摘 要： 目的探讨孕中期唐氏筛查对检出胎儿染色体异常及减少出生缺陷的实际意义。方法对扬州市9 191例孕15-20＋6周的孕妇用化学发光法对血清标志物甲胎蛋白（AFP）、人绒毛膜促性腺激素（β-HCG）和游离雌三醇（μE3）进行检测，结合孕妇年龄、体重、孕周等因素利用唐氏筛查风险评估软件计算胎儿患有21三体综合征、18三体综合征和神经管缺陷（NTD）的风险率，并对高风险孕妇进行羊水细胞染色体核型分析或B超进一步确诊。结果 9191例孕妇共筛查出611例高风险孕妇，阳性率为6.66%。347例高风险孕妇进行了羊膜腔穿刺术，经染色体核型分析共确诊10例染色体异常，其中21三体7例，18三体1例，其他染色体异常2例;143例NTD高风险孕妇经四维B超检查，最终确诊2例（脊柱裂1例、无脑儿1例）。结论中孕期唐氏筛查结合B超和羊水细胞染色体核型分析，可以有效降低出生缺陷患儿的出生率。
A personalized adhesion prevention strategy: Arslan E, Talih T, Oz B, Halaclar B, Caglayan K, Sipahi M. Comparison of lovastatin and hyaluronic acid/carboxymethyl cellulose on experimental created peritoneal adhesion model in rats.Int J Surg. 2013 Dec 4. pii: S1743-9191(13)01110-2. doi: 10.1016/j.ijsu.2013.11.010. [Epub ahead of print]
ABSTRACT pii： S1743-9191(14)00474-9. [Epub ahead of print]
Analysis on screening results of Down's syndrome in 9191 cases during the second trimester of pregnancy in Yangzhou
Objective To explore the practical value of Down's syndrome screening during the second trimester of pregnancy for detection of fetal chromosomal abnormalities and reducing birth defects. Methods Chemiluminescence was used to detect the concentrations of serum biochemical markers- alpha- fetoprotein( AFP)，β- human chorionic gonadotropin( β- h CG)，and unconjugated estriol in 9 191 pregnant women of 15- 20+ 6gestational weeks in Yangzhou，Down's syndrome assessment software combined with maternal age，maternal weight and gestational weeks was used to calculate the risk degrees of fetal trisomy 21，trisomy 18，and neural tube defects( NTDs); for the high risk pregnant women，chromosomal karyotyping of amniotic fluid cells or type- B ultrasound was conducted for further definite diagnosis. Results Among 9 191 pregnant women，611 pregnant women were high risk pregnant women，the positive rate was 6. 66%. A total of347 high risk pregnant women underwent amniocentesis，after chromosomal karyotyping，10 pregnant women were diagnosed as chromosomal abnormalities definitely，including 7 cases of trisomy 21，1 case of trisomy 18，and 2 cases of other chromosomal abnormalities; 143 high risk NTDs pregnant women received four- dimensional ultrasonography，finally，2 cases were diagnosed definitely，including one case of spina bifida and one case of anencephaly. Conclusion Down's syndrome screening during the second trimester of pregnancy combined with ultrasonography and chromosomal karyotyping of amniotic fluid cells can effectively reduce the birth rate of infants with birth defects.
An inexact study design produced misleading conclusions: To perform operative procedures in an optimized local atmosphere: Can it reduce post-operative adhesion formation? de Vries A, Mårvik R, Kuhry E. [Int J Surg 2013 Sep 27. pii: S1743-9191(13)01053-4. doi: 10.1016/j.ijsu.2013.09.005].
ABSTRACT doi：pii： S1743-9191(13)01109-6. 10.1016/j.ijsu.2013.11.009. [Epub ahead of print] No abstract available. PMID： 24316018 [PubMed - as supplied by publisher]
Role of Cathepsin A and Lysosomes in the Intracellular Activation of Novel Anti-papillomavirus Agent GS-9191
GS-9191， a bis-amidate prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)-N6-cyclopropyl-2，6-diaminopurine (cPrPMEDAP)， was designed as a topical agent for the treatment of papillomavirus-associated proliferative disorders， such as genital warts. In this study， we investigated the mechanism of conversion of GS-9191 to cPrPMEDAP. We observed that GS-9191 is hydrolyzed in the presence of the lysosomal carboxypeptidase cathepsin A (CatA) in vitro and is less efficiently metabolized in CatA-deficient fibroblasts than in control cells. In addition， knockdown of CatA by small interfering RNA (siRNA) reduced the intracellular accumulation of GS-9191 metabolites. However， intracellular CatA levels did not correlate with the susceptibility of tested cell lines to GS-9191， indicating that the CatA step is unlikely to be rate limiting for the activation of GS-9191. Further analysis showed that upon the hydrolysis of the carboxylester bond in one of the GS-9191 amidate moieties， the unmasked carboxyl group displaces L-phenylalanine 2-methylpropyl ester from the other amidate moiety. The cPrPMEDAP-L-phenylalanine conjugate (cPrPMEDAP-Phe) formed is not metabolized by Hint1 (histidine triad nucleotide binding protein 1) phosphoramidase but undergoes spontaneous degradation to cPrPMEDAP in acidic pH that can be significantly enhanced by the addition of SiHa cell extract. Pretreatment of SiHa cells with bafilomycin A or chloroquine resulted in an 8-fold increase in the intracellular concentration of cPrPMEDAP-Phe metabolite and the accumulation of GS-9191 metabolites in the lysosomal/endosomal fraction. Together， these observations indicate that the conversion of GS-9191 to cPrPMEDAP occurs in lysosomes via CatA-mediated ester cleavage， followed by the release of cPrPMEDAP， most likely through the combination of enzyme-driven and spontaneous pH-driven hydrolysis of a cPrPMEDAP-Phe intermediate.
Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development. Proc Natl Acad Sci USA 92: 9191-9195
ABSTRACT Many features of Down syndrome might result from the overdosage of only a few genes located in a critical region of chromosome 21. To search for these genes， cosmids mapping in this region were isolated and used for trapping exons. One of the trapped exons obtained has a sequence very similar to part of the Drosophila single-minded (sim) gene， a master regulator of the early development of the fly central nervous system midline. Mapping data indicated that this exonic sequence is only present in the Down syndrome-critical region in the human genome. Hybridization of this exonic sequence with human fetal kidney poly(A)+ RNA revealed two transcripts of 6 and 4.3 kb. In situ hybridization of a probe derived from this exon with human and rat fetuses showed that the corresponding gene is expressed during early fetal life in the central nervous system and in other tissues， including the facial， skull， palate， and vertebra primordia. The expression pattern of this gene suggests that it might be involved in the pathogenesis of some of the morphological features and brain anomalies observed in Down syndrome.
鼠小弟和鼠小妹 (日)中江嘉男文 ; (日)上野纪子图 ; 赵静， 文纪子译 （爱心树绘本馆， 014 . 可爱的鼠小弟||カアイ テキ ソショウテイ||ke ai de shu xiao di ; 4） 南海出版公司， [2009.8]
目的 研究脂肪肝在虞城县内流行现状与危险因素.方法 回顾性分析2007年6月在虞城县人民医院体检的乡镇职工2480人，平均年龄(41.05±9.25)岁，男性2090人，女性390人.测定体重指 数、空腹血糖、胆固醇、甘油三酯、丙氨酸转氨酶、天冬氨酸转氨酶、血压等指标，并行腹部B超检查 .结果检出脂肪肝350例(14.11%).男性332例(94.86%)，女性18例(5.14%).伴有高血脂者有226例(64.57%)，肥胖者 123例(35.14%)，伴有高血压者112例(32%)，伴空腹血糖＞6.1mmol/L者59例(16.86%)，伴脂肪性肝炎者14例(4%). 结论 脂肪肝发病率男性为主，高达94.86%，高血脂、肥胖症、高血压病、糖代谢紊乱等为脂肪肝的危险因素.
A chemical structure is a joy forever， and this is how I perceived the chemical structures of a number of antiviral compounds with which I have been personally acquainted over the past 3 decades： (1) amino acid esters of acyclovir (i.e. valaciclovir); (2) 5-substituted 2'-deoxyuridines (i.e. brivudin); (3) 2'，3'-dideoxynucleoside analogues (i.e. stavudine); (4) acyclic nucleoside phosphonates (ANPs) (i.e. cidofovir， adefovir); (5) tenofovir disoproxil fumarate (TDF) and drug combinations therewith; (6) tenofovir alafenamide (TAF， GS-7340)， a new phosphonoamidate prodrug of tenofovir; (7) pro-prodrugs of PMEG (i.e. GS-9191 and GS-9219); (8) new ANPs： O-DAPy and 5-aza-C phosphonates; (9) non-nucleoside reverse transcriptase inhibitors (NNRTIs)： HEPT and TIBO derivatives; and (10) bicyclam derivatives (i.e. AMD3100).
Background & Hypothesis. Micro RNAs are small noncoding RNAs that regulate protein expression at the post-transcriptional level. The purpose of this study was to determine if microRNA-150 (miR-150) plays a role in the regulation of blood pressure (BP). Methods & Results. We found that knockout of miR-150 resulted in a significant increase in systolic， diastolic and mean BP in mice. Vascular relaxing responses to acetylcholine were decreased significantly in miR-150 knockout (miR150-KO) mice， suggesting impaired endothelial function. Therefore， miR-150 is essential in the maintenance of normal BP and endothelial function. MiR150-KO was accompanied by a significant increase in NADPH oxidase activity and superoxide production in aortas and kidneys. MiR150-KO mice demonstrated vascular and renal remodeling. Interestingly， miR150-KO significantly increased Cyp11β2 protein expression in adrenal cortex， suggesting that miR-150 is a negative regulator of Cyp11β2. Plasma level of aldosterone was elevated in the miR150-KO mice. It was noted that daily treatment with aldosterone receptor blockade eplerenone (EPL) effectively reversed hypertension， endothelial dysfunction， increases in NADPH oxidase activity and superoxide production， and vascular and renal damage in miR150-KO mice. Conclusions. These results suggest that miR150-KO-inudced hypertension may be mediated by the upregulation of Cyp11β2 expression which led to increased biosynthesis of aldosterone. It is concluded that miR-150 is a critical regulator of Cyp11β2 in the control of BP. MiR-150 may be a novel therapeutic target for hypertension. (Supported by NIH R01 HL105362).