Brain endothelial cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in aging and neurodegeneration

The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.

Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.

Expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients:A retrospective study

Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon-stimulated genes(ISGs),including PKR,OAS1,MX1,and ISG15,in peripheral blood mononuclear cells of 45 COVID-19 patients with different severities were evaluated by real-time PCR method.Results:OAS1,MX1,PKR,and ISG15 were differently expressed in COVID-19 patients with different severity.The results showed that the expression of OAS1,MX1,PKR,and ISG15 genes was significantly(P=0.001)lower in severe patients.Conclusions:Weak and defective IFN response and subsequent disruption of ISGs may be associated with COVID-19 severity.

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.

Role of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in diabetes and its complications

Diabetes mellitus(DM)is one of the major causes of mortality worldwide,with inflammation being an important factor in its onset and development.This review summarizes the specific mechanisms of the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway in mediating inflammatory responses.Furthermore,it compre-hensively presents related research progress and the subsequent involvement of this pathway in the pathogenesis of early-stage DM,diabetic gastroenteropathy,diabetic cardiomyopathy,non-alcoholic fatty liver disease,and other complic-ations.Additionally,the role of cGAS-STING in autonomic dysfunction and intes-tinal dysregulation,which can lead to digestive complications,has been discuss-ed.Altogether,this study provides a comprehensive analysis of the research advances regarding the cGAS-STING pathway-targeted therapeutic agents and the prospects for their application in the precision treatment of DM.

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.

Effect of neuropeptide Y on white matter demyelination and serum interleukin-4 and gamma-interferon levels in the guinea pig with experimental allergic encephalomyelitis

BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to abnormal OBJECTIVE： To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 （IL-4） and gamma-interferon （IFN-γ ）, as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING： A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS： Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. METHODS： Thirty guinea pigs were randomly divided into three groups： normal control group, EAE model group, and NPY intervention group （n =10 per group）. Normal control group and EAE model group： Saline （10μ L, once） was injected into the lateral cerebral ventricle. After one week, the same volume of Freund＇s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group： EAE was modeled after one week and NPY was injected （10 μ L of 6 nmol NPY, once） into the lateral cerebral ventricle. Myelin basic protein （MBP） antigen made from rat spinal cord homogenate and Freund＇s adjuvant complete were injected subcutaneously into both post-palms （0.2 mL per palm） to establish the EAE model. MAIN OUTCOME MEASURES： White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESULTS： Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention group during the high-frequent EAE stage （P 〈 0.01）, but the serum IFN-γ level was decreased （P 〈 0.01）. Furthermore, the EAE latency was prolonged （P 〈 0.01）, the neurological scores were decreased in the high-frequent EAE stage （P 〈 0.01）, and the death rate was decreased （P 〈 0.05）. NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase （r =0.863-0.900, P 〈 0.01）, but negatively correlated with neurological scores at the peak stage （r=- -0.068 to -0.863, P 〈 0.05-0.01）. The IFN-γ level at the peak stage was negatively correlated to that in the latent phase （r = -0.683-0.650, P 〈 0.05）, but positively correlated to neurological scores at the peak stage （r =0.975, 0.845, P 〈 0.05）. CONCLUSION： NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack in an experimental model of EAE.

Clinical Efficacy and Incidence of Adverse Reactions of Entecavir Combined with Long-Acting Interferon in Treating Hepatitis B

Objective:To explore and analyze the clinical efficacy and incidence of adverse reactions of entecavir combined with long-acting interferon in treating hepatitis B.Methods:The study was conducted from January 2020 to December 2022,and the research subjects were 69 hepatitis B patients admitted to our hospital.The patients were divided into a research group(n=35)and a control group(n=34).Patients in the control group were treated with entecavir,while patients in the study group were treated with entecavir combined with long-acting interferon.The antiviral efficacy,liver function indicators,clinical effectiveness,and incidence of adverse reactions were compared between the two groups.Results:The HBV-DNA negative conversion rate and HBeAg seroconversion rate of the patients in the study group were higher than those of the control group,and the virological breakthrough rate was lower than that of the control group(P<0.05);the alanine transaminase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)levels of the patients in the study group were all lower after treatment.In the control group,the albumin(ALB)level was higher than that in the control group(P<0.05).The clinical effective rate of patients in the study group was higher than that in the control group(P<0.05);there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The treatment effect of entecavir combined with long-acting interferon in patients with hepatitis B is significant.It can effectively antiviral and improve the liver function of patients.The incidence of adverse reactions is low and can be promoted and applied.

Predictive Value of Serum pgRNA on HBeAg Clearance in Patients with Chronic Hepatitis B with Low HBeAg Levels Treated with Pegylated Interferon

Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis B patients with HBeAg positive and quantitative<50S/CO were selected for this study.The subjects underwent pegylated interferon therapy for 48-96 weeks and were followed up in the outpatient clinic after treatment.The patients were then divided into groups based on whether their HbeAg turned negative.The predictive ability of each indicator for HBeAg negative conversion was evaluated in the HBeAg negative group and the HBeAg positive group.Results:The results of logistic regression analysis suggested that pgRNA and HBcrAg were better indicators for predicting the clearance of HBeAg after treatment.Conclusion:For patients with chronic hepatitis B with low HBeAg levels,pgRNA is a good indicator in predicting HBeAg clearance during pegylated interferon therapy.

慢加急性乙型肝炎肝衰竭患者细菌感染病原菌分布及血清PCT、IFN-γ和IL-6水平变化分析

目的调查慢加急性乙型肝炎肝衰竭(HBV-ACLF)患者细菌感染病原菌分布特征,分析血清降钙素原(PCT)、干扰素-γ(IFN-γ)和白细胞介素-6(IL-6)水平预测细菌感染的效能。方法2019年12月~2023年1月我院收治的HBV-ACLF患者86例,常规分离和鉴定菌种,采用电化学发光免疫法检测血清PCT水平,采用ELISA法检测血清IFN-γ和IL-6水平,应用受试者工作特征(ROC)曲线评估血清指标联合预测HBV-ACLF患者发生细菌感染的效能。结果本组发生细菌感染者37例,未发生明确感染者49例;在37例HBV-ACLF并发细菌感染患者中,共检出68株感染病原菌,其中革兰氏阴性菌41株(60.3%),革兰氏阳性菌27株(39.7%);感染组血清PCT、IFN-γ和IL-6水平分别为(10.9±3.1)μg/L、(46.5±1.9)pg/mL和(16.9±1.6)pg/mL,均显著高于未感染组【分别为(0.9±0.1)μg/L、(20.1±2.4)pg/mL和(4.8±0.9)pg/mL,P<0.05】,28 d和90 d病死率分别为67.6%和75.7%,均显著高于未感染组(分别为8.2%和12.2%,P<0.05);经ROC分析显示,分别以PCT>3.3μg/L、IFN-γ>45.5 pg/mL和IL-6>15.4pg/mL为截断点,其联合预测HBV-ACLF患者并发细菌感染的曲线下面积(AUC)为0.874,诊断的灵敏度为93.6%,特异度为84.1%。结论HBV-ACLF患者细菌感染的病原菌分布具有一定的特征性,以革兰氏阴性菌感染为主,除检测血清PCT水平外,监测血清IFN-γ和IL-6水平可能有助于早期发现细菌感染而给予预防性处理,或能提供生存率。

Construction of Fluorescence Sensing Platform on the Basis of Carbon Nitride Nanosheet for the Detection of Interferon-γ

Purpose: Interferon-γ (INF-γ) is a cytokine that participates in the immune reaction of the body. Its level of secretion can reflect the immune response condition after the body is infected by pathogens, which is a significant indication of clinically-related diseases. Therefore, it is of great significance in application to develop a fluorescence biosensor to inspect INF-γ with rapidness, high sensitivity and high practicability. Method: The fluorescence sensor is made on the basis of the two-dimensional nano-material namely Carbon Nitride Nanosheet (CNNS) and the Aptamer probe to identify INF-γ (Apt&reg;INF-γ). CNNS can quickly quench the Cy5 fluorescent dye modified on the Apt&reg;INF-γ probe due to the Photoinduced Electron Transfer (PET), but when the INF-γ exists, Apt&reg;INF-γ specifically identifies and combines it. The complex of Apt&reg;INF-γ and INF-γ is away from CNNS, which can effectively block the fluorescent signal of Apt?INF-γ being quenched by CNNS. Result: The sensitive detection of IFN-γ protein can be achieved through the application of CNNS/Apt&reg;INF-γ fluorescence sensing platform. In this method, the intensity of the fluorescent signal is positively correlated with the concentration of IFN-γ, of which the liner response range is 0.5 - 100 ng/mL and the limit of detection is 0.303 ng/mL. In addition, this fluorescence sensing platform has the advantages of high specificity, simple operation and low costs. It can inspect the content of IFN-γ in clinical serum samples without interference. The actual recovery rate of serum samples is 97.11% - 106.96%. Conclusion: Therefore, the CNNS/Apt&reg;INF-γ sensing platform is expected to be implemented in the actual clinical detection, also conducive to developing a universal fluorescence biosensor to inspect other target materials.

TB-DNA、IGRAs、TB-Ab在肺结核中的诊断价值

目的探究结核分枝杆菌核酸(TB-DNA)、γ-干扰素释放试验(IGRAs)和结核分歧杆菌抗体(TB-Ab)检测在肺结核中的诊断价值。方法收集2022年6月至2023年1月莆田学院附属医院收治的154例疑似肺结核患者,所有患者均接受TB-DNA、IGRAs和TB-Ab检测,评价不同检测方法的检测阳性率、诊断肺结核的灵敏度、特异度、阳性预测值、阴性预测值及诊断准确率;采用受试者工作特征曲线(ROC)评估不同检测方法对肺结核的诊断效能。结果154例疑似肺结核患者中,107例确诊为肺结核(肺结核组),47例确诊为非肺结核的其他肺部疾病(对照组)。肺结核组TB-DNA、IGRAs和TB-Ab阳性率均高于对照组,差异有统计学意义(P<0.05)。TB-DNA、IGRAs检测诊断肺结核的灵敏度和诊断准确率均高于TB-Ab检测,差异有统计学意义(P<0.05),TB-DNA检测诊断肺结核的阴性预测值高于TB-Ab检测,差异有统计学意义(P<0.05)。ROC曲线分析结果显示,TB-DNA诊断肺结核的AUC为0.851(明显大于IGRAs诊断的0.770)、TB-Ab诊断的0.770,IGRAs诊断的AUC明显大于TB-Ab,差异均有统计学意义(P<0.05)。IGRAs+TB-DNA联合诊断的灵敏度、诊断准确率明显高于IGRAs单独检测(P<0.05);IGRAs+TB-Ab联合诊断的灵敏度明显高于IGRAs、TB-Ab单独检测,诊断准确率明显高于TB-Ab单独检测(P<0.05);TB-DNA+TB-Ab联合诊断的灵敏度、阴性预测值、诊断准确率明显高于TB-Ab单独检测(P<0.05)。TB-DNA、IGRAs、TB-Ab两两联合检测和三者联合检测诊断肺结核的灵敏度、特异度、阳性预测值、阴性预测值及诊断准确率比较,差异均无统计学意义(P>0.05)。结论相比TB-Ab和IGRAs检测,TB-DNA检测对肺结核的诊断价值更高;TB-DNA、IGRAs、TB-Ab两两联合检测对肺结核的诊断效能高于单一指标检测。

IFN-α对禽网状内皮组织增殖病病毒体内外增殖的抑制作用

为明确禽源α干扰素(IFN-α)对禽网状内皮组织增殖病病毒(REV)体内外增殖的抑制效果,本试验在细胞和动物水平上分别采用鸡胚成纤维(DF-1)细胞和海兰褐鸡作为模型,于REV接种前(预防)和接种后(治疗)分别添加不同浓度的禽IFN-α处理,分析禽IFN-α在体外和体内对REV增殖的影响。体外试验结果显示,与阳性对照组相比,禽IFN-α浓度为33 IU/mL的治疗组72 h细胞和上清中REV的增殖受到了显著抑制(P<0.05),禽IFN-α浓度为33 IU/mL的预防组72 h细胞中REV的增殖受到了显著抑制(P<0.05)。通过比较各组海兰褐鸡的平均体重、血液中REV阳性率和病毒载量、泄殖腔REV阳性率和排毒量、免疫器官指数和病毒载量系统评估禽IFN-α对REV体内增殖的影响,结果显示,与阳性对照组相比,禽IFN-α浓度为1 500 IU的治疗组海兰褐鸡21和28日龄时体重显著升高(P<0.05),14日龄时肝脏发育指数以及14和28日龄时的脾脏发育指数显著降低(P<0.05),14日龄时血液和脾脏中病毒载量显著降低(P<0.05),7和21日龄时泄殖腔排毒量显著降低(P<0.05)。本试验在体外细胞和体内动物2个层面均证实了禽IFN-α对REV增殖具有显著的抑制效果,这不仅为禽网状内皮组织增殖病的防控策略提供了新的思路和辅助手段,也为未来抗病毒药物的研发和应用提供了科学依据。

激光联合干扰素治疗对阴道上皮内瘤变患者阴道微生态、炎症因子及预后的影响

目的分析激光联合干扰素对阴道上皮内瘤变(VAIN)患者的阴道微生态、炎症因子以及预后的影响。方法60例VAIN患者,按随机数字表法分为对照组和研究组,每组30例。对照组患者通过二氧化碳(CO_(2))激光治疗,研究组患者通过CO_(2)激光联合干扰素治疗。比较两组患者临床治疗效果;并发症发生情况;治疗前后炎症因子指标[肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、Toll样受体2(TLR2)];生存素(Survivin)、增殖细胞核抗原(Ki-67)阳性表达情况。结果研究组患者的临床治疗总有效率96.67%高于对照组的73.33%,差异有统计学意义(P<0.05)。治疗后,研究组患者的TNF-α(9.66±0.43)ng/L、IL-10(8.83±0.54)ng/L、TLR2(6.31±0.29)ng/L均低于对照组的(12.09±0.78)、(10.79±1.36)、(7.95±0.46)ng/L,差异有统计学意义(P<0.05)。治疗后,研究组患者Survivin阳性表达率(24.45±2.97)%、Ki-67阳性表达率(20.71±2.49)%低于对照组的(36.21±3.96)、(40.58±3.83)%,差异有统计学意义(P<0.05)。研究组并发症发生率为6.67%(2/30),与对照组的10.00%(3/30)比较,差异无统计学意义(P>0.05)。结论针对VAIN患者给予VAIN患者激光联合干扰素治疗的临床效果更佳,能够有效改善炎症因子指标及Survivin、Ki-67表达情况,减少患者并发症的发生,值得推广应用。

IRF8靶向铁死亡在急性肺损伤中的作用及机制研究

目的探讨干扰素调节因子8(interferon regulatory factor 8,IRF8)在急性肺损伤(acute lung injury,ALI)中的作用及其机制。方法采用实时荧光定量逆转录聚合酶链反应(RT-qPCR)和蛋白免疫印迹(WB)检测体内外ALI模型中IRF8 mRNA和蛋白的表达。体外构建稳定过表达和敲低IRF8的A549细胞系,采用RT-qPCR检测炎症相关基因mRNA的表达;WB检测凋亡相关基因的表达。分别选取12只同窝阴性对照小鼠和12只Irf8敲除品系小鼠,构建ALI模型,收集造模后的小鼠肺组织并称重;收集并检测肺泡灌洗液中总细胞数以及总蛋白含量。采用苏木精-伊红染色及免疫荧光分析肺组织炎症浸润情况;利用RT-qPCR检测Irf8敲除小鼠肺组织炎症相关基因mRNA的表达;TUNEL染色分析肺组织凋亡情况;采用WB分别在体内外ALI模型中检测铁死亡相关信号分子的蛋白表达。结果IRF8在体内体外ALI中表达上调;体外敲低IRF8加剧细胞内炎症以及细胞凋亡,反之,过表达IRF8可在体外ALI模型中发挥保护作用;敲除Irf8加重小鼠肺损伤;进一步机制探索发现IRF8通过调控铁死亡相关信号分子表达从而减轻肺损伤。结论IRF8通过靶向铁死亡在肺损伤中发挥保护作用,为肺损伤的治疗提供潜在靶点。

小鼠白癜风疾病模型的构建及初步研究

目的比较氢醌乳膏和莫诺苯宗乳膏诱导野生型C57BL/6J小鼠产生白癜风样表型的作用,构建组织病理学相似度高、脱色效果持久稳定且成本低、易操作的白癜风样小鼠模型,为选择白癜风疾病动物模型以研究人类白癜风疾病的发病机制以及药物治疗效果、药物作用机制提供依据。方法将30只C57BL/6J小鼠随机分为3组,每组10只。3组小鼠于背部相同部位去毛后,对照组涂抹乳膏基质,莫诺苯宗组涂抹40%莫诺苯宗乳膏,氢醌组涂抹2.5%氢醌乳膏,均1次/d,建模周期为50 d。肉眼观察造模部位皮肤变化;建模结束后处死各组小鼠,取病变部位皮肤组织,进行酪氨酸酶(TYR)免疫荧光染色观察;摘眼球取血,ELISA法检测血清中TYR、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)水平。结果莫诺苯宗组和氢醌组小鼠均出现明显皮肤脱色,TYR表达平均光密度值明显降低。莫诺苯宗组和氢醌组小鼠血清TYR水平均明显低于对照组(P均<0.05),莫诺苯宗组和氢醌组比较差异无统计学意义(P>0.05);氢醌组小鼠血清IFN-γ、MMP-9水平均明显高于对照组和莫诺苯宗组(P均<0.05),血清TNF-α水平与对照组比较差异无统计学意义(P>0.05);莫诺苯宗组小鼠血清TNF-α水平明显高于对照组(P均<0.05),血清IFN-γ、MMP-9水平与对照组比较差异均无统计学意义(P均>0.05)。结论2.5%氢醌乳膏和40%莫诺苯宗乳膏涂抹法均可成功建立野生型C57BL/6J小鼠白癜风模型,其中2.5%氢醌乳膏更易诱导建立白癜风表观模型。

IFN-γ、MMP-9水平在肺结核中的表达及与其病情活动性的相关性

目的 分析血清干扰素-γ(IFN-γ)、基质金属蛋白酶-9(MMP-9)水平在肺结核患者中的表达及与其病情活动性的相关性。方法 选取2019年1至2022年12月新乡医学院第一附属医院收治的264例疑似肺结核患者作为研究对象,经确诊后分为结核组(n=204例)及非结核组(n=60例),根据病情活动情况将结核组分为活动性肺结核组(n=86例)及非活动性肺结核组(n=118例),另选取同期于本院进行健康体检者80名为健康组。比较结核组、非结核组、健康组与结核组中活动性肺结核组、非活动性肺结核组及活动性肺结核中轻症组、重症组间血清IFN-γ、MMP-9水平;分析IFN-γ、MMP-9单一及联合检测肺结核的诊断效能;采用多元Logistic回归分析影响活动性肺结核患者病情程度的相关性因素。结果 三组血清IFN-γ、MMP-9水平比较:结核组>非结核组>健康组,差异具有统计学意义(P<0.05);活动性肺结核患者血清IFN-γ、MMP-9水平均显著高于非活动性肺结核,差异有统计学意义(P<0.05);86例活动性肺结核患者中轻症54例,重症32例。重症患者病程比轻症患者长,吸烟比例及血清IFN-γ、MMP-9水平均显著高于轻症患者,差异有统计学意义(P<0.05);IFN-γ、MMP-9联合诊断肺结核的灵敏度、特异度、准确度分别为93.55%、61.54%、84.09%,均高于三者单独检测(P<0.05);经Logistic回归分析,吸烟、血清IFN-γ及MMP-9均为影响活动性肺结核患者病情程度的相关因素(P<0.05)。结论 肺结核患者血清IFN-γ及MMP-9水平显著升高,二者联合对肺结核具有较好的诊断效能,且为影响活动性肺结核病情严重程度的重要影响因素,对肺结核病情评估具有重要价值。

不同检测系统D-二聚体内源性干扰物最大抗干扰能力分析

目的对不同检测系统的D-二聚体检测时可接受的最大干扰物浓度进行分析、比较。方法随机收集50份患者样本,利用SYSMEX干扰物检测试剂盒4种干扰物胆红素F、胆红素C、溶血血红蛋白、乳糜分别与患者血浆按一定比例稀释,稀释后血浆所含干扰物质浓度与两种检测系统试剂说明书中抗干扰物最大浓度接近,分别在两种检测系统上机检测。结果当干扰物胆红素F浓度达到D-dimer HS及AcuSTAR D-dimer两种检测系统抗干扰Max浓度时,相对偏差<10%的结果占比分别为26%、46%;当干扰物胆红素C浓度达到D-dimer HS及AcuSTAR D-dimer两种检测系统抗干扰Max浓度时,相对偏差<10%的结果占比分别为18%、86%;当干扰物溶血血红蛋白浓度达到D-dimer HS及AcuSTAR D-dimer两种检测系统抗干扰Max浓度时,相对偏差<10%的结果占比分别为44%、88%;当干扰物乳糜浓度达到D-dimer HS及AcuSTAR D-dimer两种检测系统抗干扰Max浓度时,相对偏差<10%的结果占比分别为30%、58%。结论在检测D-二聚体时化学发光法抵抗高浓度内源性干扰物质能力优于免疫比浊法。