difference was observed in WOMAC pain and stiffness score between groups. The group with major MME had significantly higher joint space narrowing (adjusted MD -0.630, 95% CI: -1.250, -0.100; P = 0.021) and K-L rate progression (adjusted mean relative risk [RR] 1.310, 95% CI: 1.100, 1.600; P = 0.038) than the group with non-major MME. There was a significantly more KR progression in patients with major MME compared with those with non-major MME (adjusted RR 3.100, 95% CI: 1.100, 9.200; P = 0.042 and adjusted hazard ratio 3.500, 95% CI 1.100, 9.500; P = 0.022).@*CONCLUSIONS@#Osteoarthritic knee patients associated with medial meniscus tear with non-major MME are more responsive to arthroscopic surgery in terms of the clinical and radiologic outcomes and survival for at least 4-year follow-up; however, in terms of pain relief, arthroscopic surgery in patients with major MME is also beneficial as well as in patients with non-major MME.
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Background@#The potential benefit of arthroscopic surgery for osteoarthritic knee associated with medial meniscus tear is controversial. This study was conducted to determine the effect of pre-operative medial meniscus extrusion (MME) on arthroscopic surgery outcomes in the osteoarthritic knee associated with medial meniscus tear during a minimum 4-year follow-up.@*Methods@#This was a retrospective review of a total of 131 patients diagnosed with osteoarthritic knee associated with medial symptomatic degenerative meniscus tear who underwent arthroscopic surgery from January 2012 to December 2014 and were observed for more than 4 years. Patients were classified into two groups: MME ≥3 mm (major MME group, n = 54) and MME <3 mm (non-major MME group, n = 77). Clinical assessments, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width (JSW), were evaluated pre-operatively and at final follow-up. The longitudinal changes of clinical and radiographic parameters (WOMAC and the medial JSW change, K-L grade progression) were compared between groups unadjusted and adjusted for age, sex, and body mass index. Four-year survival rates (without progression to knee replacement [KR]) were also evaluated using a log-rank test and Cox proportional hazard regression model.@*Results@#Major MME was present in 41% of patients. After a minimum 4-year follow-up, the mean WOMAC total and pain scores improved significantly in both groups. However, the medial JSW and K-L grade worsened significantly. Patients with pre-operative major MME worsened more in WOMAC total (adjusted mean difference [MD] 3.800, 95% confidence interval [CI]: 0.900, 11.400; P = 0.037) and function (adjusted MD 3.100, 95% CI: 0.700, 6.300; P = 0.038) scores than patients with pre-operative non-major MME, and no significant difference was observed in WOMAC pain and stiffness score between groups. The group with major MME had significantly higher joint space narrowing (adjusted MD -0.630, 95% CI: -1.250, -0.100; P = 0.021) and K-L rate progression (adjusted mean relative risk [RR] 1.310, 95% CI: 1.100, 1.600; P = 0.038) than the group with non-major MME. There was a significantly more KR progression in patients with major MME compared with those with non-major MME (adjusted RR 3.100, 95% CI: 1.100, 9.200; P = 0.042 and adjusted hazard ratio 3.500, 95% CI 1.100, 9.500; P = 0.022).@*Conclusions@#Osteoarthritic knee patients associated with medial meniscus tear with non-major MME are more responsive to arthroscopic surgery in terms of the clinical and radiologic outcomes and survival for at least 4-year follow-up; however, in terms of pain relief, arthroscopic surgery in patients with major MME is also beneficial as well as in patients with non-major MME.
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Objective To investigate the effects of vascular endothelial growth factor (VEGF) on disused bone loss. Methods Tail-suspended (TS) rat models were established and evenly divided into TS+Saline group, TS+VEGF group, CON+Saline group and CON+VEGF group. During the experiment, VEGF or equivalent amount of saline was injected into the gastrocnemius muscle of the rats’ right tibia twice a week for each rat. After four weeks, the proximal tibia of the rats was scanned by micro-CT. The bone mineral density (BMD) of the trabecular bone and cortical bone, micro-structure parameters of the trabecular bone, such as bone volume per trabecular volume (BV/TV), tabecular number (Tb.N), trabecular spacing (Tb.Sp), structure model index (SMI), and cortical thickness were used as evaluation indices to study the influence of VEGF on bone loss in the proximal tibia of tail-suspended rats. Results Compared with the control rats, in tail-suspended groups, the apparent BMD, BV/TV, Tb.N, SMI of trabecular bone and the cortical thickness all decreased significantly, while the Tb.Sp and SMI significantly increased, which showed that tail suspension would cause bone loss, while the injection of VEGF would alleviate the loss of trabecular bone in tail-suspended rats. Conclusions There might exist some relationship between the status of blood supply and bone remodeling process, and by improving the status of vascular system, the disused bone loss can be alleviated.
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Objective To assess the value of ultrasound examination in transvaginal diagnosis of normal fetal heart with 11-14 weeks of gestation.Methods Totally 158 cases of normal fetal heart with high risk pregnancy and nuchal translucency thickness were examined by two ultrasoud approaches:transvaginal(TVS) and tranabdomina(TAS) in 11-14 weeks of gestation.Results The group of TVS was obviously clearer than TAS by displaying the normal fetal cardiac structural in 12 week of gestation and 13-14 weeks of gestation with significant difference between the two groups (P<0.05),respectively.No significant difference between the two groups in 11 week of gestation was observed.Conclusion The transvaginal echocardiogram is of clinical value in the high risk gravida during the late first and the early second trimester.