Quick identification of effective small interfering RNAs that inhibit the replication of coxsackievirus A16

Coxsackievirus A16 (CA16) is a major causative agent of hand, foot, and mouth disease (HFMD). It can cause myocarditis, pericarditis and fatal shock. There is no effective therapy against CA16. RNA interference (RNAi) is a powerful tool to silence gene expression. The small interfering RNA (siRNA) that induces RNA degradation has recently been used as an anti-virus agent to inhibit virus replication. In this study, we established the complete nucleotide sequence of CA16 strain Shzh05-1, and then compared the nucleotide sequences of Shzh05-1 with sequences of other CA16 strains in GenBank. We chose conserved regions between Shzh05-1 and the two other CA16 strains to design 30 siRNAs and construct siRNA-encoding plasmids. Thirteen siRNAs targeting conserved regions of the virus could effectively block replication of CA16 in cultured cells. Combination transfection of these 13 effective siRNAs could also produce a high inhibitory effect. These strategies and results suggest that RNAi has potential therapeutic use for suppression of CA16 infection.     

大鼠重复ig给予N-［（3-烯丙基-2-羟基）苯亚甲基-2-（4-苄基-高哌嗪-1-基）乙酰肼富马酸盐的药动学研究

目的 采用高效液相色谱-串联质谱法（HPLC-MS/MS）测定SD大鼠血浆中N-［（3-烯丙基-2-羟基）苯亚甲基］-2-（4-苄基-高哌嗪-1-基）乙酰肼富马酸盐（SM-1）,并计算大鼠重复ig给药的药动学参数,评价SM-1的药动学特征。方法 将60只健康SPF级SD大鼠随机分为阴性对照组、溶媒对照组和SM-1低、中、高剂量组,每组16只动物（阴性对照组和溶媒对照组为6只动物）,雌雄各半。每天ig给药1次,各组分别给予水、溶媒或SM-1 50、100、200 mg·kg^-1,给药体积10 mL·kg^-1,连续给药4周,于首次给药和末次给药阶段进行药动学采血测定。采用经验证的HPLC-MS/MS法测定SD大鼠血浆中SM-1浓度。使用Phoenix WinNonlin 7.0软件进行血药浓度-时间数据分析与药动学参数计算。结果 SD大鼠ig给予SM-1后,在50～200 mg·kg^-1剂量,SD大鼠体内的平均峰浓度（C_max）及药时曲线下面积（AUC_0～t）随剂量的增加而增加,各剂量组动物平均C_max及AUC_0～t比值与剂量比相近。连续给药后,低、中、高剂量组均未出现明显的蓄积。雌性大鼠SM-1的暴露高于雄性大鼠。结论 连续给药28 d后,SM-1在大鼠体内未出现明显的蓄积,雌性大鼠SM-1的暴露高于雄性大鼠。     

Feasibility Studies of Nebulized SARS-CoV-2 Neutralizing Antibody in Mice and Cynomolgus Monkeys

Pharmaceutical Research - Neutralizing antibodies, administrated through intravenous infusion, have shown to be highly efficacious in treating mild and moderate COVID-19 caused by SARS-CoV-2...     

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty

AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.     

腹主动脉瘤性别差异性的生物力学研究进展

腹主动脉瘤具有性别差异性,男性发病率较高,而女性的破裂发生率与术后死亡率均较高,这一性别差异性现象会影响到腹主动脉瘤患者的诊断、治疗及术后康复。本文综述了腹主动脉瘤性别差异性的研究现状,从阈值判定及生物力学、力学生物学等方面探究了腹主动脉瘤性别差异性这一现象,并指出男女腹主动脉尺寸差异、解剖结构及血管结构成分不同而导致的生物力学以及力生物学的差异,可能是导致两性腹主动脉瘤呈现出差异性的重要原因。针对腹主动脉瘤性别差异性的生物力学研究,将会为腹主动脉瘤诊断、治疗及器械设计、患者护理和康复提出基于性别差异的改进建议。     

自动协议选取能谱联合自适应迭代计算法重建技术降低腹部增强及血管成像辐射剂量及对比剂剂量的可行性

目的 探讨利用自动协议选取能谱（ASIS）扫描模式联合自适应迭代算法重建（ASiR）技术降低腹部增强及血管成像辐射剂量及对比剂剂量的可行性。方法 将64例接受腹部增强患者随机分为两组：试验组32例,采用ASIS扫描模式,应用30% ASiR和50% ASiR重建算法;对照组32例,采用120 kVp管电压,FBP重建。比较两组扫描方法辐射剂量及对比剂剂量;比较70 keV+30% ASiR图像与对照组动脉期及门静脉期肝脏及胰腺噪声、竖脊肌噪声（SMN）、肝脏CNR、胰腺CNR;对55 keV+50% ASiR图像与对照组动脉期腹主动脉及各主要分支血管CNR及门静脉期门静脉CNR以及血管图像主观评分进行统计学分析。结果 试验组动脉期及门静脉期的CTDIvol、DLP较对照组下降23.68%、23.57%和25.59%、18.45%,对比剂注射总量试验组较对照组减少16.86%。70 keV+30% ASiR动脉期及门静脉期肝脏、胰腺和竖脊肌的噪声均低于对照组（P均<0.05）。试验组55 keV+50% ASiR动脉期腹主动脉、肠系膜上动脉、腹腔干的CNR均高于对照组（P均<0.05）;静脉期门静脉的CNR和血管评分与对照组比较差异无统计学意义（P>0.05）。结论 采用ASIS扫描模式联合ASiR技术,70 keV+30% ASiR及55 keV+50% ASiR图像显示腹部脏器及腹部血管图像质量均优于传统120 kVp扫描模式的图像质量,且降低了辐射剂量及对比剂剂量。     

蜜丸合坨过程物理特性参数表征方法研究

目的：建立蜜丸合坨过程中丸块物理特性参数表征方法,考察不同放置时间对丸块物理特性参数的影响。方法：采用质构仪压缩实验测定了丸块在不同放置时间硬度、黏附力、回复性等物理特性参数变化情况。采用不同曲线拟合方法和方差分析方法研究其变化规律。结果：比较不同拟合曲线,结果表明硬度、黏附力、回复性分别采用Y=261.600 26-160.248 74×0.469 22^{^}x（R²=0.997 28）;Y=51.158 33-30.427 91×0.484 61^{^}x（R²=0.991 63）;Y=0.018 12-0.004 38×0.094 91^{^}x（R2=0.889 16）方程拟合可以很好的反应原数据点的变化;方差分析结果表明丸块在0-3h硬度和黏附力变化明显（P<0.05）;回复性基本不随放置时间的延长而改变。结论：质构仪可以量化表征蜜丸合坨过程中丸块的物理特性参数,客观反映丸块随放置时间的变化规律,为蜜丸合坨过程质量控制研究填补空白。     

DWI多b值水通道蛋白分子成像在肝纤维化早期诊断的价值

目的：探讨磁共振弥散加权成像（MR diffusion weighted imaging,MR-DWI）多b值水通道蛋白（Aquaporin,AQP）分子成像技术在肝纤维化早期诊断的价值.方法：应用乙酰唑胺作为水通道蛋白抑制剂,将对照组及肝纤维化模型组大鼠分别于乙酰唑胺静脉注射抑制前后进行常规MRI及DWI扫描.DWI扫描多b值包括0～4 500 s/mm2共18个不同b值,先按照常规方法获得“标准”表观弥散系数（ADC）值,然后再分别以200、1 500作为界值将其分为低、中和高b值.以病理学肝纤维化分期将大鼠分为S0、S1、S2、S3、S4期,比较低、中、高b值下,不同纤维化分期大鼠肝脏ADC值,并观察同一分期大鼠乙酰唑胺抑制前后,肝脏组织细胞膜上AQP表达量和活性变化情况.结果：“标准”ADC值在各分期之间均无显著性差异.在肝纤维化早期,随着肝纤维化程度的进展,肝脏组织细胞膜上AQP1表达相应增加.乙酰唑胺抑制前,在高b值下,S0期ADC值显著低于S3、S4期（P＜0.05）,其余各组比较均无明显统计学差异;但乙酰唑胺抑制后,高b ADC值比较,S0与S1比较无明显统计学差异,S0与其他各期比较、S1与S2、S1与S3/S4比较,均有明显统计学差异（均P＜0.05）.各组内乙酰唑胺抑制前后自身比较,SO、S1期抑制率分别为15.5％、16.0％,S2期抑制不明显1.9％,S3＋S4期为11.7％.结论：初步实验表明,常规方法获得“标准”ADC值并不能发现肝脏纤维化早期病变,也不能有效对其分期.磁共振DWI多b值扫描,主要是高b值下ADC值变化与肝脏细胞膜上AQP表达相关,该技术可以用于评价早期肝纤维化和对肝脏纤维化分期.