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1.
《European journal of medical genetics》2022,65(6):104495
Spondyloepimetaphyseal dysplasias (SEMDs) belong to a clinically and genetically heterogeneous group of inherited skeletal disorders defined by a defect in the growth and shape of vertebrae, epiphyses and metaphyses. Rhizomelic SEMD is characterized by a disproportionate small stature caused by severe shortening and deformation of the limbs’ proximal bones, with the cranio-facial sphere unaffected. We report a second individual, an 8-year-old girl, with autosomal recessive rhizomelic SEMD associated with a homozygous exonic missense variant, c.226G > A p.(Glu76Lys), in GNPNAT1 identified by trio genome sequencing. Our data corroborate the recent findings of Ain et al. and further delineate the clinical and radiographic features of this form of SEMD associated with rhizomelic dysplasia while outlining a potential hotspot in this newly described genetic disorder. 相似文献
2.
《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents. 相似文献
3.
目的探讨对妊娠高血压综合征患者给予硫酸镁联合硝苯地平以及酚妥拉明治疗的临床效果。方法抽取医院在2018年2月-2019年2月所接收的156例妊娠高血压综合征患者,将其按照数字随机表的方法分为单纯组和联合组,每组分别为78例。单纯组给予单纯的硫酸镁进行治疗,联合组在单纯组给予硝苯地平以及酚妥拉明进行联合治疗,比较患者的治疗效果。结果联合组的治疗有效率显著高于单纯组,治疗前血压水平差异无统计学意义(P>0.05),治疗后联合组的收缩压和舒张压水平均低于单纯组,P<0.05,两组差异有统计学意义。结论对妊娠高血压综合征患者给予硫酸镁联合硝苯地平和酚妥拉明进行联合治疗,有效改善患者的血压水平。 相似文献
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目的 建立小鼠溃疡性结肠炎模型。方法 给小鼠自由饮用5%葡聚糖硫酸钠(DSS)溶液7d后,改为蒸馏水自由饮用10d,如此进行4个循环,每天观察症状。在第1个循环和第4个循环后剖杀小鼠,取出整段结肠行实体显微镜观察及切片组织学研究。结果 所观察的症状、实体显微镜像、组织学病理改变均与人类溃疡性结肠炎类似。结论 此模型制作方法简便,重复性良好,可应用于多种实验研究。 相似文献
6.
Platelet factor 4 ( PF4) is a negativehematopoietic factor.It can inhibit the prolifera-tion of endothelial cells and hematopoietic stem/progenitor cells,particularly megakaryoryocyticcells,reversibly[1] ,inhibit DNA synthesis,blockcell cycle progression during S phase and reducethe sensibility of normal hematopoietic stem/pro-genitor cells,but not some cancer or leukemia celllines,to cytotoxic drugs and ionizing radia-tion[2 - 3] ,and it also can cause a population in-crease of the stem cel… 相似文献
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Objective Based on the Helical Ventricular Myocardial Band (HVMB) theory proposed by Torrent-Guasp,the ventricular myocardial hand extends from the root of the pulmonary artery to the root of the aorta with two helical coils.This new theory is considered as a revolutionary concept for further understanding the global, three-dimensional and functional architecture of the ven- tricular myocardium. No repot had described techniques for disecting HVMB while keepin~ the integrity of the coronmy artery sys- tern. We explored techniques for dissecting HVMB in swine.Methads 33 fresh swine hearts were randomly divided intoll groups, 3 bearts in each. 160% barium sulfate (type I)suspmmion was injected into the coronary artery system. The coronary arteries were li- gated. The strial tissue was removed following puuing the hearts in boiling water then cooling for several hours. The superficial coro- nary vessels and fat tissue around the atrio-ventricular taxi inter-ventricular sulcus we~'e preserved. Some branches of the left anterior descending artery, distal segment, of posterior descending branch, and middle and distal segment of obtuse marginal branches were mu- tilated appropriately. HVMB dissection was completed with fingers in accordnce with Torrent Guasp' s technique. Results A contin- ued bundle of muscle, originated at the root of pulmonary artery and ended at the root of aorta, was unwrapped along the major dire- tion of the cardiac muscle fiber in all of the 33 hearts with spating of the coronary artery. The swine hearts' ventricular myocandium was cumosed of two loops, with basal loop firm the root of the pulmonart artery to the anterior papillary muscle and apical from the beginning of the anterior papillary muscle to the root tithe aorta. Each loop consisted of two segments: the right segment-coincid- ing with the right ventricular free wall and the left segment-coinciding with the basal d the left ventricular free wall. Posterior papillary muscle, which belongs to the descendant segment, denmrcated the border between the descendent and the ascendant of the HVMB's apical loop. Conclusion Although controversies about the theory of the HVMB remain, we have dissected the HVMB in the swine hearts' ventricular myocardium successfully with sparing of the coronary artery systems. This dissection procedure provides technical information for the studies of associated diseases based on the theory of HVMB. 相似文献
9.
Gopala K RANGAN Yiping WANG Yuet-Ching TAY Liguang CHEN David CH HARRIS 《Nephrology (Carlton, Vic.)》1998,4(1-2):57-64
SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein. 相似文献
10.
玻璃体内注射庆大霉素致视网膜损伤的实验研究Ⅰ.组织病理学观察 总被引:1,自引:0,他引:1
为探讨庆大霉素对视网膜的毒性作用和评估玻璃体内注射庆大霉素的安全剂量,采用眼底镜观察及光镜、电镜技术对注射5种不同剂量庆大霉素的青紫蓝兔视网膜标本进行观察。结果:3000μg庆大霉素注射后眼底表现为视盘水肿,后极部视网膜大片坏死,镜下视网膜组织形态严重破坏;50~500μg剂量注射引起后极部视网膜色素改变,组织损伤早期局限在视网膜内层,晚期全层受累。提示庆大霉素对视网膜的损伤程度随注入剂量增加而加重,即使50μg的微小剂量仍可产生视网膜损伤。 相似文献