Immunogenicity of a recombinant fusion construct composed of intrinsically unstructured,low polymorphic segments derived from merozoite surface protein 2 and trophozoite exported protein 1

To overcome the extensive polymorphism found in human Plasmodium antigens and to avoid the lengthy characterization of their 3 dimensional structure and subsequent production of the native proteins we have been concentrated in large unstructured, non-or low-polymorphic fragments present in the blood stage of P. falciparum. Three fragments derived from the 2 family-specific and constant regions of merozoite surface protein (MSP2) and PFF0165c protein were previously selected for evaluation as potential single vaccine candidates. In order to increase and optimize their potential efficacy against P. falciparum infection the 3 antigens were combined in a single DNA recombinant product (FusN) and compared its antigenicity with that of single antigens in sera of volunteers living in endemic countries. Immunogenicity of the FusN was then compared with that of the mixture of 3 antigens in 3 strains of mice. Antigen specific, affinity purified human antibodies were then tested in antibody dependent cellular inhibition and merozoite opsonization assays. In addition, the antigen specific antibody response and its association with protection from malaria infection were determined. The data collected indicate that the recombinant product is an equal or better antigen /immunogen than fragments used either alone or as a mixture for vaccination in combination with adjuvant. In addition, antibody response to FusN shows a stronger association with protection than single fragments. The use of a single construct as vaccine would drastically reduce the cost of manufacturing and development of the GMP product.     

125I放射性粒子链腔道内近距离放疗的进展

放射性粒子链是将¹²⁵I粒子按照线性排列并置于管状导管中，使其剂量分布接近于圆柱形，进而适应腔道内的肿瘤放疗，发挥出单粒子所达不到的治疗效果。本文旨在综述125I放射性粒子链的发展历史、剂量分布、置入方法以及临床应用。     

血清CEA、CA72-4及CA125联合诊断胃癌术后腹膜转移

目的:探讨血清CEA、CA72-4及CA125联合诊断胃癌术后腹膜转移的价值，为临床诊治提供参考。方法:以我院于2015年11月至2016年11月因胃癌术后在本院复查且相关临床资料齐全患者120例作为研究对象并进行回顾性分析，按照有无腹膜转移分为转移组（38例）和无转移组（82例）。对比两组患者的血清CEA、CA72-4及CA125变化及单项诊断效能，并采用ROC曲线法对比三种肿瘤标志物的诊断效能。结果:转移组患者的血清CEA、CA72-4及CA125水平均高于无转移组，差异有统计学意义（P＜0.05）。三个单项指标比较，CA125灵敏度为73.3%，特异度为81.8%，均为三者最高，差异均有统计学意义（P＜0.05）。联合诊断比较，CEA+CA72-4+CA125联合检测的灵敏度最高（91.7%），但特异度最低（41.7%），差异均有统计学意义(P＜0.05)。结论:胃癌术后腹膜转移患者血清CEA、CA72-4及CA125均升高，且单项诊断CA125的灵敏度及特异度最高，而三项联合诊断的灵敏度最高，但特异度最低，值得临床参考。     

肺癌患者围化疗期血清CYFRA21-1、NSE和CA125水平变化的价值探讨

目的:探讨肺癌患者围化疗期血清细胞角蛋白19片段（CYFRA21-1）、神经元特异性烯醇化酶（NSE）和糖类抗原125（CA125）水平变化的价值。方法:选自我院于2015年12月至2017年12月期间收治的97例肺癌患者作为研究组；另选自我院于2015年12月至2017年12月期间收治的80例肺部良性病变患者作为对照组。采集患者外周静脉血，分离血清，采用电化学发光法检测CYFRA21-1、NSE和CA125含量。比较两组患者血清CYFRA21-1、NSE和CA125含量，不同临床分期化疗前后CYFRA21-1、NSE和CA125含量变化，不同疗效化疗前后CYFRA21-1、NSE和CA125含量变化。结果:研究组血清CYFRA21-1、NSE和CA125的含量高于对照组，且差异有统计学意义（P<0.05）。I-Ⅱ期和Ⅲ-Ⅳ期患者化疗后血清CYFRA21-1、NSE和CA125的含量较化疗前明显下降（P<0.05）；Ⅲ-Ⅳ期患者化疗前和化疗后血清CYFRA21-1、NSE和CA125的含量高于同期I-Ⅱ期患者（P<0.05）。CR+PR和SD+PD患者化疗后血清CYFRA21-1、NSE和CA125含量均较化疗前明显下降（P<0.05）；SD+PD患者化疗前和化疗后血清CYFRA21-1、NSE和CA125含量均高于同期CR+PR患者（P<0.05）。结论:肺癌患者血清CYFRA21-1、NSE和CA125含量明显升高，且随着病情加重含量升高越明显，化疗后其含量明显下降，有助于临床的进一步研究。     

Gastric emptying of carbohydrate drinks in term parturients before elective caesarean delivery: an observational study

BackgroundPre-operative carbohydrate (CHO) drinks have shown some benefits peri-operatively and have been incorporated into many Enhanced Recovery after Surgery (ERAS) programmes. We assessed the gastric emptying of pre-operative CHO drinks prior to elective caesarean delivery using ultrasonography.MethodsAfter a standard overnight fast, non-labouring pregnant women awaiting elective caesarean delivery underwent a standardised gastric ultrasound assessment at baseline and then every 20 min for 2 h after consuming 400 mL of a CHO drink. The gastric emptying was determined at each time-point both qualitatively and quantitatively. The primary outcome was the time taken for participants to return to a qualitative fasted Perlas grade of 0 or 1.ResultsThe gastric emptying of 40 participants was analysed. At baseline, all patients had a qualitative grade of either 0 or 1. All patients had returned to either grade 0 or 1 by 100 min. At 120 min the antral right lateral decubitus (RLD) cross-sectional area (CSA) was 8.03 cm² (95th percentile; 95% CI 7.4 to 8.3 cm²) and gastric volume per kg was 1.57 mL/kg (95th percentile; 95% CI 1.4 to 2.2). At 120 min there was no statistically significant difference from baseline for the RLD CSA (P=0.38) or gastric volume per kg (P=0.27).ConclusionsThe gastric emptying of this cohort of pregnant women suggests that 400 mL of a CHO drink can be safely consumed up to two hours before elective surgery. This study can help inform future peri-operative fasting guidelines for pregnant patients.     

α7 nAChRs expressed on antigen presenting cells are insensitive to the conventional antagonists α-bungarotoxin and methyllycaconitine

Expression of α7 nicotinic acetylcholine receptors (nAChRs) on antigen presenting cells (APCs), such as macrophages and dendritic cells, is now well established. We have shown that GTS-21, a selective α7 nAChR agonist, downregulates APC-dependent CD4⁺ T cell differentiation into regulatory T cells (Tregs) and effector Th1, Th2 and Th17 cells by inhibiting antigen processing, thereby interfering with antigen presentation. α7 nAChRs on Jurkat human leukemic T cells require functional T cell receptors (TCRs)/CD3 and leukocyte-specific tyrosine kinase to mediate nicotine-induced Ca²⁺-signaling via Ca²⁺ release from intracellular stores, and are insensitive to two conventional α7 nAChR antagonists, α-bungarotoxin (α-BTX) and methyllycaconitine (MLA). We investigated the effects of GTS-21, α-BTX and MLA on ovalbumin (OVA)-induced Th cytokine release from spleen cells isolated from OVA-specific TCR transgenic DO11.10 mice. We found that: (1) GTS-21 dose-dependently suppresses OVA-induced IFN-γ, IL-4 and IL-17 release, but neither α-BTX nor MLA alone affected the OVA-induced cytokine release. (2) Neither α-BTX nor MLA abolished the suppressive effects of GTS-21 on IFN-γ and IL-17 release from OVA-activated DO11.10 spleen cells. (3) GTS-21 significantly suppressed OVA-induced APC-dependent CD4⁺ T cell differentiation into Tregs. Neither MLA nor mecamylamine, a non-specific nAChR antagonist, abolished the suppressive effect of GTS-21 on Treg differentiation. These results suggest that α7 nAChRs on APCs involved in cytokine synthesis and T cell differentiation are insensitive to the conventional α7 nAChR antagonists, α-BTX and MLA, and that α7 nAChRs on APCs differ pharmacologically from those in neurons.     

Changes in gut microbial metagenomic pathways associated with clinical outcomes after the elimination of malabsorbed sugars in an IBS cohort

ABSTRACT

Specific diets to manage sugar malabsorption are reported to reduce clinical symptoms of irritable bowel syndrome (IBS). However, the effects of diets for malabsorbed sugars on gut microbiota signatures have not been studied, and associations with clinical outcomes in IBS have not been characterized. 22 IBS patients positively tested for either lactose-, fructose-, sorbitol- or combined malabsorptions were subjected to 2-weeks sugar elimination and subsequent 4-weeks re-introduction. 7 IBS patients tested negative for sugar malabsorption were used as controls. Nutrition and clinical symptoms were recorded throughout the study. Fecal samples were serially collected for 16S rRNA amplicon and shotgun-metagenome sequencing.

Dietary intervention supervised by nutrition counseling reduced IBS symptoms during the elimination and tolerance phases. Varying clinical response rates were observed between subjects, and used to dichotomize our cohort into visual analogue scale (VAS) responders and non-responders. Alpha -and beta-diversity analyzes revealed only minor differences regarding 16S rRNA-based fecal microbiota compositions between responder and non-responder patients during baseline or tolerance phase. In shotgun-metagenome analyzes, however, we analyzed microbial metabolic pathways and found significant differences in pathways encoding starch degradation and complex amino acid biosynthesis at baseline between IBS controls and malabsorbers, and notably, between diet responder and non-responders. Faecalibacterium prausnitzii, Ruminococcus spp. and Bifidobacterium longum largely informed these metabolic pathways.

Our study demonstrates that diet interventions for specific, malabsorbed carbohydrates reshaped the metagenomic composition of the gut microbiota, with a small community of bacterial taxa contributing to these changes rather than a single species.