The Value of γδ T Cells in Lung Infections and Advances in Diagnosis and Treatment

Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this has also led to the problem of antibiotic abuse and irrational use, which in turn has spawned the emergence of multidrug-resistant bacteria, making the treatment of lung infections more complex and difficult. In the human immune system, γδ T cells play a crucial role in defense against foreign pathogens and regulation of autoimmune responses. These cells act as a bridge between innate and adaptive immunity and can be rapidly activated in the early stages of infection to produce inflammatory factors and chemokines that attract other immune cells to the site of infection. Recent advances have shown that γδ T cells not only play a direct role in the innate immunity of pathogen infection, but are also involved in regulating the subsequent adaptive immune response. The aim of this review is to explore the mechanism of γδ T cells in lung infections and to summarize the current progress of clinical research, with the aim of providing new scientific basis and therapeutic strategies for the treatment of lung infections.

Efficacy of 2LPAPI®, a Micro-Immunotherapy Drug, in Patients with High-Risk Papillomavirus Genital Infection

Human papillomaviruses (HPVs) are well known for being linked to the development of cervical cancers, most of them being caused by the high-risk (HR) oncogenic genotypes, mainly 16 and 18. The efficacy of 2LPAPI® (Labo’Life), a micro-immunotherapy homeopathic drug, has been evaluated in HR-HPV infected women (n = 18), in a private gynecology practice, by comparing them to an untreated control group (n = 18). Patients were 20 to 45 years old and had cytology with Atypical Squamous Cells of Undetermined Significance (ASCUS) or Low grade Superficial Intra Lesions/ Cervical Intraepithelial Neoplasia Grade I (LSIL/CINI). Patients freely chose to be treated with the drug or not. Those deciding not to take the drug remained untreated and were followed as a control group. The drug was taken at the regimen of one capsule per day during 6 months. HR-HPV and cytology were evaluated at 6 and 12 months. After 12 months, HR-HPV was cleared in 78% of the patients taking the drug versus 44% in those not taking it (p = 0.086). In patients over 25 years, HR-HPV clearance in the treated group was significantly higher (81.3%) than in the control group (20%) (p = 0.004). The difference in the regression of the lesion grades almost reached statistical significance (p = 0.053). This follow-up confirms that the micro-immunotherapy drug 2LPAPI® is a safe and effective therapeutic approach to treat HR-HPV cervical lesions in women over 25 years.

T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection

Hepatitis B is caused by the host immune response and T cells play a major role in the immunopathogenesis. More importantly,T cells not only destroy hepatocytes infected by hepatitis B virus(HBV),but also control HBV replication or eradicate HBV in a noncytolytic manner.Therefore,analysis of T cell immune response during acute and chronic HBV infection is important to develop a strategy for successful viral control,which could lead to immunotherapy for terminating persistent HBV infection.There have been many attempts at immunotherapy for chronic HBV infection,and some have shown promising results.High viral load has been shown to suppress antiviral immune responses and immunoinhibitory signals have been recently elucidated, therefore,viral suppression by nucleos(t)ide analogs, stimulation of antiviral immune response,and suppression of the immunoinhibitory signals must be combined to achieve desirable antiviral effects.

The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.

Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections

Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result in a"cold tumor"-like immune silent microenvironment,allowing the persistence of IRIs.To address this challenge,an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum(CFCP)was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response.Specifically,enhanced sonodynamic therapy(SDT)from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA(dsDNA).Immunogenic dsDNA promoted dendritic cell(DC)maturation through activation of the stimulator of interferon gene(STING)and amplified the immune stimulation of neutrophils via interferon-β(IFN-β).At the same time,enhanced BAA presentation aroused humoral immunity in B and T cells,creating long-term resistance to repetitive infections.Encouragingly,CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

锰在免疫调节中的功能及其应用

锰是一种人体必需的微量元素,在发育、生殖、代谢、神经功能和抗氧化等方面发挥着重要的作用。近年来,锰在机体免疫中的重要作用逐步被认识和重视。锰作为一种损伤相关分子模式,具有强劲的免疫激活能力。锰离子诱导细胞产生大量的包括Ⅰ型干扰素在内的细胞因子,调控机体的天然免疫和适应性免疫反应,在免疫佐剂和肿瘤免疫治疗方面展现出巨大的潜力。本文首先总结了锰在机体内的稳态调节及其在机体免疫中的作用,之后对锰及其衍生物在免疫佐剂和肿瘤免疫治疗方面的一系列应用进行了详细的讨论,并对其未来的发展进行了展望。

Harnessing immunity:Immunomodulatory therapies in COVID-19

An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.

抗炎免疫疗法在发热感染相关性癫痫综合征中应用进展

发热感染相关性癫痫综合征(febrile infection-related epilepsy syndrome,FIRES)是一种以难治性癫痫持续状态为主要表现的致死性脑病,选择有效的抗癫痫药物(antiepileptic drugs,AEDs)是治疗的重点和难点。本文总结了不同抗炎免疫疗法在该病治疗中的作用机制、用药方法和不良反应,发现早期开始生酮饮食(ketogenic diet,KD)是目前最有效的治疗方法之一,尚需进一步研究以明确药物不良反应及不同药物联用的效果。

不同剂量胸腺肽-α1在肠毒素B与脂多糖复合诱导小鼠脓毒症模型中的免疫干预作用研究

目的 模拟革兰阳性球菌和革兰阴性杆菌混合感染,建立金黄色葡萄球菌肠毒素B(SEB)和脂多糖(LPS)复合诱导的小鼠脓毒症模型,观察血清炎症因子及组织蛋白表达水平的变化,探讨不同剂量胸腺肽-α1(Tα1)对脓毒症的免疫干预作用.方法 选择SPF级健康雄性BALb/c小鼠 90 只,按随机数字表法将小鼠分为对照组、Tα1 小剂量组和Tα1 大剂量组,每组 30 只.采用向小鼠腹腔注射 300 μg/kg SEB和1000 μg/kg LPS的方法复制小鼠复合感染脓毒症模型.于腹腔注射SEB2h后,给所有小鼠腹腔注射LPS 1000 μg/kg的同时Tα1 小剂量组小鼠腹部皮下注射Tα1100 μg/kg,Tα1 大剂量组小鼠腹部皮下注射Tα12000 μg/kg,对照组给予等量磷酸盐缓冲液(PBS).观察并记录各组小鼠制模后 6h的体征表现.于制模后2、4、6 h取血分离血清,采用酶联免疫吸附试验(ELISA)检测各组小鼠血清白细胞介素(IL-6,IL-10)、γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平;处死动物后留取脾脏组织,光镜下观察脾脏组织的病理学改变,采用蛋白质免疫印迹试验(Western blotting)测定脾脏组织核转录因子-κB p65(NF-κB p65)的蛋白表达水平.结果 给药后 6 h,Tα1 小剂量组和Tα1 大剂量组小鼠精神活动、进食、寒战、呼吸、竖毛、大便等体征评分均较对照组明显降低[精神活动(分):1.20±0.42、1.10±0.31 比 2.70±0.48,进食(分):1.50±0.53、1.40±0.52比 2.60±0.70,寒战(分):1.20±0.42、1.30±0.48 比 2.30±0.48,呼吸(分):1.20±0.42、1.30±0.48 比 2.40±0.70,竖毛(分):1.40±0.52、1.20±0.42 比 2.60±0.52,大便(分):1.40±0.52、1.40±0.52 比 2.40±0.52,均P<0.05].随时间延长,各组IL-6、IL-10 逐渐降低,IL-10/IL-6 比值呈先降低后升高的趋势,IFN-γ呈先升高后降低的趋势;对照组TNF-α持续降低,脾脏组织NF-κB p65 的蛋白表达水平持续升高;Tα1 小剂量组和Tα1 大剂量组TNF-α呈先降低后升高趋势,脾脏组织NF-κB p65 的蛋白表达水平呈先升高后降低趋势.给药后 2h,Tα1 小剂量组和Tα1 大剂量组IL-6、IFN-γ、NF-κB p65 的蛋白表达水平均明显高于对照组[IL-6(μg/L):2439.63±3.46、2442.38±22.53 比 2281.47±27.97,IFN-γ(μg/L):47.37±4.69、50.16±7.50 比 40.24±8.64,NF-κB p65/β-actin:0.160±0.009、0.155±0.009 比 0.108±0.005,均P<0.05],IL-10、IL-10/IL-6 比值均明显低于对照组[IL-10(μg/L):82.30±17.00、70.89±8.25 比 214.71±110.43,IL-10/IL-6:0.034±0.007、0.029±0.003比 0.094±0.048,均P<0.05];给药后 2h起Tα1 小剂量组和Tα1 大剂量组TNF-α较对照组明显降低(μg/L:774.84±136.97、1068.88±279.99 比 2712.68±718.06),持续到给药后 6h(均P<0.05).病理学观察显示,肺组织光镜下可见对照组部分肺泡壁破坏、有肺间质出血现象,Tα1 小剂量组及Tα1 大剂量组可见肺间质血管充血扩张,未见肺间质出血;肝组织光镜下可见对照组肝细胞水肿,颜色变淡,Tα1 小剂量组及Tα1 大剂量组病变较轻;肾组织光镜下可见对照组肾间质血管充血,Tα1 小剂量组及Tα1 大剂量组病变较轻;心肌组织光镜下对照组偶见血管扩张充血,Tα1 小剂量组及Tα1 大剂量组形态学表现基本正常.结论 Tα1 有利于改善SEB与LPS复合介导的脓毒症小鼠预后,增强脓毒症小鼠的免疫应答,但持续时间有限,提示Tα1 在混合感染的研究中应关注使用时机和疗程;Tα1 在SEB与LPS复合介导的脓毒症小鼠中的有效剂量范围较大,合适的应用剂量有待进一步研究.

关于新型冠状病毒感染若干问题的多学科临床诊疗推荐意见

2022年12月以来,新型冠状病毒感染(简称新冠感染)患者激增,国家卫健委推出的第十版《新型冠状病毒感染诊疗方案(试行版)》对新冠感染患者规范化诊疗具有重要指导价值。但该诊疗方案在临床具体实践中仍存在一定问题。西安交通大学第二附属医院组织多学科专家就新冠感染诊疗中仍存在的相关关键问题,如新冠感染患者的抗病毒药物选择、免疫治疗的时机、抗凝药物使用剂量、心肌损伤的处理、新冠感染后间质性肺病的治疗、新冠反弹等问题进行细化和归类,形成18条推荐意见,便于临床实践参考使用。

Pseudomonas aeruginosa:Infections and novel approaches to treatment“Knowing the enemy”the threat of Pseudomonas aeruginosa and exploring novel approaches to treatment

Pseudomonas aeruginosa is an aerobic Gram-negative rod-shaped bacterium with a comparatively large genome and an impressive genetic capability allowing it to grow in a variety of environments and tolerate a wide range of physical conditions.This biological flexibility enables the P.aeruginosa to cause a broad range of infections in patients with serious underlying medical conditions,and to be a principal cause of health care associated infection worldwide.The clinical manifestations of P.aeruginosa include mostly health care associated infections and community-acquired infections.P.aeruginosa possesses an array of virulence factors that counteract host defence mechanisms.It can directly damage host tissue while utilizing high levels of intrinsic and acquired antimicrobial resistance mechanisms to counter most classes of antibiotics.P.aeruginosa co-regulates multiple resistance mechanisms by perpetually moving targets poses a significant therapeutic challenge.Thus,there is an urgent need for novel approaches in the development of anti-Pseudomonas agents.Here we review the principal infections caused by P.aeruginosa and we discuss novel therapeutic options to tackle antibiotic resistance and treatment of P.aeruginosa infections that may be further developed for clinical practice.

胰腺癌术后免疫治疗抗感染作用机制的探讨

目的:了解免疫治疗剂胸腺肽鄄α1在胰腺癌术后抗感染中的作用机制。方法:选择60例胰腺癌根治术病人,分为用药组和对照组。用药组病人在手术后使用胸腺肽鄄α1,对照组不予使用。观察临床疗效、内毒素和细胞因子(IL鄄2、IL鄄6、IL鄄10和TNF鄄α)水平的变化,以及T淋巴细胞亚群CD3+、CD4+、CD8+和NK细胞百分率的变化。结果:胰腺癌手术组病人使用胸腺肽α鄄1后肿瘤坏死因子(TNF)鄄α水平明显下降,白介素(IL)鄄2、IL鄄10水平明显升高;手术后1周用药组的CD3+、CD4+百分率较手术前升高,且明显高于对照组。用药组术后1周临床有效率达100%,高于对照组(80%)。结论:胸腺肽鄄α1在胰腺癌术后可提高免疫力的功能,有利于病人恢复。

抗耐甲氧西林金黄色葡萄球菌感染治疗的研究进展

耐甲氧西林金黄包葡萄球菌(MRSA)是医院感染常见的致病菌,近年来医院的检出率逐渐升高,耐药程度日趋加重,已成为当今感染医学的一个亟待解决的难题。随着抗菌药物的不断开发利用,新思路及新技术在感染医学当中的应用,将开辟治疗MRSA感染的新途径。本文从不同角度介绍MRSA抗菌药物的研发、免疫治疗及RNA干扰技术在抗MRSA感染治疗中的进展。

分子模拟与微生物、自身免疫交叉识别以及肿瘤免疫治疗

分子模拟是生物界广为存在的一种自然现象。细菌等病原微生物可利用蛋白质序列或结构的相似而模拟宿主细胞某些分子的功能,从而协助其入侵与存活;另一方面,微生物也可因某些蛋白质的同源或相似而致宿主交叉免疫反应,导致自身免疫参与自身免疫疾病的发生,其本质是一种交叉识别。本室及其他研究小组发现可利用不同种属某些肿瘤相关同源分子的异源性激发特异的免疫反应,并因其同源性而交叉反应于宿主分子,从而产生抗肿瘤的自身免疫,亦即通过异种同源分子的策略主动免疫治疗肿瘤。这种模拟还可以在表位肽的水平进行,相信分子模拟的深入研究将有助于揭示进化与分子识别的本质以及自身免疫的规律,从而探索分子模拟在疾病预防与治疗中的应用。

黄芪精口服液治疗反复呼吸道感染病儿的效果

①目的 探讨中药黄芪精口服液治疗儿童反复呼吸道感染 (RRI)的效果和药理机制。②方法 RRI病儿 6 2例 ,随机分为两组 ,治疗组除给予常规抗感染、对症治疗外 ,给予口服黄芪精口服液治疗 ;对照组仅给予常规抗感染、对症治疗。观察两组病儿随访期间 (1年 )呼吸道感染情况及服药前后免疫功能的变化。③结果 治疗组显效率 (6 1.3% )和总有效率 (87.1% )均明显高于对照组 (分别为 2 9.0 % ,41.9% ) ,差异有显著意义 (χ2 =6 .90 ,13 .81,P <0 .0 1)。治疗组服药后血清IgG ,IgA和T细胞亚群CD3,CD4 ,CD8指标较服药前及对照组皆明显增高 ,差异有极显著性 (t=2 .815～ 4.2 32 ,P <0 .0 1)。

干扰素作用机制的研究进展

干扰素是具有抗病毒、抗增殖和免疫调节功能的糖蛋白。被广泛用于治疗许多疾病,如丙型肝炎、癌症和免疫介导的疾病,如多发性硬化症。本文回顾了干扰素作用机制,从干扰素抗病毒作用机制、病毒拮抗干扰素反应、干扰素抗增殖作用机制以及免疫调节作用等方面进行了综述。干扰素激活分子在病毒复制周期的许多阶段表现出抗病毒活性。同时,病毒已进化出多种策略逃逸或抑制天然免疫系统。补充外源性干扰素可以增强机体抵抗病毒感染。

免疫治疗成人反复呼吸道感染的临床疗效分析

目的研究免疫治疗成人反复呼吸道感染的临床疗效。方法选取44例反复呼吸道感染患者,通过随机数表法将患者分为干预组和常规组,各44例,对患者使用相关的治疗方法,比较两组患者的临床指标改善情况。结果干预组的治疗总有效率高于常规组,其他指标也优于常规组,P<0.05,差异具有统计学意义。结论在使用常规抗感染治疗的基础上使用有效的免疫治疗方法,可有效的提升成人反复呼吸道感染患者机体免疫力。

抗结核单克隆抗体治疗对小白鼠脾内结核杆菌增殖的影响

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病毒持续性感染引起的病程多为慢性或反复发作,难以治愈,在部分患者甚至可引发肿瘤或自身免疫性疾病等,是严重危害人类健康及造成社会重大经济负担的常见病及多发病。持续性感染难以治愈的原因涉及病毒基因组与宿主细胞染色体整合,或以附加体的形式长期存在,以及病毒的酶或蛋白抑制机体的免疫应答等特性。此外,机体天然免疫或获得性免疫低下、免疫网络失调及感染微环境改变等,也是病毒建立并维持持续性感染的原因。本文根据持续性感染难以治愈的原因,从病原学与机体免疫应答两方面研讨一些对策,希望以此为切入点,为治疗持续性感染提供新思路与新策略。