拇指背侧皮神经营养血管皮瓣修复对拇指远端软组织缺损的效果观察

目的:探讨拇指背侧皮神经营养血管皮瓣修复拇指远端软组织缺损的临床效果。方法:选取我院2014年1月至2016年12月收治的拇指远端软组织缺损患者100例,随机分为对照组和观察组。对照组采取腹部皮瓣对拇指远端软组织缺损进行修复,观察组采取拇指背侧皮神经营养血管皮瓣对其进行修复。通过随访患者,记录分析皮瓣的生存状况、感觉指标、外观以及手部功能的DASH评分比较两组的修复效果。结果:观察组50例患者皮瓣全部成活。对照组50例皮瓣全部成活。与对照组相比,观察组在触觉、温度觉、单丝、两点辨别觉、瘢痕挛缩方面明显优于对照组(P0.05),臃肿发生率明显低于对照组(P0.05)。观察组DASH评分为29.56±2.14分,对照组为38.13±3.12分,观察组的DASH评分明显低于对照组(P0.05)。结论:拇指背侧皮神经营养血管皮瓣修复拇指远端软组织缺损手术不破坏主要血管神经,对供区影响小,操作简单,修复的指腹感觉,拇指外形较佳,是较为理想的选择。     

The Mass Spectra of the Lankacidin Antibiotics

Bundlins A and B, antibiotics elaborated by Streptomyces sp. 6642 GC₁, have the unique structures which possess a seventeen-membered carbon skeleton fused with an unusual β-keto-δ-Mactonic system and a pyruvamide side chain. In the course of the structural studies of the antibiotics, we found that these compounds showed the interesting fragmentations in their mass spectra and in consequence, the investigation about the interpretation of the principal peaks together with their formation mechanism was undertaken by the aid of high resolution mass spectrometry and the measurement of meta stable ions. In addition to the two antibiotics, the mass spectra of related compounds designated T–2636 D and T-2636 F were also investigated.     

硅藻中国新记录种——比提基金长篦藻

该研究利用光学和扫描电子显微镜对采自湖南东洞庭湖国家级自然保护区的硅藻标本进行了观察,鉴定出其中一种硅藻为比提基金长篦藻(Neidium beatyi Hamilton et al.)。结果表明,该长篦藻具有以下鉴定特征:(1)线性椭圆至线性披针形的壳瓣外形。(2)壳面两侧具有3～5条纵向线。(3)向相反方向弯曲的两近缝端,呈叉状分枝的远缝端末梢及顶端的三角形硅质顶盖。(4) 16～18条/10μm的线纹密度和14～18个/10μm的孔纹密度。(5)一些孔纹内部开口周围的4～7个豆状突出物。本研究结果与比提基金长篦藻模式种群的形态特征和数量性状均吻合,故确定其为比提基金长篦藻;增加了比提基金长篦藻的新地理分布区域——中国洞庭湖。     

重组flap核酸内切酶1的表达及活性测定方法的建立

Flap核酸内切酶1(Flap endonuclease 1,FEN1)是一种能催化核酸侵入反应的核酸内切酶,可应用于信号放大检测方法,但该酶详细的表达纯化工艺尚无报道,并且活性难以准确测定,限制了其应用。通过合成嗜热古球菌Archaeoglobus fulgidus来源的FEN1基因序列,构建了p ET24a(+)-FEN1-His重组质粒,并通过优化表达条件,得到了FEN1最优表达条件为:37℃、200 r/min振荡培养8 h后,加入诱导剂IPTG至终浓度为0.05 mmol/L,再于37℃、200 r/min诱导表达11 h,最终经镍亲和层析成功纯化得到了分子量约为38 k Da的重组FEN1。同时建立了基于荧光标记探针的FEN1活性测定方法,准确测定了重组FEN1的活性,为建立基于该酶的核酸检测方法提供了可靠的酶活力依据。最终将重组FEN1用于实时荧光PCR偶联高特异核酸侵入信号扩增法检测了乙醛脱氢酶2基因(aldh2)的基因型,得到了准确的分型结果,表明重组FEN1能用于基因多态性的分型检测中,为发展基于核酸侵入反应的核酸检测方法提供了可靠的工具酶。     

内外板单瓣嵌插术与改良Brisson术治疗隐匿型阴茎的临床疗效及安全性

目的:探究内外板单瓣嵌插术与改良Brisson术治疗隐匿性阴茎的临床疗效及安全性。方法:选择2016年1月至2019年1月于我院接受治疗的176例隐匿性阴茎患儿为研究对象,按照随机数字表法将其均分为实验组与对照组(每组各88例患儿)。对照组患儿接受常规内外板单瓣嵌插术治疗,实验组患儿接受改良Brisson术进行治疗,对比两组患儿的手术时间、治疗前后生活质量评分、术后阴茎伸长长度及各类并发症的发生率,并对两组患儿实施为期3个月的随访,对比两组患儿家长对治疗的满意度。结果:(1)实验组患儿手术时间选择短于对照组,阴茎伸长长度明显大于对照组(P<0.05);(2)实验组患儿术后并发症发生率显著低于对照组患儿(P<0.05);(3)实验组患儿术后各维度评分均高于对照组(P<0.05);(4)术后随访显示,实验组患儿家长对治疗满意度显著高于对照组患儿家长(P<0.05)。结论:相比于内外板单瓣嵌插术,改良Brisson术治疗隐匿性阴茎的临床效果和安全性均更优,且远期随访满意度较高。     

Molecular docking based virtual screening of natural compounds as potential BACE1 inhibitors: 3D QSAR pharmacophore mapping and molecular dynamics analysis

Beta-site APP cleaving enzyme1 (BACE1) catalyzes the rate determining step in the generation of Aβ peptide and is widely considered as a potential therapeutic drug target for Alzheimer’s disease (AD). Active site of BACE1 contains catalytic aspartic (Asp) dyad and flap. Asp dyad cleaves the substrate amyloid precursor protein with the help of flap. Currently, there are no marketed drugs available against BACE1 and existing inhibitors are mostly pseudopeptide or synthetic derivatives. There is a need to search for a potent inhibitor with natural scaffold interacting with flap and Asp dyad. This study screens the natural database InterBioScreen, followed by three-dimensional (3D) QSAR pharmacophore modeling, mapping, in silico ADME/T predictions to find the potential BACE1 inhibitors. Further, molecular dynamics of selected inhibitors were performed to observe the dynamic structure of protein after ligand binding. All conformations and the residues of binding region were stable but the flap adopted a closed conformation after binding with the ligand. Bond oligosaccharide interacted with the flap as well as catalytic dyad via hydrogen bond throughout the simulation. This led to stabilize the flap in closed conformation and restricted the entry of substrate. Carbohydrates have been earlier used in the treatment of AD because of their low toxicity, high efficiency, good biocompatibility, and easy permeability through the blood–brain barrier. Our finding will be helpful in identify the potential leads to design novel BACE1 inhibitors for AD therapy.     

腓肠肌皮瓣联合负压封闭引流治疗胫骨慢性骨髓炎及软组织缺损的临床研究

目的:研究腓肠肌皮瓣联合负压封闭引流治疗胫骨慢性骨髓炎及软组织缺损的临床疗效。方法:选取2013年10月到2014年10月我院收治的胫骨慢性骨髓炎及软组织缺损患者68例,按照手术方式不同将患者分为研究组(n=39例)和对照组(n=29例),其中研究组给予腓肠肌皮瓣联合负压封闭引流治疗,对照组给予常规手术方法治疗,比较两组临床疗效、C反应蛋白(CRP)变化、治愈时间以及复发率。结果:研究组治愈率94.9%(37/39)显著高于对照组的75.9%(22/29),两组比较差异具有统计学意义(P0.05);研究组CRP变化和治愈时间均显著优于对照组,两组比较差异具有统计学意义(P0.05);研究组复发率显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论:腓肠肌皮瓣联合负压封闭引流治疗胫骨慢性骨髓炎及软组织缺损具有较高治愈率,能显著降低炎性反应,缩短愈合时间,降低复发率。     

Interaction between APC and Fen1 during breast carcinogenesis

Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER – adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) – promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and effective targeted chemopreventive and chemotherapeutic agents.     

负压封闭引流技术在腹部带蒂皮瓣供瓣区的应用

目的:探讨负压封闭引流(vaccumsealingdrainage,VSD)技术在腹部带蒂皮瓣供瓣区中的治疗作用。方法:10例上肢深度创面大小为9×6 cm-14×9 cm,创面清创后行腹部带蒂皮瓣移植,皮瓣面积10×7 cm-20×15 cm,供瓣区应用VSD覆盖,医用半透性贴膜封闭整个术区,连接中心负压,持续低负压吸引,每日外用1000 mL生理盐水持续冲洗VSD。约3周后行皮瓣断蒂术,供瓣区植皮。结果:10例皮瓣全部存活,1例患者术后当天引流区域出现疼痛,经止痛治疗后未再出现。1例患者术后2周出现VSD堵塞,经处理后恢复正常引流。无VSD装置更换病例。供瓣区周边皮肤无浸渍及感染现象,VSD撤除后见基底肉芽组织生长新鲜,创面均无感染,移植皮片存活。结论:VSD技术可以有效保护供瓣区,刺激肉芽生长,为后期皮片移植闭合创面提供了良好条件。VSD技术可安全有效的应用于腹部带蒂皮瓣供瓣区。     

Crystal Structure of the Human Rad9-Hus1-Rad1 Clamp

Three evolutionarily conserved proteins, Rad9, Hus1, and Rad1, form a heterotrimeric 9-1-1 complex that plays critical roles in cellular responses to DNA damage by activating checkpoints and by recruiting DNA repair enzymes to DNA lesions. We have determined the crystal structure of the human Rad9 (residues 1-272)-Hus1-Rad1 complex at 2.5 Å resolution. The 9^1-272-1-1 complex forms a closed ring, with each subunit having a similar structure. Despite its high level of similarity to proliferating cell nucleus antigen in terms of overall structure, the 9^1-272-1-1 complex exhibits notable differences in local structures, including interdomain connecting loops, H2 and H3 helices, and loops in the vicinity of the helices of each subunit. These local structural variations provide several unique features to the 9-1-1 heterotrimeric complex—including structures of intermolecular interfaces and the inner surface around the central hole, and different electrostatic potentials at and near the interdomain connecting loops of each 9-1-1 subunit—compared to the proliferating cell nucleus antigen trimer. We propose that these structural features allow the 9-1-1 complex to bind to a damaged DNA during checkpoint control and to serve as a platform for base excision repair. We also show that the 9^1-272-1-1 complex, but not the full-length 9-1-1 complex, forms a stable complex with the 5′ recessed DNA, suggesting that the C-terminal tail of Rad9 is involved in the regulation of the 9-1-1 complex in DNA binding.