A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

OBJECTIVETo analyze possible difference in bronchial asthma between ethnic and geographic groups and explore its correlates among Uygur and Han adults in Turpan Prefecture, Xinjiang.

METHODSOne hundred and sixty-six clinically diagnosed asthmatic patients at Turpan Prefecture Hospital, Xinjiang, 86 of Uygur and 80 of Han ethnic, and 166 1:1 matched controls from ophthalmological outpatient department at the same hospital were recruited into the study. Interview with questionnaire was conducted and serum levels of eosinophilic cation protein (S-ECP), total IgE (T-IgE) and specific IgE (S-IgE) were measured for all of the participants to study related factors for asthma with univariate and multivariate conditional logistic regression analyses.

RESULTSBronchial infection (OR(U) = 5.111, 95%CI: 1.203 - 21.710; OR(H) = 2.498, 95%CI: 1.471 - 5.069), family history of asthma (OR(U) = 3.078, 95%CI: 1.812 - 5.188; OR(H) = 2.711, 95%CI: 1.010 - 6.176), personal allergy history (OR(U) = 2.083, 95%CI: 1.043 - 4.162; OR(H) = 3.998, 95%CI: 1.739 - 9.198), weather change (OR(U) = 2.218, 95%CI: 1.199 - 3.778; OR(H) = 1.733, 95%CI: 1.004 - 2.994) and positive S-IgE (OR(U) = 1.592, 95%CI: 1.018 - 2.491; OR(H) = 3.858, 95%CI: 2.246 - 8.507) correlated with asthma in patients of both Uygur and Han ethnic. Percentage of asthma attack induced by respiratory infection [59.30% (51/86)] and weather change [36.05% (31/86)] in Uygur patients was significantly higher than that in Han ethnic [42.50% (34/80) and 21.25% (17/80), respectively], but percentage of those with personal allergy history [48.75% (39/80)] and positive S-IgE [52.50% (42/80)] in Han ethnic was significantly higher than that in Uygur [32.56% (28/86) and 30.23% (26/86), respectively]. Levels of S-ECP and T-IgE in patients with moderate and severe asthma of both Uygur and Han ethnic [(S-ECP(U) = 7.95 +/- 3.98) microg/L, S-ECP(H) = (11.21 +/- 4.74) microg/L, T- IgE(U) = (72.23 +/- 45.92) kU/L, T-IgE(H) = (108.81 +/- 64.07) kU/L, respectively]were significantly higher than those in controls of the same ethnic [S- ECP(U) = (1.94 +/- 1.16) microg/L, S-ECP(H) = (2.07 +/- 1.63) microg/L, T-IgE(U) = (46.19 +/- 32.47) kU/L, T-IgE(H) = (50.97 +/- 38.51) kU/L; t values were 8.96, 10.52, 2.81, 4.97, P < 0.01], higher in Han ethnic than those in Uygur (t values were 3.01, 2.68, P < 0.01).

CONCLUSIONBronchial infection, family asthma history, personal allergy history, weather change and positive S-IgE all were important correlates of asthma in Turpan Prefecture, Xinjiang. Levels of S-ECP and T-IgE in patients with moderate and severe asthma increased during its attacks, higher in Han ethnic than those in Uygur. Genetic and environmental factors may be involved in occurrence and development of asthma.

Adult ; Asthma ; blood ; epidemiology ; ethnology ; Causality ; China ; epidemiology ; Climate ; Environmental Exposure ; Eosinophil Cationic Protein ; blood ; Female ; Humans ; Immunoglobulin E ; blood ; Logistic Models ; Male ; Pedigree ; Surveys and Questionnaires

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.
Biopsy/adverse effects* ; Cardiomegaly/pathology* ; Cardiomyopathy, Hypertrophic/diagnosis* ; Eosine Yellowish-(YS) ; Fibrosis ; Heart Defects, Congenital ; Hematoxylin ; Humans ; Lipofuscin ; Male ; Myocardium/pathology* ; Retrospective Studies

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca²⁺ gene variation) and to compare clinical phenotypes of HCM patients with Ca²⁺ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca²⁺ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca²⁺ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca²⁺ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca²⁺ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca²⁺ gene variant group (only 1 Ca²⁺ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca²⁺ gene variation (Ca²⁺ gene variation group). Compared with gene negative group, patients in Ca²⁺ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca²⁺ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca²⁺ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca²⁺ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca²⁺ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca²⁺ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca²⁺ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca²⁺ gene variation.
Humans ; Cardiac Surgical Procedures/methods* ; Cardiomyopathy, Hypertrophic/genetics* ; Echocardiography ; Electrocardiography ; Phenotype ; Sarcomeres/genetics* ; Adult