Rational Design of a Skin- and Neuro-Attenuated Live Varicella Vaccine: A Review and Future Perspectives

Primary varicella-zoster virus (VZV) infection causes varicella, which remains a prominent public health concern in children. Current varicella vaccines adopt the live-attenuated Oka strain, vOka, which retains the ability to infect neurons, establish latency and reactivate, leading to vaccine-associated zoster in some vaccinees. Therefore, it is necessary to develop a safer next-generation varicella vaccine to help reduce vaccine hesitancy. This paper reviews the discovery and identification of the skin- and neuro-tropic factor, the open reading frame 7 (ORF7) of VZV, as well as the development of a skin- and neuro-attenuated live varicella vaccine comprising an ORF7-deficient mutant, v7D. This work could provide insights into the research of novel virus vaccines based on functional genomics and reverse genetics.     

脐带挤压与延迟断脐对胎龄<34周早产儿早期预后影响的Meta分析

目的分析脐带挤压与延迟断脐对胎龄<34周早产儿早期预后的影响。方法计算机检索PubMed、Web of Science、Embase、Cochrane Library、CINAHL、中国知网、万方数据库、维普数据库和中国生物医学文献服务系统数据库从建库到2021年11月发表的胎龄<34周早产儿脐带挤压与延迟断脐的随机对照试验。由2名研究人员根据纳入和排除标准，独立对文献进行筛选和质量评价，并提取数据，采用Review Manger 5.4进行Meta分析。结果最终纳入11篇文献，共1 621例早产儿，其中脐带挤压组809例，延迟断脐组812例。Meta分析结果显示，与延迟断脐相比，脐带挤压提高了早产儿出生后平均血压（WMD=3.61，95%CI：0.73~6.50，P=0.01），但增加了早产儿严重脑室内出血的发生率（RR=1.83，95%CI：1.08~3.09，P=0.02），两者在早产儿出生后血红蛋白水平、红细胞压积、输血率、光疗率、血清胆红素峰值及脑室周围白质软化、坏死性小肠结肠炎等并发症发生的影响差异均无统计学意义（P>0.05）。结论与延迟断脐相比，脐带挤压可能增加胎龄<34周早产儿严重脑室内出血的风险，但仍需更多高质量、大样本的随机对照试验进一步证实。     

早产儿支气管肺发育不良出院后随访管理专家共识

支气管肺发育不良（bronchopulmonary dysplasia，BPD）是早产儿常见的慢性肺部疾病，严重影响其生存质量。BPD不仅威胁早产儿生命，还可能留有严重后遗症，比如喂养困难、反复下呼吸道感染、气道高反应性疾病、生长发育迟缓及神经发育迟缓等。为了进一步规范BPD早产儿出院后的随访管理，海峡两岸医药卫生交流协会新生儿学专业委员会新生儿循证医学学组基于国内外临床证据，结合临床实践经验，主要从BPD早产儿出院后呼吸系统疾病、生长发育、肺动脉高压、神经发育不良、代谢性骨病及疫苗接种的随访与管理等方面制定了该专家共识。 用格式：引用格式:中国当代儿科杂志，2022，24（5）：455-465     

肥胖症儿童脂溶性维生素A、D、E水平及其影响因素

目的调查肥胖症儿童脂溶性维生素A、D、E水平，并分析其影响因素。方法选取2019年1月至2021年4月就诊于西安市儿童医院营养科的273例肥胖症儿童（肥胖症组）为研究对象，同期健康体检的226例正常体重儿童为对照组。对两组儿童进行体格及体成分的测量，并检测血清维生素A、D、E浓度。结果与对照组比较，肥胖症组血清维生素A［（1.32±0.21）μmol/L vs（1.16±0.21）μmol/L］、维生素E［（9.3±1.4）mg/L vs（8.3±1.2）mg/L］水平较高（P<0.001），25羟维生素D［25-hydroxyvitamin D，25(OH)D］水平［（49±22）nmol/L vs（62±24）nmol/L］较低（P<0.001）。在肥胖症组中，边缘型维生素A缺乏率为5.5%（15/273），维生素D缺乏/不足率为56.8%（155/273），维生素E不足率为4.0%（11/273）。控制体重指数和腰身比后，肥胖症儿童维生素A水平与年龄呈正相关（P<0.001），维生素E和25(OH)D水平与年龄呈负相关（P<0.001）。在控制年龄因素后，未发现肥胖症儿童血清维生素A、维生素E、25(OH)D水平与其肥胖程度、体脂百分比、肥胖时长的相关性，但维生素A和维生素E水平与其腰身比呈正相关（P<0.001）。结论肥胖症儿童的血清维生素A和维生素E水平较高，尤其是腹型肥胖者，而血清维生素D营养状况较差，且随着年龄的增长，状况愈差。因此，应关注肥胖症儿童维生素D营养状况并积极补充。     

超早产儿/超低出生体重儿临床结局的性别差异：一项倾向性评分匹配研究

目的通过倾向性评分匹配方法，探讨性别对超早产儿/超低出生体重儿（extremely preterm infant/extremely low birth weight infant，EPI/ELBWI）临床结局的影响。方法回顾性分析2011年1月1日至2020年12月31日住院的731例EPI或ELBWI的临床资料，将731例EPI/ELBWI分成男婴组与女婴组。通过倾向性评分匹配方法1∶1匹配，匹配变量包括：胎龄、出生体重、放弃积极治疗比例、小于胎龄儿比例、使用肺表面活性物质比例、1 min Apgar评分≤3分比例、机械通气比例、机械通气时间、产前使用疗程不足糖皮质激素比例和妊娠期高血压疾病比例，比较两组患儿住院期间主要并发症的发生率和出院存活率。结果匹配前，男婴组新生儿呼吸窘迫综合征、支气管肺发育不良、重度脑室内出血、脑室周围白质软化、坏死性小肠结肠炎、动脉导管未闭的发生率均显著高于女婴组（P<0.05）；匹配后，男婴组仅支气管肺发育不良的发生率显著高于女婴组（P<0.05）。匹配前后，两组患儿的出院存活率差异均无统计学意义（P>0.05）。结论男婴EPI/ELBWI并发支气管肺发育不良的风险高于女婴，但男婴和女婴EPI/ELBWI的转归相似。     

超声引导下不同部位中心静脉置管在婴幼儿休克中的应用及临床分析

目的分析超声引导下不同部位中心静脉置管在婴幼儿休克中应用的临床特点，探讨在婴幼儿休克中应如何快速选择中心静脉置管部位。方法回顾性收集2016年1月至2020年12月广东医科大学附属东莞儿童医院儿童重症监护室收治的112例诊断为休克并进行中心静脉置管的婴幼儿临床资料，根据是否在超声引导下进行置管分为超声组（70例）及体表定位组（42例），总结分析患儿在超声引导下不同部位置管的应用情况，对各部位置管的一针成功率、总成功率、置管时间及并发症进行比较。结果与体表定位组相比，超声组颈内静脉及股静脉置管的一针成功率增高，置管时间缩短，并发症发生率减少（P<0.05）。超声组中，行颈内静脉置管比例最高（51%，36/70），其次为股静脉（33%，23/70），锁骨下静脉最少（16%，11/70）。超声引导下不同置管部位比较，颈内静脉成功置管时间最短［5.5（5.0，6.5）min］（P<0.05）；不同置管部位的并发症发生率比较差异无统计学意义（P>0.05）。结论在婴幼儿休克状态下，应用超声引导下行颈内静脉置管可作为临床医生优先选择的置管方式。     

Antiproliferative activity and standardization of Tecomella undulata bark extract on K562 cells

Ethnopharmacological relevance

The bark of Tecomella undulata is primarily used in the treatment of syphilis, painful swellings and cancer by traditional healers. Also, it is claimed to be useful in treating urinary discharges, enlargement of spleen, leucorrhoea, leukoderma, tumors, liver disorders, gonorrhea, gout and promotes wound healing in Indian traditional system of medicine.

Aim

To establish a scientific validation for the antitumor effects of Tecomella undulata bark and explore the mechanistic pathway in chronic myeloid leukemia cell line, K562. The study was further extended to standardize the extract using quercetin as biomarker.

Methods

Induction of apoptosis by chloroform extract of Tecomella undulata bark (CTUB) was determined by MTT, Annexin V and caspase activation assays. The cell cycle analysis was done by flow cytometer and nuclear staining by DAPI. The standardization of the extract was performed through reverse phase-HPLC method under PDA detection.

Result

Results clearly showed the induction of apoptosis by CTUB in K562 cells. The effect was found to be dose dependent, having IC₅₀ of 30 μg/ml with activation of FAS, FADD, caspase 8, caspase 3/7 and fragmentation of DNA. The bioactive CTUB was determined to possess 0.03% (w/w) of quercetin.

Conclusion

The investigation clearly demonstrated the potential antitumor effect of CTUB, thereby validating the traditional claim. Quercetin, known to have anticancer activity is being reported and quantified for the first time from the bark of Tecomella undulata.     

Investigation of the in vitro and ex vivo acetylcholinesterase and antioxidant activities of traditionally used Lycopodium species from South America on alkaloid extracts

Ethnopharmacological relevance

The study was aimed at evaluating medicinal and therapeutic potentials of two Lycopodiaceae species, Lycopodium clavatum (L.) and Lycopodium thyoides (Humb. & Bonpl. ex Willd), both used in South American folk medicine for central nervous system conditions. Alkaloid extracts were evaluated for chemical characterization, acetylcholinesterase and antioxidant activities.

Materials and methods

The alkaloid extracts obtained by alkaline extraction were determined for each species by GC/MS examination. The evaluation of the anticholinesterase and the antioxidant activities of the extracts were tested by determining in vitro and ex vivo models. Effects on acetylcholinesterase (AChE) were tested in vitro using rat brain homogenates and ex vivo after a single administration (25, 10 and 1 mg/kg i.p.) of the alkaloid extracts in mice. The in vitro antioxidant effects were tested for the 2-deoxyribose degradation, nitric oxide (NO) interaction, 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and total reactive antioxidant potential (TRAP). After an acute administration (25 and 10 mg/kg i.p.) of the extracts in middle-aged (12 months) mice, the antioxidant effects were estimated through the thiobarbituric acid reactive substances test (TBARS), and the antioxidant enzymes activities for catalase (CAT) and superoxide dismutase (SOD) were measured.

Results

AChE activity was inhibited in vitro by the alkaloid-enriched extracts of both Lycopodium species in a dose and time-dependent manner in rat cortex, striatum and hippocampus. A significant inhibition was also observed in areas of the brain after acute administration of extracts, as well as decreased lipid peroxidation and increased CAT activity in the cortex, hippocampus and cerebellum. A moderate antioxidant activity was observed in vitro for the extracts. Chemically, the main alkaloids found for the two species were lycopodine and acetyldihidrolycopodine.

Conclusion

This study showed that the biological properties of the folk medicinal plants Lycopodium clavatum and Lycopodium thyoides include AChE inhibitory activity and antioxidant effects, two possible mechanisms of action in Alzheimer's related processes.     

7,7'-Dimethoxyagastisflavone-induced apoptotic or autophagic cell death in different cancer cells

7,7'-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus × media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells.     

电针12h对颅脑损伤大鼠脑组织[Ca（2＋）]i和NE含量影响的实验研究

目的：对电针12h对颅脑损伤大鼠脑组织[Ca2＋]i和NE含量的影响进行实验研究。方法：采用激光共聚焦显微镜的动态扫描功能和荧光分子探针技术,从针灸血清学和细胞学角度,对针刺通过颅脑损伤大鼠血清影响SY5Y细胞[Ca2＋]i进行研究;采用高效液相色谱法研究电针对颅脑损伤大鼠脑组织NE含量的影响。结果：各组血清孕育12h后SY5Y细胞[Ca2＋]i相比较显示,模型对照组的荧光强度明显高于空白对照组（P﹤0.01）,针刺治疗组的荧光强度明显低于模型对照组（P﹤0.05）;各组大鼠脑组织NE含量相比较,模型对照组显著高于空白对照组（P﹤0.01）,针刺治疗组明显低于模型对照组（P﹤0.05）。结论：电针12h可减慢颅脑损伤大鼠脑组织[Ca2＋]i和NE含量的上升趋势,提示电针可能是通过抑制脑皮质内大量NE聚集,降低皮质神经元的兴奋性,从而抑制细胞内Ca2＋滞留和超载,减轻脑水肿,对脑组织起到保护作用。