Immune response to inactivated bacterial vector carrying the recombinant K39 antigen of Leishmania infantum in mice

Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.

Using Bacterial Vectors for Probable Vaccines: From Molecular Mechanism to Cancer Therapy

Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.

An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria

Fusobacterium nucleatum(F.nucleatum),an oral anaerobe,is prevalent in colorectal cancer and is closely related to increased cancer cell growth,metastasis,and poor treatment outcomes.Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F.nucleatum,thereby enhancing cancer treatment.Although adjuvants have been employed to enhance the immune response,the vaccine’s effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens.In this study,we developed a minimalistic,biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F.nucleatum membranes.Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant,the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells,maximizing their ability to achieve effective antigen presentation and strong downstream immune progress.Notably,the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects,eliminating F.nucleatum without affecting intratumoral and gut microbiota.It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F.nucleatum-infected colorectal cancer.Overall,this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.

Comparing invasive effects of five foodborne bacterial pathogens in human embryonic intestine 407 cells and human ileocecum HCT-8 cells

Objective: To refine the infectious doses of enteric bacterial pathogens in animal assays and vaccine clinical trials by studying the invasion kinetics of five bacterial pathogens with human intestinal cells.Methods: Utilizing in vitro cultured cell invasion assays with gentamicin-killing step,the invasive effects were analyzed in foodborne pathogens including Salmonella,Shigella, Yersinia, Escherichia coli(E. coli) O157 and opportunistic pathogens Citrobacter in human embryonic intestine 407 cells and ileocecum HCT-8 cells at multiplicities of infection(MOIs) of 0.04–4 000.00 E. coli HS served as a noninvasive control.Results: The study results showed that the bacterial invasive efficiency and the average number of internalized bacteria per host cell changed with different starting MOIs. Higher starting MOIs did not always produce more bacterial internalization. The bacterial invasion effects varied with different bacterial strains and host cell lines. E. coli O157:H7 did invade human ileocecum HCT-8 cells.Conclusions: This study shows that these bacteria possess different invasive patterns at various starting MOIs and also in different cell lines. The results could help to figure out the appropriate infectious doses of the bacteria in animal assays and in vaccine clinical trials. The bacterial invasion kinetics is also valuable in evaluating the safety and efficacy of live attenuated bacterial vaccines.

DNA Vaccines Approach:From Concepts to Applications

DNA vaccines are the third generation vaccines based on purified plasmid preparations containing transgenes that encode antigenic/therapeutic proteins or peptides capable of triggering an immune response against a wide range of diseases. This vaccine platform presents several attributes that confer distinct advantages over other vaccine technologies in terms of safety, ease of fabrication and stability. Many aspects, such as antigen expression and especially vector design, are under study because of their great influence on immunogenicity and efficacy of DNA vaccines. In this regard, with the attempt of improving the efficiency of DNA vaccines, co-expression of stimulatory sequences and diverse vector delivery systems are being optimized. With this in mind, this review aims to giving a conceptual approach of DNA vaccines, explaining their mechanisms of action and listing the already licensed veterinary DNA vaccines presented in the market.

Adjuvant activity of Pasteurella multocida A strain,Pasteurella multocida B strain and Salmonella typhimurium bacterial DNA on cellular and humoral immunity responses against Pasteurella multocida specific strain infections in Balb/c mice

Objective: To evaluate the effects of Pasteurella multocida(P. multocida) vaccines on the expression and release of antibodies, interleukin(IL)-6 and IL-12 by serum. Methods: Balb/c mice were immunized with two formalin and iron inactivated vaccine doses within 2 weeks. The vaccines were adjuvant with P. multocida A strain, P. multocida B strain and Salmonella typhimurium bacterial DNA(AbDNA, BbDNA and SbDNA for short, respectively). The animals were challenged 4 weeks after immunization. Blood of mice was collected to detect the change of specific antibody, IL-6, and IL-12 using ELISA. Results: The specific antibody and interleukins in the immunized group increased significantly compared to the control mice after vaccination and challenge(P<0.05). The highest release of these cytokines was obtained by P.multocida inactivated with iron and adjuvant with AbDNA at a concentration of 25 μg/mL. The antibody titer peak was 0.447 in mice vaccinated with iron-killed whole-cell antigen adjunct with AbDNA. The time-courses of release showed that bacterial DNA was able to stimulate IL-6 and IL-12 production more than alum(P<0.05). Conclusions: Our findings introduce that bacterial DNA is capable of releasing an immunological response with several cytokines.These indicate that bacterial DNA entrapped with killed P. multocida antigen is a new and effective adjuvant to enhance specific immunity and resistance of animal against the infectious pathogen, which could simplify the development of highly promising strong adjuvant.

Case of acute pancreatitis associated with Campylobacter enteritis

A 25-year-old man was admitted with the chief complaints of right flank pain,watery diarrhea,and fever.Blood tests revealed high levels of inflammatory markers,and infectious enteritis was diagnosed.A stool culture obtained on admission revealed no growth of any significant pathogens.Conservative therapy was undertaken with fasting and fluid replacement.On day 2 of admission,the fever resolved,the frequency of defecation reduced,the right flank pain began to subside,and the white blood cell count started to decrease.On hospital day 4,the frequency of diarrhea decreased to approximately 5 times per day,and the right flank pain resolved.However,the patient developed epigastric pain and increased blood levels of the pancreatic enzymes.Abdominal computed tomography revealed mild pancreatic enlargement.Acute pancreatitis was diagnosed,and conservative therapy with fasting and fluid replacement was continued.A day later,the blood levels of the pancreatic enzymes peaked out.On hospital day 7,the patient passed stools with fresh blood,and Campylobacter jejuni/coli was detected by culture.Lower gastrointestinal endoscopy performed on hospital day 8 revealed diffuse aphthae extending from the terminal ileum to the entire colon.Based on the findings,pancreatitis associated with Campylobacter enteritis was diagnosed.In the present case,a possible mechanism of onset of pancreatitis was invasion of the pancreatic duct by Campylobacter and the host immune responses to Campylobacter.

微生态制剂联合肠内营养治疗2型糖尿病并发肺结核的效果分析

目的探讨微生态制剂联合肠内营养辅助治疗2型糖尿病并发肺结核(T2DMTB)患者的临床疗效。方法将2019年1月至2020年12月收治的77例T2DMTB患者随机分为正常饮食组(A组,19例)、微生态制剂组(B组,19例)、肠内营养组(C组,19例)和微生态制剂+肠内营养组(D组,20例),4组均给予常规抗结核及降糖治疗。比较4组患者治疗效果,治疗1个月后痰涂片转阴情况、免疫指标及离子指标变化情况等。结果4组患者结核痰涂片转阴率差异有统计学意义(χ^(2)=19.204,P=0.0038),其中A组转阴率为52.63%,B组转阴率为36.84%,C组转阴率为57.89%,D组转阴率为95%;治疗前后4组患者免疫水平无显著差异(P>0.05);与治疗前比较,A组Na^(+)、Pi水平升高,B组Na^(+)、Pi、Mg^(2+)离子水平升高,C组Na^(+)、Pi、Mg^(2+)、Fe^(2+)水平升高,D组P、Fe^(2+)水平升高,差异均有统计学意义(P<0.05)。结论微生态制剂联合肠内营养有助于提高痰涂片转阴率,显著改善2型糖尿病并发肺结核患者的临床治疗效果。

嗜水气单胞菌感染大口黑鲈肠炎模型的建立及评价

【目的】采用嗜水气单胞菌(Aeromonas hydrophila)感染建立稳定大口黑鲈(Micropterus salmoides)的细菌性肠炎模型,并确定导致肠炎发生的细菌浓度和作用时间。【方法】150尾健康的大口黑鲈随机分为5组:对照组和4个试验组(感染浓度分别为1×10^(8)、1×10^(7)、1×10^(6)和1×10^(5) CFU/mL),通过腹腔注射方式进行人工感染。通过临床症状、剖检病变及评分、组织学变化及评分、肠道组织超微结构变化和炎症因子基因表达量评价各试验组造模效果。【结果】攻毒后试验组表现出游动慢,摄食下降的现象,且在攻毒第2和第3天时,1×10^(8) CFU/mL攻毒组有死亡现象。剖检后可见肛门红肿、外突,腹鳍和腹部皮肤出血等症状,肠道充血、出血,部分可见肠液潴留等。各组大体病理得分与细菌的感染浓度呈正相关,与感染时间呈负相关。组织学观察可见肠道固有层充血、水肿、增厚,并伴有炎性细胞浸润,黏膜上皮损伤脱落、细胞变性、坏死、增生,杯状细胞数目明显增加;组织病理得分随细菌浓度升高而升高,随感染时间呈现先上升后下降的趋势,在感染第5天得分最高。肠道组织超微结构变化显示,攻毒组肠道微绒毛损伤脱落,形态紊乱,上皮细胞排列紊乱,线粒体水肿,出现空泡,部分细胞胞浆中细胞器溶解甚至消失,杯状细胞数目增多。各试验组炎症因子表达量的变化与细菌浓度有关,IL-15、IL-8、TNF-α和IL-1β的表达量随细菌浓度的升高而升高,且随时间呈现先上升后下降的趋势。IL-10、IL-11和TGF-β_(2)的表达量与感染浓度呈负相关,其中IL-10和IL-11的基因表达量变化显著低于对照组,TGF-β_(2)的基因表达量变化不显著。【结论】1×10^(7) CFU/mL攻毒组在整个试验过程中未出现死亡,病理学观察显示肠道有较明显的病理损伤。因此,为构建接近临床条件的细菌性肠炎模型,选择攻毒剂量为200μL 1×10^(7) CFU/mL的菌液作为肠道病理损伤模型的感染浓度。

动物疫病活载体疫苗研究进展

活载体疫苗是以细菌或病毒作为载体表达外源抗原和治疗因子的载体系统,具有安全性高、毒力返祖风险低、成本低,可诱导免疫机体产生高水平的体液免疫、细胞免疫或黏膜免疫等优点,是目前最具发展潜力的基因工程疫苗之一,在动物疫病防控领域应用较多。病毒载体包括DNA病毒(如腺病毒、腺相关病毒和痘病毒等)和RNA病毒(如新城疫病毒、流感病毒等);细菌载体包括减毒致病菌与非致病菌两类,主要包括乳酸菌、沙门氏菌、大肠杆菌等。活载体疫苗常用的抗原呈递策略有载体-宿主平衡致死系统、微生物表面展示系统。多种疫苗载体的开发及抗原呈递策略的选择,使得活载体疫苗的使用价值最大化。不同载体疫苗在预防疫病方面均有不同优缺点,应根据实际情况选择最优最适合的活载体疫苗。本文综述了动物疫病防控领域的病毒和细菌活载体疫苗研究进展及其抗原呈递方式,以期为活载体疫苗的进一步研究提供参考。

呼吸道感染细菌联合疫苗制备及其免疫效果评价

目的探讨呼吸道感染细菌联合疫苗对免疫效果的影响。方法分离培养6种呼吸道感染细菌(溶血性链球菌、流感嗜血杆菌B型、肺炎链球菌、金黄色葡萄球菌、铜绿假单胞菌及肺炎克雷伯菌),制成联合疫苗。根据联合疫苗质量浓度分为对照组(生理盐水)、低水平组(0.1 g/L疫苗)、中水平组(0.3 g/L疫苗)及高水平组(0.5 g/L疫苗)。各组疫苗作用于人外周血单个核细胞,检测外周血单个核细胞增殖活性、淋巴细胞表型的变化及细胞因子水平。各组疫苗作用于SPF级小鼠,测定各组小鼠迟发型超敏反应、脾脏指数、胸腺指数、巨噬细胞吞噬指数及血清溶血素含量。结果人外周血各组单个核细胞增殖活性、γ干扰素、白细胞介素-2水平均随时间延长而升高,且在相同时间,联合疫苗质量浓度越高,各指标水平越高(P<0.05)。与对照组比较,低、中、高水平组单个核细胞CD4+、CD19+水平升高,CD8+水平降低,且随着联合疫苗质量浓度越高,各指标水平变化越明显(P<0.05)。与对照组小鼠比较,低、中、高水平组小鼠迟发型超敏反应、脾脏指数、胸腺指数、吞噬指数、溶血素水平升高,且随着联合疫苗质量浓度越高,各指标水平越高(P<0.05)。结论呼吸道感染细菌联合疫苗有利于提高细胞及体液免疫能力,且联合疫苗质量浓度为0.5 g/L时,可获得的免疫效果最佳。

鱼类迟缓爱德华氏菌肠溶口服疫苗的制备及免疫保护效应研究

本文采用海藻酸钠作为载体,采用乳化复沉淀方法包裹迟缓爱德华氏菌(Edwardsiella tarda)全菌制备疫苗微球。制备工艺研究结果表明:3%(m/v)海藻酸钠溶液,4%(m/v)CaCl_(2)溶液,水油相比1∶2,乳化剂Span801%,搅拌速度1200 r/min为最佳制备工艺,微球包埋率达91.04%,微球平均粒径(16.51±11.87)μm。通过人工胃肠液对疫苗微球的耐受性进行分析,微球在体外人工模拟胃液和肠液中16h释放率分别为0.8%和98.1%。用表达有绿色荧光蛋白的大肠杆菌做示踪标记,口灌免疫半滑舌鳎(Cynoglossus semilaevis Gunther),疫苗能耐受胃的酸性环境影响,通过前消化道到达后肠。免疫保护效应研究表明,口腔灌注疫苗后,出现特异性和非特异性免疫应答,疫苗组在初免后第14天血清效价达到峰值1∶322;外周血白细胞吞噬率在初免后第14天达到峰值27.06%,吞噬指数在初免后第14天达到峰值1.65。初免后第28天用迟缓爱德华氏菌活菌攻毒,对照组死亡率58.82%,疫苗组死亡率13.33%,免疫保护率为77.33%。本研究优化了鱼类肠溶口服疫苗的制备工艺,疫苗免疫评价结果表明,该口服疫苗可以有效激活鱼体免疫反应,预防鱼类疾病发生。

细菌外膜囊泡应用于肿瘤治疗

细菌外膜囊泡(outer membrane vesicles,OMVs)是由革兰氏阴性菌分泌的纳米囊泡,主要由细菌外膜和周质成分组成,因此表面富集的病原体相关分子模式(PAMPs)使OMVs能激起强烈的免疫反应。在抗肿瘤研究中,OMVs主要被用于抗肿瘤药物的递送,不仅能增加药物的肿瘤富集还能激活免疫反应协同杀伤肿瘤;同时,OMVs也用于开发肿瘤疫苗的佐剂,可显著提高免疫响应的能力。本综述主要概括了OMVs的生物发生机理、OMVs对宿主免疫系统的影响及其在肿瘤治疗中的研究进展。

合成生物学助力细菌疫苗研发

细菌感染已成为全球第二大死亡因素,给人类健康与公共安全造成了巨大威胁。抗生素一直是治疗细菌感染最为主要的手段,但越来越严重的耐药问题给传统的抗生素疗法带来了严峻挑战。除了抗生素之外,疫苗被认为是防治传染性疾病传播最为科学、经济、安全和有效的手段,在人类抗击病原体感染斗争中发挥了重要作用。然而,细菌基因组庞大,致病机制复杂,研发疫苗存在有效抗原筛选、设计、制备难,抗原组合配伍难,有效性评价难,研发周期长等诸多瓶颈,导致细菌疫苗研发进展缓慢,尤其是临床常见的严重耐药致病菌尚无有效的疫苗可用。合成生物学是一门新兴的交叉学科,近年来在疫苗研究领域已经得到了广泛应用,包括抗原的筛选、理性设计、配伍组合,载体、佐剂和递送系统的设计以及免疫应答调控等。本文综述了细菌疫苗研究的现状以及耐药细菌疫苗临床试验研究进展,总结了合成生物学技术在几种重要类型细菌疫苗研发中的应用进展,最后对相关前景进行了展望。合成生物学在疫苗的形式、疫苗递送、疫苗的研制效率等方面为研究人员提供了更为广阔的空间,未来,应最大化地发挥合成生物学的优势,充分发展和应用合成生物学技术手段,建立科学、理性、有效、可行的管理制度,建设生物安全保障法律体系和监管措施,高效推动细菌疫苗研发,解决抗生素耐药问题,造福人类健康。

合成生物学在基于微生物载体肿瘤疫苗设计中的应用

合成生物学有望创造具备独特优势的抗肿瘤微生物疫苗,合成生物学改造的微生物更能适应肿瘤微环境并在其中富集与增殖,削弱或者逆转免疫抑制细胞的功能,并增强肿瘤抗原的呈递,诱发多种先天与适应性抗肿瘤免疫反应,所以合成生物学已成为肿瘤疫苗研究的重要工具。本文总结了合成生物学在细菌和病毒载体肿瘤疫苗开发中的几个关键应用,其中包括减弱微生物载体毒性的方法,例如去除、失活或修改其致病基因等。讨论了增强它们在肿瘤组织中的趋向性和适应性的策略,如改变它们的细胞入侵分子或引入环境控制的基因表达系统等;也讨论了降低全身毒性的方法。为了充分利用微生物复制引起的肿瘤微环境改变的潜力,多种合成生物学手段被用于改造微生物载体,这些方法包括将外源基因引入微生物基因组,使其生产诸如细胞因子、趋化因子或单克隆抗体等分子,这些分子可以增强先天和适应性免疫细胞的招募和激活,促进肿瘤细胞免疫原性死亡,并增强肿瘤相关抗原的呈递。此外,还探讨了将肿瘤抗原引入载体中的方法,例如不同的装载方式、位置和释放机制。开发微生物载体肿瘤疫苗存在重大挑战,包括安全性问题、抗载体免疫与抗肿瘤免疫的复杂关系和肿瘤生物学的复杂性,克服这些困难将成为未来研究的重要方向。

布鲁氏菌A19株菌影疫苗的构建及其免疫效果评价

为开发一种安全有效的布鲁氏菌疫苗,解决现有A19、S2和M5等弱毒疫苗存在较强毒力可感染人,且无法通过血清学方法将其免疫抗体与野毒感染抗体进行鉴别区分的问题,本试验将含有噬菌体PhiX174裂解酶基因E的质粒转化至A19疫苗株,构建菌影疫苗(A19-BG)菌株,并检验其遗传稳定性及对小鼠的安全性、免疫效果和保护效果。结果显示,构建成功的A19-BG菌株传代20代仍稳定,热诱导48 h后可完全灭活,菌体穿孔明显。A19-BG疫苗免疫小鼠7 d后免疫部位无不良反应,14 d后脾脏无可见病理变化,与空白对照组相比脾脏重量无显著差异(P>0.05)。一免和二免后14 d,免疫小鼠的布鲁氏菌抗体、白细胞介素4(IL-4)和γ干扰素(IFN-γ)水平持续升高,产生了良好的体液和细胞免疫反应。布鲁氏菌2308强毒株攻毒免疫小鼠,免疫保护率可达87.5%,保护效果良好。结果表明,构建的A19-BG疫苗具有良好的稳定性、安全性、免疫效果和保护效果,有望成为一种极具潜力的布鲁氏菌新型疫苗。

林麝出血性肺炎病原菌的分离鉴定和菌影疫苗的制备

为了科学有效防控林麝出血性肺炎,本试验对发生出血性肺炎的死亡林麝进行病理剖检,采取病变肺脏进行细菌分离纯化、生化和16S rRNA测序鉴定及耐药性检测,并制备菌影疫苗开展小鼠免疫保护试验。结果显示,从表现典型出血性肺炎病变的林麝肺脏样本中分离鉴定出3株大肠杆菌,分离株对小鼠均有致病性,药敏试验均为多重耐药菌株;采用0.4 mg/mL氢氧化钠溶液裂解大肠杆菌分离株制备菌影疫苗,以0.5×10^(8)CFU/只剂量2次免疫小鼠后能提供100%的免疫保护。结果表明,从患出血性肺炎的林麝肺脏中分离到致病性大肠杆菌,制备的菌影疫苗对小鼠具有良好的免疫保护效果,为林麝大肠杆菌性出血性肺炎的防控提供了新思路。

Necrotic enteritis and antibiotic-free production of broiler chickens:Challenges in testing and using alternative products

The global trend towards raising broiler chickens without the use of in-feed antibiotics(IFAs)means that there is an ongoing need to develop alternative treatments capable of delivering the benefits that IFAs previously provided.IFAs supported the productivity performance of chickens and played a key role in maintaining their health.Necrotic enteritis(NE)is an important disease of broilers that affects health,productivity,and welfare,and was previously well controlled by IFAs.However,with the reduction in IFA use,NE is resurgent in some countries.Vaccines and various feed additives,including pre-,pro-,and postbiotics,phytobiotics,fatty acids,and phage therapies have been introduced as alternative methods of NE control.While some of these feed additives have specific activity against the NE pathogen,Clostridium perfringens,most have the more general goal of reinforcing gut health.Extensive reviews of the effects of many of these feed additives on gut health have been published recently.Hence,rather than cover previously well reviewed areas of research this review focuses on the challenges and pitfalls in undertaking experimental assessment of alternative NE treatments and translating laboratory research to real world commercial production settings.The review is based on the author's particular experience,reading,thoughts,and analysis of the available information and inevitably presents a particular understanding that is likely to be at odds with others thinking on these issues.It is put forward to stimulate thinking and discussion on the issues covered.

盐酸小檗碱联合蒙脱石散灌肠治疗小儿急性细菌性肠炎的临床效果

目的:分析在小儿急性细菌性肠炎治疗中应用盐酸小檗碱联合蒙脱石散灌肠治疗的效果。方法:选取2019年8月—2022年8月江苏省宝应县人民医院收治的94例急性细菌性肠炎患儿为研究对象,采用抛硬币法将其分为试验组和对照组,各47例。对照组给予抗生素、补液等基础治疗,试验组在对照组基础上给予盐酸小檗碱及蒙脱石散灌肠治疗,比较两组治疗效果、症状改善时间、体液免疫检测指标、生活质量。结果:试验组总有效率高于对照组,差异有统计学意义(P<0.05)。试验组退热、腹泻缓解、呕吐改善、大便常规恢复正常时间均短于对照组,差异有统计学意义(P<0.05)。治疗前,两组体液免疫检测指标水平比较,差异无统计学意义(P>0.05);治疗后,试验组IgG、IgM及IgA水平均高于对照组,差异有统计学意义(P<0.05)。治疗前,两组生活质量评分比较,差异无统计学意义(P>0.05);治疗后,试验组生理、精神、认知评分均高于对照组,差异有统计学意义(P<0.05)。结论:在小儿急性细菌性肠炎治疗中应用盐酸小檗碱和蒙脱石散灌肠的效果显著,能够缩短患儿症状缓解时间,提高其免疫功能及生活质量。

血清iNOS、TREM-1、IL-1Ra表达与细菌感染性肠炎患者病情严重程度的关系及其临床意义研究

目的探究细菌感染性肠炎患者血清诱导型一氧化氮合酶(iNOS)、髓样细胞触发受体-1(TREM-1)和白细胞介素-1受体拮抗剂(IL-1Ra)表达的临床意义。方法前瞻性选取2021年2月—2023年2月广州中医药大学东莞医院收治的120例细菌感染性肠炎患者为研究对象。采集患者粪便标本,分析感染病原菌的病原学特点;根据病情严重程度将患者分为轻度组28例、中度组79例和重度组13例。另选取同期本院体检的健康体检者60例为对照组。比较各组炎症因子[血清降钙素原(PCT)、C反应蛋白(CRP)]、iNOS、TREM-1、IL-1Ra水平;采用Pearson相关分析iNOS、TREM-1、IL-1Ra与炎症因子水平的相关性;采用受试者工作特征(ROC)曲线分析血清iNOS、TREM-1、IL-1Ra对重度细菌感染性肠炎的诊断价值。结果120例细菌感染性肠炎患者共检出176株病原菌,其中氏阳性菌38株(21.59%),革兰阴性菌138株(78.41%)。4组血清PCT、CRP、iNOS、TREM-1、IL-1Ra水平比较,差异均有统计学意义(P<0.05);重度组、中度组、轻度组和对照组依次降低(P<0.05)。Pearson相关性分析结果显示,iNOS、TREM-1、IL-1Ra水平与PCT、CRP水平均呈正相关(P<0.05)。ROC曲线分析结果显示,iNOS最佳截断值为50.07 ng/L,诊断重度细菌感染性肠炎的敏感性和特异性分别为76.92%(95%CI:0.462,0.950)、81.31%(95%CI:0.726,0.882);TREM-1最佳截断值为70.11 pg/mL,诊断的敏感性和特异性分别为84.62%(95%CI:0.546,0.981)、85.05%(95%CI:0.769,0.912);IL-1Ra最佳截断值为271.75 ng/L,诊断的敏感性和特异性分别为92.31%(95%CI:0.640,0.998)、66.36%(95%CI:0.566,0.752)。结论细菌感染性肠炎患者血清iNOS、TREM-1、IL-1Ra表达升高,与患者病情严重程度存在相关性;三者在诊断重度细菌感染性肠炎方面具有良好的诊断价值,或可作为临床评估细菌感染性肠炎病情的潜在指标。