A Novel PspA Protein Vaccine Intranasal Delivered by Bacterium-Like Particles Provides Broad Protection Against Pneumococcal Pneumonia in Mice

Background: Streptococcus pneumoniae is a major pathogen accounting for a large number of pneumococcal disease in worldwide. Due to the mucosal immune pathway induces both systemic and mucosal immune responses, the potential strategy to prevent pneumococcal disease may be to develop a mucosal vaccine.

Method: In this study, we developed an intranasal pneumococcal protein vaccine based on a bacterium-like particle (BLP) delivery system. PspA is expressed and exposed on the surface of all pneumococcal strains, which confers the potential to induce immune responses to protect against pneumococcal infection. We fused one of the pneumococcal surface proteins (PspA, family2 clade4) with the protein anchor (PA) protein in order to display PspA on the surface of BLPs.

Result: The current results showed that intranasal immunization with BLPs/PspA-PA efficiently induced both PspA-specific IgG in the serum and PspA-specific IgA in mucosal washes. And intranasal immunization of BLPs/PspA-PA could provide complete protection in a mouse challenge model with pneumococci of different two clades of both homologous and heterologous PspA families.

Discussion and conclusion: Thus, targeted delivery of multiple bacterial antigens via BLPs may prevent pneumococcal disease by inducing both systemic and mucosal immune responses.     

A photo-switchable and thermal-enhanced fluorescent hydrogel prepared from N-isopropylacrylamide with water-soluble spiropyran derivative

Herein, a photo-switchable and thermal-enhanced fluorescent hydrogel has been fabricated from N-isopropylacrylamide (NIPAAm) with a mixture of water-soluble acryloyl-α-cyclodextrin/acryloyl-α-cyclodextrin-spiropyran (acryloyl-α-CD/ acryloyl-α-CD-SP) as cross-linkers. The physical properties, photochromic properties, and fluorescent behavior of the hydrogel were characterized. The fluorescence emission of the hydrogel can be reversibly switched ‘on/off’ by UV/visible light irradiation, and meanwhile the fluorescence intensity can be enhanced by increasing the temperature above the volume phase transition temperature (VPTT) of the hydrogel. The hydrogel also shows spatiotemporal fluorescent behavior, excellent cytocompatibility, and fatigue resistance in photochromic and photo-switchable fluorescent behaviors.     

创建人体解剖学以临床为导向的立体化课堂教学新模式

培养具备初步临床能力、终身学习能力和良好职业素质的临床医学毕业生,实现地方高校培养应用型人才的目标。设计以临床案例为导向的人体解剖学教学内容,创建立体化的人体解剖学教学方法、教学手段、成绩评定体系——学生课前搜集资料,课堂讨论教学病例,教师结合传统课堂教学与网络信息化教学。以临床为导向的立体化课堂教学新模式,极大地激发了学生的学习兴趣,培养了学生的早期临床思维能力和合格医生所需的综合素质;同时提高了教师的教学效果、教学效率,充分实现了教学手段的现代化。真正实现了"基础与临床课程交叉渗透、早期接触临床"的医学教育新理念。     

Resolution of HBV infection occurs sooner than recovery of renal disease in adult serum HBsAg‐negative HBV–associated glomerulonephritis

Most cases of hepatitis B virus–associated glomerulonephritis (HBV‐GN) occur in children and present with serum HBsAg positivity. Few studies have investigated adult patients with HBV‐GN who are serum HBsAg‐negative. This study aimed to determine the clinical and pathological features of adult patients with HBV‐GN who are serum hepatitis B surface antigen (HBsAg)‐negative. Clinical, pathologic, and laboratory findings were collected and analyzed in a cohort of 27 adult patients with HBV‐GN who were serum HBsAg‐negative upon diagnosis. The study population included mostly men of middle age (40‐59 years). Clinically, patients presented with nephrotic syndrome. Serum immunoglobulin G levels were low, whereas serum immunoglobulin M, immunoglobulin A, complement C3 (C3), and complement C4 (C4) levels as well as liver and renal function tests were normal in most or all patients. Among the 27 patients, 21 tested positive for HBV antibodies. Membranous nephropathy was the dominant pathological form on kidney biopsy. In addition, only a few patients showed a “full house” staining pattern and renal immune deposit of complement C1q (C1q). Serum HBsAg‐negative HBV‐GN may represent a late stage of HBV infection. We recommend routine testing for HBV markers on renal biopsy in regions where HBV is prevalent, even when tests for serum HBV markers are negative.     

Report of a Chinese Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome

Purpose

We aimed to report the clinical manifestations and immunological features of activated phosphatidylinositol 3-kinase δ syndrome 1 (APDS1) in a Chinese cohort. Moreover, we investigated the efficacy and safety of rapamycin therapy for Chinese patients with APDS1.

Methods

Fifteen Chinese patients with APDS1 from 14 unrelated families were enrolled in this study. These patients were diagnosed based on clinical features, immunological phenotype, and whole-exome sequencing. Four patients were treated with rapamycin, and the clinical efficacy and safety of rapamycin were observed. The changes of phosphorylation of Akt and mammalian target of rapamycin (mTOR) signaling pathway after rapamycin treatment were detected by flow cytometry and real-time PCR.

Results

The common clinical manifestations of the patients included lymphadenopathy (93%), recurrent sinopulmonary infections (93%), hepatosplenomegaly (93%), and diarrhea (78%). Epstein-Barr virus (EBV) (80%) and fungus (Aspergillus) (47%) were the most common pathogens. Immunological phenotype included elevated Immunoglobulin (Ig) M levels (100%), decreased naive T cells, increased senescent T cells, and expanded transitional B cells. Whole-exome sequencing indicated that 13 patients had heterogeneous PIK3CD E1021K mutations, 1 patient had heterogeneous E1025G mutation and 1 patient had heterogeneous Y524N mutation. Gain-of-function (GOF) PIK3CD mutations increased the phosphorylation of the Akt-mTOR signaling pathway. Four patients underwent rapamycin therapy, experiencing substantial improvement in clinical symptoms and immunological phenotype. Rapamycin inhibited the activated Akt-mTOR signaling pathway.

Conclusions

We described 15 Chinese patients with APDS1. Treatment with the mTOR inhibitor rapamycin improved patient outcomes.

     

An efficient forward-secure group certificate digital signature scheme to enhance EMR authentication process

The frequently used digital signature algorithms, such as RSA and the Digital Signature Algorithm (DSA), lack forward-secure function. The result is that, when private keys are renewed, trustworthiness is lost. In other words, electronic medical records (EMRs) signed by revoked private keys are no longer trusted. This significant security threat stands in the way of EMR adoption. This paper proposes an efficient forward-secure group certificate digital signature scheme that is based on Shamir’s (t,n) threshold scheme and Schnorr’s digital signature scheme to ensure trustworthiness is maintained when private keys are renewed and to increase the efficiency of EMRs’ authentication processes in terms of number of certificates, number of keys, forward-secure ability and searching time.     

Current Immunological and Molecular Biological Perspectives on Seafood Allergy: A Comprehensive Review

Seafood is an important component in human diet and nutrition worldwide. However, seafood also constitutes one of the most important groups of foods in the induction of immediate (type I) food hypersensitivity, which significantly impacts the quality of life and healthcare cost. Extensive efforts within the past two decades have revealed the molecular identities and immunological properties of the major fish and shellfish allergens. The major allergen involved in allergy and cross-reactivity among different fish species was identified as parvalbumin while that responsible for shellfish (crustaceans and mollusks) allergy was identified as tropomyosin. The cloning and expression of the recombinant forms of these seafood allergens facilitate the investigation on the detailed mechanisms leading to seafood allergies, mapping of IgE-binding epitopes, and assessment of their allergenicity and stability. Future research focusing on the immunological cross-reactivity and discovery of novel allergens will greatly facilitate the management of seafood allergies and the design of effective and life-long allergen-specific immunotherapies.     

Negative regulation of Nod‐like receptor protein 3 inflammasome activation by T cell Ig mucin‐3 protects against peritonitis

The Nod‐like receptor protein 3 (NLRP3) inflammasome plays roles in host defence against invading pathogens and in the development of autoimmune damage. Strict regulation of these responses is important to avoid detrimental effects. Here, we demonstrate that T cell Ig mucin‐3 (Tim‐3), an immune checkpoint inhibitor, inhibits NLRP3 inflammasome activation by damping basal and lipopolysaccharide‐induced nuclear factor‐κB‐mediated up‐regulation of NLRP3 and interleukin‐1β during the priming step and basal and ATP/lipopolysaccharide‐induced ATP production, K⁺ efflux, and reactive oxygen species production during the activation step. Residues Y256/Y263 in the C‐terminal region of Tim‐3 are required for these inhibitory effects on the NLRP3 inflammasome. In mice with alum‐induced peritonitis, blockade of Tim‐3 exacerbates peritonitis by overcoming the inhibitory effect of Tim‐3 on NLRP3 inflammasome activation, while transgenic expression of Tim‐3 attenuates inflammation by inhibiting NLRP3 inflammasome activation. Our results show that Tim‐3 is a critical negative regulator of NLRP3 inflammasome and provides a potential target for intervention of diseases with uncontrolled inflammasome activation.     

某装甲部队职业性下腰痛官兵心理状态的分析

目的探讨在现代军事训练及作业条件下,患有职业性下腰痛官兵的心理健康状态。方法选取某部官兵正常组150人,下腰痛组120人,采用自编被试官兵基本情况调查表,症状自评量表,应对方式问卷,社会支持评定量表进行测试,并进行统计学t检验和方差分析。结果下腰痛组症状自评量表中躯体化、强迫、人际关系敏感及焦虑与正常对照组比较有显著性差异(t=2.144,2.050,2.130,3.342;P0.05);下腰痛组中主观支持、对支持的利用度、社会支持总分、自责及求助与正常对照组比较有显著性差异(t=3.093,2.614,2.932,1.953,2.454;P0.05);③不同的文化程度会影响客观支持、主观支持、社会支持总分、解决问题、自责、求助、幻想和退避,并且差异显著(F=4.15,5.84,5.13,5.02,4.98,4.01,7.25,3.12;P0.05);④不同的军龄会影响客观支持、对支持的利用度以及应对方式的各个因子,并且差异显著(F=3.24,3.02,5.13,8.24,5.36,10.88,9.67,3.87;P0.05)。结论下腰痛官兵的心理状态与应对方式,社会支持密切相关。