A second individual with rhizomelic spondyloepimetaphyseal dysplasia and homozygous variant in GNPNAT1

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.     

Comparison of Foaming Properties Between the Shirasu Porous Glass Membrane Device and Tessari’s Three-way Stopcock Technique for Polidocanol and Ethanolamine Oleate Foam Production: A Benchtop Study

PurposeTo compare the characteristics of polidocanol (POL) and ethanolamine oleate (EO) sclerosing foams produced by a Shirasu porous glass membrane (SPGM) device with those made using a 3-way stopcock (3WSC).Materials and MethodsFoam half-life times were measured in an ex-vivo benchtop study. Computed tomography (CT) images of each foam were obtained over the time course, and a CT texture analysis was conducted. The bubble size in each foam was measured by an optical microscope.ResultsMedian foam half-life times were longer in the SPGM group than in the 3WSC group (POL: 198 vs 166 s, P = .02; EO: 640 vs 391 s, P < .01). In the CT texture analysis, median standard deviation (SD) and entropy (randomness) were lower, and median energy (uniformity) and gray-level cooccurrence matrix (GLCM) homogeneity were higher in the SPGM group than in the 3WSC group (POL SD: at 30 s and 50–300 s; POL entropy: at 0–60 s; EO SD: at 0–600 s; EO entropy: at 0–460 s; POL energy: at 0–40 s; POL GLCM homogeneity: at 0–250 s; EO energy: at 0–360 s; EO GLCM homogeneity: at 0–480 s; all P < .05). Median bubble diameters in the SPGM group and in the 3WSC group were 69 and 83 μm (P < .01), respectively, in the POL foam; and 36 and 36 μm (P = .45), respectively, in the EO foam.ConclusionsPOL and EO foams had greater uniformity and longer foam half-life time when prepared with an SPGM device than with a 3WSC.     

头孢洛扎硫酸盐制备方法的改进

将起始原料ACLE·HCl首先与7-位侧链噻二唑化合物TATD反应，然后再与吡唑化合物UBT进行反应，并用三氟乙酸进行脱保护基反应。最后经过纯化析晶，合成头孢洛扎硫酸盐。该工艺得到头孢洛扎硫酸盐的纯度高，原料易得，纯化时不需要过柱，更适合工业化生产。     

盐酸氨溴索治疗小儿支气管肺炎的临床分析

目的分析研究盐酸氨溴索用于小儿支气管肺炎的临床效果。方法将本院2017年12月—2018年12月期间收治的小儿支气管肺炎患儿88例按照随机双盲法均分为对照组和治疗组,予以对照组44例患儿常规治疗,予以治疗组44例患儿常规治疗联合氧气驱动雾化吸入盐酸氨溴索治疗,对两组患儿的临床疗效和临床症状缓解时间进行对比。结果与对照组相比,治疗组患儿咳嗽、咳痰、胸片改善时间及肺部干湿啰音缓解时间均显著短于对照组,组间差异具有统计学意义(P<0.05),治疗组的临床总有效率为95.45%(42/44),明显高于对照组77.27%(34/44),组间差异具有统计学意义(P<0.05)。结论小儿支气管肺炎在临床常规治疗的基础上加用盐酸氨溴索治疗有助于患儿临床症状的缓解,效果明显。     

硫酸镁、硝苯地平和酚妥拉明治疗妊高症

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。     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

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.     

Using online content uniformity measurements for rapid automated process development exemplified via an X-ray system

This paper addresses the relevance of automated content testing for the rapid automated process development (RAPD). Our previous work demonstrated that RAPD allowed a fast and efficient development of a continuous capsule-filling process. Target was the mean weight and the relative standard deviation of the weight. Likewise important are the content and the content uniformity. However, an implementation demands a certain level of automation. In general, technology is available that can detect active pharmaceutical ingredient (API) inside the capsules but the final application is linked to additional development and investment in machinery. To eliminate doubts regarding the benefits of an automated content check within the RAPD we present an application example. First, an X-ray system was used to detect barium sulfate accurately inside capsules. Second, a process was developed where barium sulfate was filled. The concentration of excipients was modified in the experiments, as well as the setting of the process parameter. The obtained model provided an explicit understanding of the process. Subsequently, the content uniformity model was compared to a model of the capsule weight relative standard deviation, confirming the benefits of an automated content check in the RAPD. Moreover, we presented another example illustrating the advantages of a connected continuous filling process, which permits evaluation of all process steps and their interactions (i.e. evaluation of the entire process).     

胃肠安丸对葡聚糖硫酸钠诱导溃疡性结肠炎小鼠的治疗作用及机制

目的探讨胃肠安丸对葡聚糖硫酸钠(DSS)诱导溃疡性结肠炎小鼠的治疗作用及机制。方法SPF级C57BL/6小鼠60只,除正常对照组小鼠外,其余小鼠均给予2.5%DSS水溶液,自由饮用7 d制备溃疡性结肠炎模型,模型评价后再随机分为模型组、美沙拉嗪组及胃肠安丸高剂量组、中剂量组、低剂量组。胃肠安丸低、中、高剂量组分别给予0.015、0.03、0.06 g/(kg·d)胃肠安丸混悬液0.5 mL灌胃,1次/d;美沙拉嗪组给予0.52 g/(kg·d)美沙拉嗪混悬液0.5 mL灌胃,1次/d;正常对照组和模型组给予等体积纯水灌胃,均连续干预10 d。对比各组小鼠疾病活动指数(DAI)评分、结肠长度,用HE染色观察小鼠结肠组织病理形态学变化,用流式细胞术检测脾组织中Treg、Th17、CD4^+、CD8^+细胞百分比,ELISA法检测血清细胞因子TNF-α、IL-6、IL-8、IL-10、CRP水平。结果药物干预过程中,各组小鼠体质量均逐日增加,腹泻、便血、体质量下降等症状逐日缓解,与模型组相比,美沙拉嗪组和胃肠安丸高剂量组能更快地缓解上述症状,2组DAI评分逐日下降(P<0.05)。药物干预结束后,与模型组比较,胃肠安丸高剂量组和美沙拉嗪组小鼠结肠较长(P<0.05),结肠组织充血、间质水肿及炎性细胞浸润较轻,CD4^+、CD8^+、Treg细胞百分比及血清IL-10水平较高(P<0.05),Th17细胞百分比及血清TNF-α、IL-6、IL-8、CRP水平较低(P<0.05)。结论胃肠安丸对DSS诱导的小鼠肠道黏膜损伤有一定的修复作用,其作用机制可能与恢复Treg/Th17免疫平衡以及调节相关细胞因子水平有关。     

小儿豉翘清热颗粒治疗疱疹性咽峡炎临床研究

目的:观察小儿豉翘清热颗粒治疗疱疹性咽峡炎的临床疗效及安全性。方法:选取79例疱疹性咽峡炎患儿,随机分为对照组39例和治疗组40例,对照组常规给予利巴韦林气雾剂治疗,治疗组使用小儿豉翘清热颗粒联合利巴韦林气雾剂治疗。比较2组患儿临床症状、体征消失时间,观察2组总体疗效及用药安全性。结果:与对照组比较,治疗后治疗组症状体征恢复时间均更短,总体疗效更优,差异有统计学意义(P<0.05)。2组患儿用药期间不良反应发生情况比较,差异无统计学意义(P>0.05)。结论:小儿豉翘清热颗粒联合利巴韦林气雾剂治疗小儿疱疹性咽峡炎,可缩短临床症状、体征消失的时间,增加总疗效率且不增加药物不良反应,比传统抗病毒治疗更加有效。