关于新药DPP-4抑制剂市场表现及国内企业该药研发立项的思考建议

近年来随着新型降糖药的出现,糖尿病药物市场呈现快速增长趋势,目前仅次于肿瘤用药,居全球药品销售排行第二位.DPP-4抑制剂作为一种治疗糖尿病的较新型药物,目前主要用于2型糖尿病的治疗.该类产品凭借其耐受性及安全性较好、低血糖发生率低、可口服等优势,在国内外临床指南中逐步得到充分认可,治疗地位不断提升,逐渐成为降糖药物市场的主力之一.因此,DPP-4抑制剂国内市场方兴未艾,其进医保后将释放更大市场空间,也是各大国内药企研发抢仿的热点所在.本文建议国内企业在研发立项DPP-4抑制剂这类新药时,不应盲目跟从热点,还需关注其临床需求、新药安全性评价、剂型优化选择并结合企业自身情况等进行综合评估.     

Time-Dependent Seismic Performance of Coastal Bridges Reinforced with Hybrid FRP and Steel Bars

To increase the durability and seismic resilience of coastal bridges, a hybrid reinforced concrete (HRC) bridge that incorporates both glass fiber-reinforced polymer (GFRP) bars and steel bars is proposed. The time-dependent seismic performance of the HRC bridge is comprehensively investigated at three levels, namely the material, bridge column and bridge structure levels. First, the decrease of tensile strength of GFRP bars over time is analyzed based on the Arrhenius theory, and corrosion initiation time and performance deterioration of steel bars are determined by Fick’s second law and an empirical formula. Second, an efficient finite element modeling method for aging HRC bridge columns is proposed. Simulation of the compression/tension behavior and the fracture failure of the GFRP bar is described. Hysteretic analysis is further conducted to investigate the time-dependent energy dissipation, ductility, residual displacement, bearing capacity and post-yield stiffness ratio. Meanwhile, comparisons of HRC bridge columns to reinforced concrete (RC) references are provided. Third, the seismic demand and damage evolution of deteriorated HRC bridge structures are investigated through dynamic time-history analysis. The results indicate that the corrosion-resistant GFRP bars contribute to improving the bearing capacity and to reducing the residual displacement of the HRC bridge. With an increase in service time, the seismic damage to the bridge column, abutment and expansion bearing increases, but the damage to fixed bearing decreases. Research results presented herein show that the HRC bridge is a promising alternative structure scheme in the marine environment.     

PRK术后角膜上皮下雾状混浊的相关因素分析

为探讨准分子激光角膜切削术（ｐｈｏｔｏｒｅｆｒａｃｔｉｖｅｋｅｒａｔｅｃｔｏｍｙ，ＰＲＫ）后角膜上皮下雾状混浊（ｈａｚｅ）的原因及影响因素，对ＰＲＫ后６个月时屈光度在－１．００～－１８．５０Ｄ的３１６例（６１５只眼）近视眼的ｈａｚｅ相关因素进行观察和比较。结果：ＰＲＫ后６个月时ｈａｚｅ发生率为４４．７％，１级或以上ｈａｚｅ为１３．３％。ｈａｚｅ的发生率及密度随屈光度增高而增加（Ｐ＜０．０００１），也随切削深度的增加而增加（Ｐ＜０．０００１），术前非接触眼压超过１８ｍｍＨｇ者，ｈａｚｅ的发生率和密度增加（Ｐ＜０．００５），男性较易发生ｈａｚｅ（Ｐ＝０．０００１），与年龄呈负相关（Ｐ＜０．０５）。而角膜厚度、术前戴用接触镜及散光对ｈａｚｅ的影响不显著。结论：高度近视（＞－６．０Ｄ）和过深的切削（＞８０μｍ）是引起ｈａｚｅ的主要原因。术前眼压偏高、年龄偏低对ｈａｚｅ也有明显影响。对ＰＲＫ治疗高度近视应持审     

Autophagic and apoptotic cell death in amniotic epithelial cells

The aim of this paper is to determine if autophagic cell death is associated with apoptosis and whether it participates in the process of term amniotic rupture. Forty pieces of fresh term amnions, including twenty from a position near the margin of the placentas and twenty from the margin of the naturally ruptured part of the placentas in term gestation were collected, respectively. The amnions were examined by scanning electron microscopy (SEM) and amniotic epithelial (AE) cells were examined by transmission electron microscopy (TEM). Autophagic and apoptotic cell death (PCD) were assayed by laser scanning confocal microscopy (LSCM) or flow cytometry using monodansylcadaverin (MDC) and propidium iodide (PI) stain. BCL(2) and BAX were examined by immunoblotting. Under SEM the amniotic epithelia appeared normal in the position near the placenta. They had an atrophied appearance in the margin of their natural broken parts. In the AE cells PCD was divided into three subtypes by TEM: autophagic cell death with positive stains of MDC and PI; apoptotic cell death; and the mixed type. Quantitative detection showed that there were more death cells, including autophagic and apoptotic, in the AE cells near the ruptured parts than near the placentas. An increased expression of BAX and a decreased expression of BCL(2) protein in the AE cells near the broken margin were observed. Apoptotic and autophagic cell death by the intrinsic pathway are the basic event in the AE cell and they are involved in the cause of membrane rupture of the human amnion in term gestation.     

Intermediate and long term clinical effects of uterine arterial embolization with sodium alginate microspheres in treatment of diffuse adenomyosis

OBJECTIVE: To study intermediate and long term efficacy of uterine arterial embolization (UAE) with sodium alginate microspheres (KMG) at diameters 500-00 microm in treatment of diffuse adenomyosis. METHODS: Totally 40 patients with standard diffuse adenomyosis were enrolled and treated with UAE. KMG at diameters 500-700 microm for vascular embolization were used to embolize the arteries. The degree of dysmenorrhea, amount of menorrhea and uterine volume, as well as the level of serum CA125, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) were investigated before and after UAE. RESULTS: The follow up rates were 100% (40/40), 100% (40/40), 80% (32/40), 68% (27/40), 58% (23/40) after uterine arterial UAE 12, 24, 36, 48 and 60 months respectively. The early, intermediate and long-term effective rates were 90% (36/40), 88% (28/32), 83% (19/23). The degree of dysmenorrhea, the amount of menorrhea and the uterine volume, as well as serum CA125 all decreased significantly 3 months after UAE at varying degrees (P < 0.05). Compared with other follow-up time, the degree of dysmenorrhea and the amount of menorrhea declined to their lowest point at 6 month after UAE (P < 0.01). Paralleled with the decrease of volume of uterine, serum CA125 also decreased significantly and reached the lowest level 12 months later compared with other follow-up times (P < 0.01). Even at the 12th month after UAE serum CA125 was not normal and FSH, LH and E2 did not change all the times after UAE, (P > 0.05). No recurrence was found during the 60 months after UAE. CONCLUSION: KMG used in UAE at diameters 500-700 microm has good intermediate and long term effectiveness in treatment of diffuse adenomyosis with no side effects.     

Cumulative and residual risks of small for gestational age neonates after changing pregnancy-smoking behaviors

This retrospective cohort study examines the relationship between changing pregnancy-smoking behaviors, from the first to the second pregnancy, on second-pregnancy rates of small for gestational age (SGA) neonates. Electronic birth records provided data on 5107 pregnant women who had two singleton births in Kansas City, MO, from 1994 to 2003. Pregnancy-smoking behavior was classified by smoking status (nonsmoker [NS] or smoker [SMK]) during the first (previous)/second (current) pregnancy: NS/NS, NS/SMK, SMK/SMK, and SMK/NS. The overall second-pregnancy SGA rate was 6.7% and varied with pregnancy-smoking behavior: 5.9%, NS/NS; 6.6%, SMK/NS; 12.5%, NS/SMK; and 12%, SMK/SMK; P < 0.001 Current pregnancy-smoking was associated with increased odds ratio (OR) of SGA; SMK/SMK (OR, 2.80; 95% confidence interval [CI], 2.00 to 3.93) versus NS/SMK (OR, 1.83; 95% CI, 1.19 to 2.82) versus SMK/NS (OR, 1.31; 95% CI, 0.65 to 2.65) versus NS/NS (OR, 1.00; 95% CI, reference). Being black (OR, 3.73; 95% CI, 2.91 to 4.79) and having medical risk factors (OR, 1.31; 95% CI, 1.09 to 1.74) also were significantly associated with a SGA neonate in second pregnancy. In conclusion, risk of delivering a SGA neonate in a current pregnancy is related to current rather than previous pregnancy-smoking. Therefore, antismoking socialization during pregnancy should focus on preventing and stopping current pregnancy-smoking, irrespective of past behavior.     

抗氧化剂在防治阿尔茨海默病中的效果和安全性评价

阿尔茨海默病（Alzheimer＇s disease,AD）属于常见的神经退行性疾病,以进行性认知功能减退为主要特征,至今病因未明,也没有治愈AD的有效方法.抗氧化剂可以清除体内自由基,有助于预防和治疗与氧化应激相关的疾病,现已在抗衰老以及肿瘤、心血管疾病的防治中广泛使用.近年来,国内外学者尝试用抗氧化剂防治AD,但其使用剂量不同于在防治其他疾病时的用量,可能会带来潜在的危险.抗氧化剂在防治AD中的疗效和安全性究竟怎样？近年来出现了越来越多的负面结果和讨论,因此有必要客观评价该类药物在AD中的临床效果和安全性.