Plasmodium falciparum: Rosettes do not protect merozoites from invasion-inhibitory antibodies

Rosetting is a parasite adhesion phenotype associated with severe malaria in African children. Why parasites form rosettes is unknown, although enhanced invasion or immune evasion have been suggested as possible functions. Previous work showed that rosetting does not enhance parasite invasion under standard in vitro conditions. We hypothesised that rosetting might promote invasion in the presence of host invasion-inhibitory antibodies, by allowing merozoites direct entry into the erythrocytes in the rosette and so minimising exposure to plasma antibodies. We therefore investigated whether rosetting influences invasion in the presence of invasion-inhibitory antibodies to MSP-1. We found no difference in invasion rates between isogenic rosetting and non-rosetting lines from two parasite strains, R29 and TM284, in the presence of MSP-1 antibodies (P = 0.62 and P = 0.63, Student's t test, TM284 and R29, respectively). These results do not support the hypothesis that rosettes protect merozoites from inhibitory antibodies during invasion. The biological function of rosetting remains unknown.     

幽门螺杆菌疫苗诱导的免疫保护反应及临床试验研究进展

幽门螺杆菌(Helicobacter pylori,Hp)是一种微需氧、寄生于胃黏膜表面的革兰阴性致病菌,可导致各种不同的疾病,如慢性活动性胃炎、胃和十二指肠溃疡,甚至包括胃黏膜相关淋巴样组织(mucosa-associated lymphoid tissue,MALT)淋巴瘤和胃腺癌等恶性疾病。目前根除Hp主要依靠包括2种抗生素、铋剂和质子泵抑制剂(proton pumpinhibitors,PPI)在内的四联疗法。随着Hp耐药性的增强,研发Hp疫苗成为防治Hp感染的新途径。Hp疫苗能够诱导机体产生抗原特异性血清IgG和黏膜sIgA体液免疫反应以及抗原特异性CD4+T细胞免疫反应等的有效免疫保护反应。     

免疫性血小板减少性紫癜动物模型建立方法与应用评价

免疫性血小板减少性紫癜(immune thrombocytopenic purpura,ITP)是血液系统自身免疫性疾病,临床以皮肤、黏膜自发性出血为主要症状。鉴于ITP发病机理目前尚不清晰,因此,探讨人类ITP发病相近或相似的动物模型有助于对ITP发病机制的认识与治疗效果的评估。但就目前状况分析,被动型与主动型的ITP造模方法虽对研究ITP发病机制与药理学研究提供了研究工具,但也存在一些尚待解决的实际问题。因此,系统回顾ITP动物模型复制方法,并给予适当评价,有助于发现、应用并完善现有的动物模型,也能更好的探索新的ITP动物模型来研究发病过程与药物治疗的效应机制。     

腹腔镜疝修补术与传统修补术治疗腹股沟疝的效果比较

目的:探讨腹腔镜手术修补腹股沟疝的临床效果,为普外科手术治疗提供可借鉴的方法。方法:选取2011年5月-2013年8月在我院接受疝修补术的112例患者的临床资料进行分析。根据手术方式,将所选病例分为传统开腹式疝修补术组(48例)和腹腔镜疝修补术组(64例)。分析并比较两组患者的术中出血量、手术时间、排气时间、肢体活动时间、复发率及并发症的发生率等。结果:腹腔镜疝修补术组患者的术中出血量、手术时间、排气、肢体活动及住院时间等临床指标均显著优于采用传统疝修补术的患者,差异显著且具有统计学意义(P0.05)。腹腔镜疝修补术组并发症发生率为21.88%,虽然低于传统疝修补术组(39.58%),但无显著性差异(P0.05)。腹腔镜疝修补术组复发率为3.13%,明显低于传统疝修补术组(8.33%),差异具有统计学意义(P0.05)。结论:腹腔镜疝修补术具有创伤小、恢复快及复发率低等优势,效果显著值得推广。但术后易发生肠粘连、阴囊血肿等并发症,术中应妥善处理,尽量减少或避免并发症的发生率。     

不同病毒载量慢性乙型肝炎患者树突状细胞B7-H1表达及对免疫功能的影响

目的：观察慢性乙型肝炎患者外周血树突状细胞表面共刺激分子B7-H1 的表达及对免疫功能的影响。方法：检测慢性乙型肝炎患者肝功能、HBV-DNA 水平,将患者分为高病毒载量高ALT 组（A 组）、高病毒载量低ALT 组（B 组）、低病毒载量组（C 组）及正常对照组（D 组）。流式细胞术检测各组患者外周血树突状细胞表面HLA-DR、CD80、CD86、CD83、CD1a、B7-H1 表达,酶联免疫吸附试验（ELISA）检测DC 培养上清液和混合淋巴细胞培养上清液中细胞因子IL-12、IL-10 水平。结果：慢性乙肝患者的树突状细胞膜表面分子HLA-DR、CD80、CD86、CD83、CD1a的表达均明显降低（A、B、C组与D组比较分别为42.3± 4.9 %、46.7± 7.0%、52.5± 6.3 %vs 94.5± 3.5 %;34.5± 5.3 %、39.9± 6.4 %、45.6± 5.2 %vs 90.6± 6.5 %;38.2± 8.6 %、36.1± 5.4 %、42.5± 6.8 % vs87.7± 5.1 %;28.3± 6.5 %、25.6± 3.4 %、33.5± 4.3% vs 82.6± 4.8 %;32.3± 5.8 %、29.3± 5.3 %、48.3± 4.9 % vs 68.2± 5.2 % P〈0.05）,B7-H1 表达水平明显升高（27.48± 21.4 %、21.83± 20.2 %、15.43± 10.32 %vs 4.23± 2.2%P〈0.05）。B7-H1 表达水平与ALT呈正相关,与IL-12 水平呈负相关。结论：慢性乙型肝炎患者树突状细胞功能低下,其机制可能与树突状细胞高表达B7-H1 有关。B7-H1 高表达抑制了淋巴细胞的功能,导致乙型肝炎病毒持续感染。     

Downregulation of immune response by the human cytokines Interleukin-32α and β in cell-mediated rejection

Xenotransplantation of porcine organs has the potential to help overcome the severe shortage of human tissues and organs available for human transplantation. However, numerous hurdles such as immune-mediated xenograft rejection remain before clinical xenotransplantation.In this study, we elucidated the role of human TNF-α-inducing factor, Interleukin-32 (IL-32), in porcine kidney cells (PK-15) during cell-mediated rejection by examining host cell responses. CD8⁺ and CD4⁺ T cells numbers were reduced in the lymph nodes of PK-15/IL-32β injected mice. CD3⁺ Tcells were in mice injected with control cells but PK-15/IL-32α- and PK-15/IL-32β-injected cell numbers were lower in lymphnodes than un transfected controls. In Mixed lymphocyte reaction cultures, the rates of cell proliferation were increased in both PK-15/IL-32α- and PK-15/IL-32β-injected groups compared to the untransfected control groups. The Stable porcine PK-15 cells expression IL-32α and IL-32β inhibited cytotoxic T lymphocyte (CTLs) after cellular xenograft. Our results suggest that human IL-32α and IL-32β regulates on xenograft rejection in cellular xenotransplantation.     

TLR8 activation and inhibition by guanosine analogs in RNA: Importance of functional groups and chain length

Toll-like receptor 8 (TLR8) is an important component of the human innate immune system that recognizes single stranded RNA (ssRNA). Recent X-ray crystal structures of TLR8 bound to ssRNA revealed a previously unrecognized binding site for a 5′-UpG-3′ dinucleotide. Here we use an atomic mutagenesis strategy coupled with a cellular TLR8 activation assay to probe the importance of specific functional groups present on the guanine base in RNA-mediated receptor agonism and antagonism. Results from RNA analogs containing 7-deazaguanosine, 2-aminopurine and inosine confirm the importance of guanine N7, O6 and N2, respectively, in TLR8 activation. Nevertheless, these RNAs each retained TLR8 antagonism activity. RNA containing 7-deaza-8-azainosine (7d8aI) was prepared from a novel phosphoramidite and found to be a weaker TLR8 activator than guanosine-containing RNA. However, 7d8aI-containing RNA also retained TLR8 antagonism activity indicating that removal of multiple TLR8 H-bonding sites on guanine is insufficient for blocking TLR8 antagonism by guanine-containing RNA. We also identified an oligoribonucleotide length dependence on both TLR8 activation and antagonism. These studies extend our understanding of the effects of nucleobase modification on immune stimulation and will inform the design of novel RNA-based therapeutics.     

脾氨肽辅助抗结核药物治疗肺结核的临床疗效观察

摘要 目的：观察脾氨肽辅助抗结核药物治疗肺结核的临床疗效。方法：随机数值表法将2016年6月～2021年6月本院收治的120例肺结核患者分为观察组、对照组。对照组予常规抗结核药物治疗,观察组予脾氨肽辅助抗结核药物治疗。评价两组肺部病灶变化情况、肺部空洞变化情况;检测两组治疗2、4、6个月时痰培养转阴率;检测两组治疗前后外周血T淋巴细胞亚群CD3⁺、CD4⁺及CD4⁺/CD8⁺比值。结果：观察组肺部病灶变化、肺部空洞变化疗效的总有效率分别为95.00%、93.33%,明显高于对照组的83.33%、80.00%（P＜0.05）。两组在治疗6个月时的痰培养转阴率无显著差异（P＞0.05）,但观察组在治疗2、4个月时的痰培养转阴率均显著高于对照组（P＜0.05）。两组治疗前及对照组治疗前后的CD3⁺、CD4⁺及CD4⁺/CD8⁺比值比较无明显差异（P＞0.05）,但观察组治疗后的CD3⁺、CD4⁺及CD4⁺/CD8⁺比值均显著高于本组治疗前及对照组治疗后（P＜0.05）。结论：脾氨肽辅助抗结核药物治疗肺结核有助于提升临床疗效,可能与提升患者的免疫功能水平有关,值得临床进一步研究。     

Cryo-EM Studies of Virus-Antibody Immune Complexes

Antibodies play critical roles in neutralizing viral infections and are increasingly used as therapeutic drugs and diagnostic tools. Structural studies on virus-antibody immune complexes are important for better understanding the molecular mechanisms of antibody-mediated neutralization and also provide valuable information for structure-based vaccine design.Cryo-electron microscopy(cryo-EM) has recently matured as a powerful structural technique for studying bio-macromolecular complexes. When combined with X-ray crystallography, cryo-EM provides a routine approach for structurally characterizing the immune complexes formed between icosahedral viruses and their antibodies. In this review, recent advances in the structural understanding of virus-antibody interactions are outlined for whole virions with icosahedral T = pseudo 3(picornaviruses) and T = 3(flaviviruses) architectures, focusing on the dynamic nature of viral shells in different functional states. Glycoprotein complexes from pleomorphic enveloped viruses are also discussed as immune complex antigens. Improving our understanding of viral epitope structures using virus-based platforms would provide a fundamental road map for future vaccine development.     

隧道法内镜下粘膜下剥离术治疗食道粘膜下肿瘤的临床价值

摘要 目的：探讨隧道法内镜下粘膜下剥离术治疗食道粘膜下肿瘤的临床价值。方法：2014年2月至2017年9月选择在本院诊治的食道粘膜下肿瘤患者172例，根据手术方法的不同分为观察组100例与对照组72例。观察组给予隧道法内镜下粘膜下剥离术，对照组给予内镜粘膜下剥离术治疗，记录与随访两组的预后情况。结果：两组手术时间对比无差异(P>0.05)，观察组的术中出血量、术后禁食天数与术后住院时间显著少于（短于）对照组(P<0.05)。观察组术后3 d的并发症发生率为3.0 %，显著低于对照组的15.3 %(P<0.05)。观察组术后1 d与术后14 d的血清IL-2、sIL-2R含量都显著低于对照组(P<0.05)。随访2年，观察组的1年与2年复发率分别为2.0 %和6.0 %，显著低于对照组的8.3 %和15.3 %(P<0.05)。结论：隧道法内镜下粘膜下剥离术治疗食道粘膜下肿瘤能减少创伤，减少并发症的发生，降低复发率，并促进患者免疫功能的恢复。