Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

Host–microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling

ABSTRACT

Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases.     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.     

化浊清解愈溃煎对溃疡性结肠炎大鼠p38MAPK、TNF-α、IL-4的影响

目的观察化浊清解愈溃煎对溃疡性结肠炎(UC)大鼠血清及结肠组织p38MAPK、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)含量的影响。方法清洁级Wistar雄性大鼠50只按随机数字表法分为两组,空白组8只,其余大鼠均为造模组。采用TNBS/乙醇联合造模法构建UC大鼠模型。造模成功后按照随机数字表法将模型大鼠分为模型组、西药组(予美沙拉嗪肠溶片混悬液0.42 g/kg)及中药高、中、低剂量组。中药高、中、低剂量组予化浊清解愈溃煎中药混悬液,剂量分别为22、11、5.5 g/(kg·d),每日灌胃1次,疗程14 d。采用免疫组化法检测各组大鼠结肠组织内p38MAPK的蛋白表达量。ELISA法检测各组大鼠血清内TNF-α、IL-4含量。结果与空白组比较,模型组一般情况较差,血清中TNF-α含量显著升高(P<0.05),IL-4含量则明显降低(P<0.05),结肠组织中p38MAPK水平明显升高(P<0.05)。与模型组比较,西药组、中药各剂量组大鼠一般生存状况改善明显,血清中TNF-α含量下降,IL-4含量明显升高,尤以中药高剂量组和西药组疗效显著(P<0.05)。结论化浊清解愈溃煎高、中剂量可改善UC大鼠一般生存状况,并通过调节血清中IL-4含量,下调TNF-α表达水平和结肠组织中p38MAPK蛋白表达水平而达到保护结肠黏膜和治疗UC的作用。     

Prenatal diagnosis of mosaicism for a distal 5p deletion in a single colony at amniocentesis in a pregnancy with a favorable outcome and a review of mosaic distal 5p deletion

ObjectiveWe present prenatal diagnosis of mosaicism for a distal 5p deletion in a single colony at amniocentesis with a favorable outcome, and we review the literature of mosaic distal 5p deletion.Case ReportA 35-year-old primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed the result of 46,XY,del(5)(p13)[1]/46,XY[19]. Among 20 colonies of cultured amniocytes, all four cells in one colony had a karyotype of 46,XY,del(5)(p13) with a distal deletion of 5p13→pter, while the rest 19 colonies had a karyotype of 46,XY. Repeat amniocentesis was performed at 21 weeks of gestation. Conventional cytogenetic analysis revealed a karyotype of 46,XY in all 20 colonies. Simultaneous array comparative genomic hybridization (aCGH) using the DNA extracted from the uncultured amniocytes revealed no genomic imbalance. Prenatal ultrasound findings were unremarkable. At 38 weeks of gestation, a 3621-g male baby was delivered with no phenotypic abnormality. The cord blood had a karyotype of 46,XY. Postnatal urinary cells analysis by interphase fluorescence in situ hybridization (FISH) using a 5p terminal FISH probe detected no abnormal cell in the urine.ConclusionMosaicism for a distal 5p deletion in a single colony at amniocentesis can be associated with a favorable outcome.     

Additional bedtime H2‐receptor antagonist for the control of nocturnal gastric acid breakthrough: A Cochrane systematic review

OBJECTIVES: To assess the effectiveness and safety of additional bedtime H₂‐receptor antagonists (H₂RAs) in suppressing nocturnal gastric acid breakthrough (NAB) via a systematic review. METHODS: Eligible trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2004), MEDLINE (January 1966–June 2004), EMBASE (January 1980–June 2004) and CINAHL (January 1982–June 2004). Additional hand‐searching was conducted on the proceedings of correlated conferences, eight important Chinese journals and references of all included trials. All randomized controlled trials evaluating H₂RAs for the control of NAB were eligible for inclusion. The systematic review was conducted using methods recommended by The Cochrane Collaboration. RESULTS: Only two randomized crossover studies, comprising 32 participants, met the inclusion criteria. Because the design, dosage and duration of the treatments were different between the studies, it was not possible to conduct meta‐analysis. There were no consistent conclusions found between the two included studies in evaluating H₂RAs for the control of NAB. CONCLUSIONS: No implications for practice at this stage can be concluded. Appropriately designed large‐scale randomized controlled trials with long‐term follow up are needed to determine the effects of additional bedtime H₂RAs in suppressing NAB.     

谷氨酸对腺苷A2A受体调节一氧化氮合酶活力的影响

目的探讨谷氨酸是否能够影响腺苷A2A受体对一氧化氮合酶（NOS）活力的调节。方法用1000ng／ml脂多糖（LPS）刺激小胶质细胞，分别加入100nmol／L A2A受体激动剂CGS21680以及不同浓度的谷氨酸（0，1，0，25，0，5mmol／L）干预，观察NOS活力变化。结果LPS诱导NOS活力增高，激活A2A受体可以产生抑制作用；0，25及0．5mmoL／L谷氨酸和A2A受体激动剂同时存在时，NOS活力进一步增高。结论高浓度谷氨酸可逆转腺苷A2A受体激动剂抑制升高NOS活力的作用。     

强迫谱系障碍与第Ⅱ组代谢型谷氨酸受体相关候选基因位点的连锁分析

目的 了解代谢型谷氨酸受体mGlu2受体（mGluR2）基因、mGlu3受体（mGluR3）基因等与强迫谱系障碍（OCSDs）的连锁关系。方法 选取一个连续三代发病的强迫谱系障碍家系，采集到该家系中12个正常个体，8个受累个体的血样，选取mGluR2、mGluR3基因附近7对微卫星标记引物，采用两点和多点非参数分析的方法对该家系进行连锁分析。结果 7对微卫星标记位点的两点和多点非参数分析LOD值（NPL值），位于mGluR3基因附近的标记D7S644两点非参数分析NPL值为1．719（P=0．078），多点非参数分析NPL值为1．712（P=0．078），达到验证性连锁的阈值（NPL=1．2），但未达到提示性连锁的阕值（NPL=2．2），D7S2481两点非参数分析NPL值为0．628（P=0．179），多点非参数分析NPL值为0．852（P=0．141），接近验证性连锁的阈值，其余5对微卫星标记位点非参数分析NPL值均未达到验证性连锁的阈值。结论 提示mGluR3基因与OCSDs可能存在连锁关系，不能排除mGluR2基因与OCSDs的相关性。