Objective: For the purpose of finding new bioactive agents from ethnic medicines, the chemical study on Dai Medicine Cassia alata was carried out. Methods: The chemical constituents from the twigs of C. alata were isolated by column chromatographic methods of silica gel, MCI-Gel resin, Sephadex LH-20, and HPLC. The structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. The cytotoxicity of this compound for NB-4, A-549, SHSY5Y, PC-3, and MCF-7 cells line was also evaluated by using the MTT method. Results: Four 2-arylbenzofuran compounds were isolated from this plant and identified as 7- methoxy-2-(4-methoxyphenyl)-3,5-dimethylbenzofuran (1), moracin N (2), 2-(2'-methoxy-4'-hydroxy-aryl)-3-methy-6-hydroxybenzofuran (3), and moracin P (4). Conclusion: Compound 1 is a new compound named as 7-methoxy-2-(4-methoxyphenyl)-3,5-dimethylbenzofuran. Compound 1 also displays the high cytotoxicity to tested cancer cell-line.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; surgery ; Chromogranins ; metabolism ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Prognosis ; Synapsins ; metabolism

The standardized training is an indispensible stage for the improvement of residents' comprehensive quality and for the training of high-qualified talents.The article preliminarily explored the standardized training model for residents,which was in accordance with the characteristics of the department of cardiology mainly from four aspects:the set-up of reasonable training program,the training of practical skills,the training of humanistic quality and the training of life-long learning ability.

OBJECTIVETo study the role of BH3-only gene in oxaliplatin-induced apoptosis of human colon cancer cell line, and to explore the associated mechanisms.

METHODSTwo strains of human colon cancer cell line SW480 and HT29 were selected, and treated respectively with different concentrations of oxaliplatin (0.3, 0.6, 1.25, 2.5, 5, 10 and 20 mg/L). Cell growth and inhibition were detected by MTT method. Apoptosis was measured by flow cytometry. Bim and PUMA expressions were examined by fluorescence quantitative PCR.

RESULTSAfter treatment of different oxaliplatin concentrations in human colon carcinoma cells SW480 line, the cell growth was inhibited in a dose-dependent manner, while Bim and PUMA expressions were significantly up-regulated. While HT29 cell lines received the same treatment, no obvious inhibition of cell growth and up-regulation of Bim and PUMA expression were found. When SW480 cells were exposed to 5 mg/L and 10 mg/L of oxaliplatin for 24 h, the early apoptotic rates were (4.87±0.55)% and (12.10±1.04)%; for 48 h, the early apoptotic rates were (11.47±0.85)% and (30.07±2.01)%; for 72 h, the early apoptotic rates were (28.99±2.12)% and (38.32±3.15)% respectively, which were all significantly higher than those in control group [(0.30±0.10)%, (0.40±0.10)% and (0.50±0.20)%, all P<0.01]. In HT29 cells, the differences of apoptotic rates between oxaliplatin treatment group and control group were not statistically significant (all P>0.05).

CONCLUSIONSOxaliplatin can inhibit colon cancer cell line SW480 growth and induce apoptosis. Induction of apoptosis of colon cancer cells by oxaliplatin may be associated with the up-regulation of BH3-only proteins, Bim and PUMA.

Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Bcl-2-Like Protein 11 ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; pathology ; Humans ; Membrane Proteins ; metabolism ; Organoplatinum Compounds ; pharmacology ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism

OBJECTIVETo analyze the molecular basis for an individual with ABx09 phenotype of ABO subtype.

METHODSThe ABO group antigens on red blood cells of the proband were identified by monoclonal antibodies, and the ABO antibody in serum was detected by standard A, B, O cells. The exons 1 to 7 of ABO gene were amplified by polymerase chain reaction (PCR) respectively and the PCR products were sequenced directly. The amplified products for exons 5 to 7 were also cloned by TOPO TA cloning sequencing kit to split the two alleles apart, selected colonies were sequenced bidirectionally for exons 5 to 7 of the ABO gene. The samples of the proband's parents were collected, then serological test of the blood group and sequence analysis for exons 6 and 7 of ABO gene were preformed.

RESULTSBoth A and B antigens were detected on red blood cells of the proband and there was anti-B antibody in the serum. There was no G deletion at position 261, while 297AG in exon 6, 467CT, 526CG, 657CT, 703GA, 796CA, 803GC, 889GA and 930GA heterozygote in exon 7 were detected by direct DNA sequencing, which can be assigned for A102Bx09 genotype. After cloning and sequencing, two alleles A102 and Bx09 were obtained. The sequence of Bx09 had one nucleotide changes (G to A) at position 889 compared with that of B101, which resulted in an amino acid change of Glu to Lys at 297 position. The Bx09 in the proband was inherited from her mother by family investigation.

CONCLUSIONG to A at nt889 of alpha-1,3 galactosyltransferasegene can result in Bx09 phenotype, with the presence of anti-B antibody in serum.

ABO Blood-Group System ; genetics ; metabolism ; Adolescent ; Alleles ; Base Sequence ; Blood Grouping and Crossmatching ; Female ; Gene Frequency ; Genotype ; Humans ; Molecular Sequence Data ; Pedigree ; Phenotype

BACKGROUNDDetection of coronary microembolization is of clinical importance for patient management and prediction of long-term outcome. However, there are few studies of the changes of magnetic resonance imaging after coronary microembolization. This study was designed to investigate the imaging of the left ventricle using delayed contrast enhanced magnetic resonance imaging as well as the left ventricular ejection fraction after coronary microembolization in animal models.

METHODSEight miniswine, of either sex (body weight 21-25 kg), were used to make the coronary microembolization model. After coronary angiography, a 2.8F infusion catheter was placed in the left anterior descending artery with the tip located between the second and third diagonal branches. Microspheres with the diameter of 42 microm and mean dosage of 1.2 x 10(5) were selectively infused into the left anterior descending artery. First pass and stressed first pass perfusion scan were performed after cine images were acquired. Then a second bolus of 0.15 mmol/kg gadolinium DTPA was given at a rate of 2 ml/s. Ten minutes later, delayed contrast enhanced magnetic resonance images of the left ventricular wall were evaluated. Serum changes of tumor necrosis factor alpha (TNF-alpha) were evaluated by enzyme-linked immunosorbent assay (ELISA).

RESULTSHypoenhancement was not observed at first pass perfusion at the anterior wall of the left ventricle. Hyperenhancements of the anterior-septal and anterior wall of the left ventricle was in evidence on delayed enhancement images 6 hours after microembolization and disappeared one week later. The characteristic change of coronary microembolization on delayed contrast enhanced magnetic imaging was non-enhanced regions within the hyperenhancement zone. Left ventricular ejection fraction measured by magnetic resonance imaging decreased significantly from 0.451 +/- 0.063 at baseline to 0.362 +/- 0.070 at the sixth hour (P < 0.01), and recovered to 0.431 +/- 0.053 one week later (P < 0.01 vs 6th hour). Compared with baseline values, the left ventricular end systolic volume enlarged significantly at 6th hour and at one week after microembolization (P < 0.05 and P < 0.01 respectively). Serum TNF-alpha increased significantly at 6th hour (22.62 +/- 6.96) pg/ml compared with baseline (16.83 +/- 3.45) pg/ml (P < 0.05) and it further increased to (27.44 +/- 3.97) pg/ml at one week after coronary microembolization and was significantly higher than that at baseline (P < 0.01).

CONCLUSIONSOn delayed contrast enhanced magnetic resonance imaging, hyperenhancement of the anterior-septal and anterior wall of the left ventricle show at 6th hour but not at one week after coronary microembolization. This might represent the characteristic imaging after coronary microembolization. The left ventricular ejection fraction decreased at 6th hour and recovered one week later after coronary microembolization. Although impairment of left ventricular function could be recovered at 1 week after coronary microembolization, the left ventricular remodeling process still continued in concert with continuously elevation of serum TNF-alpha.

Animals ; Contrast Media ; Coronary Angiography ; Embolization, Therapeutic ; methods ; Female ; Hemodynamics ; Image Enhancement ; methods ; Magnetic Resonance Imaging ; methods ; Male ; Swine ; Ventricular Function, Left

This study was aimed to investigate the distribution of rare blood group in Zhejiang Han population. The H(-) (H system), GPA(-) and s(-) (MNS), Rhnull, Rhmod, D--, CCDEE, CCdEE (variations of Rh), GPC(-) (Gerbich), i(+) (I), Lu(b-) (Lutheran), Js(b-) and k(-) (Kell), Fy(a-) (Duffy), Ok(a-) (Ok), Di(b-) (Diego) phenotypes were screened by serological or molecular methods. Jk (a-b-) phenotype was detected by urea hemolytic test. The results showed that one Di (a+b-) individual was found in 1618 blood donors, three Fy (a-b+) individuals in 1007 donors and one CCdEE individual in 633 Rh negative donors. No Jk (a-b-), H(-), GPA(-), s(-), GPC(-), i(+) (adult), Lu(b-), k(-), Js(b-), Lu(b-) and Ok(a-) phenotypes were found in this large scale survey. It is concluded that Di (a+b-), Fy (a-b+), CCdEE phenotypes are confirmed in the blood donors and this study provides the distribution data of erythrocyte rare blood group in Zhejiang Han population.
Asian Continental Ancestry Group ; genetics ; Blood Group Antigens ; genetics ; Blood Grouping and Crossmatching ; methods ; Erythrocytes ; immunology ; Humans ; Molecular Biology ; Phenotype

A highly sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of retinamido-ester in rat plasma was developed and validated. A simplified protein precipitation with acetonitrile was employed for the sample preparation. The separation was carried out on an Agilent TC C18 column (150 mm x 4.6 mm ID, 5 microm particle size) with the mobile phase consisted of methanol-water-formic acid (93: 7: 0.1). Simvastatin was used as internal standard. The detection was performed on a trap-quadrupole tandem mass spectrometer by selected reaction monitoring (SRM) scan mode via atmospheric pressure chemical ionization (APCI). The range of calibration curve was 0.05-50 ng x mL(-1) and the limit of quantification was 10 pg x mL(-1). The intra- and inter-day precision values were between 95.97% and 104.43%, and RSD was between 4.63% and 10.69%, respectively. This method was applied to determine the pharmacokinetic parameters. The main pharmacokinetic parameters of retinamido-ester after oral administration via gastric gavage of 2.5, 5, 10 mg x kg(-1) were as follows, T(1/2): (11.28 +/- 7.23), (8.90 +/- 3.82), (8.01 +/- 5.65) h; AUC(0-infinity): (103.41 +/- 61.46), (190.23 +/- 74.99), (421.66 +/- 229.20) ng x h x mL(-1); MRT: (6.31 +/- 0.75), (5.98 +/- 0.71), (6.18 +/- 0.97) h; CL/F: (30.10 +/- 13.67), (29.58 +/- 10.59), (31.18 +/- 17.51) L x h(-1) x kg(-1); Vd/F: (414.94 +/- 159.82), (356.16 +/- 139.85), (369.28 +/- 322.72) L x kg(-1), respectively.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; methods ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods ; Tretinoin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics

Objective:To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis (AD) at the early stage, and to compare the efficacy of every-other-day (Qod) regimen versus twice-a-week (Biw) regimen against recurrence in the remission stage of AD.Methods:A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals (including Beijing Children′s Hospital, Capital Medical University, etc), and randomly divided into the Qod group (76 cases) and the Biw group (74 cases). In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment (ISGA) scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results:A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 (1.0, 3.0) and 2.0 (1.0, 4.1) after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children (62.7%) achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients (44 in the Qod group and 39 in the Biw group). In addition, recurrence occurred in 19 (43.2%) and 12 (30.8%) patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups ( χ2 = 1.36, P = 0.243) ; the average time to recurrence was 64.25 (95% CI: 53.33 - 75.17) days and 75.78 (95% CI: 65.46 - 86.10) days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index (EASI) scores, ISGA scores, pruritus numerical rating scale (NRS) scores, or quality-of-life scores between the two groups (all P > 0.05) at any time points, except for the ISGA scores at week 12 (Biw group: 0 [0, 1] point vs. Qod group: 1 [0, 1] point; Z = -2.31, P = 0.021). A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 (37.7%) patients experienced discomfort at the medication site, which mainly referred to pain (45 cases, 30.8%) and mostly occurred in the tender and skinfold areas. Conclusions:Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.