A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development

Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.     

Non-alcoholic fatty liver disease and neurological defects

Introduction and ObjectivesNonalcoholic fatty liver disease (NAFLD) can be considered one of the most common causes of liver disease in our days and is regarded as one of the newest vascular risk factors for cerebrovascular and other neurological diseases.Materials and methodsWe studied a group of neurological outpatients, divided into two homogenous groups based on the presence or absence of NAFLD.Results and conclusionsWe testified an independent relationship between NAFLD and common vascular risk factors (age, sex, educational level, BMI, cholesterol and lipid assessment, Hb1ac). At the same time, we ascertained an independent relationship between NAFLD and more recently recognized vascular risk factors, such as lack of folate, vitamin B12 and vitamin D-OH25, and increased levels of homocysteine. Finally, we have documented that NAFLD showed worse executive and frontal functions, and behavioral changes, such as depressive mood and anxiety, and apathy.     

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

早产儿消化道穿孔的病因及影响预后的危险因素分析

目的:探讨早产儿消化道穿孔的病因，分析影响早产儿消化道穿孔短期预后不良的危险因素。方法:回顾性分析山西省 儿童医院新生儿外科2015年1月—2021 年5月诊治的89 例早产儿消化道穿孔的临床资料。根据术后3 个月时结局分为生存 组和预后不良组。比较两组术前、术中及术后与早产儿消化道穿孔预后不良相关的因素，采用Logistic 回归分析筛选早产儿消 化道穿孔预后不良的危险因素。结果:早产儿消化道穿孔的病死率为25.84%，坏死性小肠结肠炎（NEC）和胃壁肌层缺损是早产 儿消化道穿孔常见的病因。单因素分析显示生存组患儿从发现气腹至手术时间在8 h 之内的比例显著高于预后不良组 （χ2=15.22，P＜0.01）。预后不良组合并脓毒性休克的比例显著高于生存组（χ2=33.19，P＜0.01）。预后不良组术后合并需非计划二次 手术的并发症比例显著高于生存组（χ2=7.24，P＜0.01）。Logistic 回归分析显示脓毒性休克（OR=0.06，95%CI:0.02~0.21，P＜0.01）和 气腹至手术时间大于8 h（OR=0.23，95%CI:0.07~0.81，P＜0.05）是早产儿消化道穿孔短期预后不良的危险因素。结论:NEC 和胃 壁肌层缺损是早产儿消化道穿孔的主要病因，脓毒性休克和从气腹发生至手术时间大于8 h 是早产儿消化道穿孔短期预后 不良的危险因素。     

二补助育汤对胚胎着床障碍小鼠子宫血管生成相关因子表达的影响

目的：探讨二补助育汤对胚胎着床障碍模型小鼠子宫内膜形态及血管生成素-1（Ang-1）mRNA、血管内皮生长因子（VEGF）mRNA的表达和定位的影响。方法：24只ICR雌性小鼠随机分为空白组、模型组、戊酸雌二醇组、二补助育汤组，每组6只，用米非司酮建立胚胎着床障碍动物模型，各组给予相应药物灌胃，妊娠第5天处死小鼠后，检测各组妊娠率、平均着床位点数、子宫内膜Ang-1和VEGF mRNA表达量及其蛋白定位。结果：模型组小鼠平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量明显低于空白组（均P<0.05）；与模型组比较，二补助育汤组平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量显著提高（均P<0.05）。结论：二补助育汤可提高子宫内膜Ang-1和VEGF蛋白表达量，促进子宫内膜血管生成，从而提高子宫内膜容受性。     

基于家庭的心理治疗对强迫障碍治疗的研究进展

强迫障碍(obsessive-compulsive disorder,OCD)是常见的难治性精神疾病,经过心理治疗和药物治疗仅有40%~60%患者获得缓解,患者残留各种症状和功能障碍。心理治疗是OCD治疗的重要组成部分,家庭因素在疾病的发生、维持和预后中起重要作用,以家庭为基础的心理治疗越来越受到重视。文章就对OCD采用基于家庭的心理治疗的必要性和进展进行综述,研究显示患者家属的精神心理状态和家庭顺应性等因素与OCD治疗效果密切相关,而家庭成员高度参与,针对家庭因素干预的基于家庭的心理治疗策略可以增强治疗效果,改善患者家庭功能。文章为强迫障碍的临床优化治疗提供了实践依据。     

新诊断2型糖尿病常见中医证型与非酒精性脂肪肝及其相关危险因素分析

目的探讨新诊断2型糖尿病(T2DM)常见中医证型与非酒精性脂肪肝(NAFLD)及其相关危险因素的相关性,为中西医结合治疗提供临床指导。方法选择沧州中西医结合医院门诊和病房收治的300例新诊断T2DM患者作为研究对象,根据其是否合并NAFLD分为合并NAFLD组,单纯T2DM组。记录2组一般资料,依照《糖尿病中医防治指南》对所有患者进行辨证分型,记录2组腰围、身高、体质量、体质量指数(BMI)、肝功指标[丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)]、血脂指标(TG、TC、HDL-C、LDL-C)及血尿酸(SUA)、空腹血糖(FPG)、空腹胰岛素(FINS)、空腹C-肽(FC-P)、胰岛素抵抗指数(HOMA-IR),分析各中医证型与客观化指标的关系。结果合并NAFLD组124例,单纯T2DM组176例,2组性别、年龄比较差异无统计学意义(P均>0.05);合并NAFLD组的痰湿郁阻证占比明显高于T2DM组(P<0.05),其余分型占比组间比较差异无统计学意义(P均>0.05);合并NAFLD组的腰围、BMI、TG、TC、FC-P、HOMA-IR均显著高于T2DM组(P均<0.05),其余指标2组比较差异无统计学意义(P均>0.05);非条件Logistic回归分析显示,NAFLD的独立危险因素为BMI、TG、HOMA-IR。结论痰湿郁阻证是T2DM合并NAFLD患者的最常见证型,肥胖、胰岛素抵抗、脂质代谢紊乱是T2DM合并NAFLD患者的独立危险因素。     

2009-2018年资阳市手足口病流行病学及病原学特征分析

目的 研究2009-2018年资阳市手足口病的流行病学及病原学特征，为有效防控手足口病提供理论依据。方法 从中国疾病控制中心监测信息报告管理系统获取以乡镇为单位的手足口病数据，进行三间分布描述，利用ArcGIS 10.1软件制作专题地图。结果 资阳市2009-2018年累计报告病例19195例，年平均发病率为61.72/10万，虽总体上呈升高的趋势；各乡镇均有手足口病报告；每年有两个发病高峰，分别是5-7月和9-11月，其中5-7月为主高峰，9-11月为次高峰；男女性别比为1.44[DK]∶1，5岁以下儿童共发病18209例，占比为94.9%。2015年之前优势毒株为EV71和CoxA16，2015年之后优势毒株为其他肠道病毒。结论 资阳市手足口病发病呈持续升高态势。手足口病的优势毒株近年来在改变，应增加人肠道病毒的监测种类，落实综合性防控措施，预防和控制手足口病的流行。     

尿毒清颗粒治疗慢性肾功能衰竭临床研究

目的:观察尿毒清颗粒治疗慢性肾功能衰竭(CRF)的临床疗效及其对钙磷代谢、结缔组织生长因子(CTGF)的影响。方法:选取120例CRF患者,按随机数字表法分为对照组和观察组各60例。对照组采用常规治疗,包括控制饮食、纠正酸碱、水电解质平衡;观察组在对照组的基础上加用尿毒清颗粒治疗。2组均连续治疗2个月,观察比较2组肾功能[肌酐(SCr)、血尿素氮(BUN)]、血磷(P3-)、血钙(Ca2+)、甲状旁腺激素(PTH)、CTGF指标水平变化,并评定2组临床疗效及不良反应情况。结果:观察组总有效率为80.00%,对照组为61.67%,2组比较,差异有统计学意义(P<0.05)。治疗后,2组SCr、BUN水平均较治疗前降低(P<0.05),且观察组SCr、BUN水平均低于对照组(P<0.05)。治疗后,2组PTH、CTGF、P3-水平较治疗前降低(P<0.05),Ca2+水平较治疗前升高(P<0.05);观察组PTH、P3-、CTGF水平均低于对照组(P<0.05),Ca2+水平高于对照组(P<0.05)。观察组不良反应发生率为3.33%,对照组为16.67%,2组比较,差异有统计学意义(P<0.05)。结论:尿毒清颗粒治疗CRF临床疗效显著,可有效调节钙磷代谢、CTGF平衡,改善肾功能,且安全性较高。