高频能量多普勒超声在类风湿性关节炎治疗监测中的应用

目的：探讨利用高频能量多普勒超声测定滑膜厚度、滑膜血流评估类风湿性关节炎(RA)疗效的价值。方法临床明确诊断的 RA 患者36例,给予甲氨蝶呤片或重组人Ⅱ型肿瘤坏死因子α受体抗体融合蛋白治疗24周。治疗前后对双手第2掌指关节(MCP2)、双腕关节进行滑膜厚度、滑膜血流积分检查,同时进行血沉、C 反应蛋白(CRP)及 DAS28检查,以超声指标与 DAS28、血沉、CRP 进行相关性分析。结果无论治疗前后,MCP2滑膜厚度、腕关节滑膜厚度、MCP2滑膜血流积分与 DAS28的相关性最强(P <0.05),MCP2滑膜血流积分与 CRP 也具有良好的相关性。结论利用高频超声检测 MCP2以及腕关节的滑膜厚度和滑膜积分,均能有效评估 RA 患者的病情活动程度,并作为疗效评价的一种手段,具有一定的价值。     

Appl1 is essential for the survival of Xenopus pancreas,duodenum, and stomach progenitor cells

An understanding of the molecular mechanisms governing the survival of organ progenitor cells in vivo is crucial for in vitro tissue regeneration. Here, we have found that Xenopus appl1 and akt2 share a similar embryonic expression pattern, showing characteristic expression in the central nervous system as well as in the pancreas and part of the stomach/duodenum (SD) at tadpole stages of development. Specific knockdown of appl1 in endoderm or inhibition of akt activity did not affect the formation of endodermal organ primordia at tail bud stages of development, but led to a gut‐coiling defect, strong apoptosis in endodermal organs, and pancreas and SD hypoplasia or even aplasia at tadpole stages of development. Furthermore, appl1 is required for akt phosphorylation and akt2 in turn can rescue appl1 knockdown phenotypes. Together, our data suggest that appl1‐akt signaling is specifically required for the survival of pancreas and SD progenitor cells in Xenopus laevis embryos. Developmental Dynamics 239:2198–2207, 2010. © 2010 Wiley‐Liss, Inc.     

Developmental expression of sideroflexin family genes in Xenopus embryos

Emerging evidence indicates that mitochondrial carriers are not only crucial for metabolism, but also important for embryonic development. Sideroflexin is a novel family of mitochondrial tricarboxylate carrier proteins, of which the in vivo function is largely unknown. Here, we report on the expression patterns of five sideroflexin genes in Xenopus embryos. Whole‐mount in situ hybridization analysis reveals that while sideroflexin2 is expressed in the pancreas, sideroflexin1 and 3 display a complex expression in the central nervous system, somites, pronephros, liver, and pancreas. In contrast, only a weak expression of sideroflexin4 and 5 was detected in embryonic brain. Taken together, the five sideroflexin genes show both overlapping and nonoverlapping expression during Xenopus embryogenesis. As the primary structures of the five sideroflexin proteins are also quite similar, their functional redundancy should be taken into consideration for gene targeting studies. Developmental Dynamics 239:2742–2747, 2010. © 2010 Wiley‐Liss, Inc.     

高原寒区战时环境猪肢体枪弹伤简化初期外科处理原则

目的研究高原寒区战时环境下枪弹伤后伤道初期外科处理原则。方法 108头小型猪随机分为高原战时致伤传统清创延期缝合固定组（GCT）、高原战时致伤一期清创固定缝合组（GYQ）、高原战时致伤简单清创引流延期缝合外固定架固定组（GJD）3组,分别于每组伤后6、12、24、36、48、72 h进行相应的初期外科处理。结果 （1）高原战时环境伤道组织肉眼可辨的炎性分界时间为伤后12~24 h;（2）伤道组织在伤后24 h明显肿胀,36~48 h肿胀达高峰,清创后7 d组织肿胀显著消退;（3）伤道感染最早发生在伤后24 h,伤后12~24 h清创细菌清除率最高;（4）GYQ组各时相点初期外科处理的伤道局部总感染率都很高,GCT组和GCT组36 h以后各时相点处理的局部总感染率均很高,GJD组在伤后的6~24 h初期外科处理的未见感染发生,36 h以后各时相点的局部总感染率与GCT组相似;（5）伤道闭合后28 d解剖动物发现,局部感染动物大多有全身脓毒血症,在肺、肝、脑、肾等处均有广泛的散在的脓肿形成,早期死亡动物在肺、肝、肾等脏器也可见广泛的出血点。GCT组和GYQ组早期死亡率较高,GJD组在任一时相点均未见死亡动物。结论高原战时环境肢体枪弹伤不行一期缝合、不做骨折一期内固定,伤后早期不宜扩大清创范围,伤后6~24 h实施简单初期外科处理是可行的,伤口延期缝合较佳时机在清创后7 d,应尽早应用外固定架进行骨折有效固定。     

Modified coronoid process grafts combined with sagittal split osteotomy for treatment of bilateral temporomandibular joint ankylosis.

PURPOSE: This article describes the use of autogenous coronoid process grafts for lengthening the ramus in patients with long-standing temporomandibular joint (TMJ) ankylosis and severe mandibular retrognathia. PATIENTS AND METHODS: A retrospective clinical study of 6 cases of bilateral TMJ ankylosis surgically treated during a 3-year period from June 1996 to March 1999 was performed. All patients were treated by condylectomy, mandibular sagittal split osteotomy, and immediate autogenous coronoid process grafts. Clinical examination, radiographs, and photographs were used postsurgically to evaluate the grafts, condylar function, and facial appearance. RESULTS: Very satisfactory postsurgical results were obtained in terms of function of the TMJ, the airway, and aesthetics. CONCLUSION: In children suffering from TMJ ankylosis, the coronoid process can be used for mandibular lengthening.     

骨牵张技术治疗下颌骨陈旧性骨折

目的：观察骨牵张技术在下颌骨骨折错位愈合二期矫治中的应用。方法：采用内置术骨牵张器治疗2例因外伤造成的下颌骨错位愈合及下颌偏斜的患者，骨牵张器每天延长颌骨约1mm，直至下颌骨体部被延长得到理想的位置。结果：2例患者受损侧的下颌骨体分别被延长11mm和7mm，无论是咬关系还是面部外形均得到明显的改善。结论：骨牵张器为治疗陈旧性颌骨骨折的继发畸形提供了可行且有效的方法。     

中药单体逆转紫杉醇耐药作用机制的研究进展

紫杉醇是多种癌症的一线化疗药物,但其耐药性的产生使得其后期治疗疗效大大降低,增加了癌症患者的死亡率及复发率,严重限制了其临床应用。目前,临床上的一些中药复方、中成药、中药注射液等辅助化疗药物治疗癌症患者的应用已十分广泛,中药在提高化疗药物疗效、降低化疗不良反应及改善预后等方面均展示出独特的优势,但其发挥逆转化疗药物耐药的作用机制及有效单体成分尚未明确,在不同癌症类型的应用方面也十分局限,值得进一步挖掘和探究。该文总结了近年与紫杉醇联用具备协同抗肿瘤疗效的中药单体成分,并分类列举了其发挥逆转紫杉醇耐药作用的具体机制及药理活性,发现中药单体不仅通过作用于膜转运蛋白促进紫杉醇在肿瘤细胞内的蓄积、抑制多药耐药相关蛋白及代谢酶表达抑制紫杉醇的代谢、调控细胞凋亡基因、因子水平及凋亡相关通路促进紫杉醇发挥细胞增殖抑制作用,还可通过调控微小RNA（microRNA）及长链非编码RNA（lncRNA）表达水平、抑制肿瘤干细胞特性及肿瘤代谢重编程、改善肿瘤微环境、触发肿瘤细胞死亡性自噬及氧化应激反应等方面显著提高紫杉醇的化疗敏感性,为明确中药单体联合紫杉醇抗肿瘤的具体机制提供理论基础,对中药新药开发及临床寻找紫杉醇的联合用药具有重要意义,也对中药与其他化疗药物联合应用的探究具有一定参考价值。     

无骨折脱位型胸脊髓损伤的诊治分析

目的 通过7例无骨折脱位型胸脊髓损伤的治疗分析,提高对该病的诊治水平。方法 本组7例按Frankel脊髓损伤分级：A级2例,B级2例,C级3例。其中5例行了MRI检查。手术治疗2例,保守治疗5例。结果 经10个月至8年2个月随访,4例完全恢复,2例部分恢复,1例无恢复。结论 MRI检查对无同骨折脱位型胸脊髓损伤的诊治具有重要意义;不完全性无骨折脱位型胸脊髓损伤的疗效满意。     

骨肉瘤组织中环氧合酶-2和基质金属蛋白酶-2的表达及其意义

目的探讨环氧合酶-2(COX-2)和基质金属蛋白酶-2(MMP-2)在骨肉瘤中表达的临床意义.方法采用免疫组织化学方法(S-P法)检测31例骨肉瘤组织标本中COX-2和MMP-2蛋白的表达.结果骨肉瘤组织中COX-2和MMP-2蛋白的阳性率分别为61.30%和54.80%,显著高于对照组骨软骨瘤组织(P＜0.05).COX-2的表达与骨肉瘤组织分级、肺转移有关(P=0.033,P=0.008).MMP-2的表达与肺转移有关(P=0.019),而与组织分级关系不大(P=0.821).COX-2的表达与MMP-2的表达密切相关(r=0.007,P=0.008).二者的表达与患者的性别、年龄无关.结论在骨肉瘤中,COX-2、MNP-2参与肿瘤发生发展过程,并且它们之间具有协同作用.     

Catalytic N-methyl amidation of carboxylic acids under cooperative conditions

Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry and the construction of this motif with high atom economy is the focus of the current research. Specifically, N-methyl amides are valuable building blocks in natural products and pharmaceutical science. Due to the volatile nature of methyl amine, the generation of N-methyl amides using simple acids with high atom economy is rare. Herein, we disclose an atom economic protocol to prepare this valuable motif under DABCO/Fe₃O₄ cooperative catalysis. This protocol is operationally simple and compatible with a range of aliphatic and (hetero)aromatic acids with very good yields (60–99%). Moreover, the Fe₃O₄ can be easily recovered and high efficiency is maintained for up to ten cycles.

The generation of N-methyl amides using simple acids with high atom economy is rare owning to the volatile nature of methyl amine. Herein, an atom economic protocol was disclosed to prepare this valuable motif under DABCO/Fe₃O₄ cooperative catalysis.

Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry.¹ It is widely distributed in natural products, synthetic drugs and functional polymers, and is also the key chemical connection in proteins.² It has been shown that amide bond formation alone accounts for 65% of all preliminary screening reactions in the pharmaceutical industry.³ This means the generation of amide bonds with high atom efficiency is of high practical importance. And not surprisingly, ‘amide formation avoiding poor atom economy reagents’ was voted as the top challenge for organic chemistry by the ACS Green Chemistry Institute in 2007.³From synthetic point of view, the ideal way to produce amide bonds would be the direct coupling of readily available carboxylic acids and amines, but this process is thermodynamically unfavourable due to the formation of the corresponding carboxylate-ammonium salt,⁴ therefore, stoichiometric amount of coupling reagents, such as DCC, DIC, EDCI, HATU, HBTU, HCTU, SOCl₂, BOP, acid chloride etc, are generally required to sidestep thermal conditions for amide bond formation.⁵ These reagents are highly successful, but the process generally suffers from poor atom economy and side products removal issue especially in the large-scale applications.⁵ To overcome these drawbacks, “nonclassical” amide bonds formation routes were investigated.⁶ In these processes, the catalyst takes the role of a coupling reagent in generating an active ester suitable for amidation in a waste-free manner. However, these processes have not been applied in the preparation of N-methyl amides, probably because the methyl amine was delivered in its hydrochloride salt, alcoholic or aqueous form due to its volatile nature.On a different note, N-methyl amides are extensively presented in numerous natural products and pharmaceutical molecules, as shown in Fig. 1,⁷ and the methylation of amides is a promising way to improve the pharmacological property of molecules.⁸ However, the synthesis of N-methyl amides compounds relies heavily on non-catalytic approaches.^5,9 Catalytic approaches were also investigated by Hisaeda,¹⁰ Kundu,¹¹ Li,¹² Guo,¹³ Yu,¹⁴ Maruoka,¹⁵ Wang,¹⁶ Chen,¹⁷ Lamaty¹⁸ and their co-workers starting from nitriles, primiary amides, aldoximes, aldehydes, lignin, carbamoylsilane and alcohols. Until recently, Thakur,¹⁹ Marce,²⁰ Sadeghzadeh²¹ and their co-workers developed elegant N-methyl amidation approach starting from carboxylic acids under nano-MgO, diatomite Earth@IL/ZrCl₄ and Mg(NO₃)₂·6H₂O catalysis respectively, while limitations like poor substrate scope or sophisticated tailored catalyst still persist. Mindful of all the above issues, developing an N-methyl amidation process of simple carboxylic acids, which is still of great challenge in synthesis, and establishing a broad (hetero)aryl scope with high atom economy from commercial available reagents and catalysts were critical considerations in this study. Moreover, the significance of N-methyl amides combined with our interests in the development of green synthetic approaches motivated us to explore the direct coupling of the carboxylic acids and isothiocyanates. To the best of our knowledge, this is the first successful work using isothiocyanatomethane to prepare N-methyl amides.Open in a separate windowFig. 1Marketed drugs bearing N-methyl amide group.Our initial investigation begins with phenylacetic acid and isothiocyanatomethane as model substrate for condition optimization. Using acetonitrile as solvent, only trace amount of product was detected under catalyst free or p-toluenesulfonic acid (PTSA) catalysis conditions (