MyomiRs 在维甲酸诱导舌发育异常中对舌肌分化调控的机制研究

目的：检测维甲酸（Retinoic acid,RA）诱导小鼠胚胎腭裂模型中胎鼠舌体发育过程中肌相关 microRNAs（MyomiRs）、成肌调节因子（Myogenic regulatory factors,MRFs）以及 Pax 基因的表达变化,探究 MyomiRs 在舌肌分化过程中的调控作用,推测RA 致胎鼠腭裂伴发舌异常的可能机制。方法：建立 RA 诱导小鼠胚胎腭裂模型,分别在 E13．5、E14．5、E15．5收集胎鼠舌体组织,用 SYBR GreenⅠ实时定量 PCR 检测舌体中 MRFs 和 Pax 基因的表达;用 TaqMan 探针实时定量 PCR 检测舌体中 MyomiRs 的表达。结果：胎鼠舌体发育过程中,正常组 miR-1和 miR-206相对表达量均持续上升,RA 诱导组二者变化趋势与正常组相似,但相对表达量均低于正常组,miR-1的结果在 E14．5和 E15．5具有统计学意义（P ＜0．01）,miR-206的结果在 E13．5具有统计学意义（P ＜0．05）。正常组和 RA 诱导组胎鼠舌体中 MyoD 和 Myf5相对表达量都在 E14．5达到峰值,随后下降。RA 诱导组 MyoD 的表达在 E14．5显著低于正常组（P ＜0．05）,在 E15．5显著高于正常组（P ＜0．01）;RA 诱导组 Myf5的表达在 E15．5显著低于正常组（P ＜0．05）。正常组和 RA 诱导组胎鼠舌体中 Pax3表达均在 E14．5达到峰值,Pax7表达均在 E15．5达到峰值。RA 诱导组 Pax3的表达在 E14．5显著高于正常组（P ＜0．05）;Pax7的表达则在 E13．5显著高于正常组（P ＜0．01）。结论：在舌肌分化过程以及RA 诱导腭裂胎鼠的舌发育异常中,miR-1／miR-206与 Pax3／Pax7及 Myf5／MyoD 的表达趋势具有相关性。RA 可能通过下调 miR-1／miR-206而靶向上调 Pax3／Pax7,进而下调 MyoD ／Myf5表达,从而抑制舌肌分化,导致舌肌发育异常。     

Extracts of Monascusus Purpureus beyond Statins——Profile of Efficacy and Safety of the Use of Extracts of Monascus Purpureus

Monascus purpureus is a fungus that has been tradi-tionally used in China for thousands of years to produce ricewine . Traditionally the fungus is used to ferment non-gluti-nous cooking of rice ,to produce a kind of famous red ricewine .Its main traditional indications consist of disordersdue to the accumulation of fats (nosologically linked withthe problems of stasis of circulation in traditional Chinesemedicine) ,liver disorders and some forms of tumor as ithelps i mprove the circulation of …     

An inter- and intra-laboratory comparison of breath ¹³CO₂analysis

BACKGROUND: 13C breath test analysis requires accurate 13CO2 measurements. AIM:: To perform a multicentre study to evaluate the repeatability and reproducibility of breath 13CO2 analysis. METHODS: Two series of 25 paired randomly coded tubes (each consisting of 23 13CO2-enriched breath samples and two samples of standard reference pure CO2 with certified delta 13CPDB) were sent to participating centres for 13CO2 measurement. Each series of tubes was analysed 10 days apart. The repeatability and reproducibility of 13C measurements was assessed by Mandel's k and h statistics. RESULTS: Twenty-two centres participated in the study: 18 showed good inter- and intra-laboratory variability, whilst four showed abnormally high inter- or intra-laboratory variability. Breath test results were also significantly affected by the accuracy of the 13C analytical procedures. CONCLUSIONS: A low accuracy of 13C measurements may significantly affect the results of breath tests, leading to inappropriate clinical decisions. Standardization of 13C analysis is required to guarantee optimal 13C measurements and accurate 13C breath test results.     

HPLC法对注射用羟氨苄青霉素钠含量的影响因素测试

利用高效液相色谱法对3个批号，经3000LS强光照射不同时间的注射用羟氨苄青霉素钠进行稳定性测试，结果表明注射用羟氨苄青霉素钠在强光照射下不稳定，含量不断降低，但经3000LS强光照射10天内含量仍均在标准含量80％以上。     

Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study

Background

Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients.

Methods

Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 10⁷ DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively.

Results

The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together.

Conclusion

Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.

Trial Registration

Current Controlled Trials: ISRCTN45563569     

Indinavir trough concentration as a determinant of early nephrolithiasis in HIV-1-infected adults

Indinavir plasma levels are associated with antiretroviral efficacy; however, little data are available regarding toxicity. We assessed the relationship between indinavir pharmacokinetic (PK) characteristics and severe nephrolithiasis as well as other severe or serious adverse reactions. Patients included in the ANRS CO8 APROCO-COPILOTE cohort and receiving 800 mg indinavir three times daily as a first-line protease inhibitor were eligible for this study. To be included in the analysis, their plasma sample at month 1 (M1) had to be available (n = 282) to estimate using population PK modeling, indinavir PK characteristics, ie, maximum (Cmax) and trough plasma (Cres) concentrations, area under the curve (AUC), and observed/predicted concentration ratio (CR). A Cox model was used to estimate the independent effect of Cmax, Cres, AUC, and CR on the hazard of severe nephrolithiasis and serious adverse reactions. At M1, median Cmax was 6205 ng/mL, Cres 631 ng/mL, AUC 24,242 ng . h/mL, and CR 0.6. After a median follow up of 12 months, 11% of patients (30 of 282) had experienced at least one serious adverse reaction among which 12 were nephrolithiasis. In the multivariate analyses, early high indinavir Cres (ie, >/=1000 ng/mL at M1) was associated with a higher rate of severe nephrolithiasis (hazard ratio = 6.7; 95% confidence interval = 1.8-25.2; P < 0.01) and was also associated with a higher rate of all serious adverse reactions but only when nephrolithiasis were included among those cases. Prospective and early indinavir Cres determination should be recommended in the patient's care management and dosage adjustments.