Complete recovery of filler-induced visual loss following subcutaneous hyaluronidase injection

The rise in popularity of hyaluronic acid (HA) dermal filler injection has caused an exceptional increase in the number of cases of reported irreversible blindness. Here, we reported a case of ischemic optic neuropathy and ophthalmoplegia following subcutaneous HA filler injection with complete visual recovery. A 31-year-old Chinese woman presented with sudden onset of right monocular visual impairment associated with diplopia. Patient had received a hyaluronic acid-containing ?ller injection for nasal dorsum augmentation twelve hours prior to presentation. Visual acuity of the right eye was counting finger. A right relative afferent pupillary defect was demonstrated with ophthalmoplegia. Humphrey visual field test disclosed a right inferior altitudinal field defect with impairment of colour vision. Computed tomography of the orbit revealed mild enlargement of the right medial and inferior recti muscles. Our patient showed a tremendous improvement of vision after a subcutaneous hyaluronidase injection with complete visual recovery within 2 weeks.     

Artificial oocyte activation: physiological,pathophysiological and ethical aspects

Infertile couples with low oocyte yield in combination with abnormal semen parameters may experience intra-cytoplasmic sperm injection (ICSI) failure. An established factor associated with ICSI failure is oocyte activation deficiency (AOD). The latter originates from seminal contributors, such as phospholipase C-zeta (PLCζ) that is not adequate to produce calcium (Ca²⁺) oscillations for oocyte activation. Apart from this natural activator, other stimulants, such as A23187, ionomycin, strontium chloride or even electric pulses, have been used in embryological laboratories to overcome AOD and ICSI failure. The aim of the present narrative review is to discuss the role of Ca⁺² oscillations in oocyte activation and summarize the evidence concerning the use of oocyte activators as agents for artificial oocyte activation (AOA). Studies in humans and animals have emerged many physiological, pathophysiological and ethical aspects of AOA. In conclusion, in mammalian eggs, the cytosolic Ca⁺² oscillations derive from a periodic release of Ca⁺² from intracellular pools. PLCζ, as well as artificial stimulants, have been used to produce Ca⁺² oscillations for AOA. As the latter may increase the risk of epigenetic induced malformations, further studies are required to clarify whether AOA constitutes an effective and safe method to overcome ICSI failure.

Abbreviations: AOA: artificial oocyte activation; AOD: oocyte activation deficiency; Ca⁺²: Calcium; CAMKII: Ca⁺²/calmodulin-dependent protein kinase II; CICR: calcium-induced calcium-release; DAG: diacylglycerol; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICSI: intra-cytoplasmic sperm injection; InsP₃R: inositol-trisphosphate receptor; IP₃: inositol 1,4,5-trisphosphate; IVF: in vitro fertilization; MAP: mitogen-activated protein; MII: metaphase II; NADP: nicotinic acid adenine dinucleotide phosphate; NO: nitric oxide; PAWP: post-acrosomal WW-binding domain protein; PIP₂: phosphatidylinositol 4,5-bisphosphate; PLC: phospholipase C; PLCζ: phospholipase C-zeta; SOAFs: spermatozoon-released oocyte-activating factors; Sr⁺²: strontium; TFF: total fertilization failure     

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.     

冠心病心绞痛患者行丹参多酚酸盐治疗的效果

目的分析冠心病心绞痛患者采取丹参多酚酸盐治疗效果及安全影响。方法选取本院2017年7月-2018年6月接收的冠心病心绞痛患者72例为研究对象,随机分为两组,各36例,对照组行丹参注射液治疗方案,研究组则接受丹参多酚酸盐治疗方案,对比两组临床疗效及不良反应发生率。结果在治疗总有效率方面,对照组是72.22%,研究组是94.44%,研究组较对照组更高,差异有统计学意义(P<0.05);在不良反应发生率方面,对照组与研究组分别是8.33%和5.56%,研究组与对照组差异统计学无意义(P>0.05);研究组心绞痛发作次数较对照组更低,差异存在统计学意义(P<0.05);而运动诱发ST段压低1 mm时间、运动诱发心绞痛发作时间及总运动代谢量,对照组与研究组差异统计学无意义(P>0.05)。结论冠心病心绞痛疾病治疗期间,应用丹参多酚酸盐治疗方案,不仅可以减少冠心病心绞痛发作次数,同时有助于改善患者临床症状,促进治疗效果的提高,此外,具有较高的安全性。     

胃神经官能症予以中西医结合治疗

目的:观察胃神经官能症予以中西医结合治疗的效果。方法:选取我院2018年4月-2019年4月收治的134例胃神经官能症患者进行研究,依照治疗方法的不同,将其分为参照组和研究组两组,每组各67例,参照组实施穴位注射治疗,研究组在参照组的基础上采用中药剂柴胡桂枝汤治疗,对两组患者治疗前后的中医症状体征积分、焦虑评分、抑郁评分、治疗总有效率及复发情况进行观察和比较。结果:治疗前两组患者的食少纳差、胃脘胀痛、少寐多梦及神疲乏力等中医症状体征积分差异不明显(P>0.05),治疗后研究组患者的食少纳差、胃脘胀痛、少寐多梦及神疲乏力等中医症状体征积分明显比参照组优(P<0.05);治疗前两组患者的焦虑评分及抑郁评分差异不明显(P>0.05),治疗后研究组患者的焦虑评分、抑郁评分及复发率明显比参照组低(P<0.05);治疗总有效率明显比参照组高(P<0.05)。结论:穴位注射与中药剂柴胡桂枝汤联合治疗胃神经官能症,可使患者临床症状得到明显改善及治疗有效率得到提高,缓解患者产生的焦虑、抑郁情绪,并且还能使患者治疗后的复发率得到降低,值得进行临床应用和推广。     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.     

复方丹参滴丸对老年冠心病患者血流变学、血脂及炎性反应递质的影响

目的：探究复方丹参滴丸对老年冠心病患者血流变学、血脂及炎性反应递质的影响。方法：选取2015年1月至2017年12月海南省人民医院收治的老年冠心病患者154例作为研究对象，按照随机数字表法随机分为对照组和观察组，每组77例。对照组采用常规西药治疗，观察组在此基础上加服复方丹参滴丸。比较治疗前后2组患者的血流变学、血脂、炎性反应递质和疗效。结果：观察组治疗有效率为92.21%，明显高于对照组治疗有效率79.22%，差异有统计学意义（P<0.05）。治疗后，2组总胆固醇（TC）、三酰甘油（TG）和低密度脂蛋白（LDL）水平均升高，差异有统计学意义（P<0.05），且观察组高于对照组，2组差异有统计学意义（P<0.05）。2组血流变学指标、高密度脂蛋白（HDL）、IL-6和TNF-α水平治疗后均降低（P<0.05），且观察组降低更明显，差异有统计学意义（P<0.05）。结论：复方丹参滴丸联合常规西药治疗冠心病患者，能够调节脂代谢，降低炎性反应，改善血流变学。     

参麦注射液联合阿替普酶静脉溶栓治疗45例急性缺血性脑卒中患者的疗效观察

目的:探究参麦注射液联合阿替普酶静脉溶栓治疗急性缺血性脑卒中(AIS)患者疗效及安全性。方法:选取某院90例AIS患者,按照治疗方案不同分为对照组和观察组,各45例。对照组采用阿替普酶静脉溶栓治疗,观察组在对照组基础上加用参麦注射液治疗,观察分析两组临床疗效及不良反应发生情况。结果:观察组治疗总有效率高于对照组(P<0.05),观察组总不良反应发生率低于对照组(P<0.05)。结论:参麦注射液联合阿替普酶静脉溶栓治疗AIS可提升疗效,提高临床安全性。     

基于中心复合序贯设计法丹参川芎嗪注射液水沉工艺优化

目的基于质量源于设计(QbD)理念和序贯设计法优化丹参川芎嗪注射液前处理过程中的水沉工艺。方法研究联用了鱼刺图法及基于全局式序贯设计的中心复合实验法作为优化方法,在基础实验设计中关键参数维度的轴向方向增加实验点,再进行新的多元线性回归拟合,最终得到了水沉工艺的设计空间并对其进行了验证,同时给出了较为稳健且全面的操作空间。结果根据设计空间,推荐操作空间为水沉体系pH值为3.1～3.4时,加水倍量3.25～5.00,静置时间为7～17 h,静置温度为7℃。结论首次在中药制药过程工艺优化中引入序贯设计法。相较于样本量巨大的均匀空间网格设计、正交设计等实验设计方法而言,序贯设计在实现与前者同样的样本对可行域覆盖程度的基础上,能够有效降低工艺优化实验的工作量,避免样本与人力物力的浪费,同时保证较高的模型预测性能。