Objective To study the immune intervention effect and mechanism of blockage of macrophage-mediated PD1 /PD-L1 pathways with functional PD-L1(programmed cell death ligand-1,PD-L1)monoclonal antibody upon tuberculosis(TB)relapse in mice. Methods Female C57BL/6 mice were infected by tail vein injection of 106CFU M. tuberculosis H37Rv to obtain active TB infection. Two weeks postinfection, the mice in different groups were administered isoniazid(10 mg/kg)(group ISO)and isoniazid combined with PD-L1 monoclonal antibody(50 μg/each)(group ISO+PD-L1)respectively,continued for four weeks to obtain latent infection. The subsequent relapse was monitored. Among the treatment groups,the TB relapse was induced by TNF-α antibody(50 ug/each)for four weeks from the beginning of latent stage. At each scheduled time point, bacterial loads and pathological changes in the lung, spleen and liver were quantitatively analyzed,thereby,the in vivo intervention effect of PD-L1 monoclonal antibody on tuberculosis recurrence in mice was revealed. The in vitro experiment was further explored whether knock-down the expression of PD-L1 on the infected macrophages could accerlate the macrophage apoptosis. Results The bacterial burden reached 3-4 Lg(CFU/mL),and granuloma lesions were extensive in the lung, spleen and liver in the all infected groups, which appeared as active TB stage at 2nd week postinfection. After treated,the bacterial burden of the lung,spleen and liver was decreased, and the pathological lesions alleviated in the group ISO and group ISO+PD-L1, compared with the model control group, showing significant differences, but there was no significant difference between the two treatment groups. However, compared with the group ISO,the group ISO+PD-L1 had a significantly lower bacterial load and milder pathological lesions during the relapse period. Futhermore, knock-down the expression of PD-L1 on macrophages with anti-PD-L1 or PD-L1-siRNA promoted apoptosis in macrophages. Conclusions Blockade of the PD1/PD-L1 pathway by PD-L1 functional antibody can inhibit TB relapse in mice,and knock-down the expression of PD-L1 on macrophages or PD1/PD-L1 pathway with functional antibody can promote apoptosis in macrophages,which together indicate that PD-L1 blockage can effectively promote isoniazid treatment of TB and remarkably inhibit the recurrence of TB in mice.

Objective TNF-α monoclonal antibody drugs are widely used to treat conditions such as rheumatic arthritis and ankylosing spondylitis. On the other hand, it is also a wide concern that the application of these drugs may increase the susceptibility of patients to infections such as tuberculosis and listeriosis. The aim of this study was to establish a mouse model of Listeria monocytogenes infection and to evaluate the effect of TNF-α monoclonal antibody on the host susceptibility to this infection. Methods Six SPF 14-week old female C57BL/6 mice and 12 SPF 14-week old female TNF-α humanized mice were injected with saline or adalimumab intravenously, and challenged with intraperitoneal injection of 104 CFU Listeria monocytogenes 24 h later. After one day or 4 days, the mice were sacrificed to examine the pathological lesions and the bacterial load in the spleen and liver. Results Four days after infection, the area of microabscess in the liver tissues was significantly increased in the adalimumab-treated group. The bacterial load in the spleen and liver tissues of the adalimumab-treated group was significantly higher than that of the C57BL/6 mouse control group and TNF-α humanized mouse control group (P ＜ 0. 05). However, the distribution of macrophages in the liver tissues and B cells in the spleen tissues were similar among groups. Conclusions TNF-α plays an important role in the host immune responses to Listeria monocytogenes infection. After the intervention with TNF-α monoclonal antibody, the progress of host disease is significantly exacerbated.

Objective:To explore the efficacy and clinical significance of Eltrombopag combined with immunosuppression therapy(IST) in the treatment of severe aplastic anemia (SAA) in children.Methods:Clinical data of 63 children with initially diagnosed SAA in the Department of Hematology of Xinxiang Central Hospital from May 2017 to June 2019 were retrospectively analyzed.All of them were all donors without siblings and they were classified into observation group (31 cases) and control group (32 cases). Patients in the observation group received IST combined with Eltrombopag treatment, and those in the control group received IST treatment.The Chi- square test was used to compare the overall remission (OR) rate and complete remission (CR) rate at 3 months, 6 months and 12 months, and incidence of infection and significant bleeding between groups.The t-test was used to compare the application of gra-nulocyte colony stimulating factor, the mean red blood cell transfusion, and the mean platelet infusion volume between groups.Kaplan-Meier method was adopted to analyze the 2-year overall survival (OS) rate and failure-free survival (FFS) rate, followed by the Log- rank test. Results:The 3-month and 6-month OR rate of the observation group were 61.29%(19/31 cases) and 80.64% (25/31 cases), respectively, which was significantly higher than that of the control group [37.50%(12/32 cases) and 59.38%(19/32 cases), χ2=45.27, 43.81, respectively, all P<0.05]. The 3-month and 6-month CR rate of the observation group were 32.26%(10/31 cases) and 45.16%(14 /31 cases), respectively, which was significantly higher than that of the control group [15.62%(5/32 cases) and 28.13%(9/32 cases), χ2=47.02, 48.35, respectively, all P<0.05]. The 12-month OR rate and CR rate in the observation group were 83.87%(26/31 cases), and 64.52%(20/31 cases), respectively, which were 81.25%(26/32 cases), and 59.38%(19/32 cases), respectively in the control group, and no significant differences in them were detected between the two groups (all P>0.05). The total amount of granulocyte colony stimulating factors [(13.58±4.28) doses vs.(23.24±6.68) doses, t=2.591], and the mean infusion volume of red blood cells [(5.48±1.67) U vs.(10.58±3.67) U, t=2.040] and platelets (4.15±2.47) bags vs.(9.15±3.87) bags, t=2.744) used in observation group within 6 months of treatment were significantly lower than those of the control group (all P<0.05). The rate of infection (16.13% vs.43.75%, χ2=47.12) and significant bleeding (16.13% vs.37.50%, χ2=44.52) in the observation group were significantly lower than those of the control group (all P<0.05). The 2-year OS rate of the observation group and control group were 93.55% (29/31 cases), and 87.50% (28/32 cases), respectively.No significant difference in the OS rate was found between groups ( P=0.407 3), nor as the 2-year FFS rate(87.10% vs.78.13%, P=0.326 6). Conclusions:IST combined with Eltrombopag can significantly improve the early treatment response rate of SAA children without a sibling identical donor, which can reduce red blood cell and platelet transfusion, and the incidence of infection and bleeding.

Objective:To investigate the expression of IL-18, IL-18-binding protein a(IL-18BPa) and IL-18 receptor α(IL-18Rα) by peripheral blood CD4 + Th17 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expression. Methods:This study enrolled 45 outpatients with AR and 23 healthy control subjects receiving physical examination in the First Affiliated Hospital of Jinzhou Medical University from October 2019 to September 2020. According to the results of skin prick test, the 45 patients were divided into two groups: AR group with positive results (24 cases) and nAR group with negative results (21 cases). Blood samples of them were collected. Flow cytometry was used to analyze the effects of allergens on the expression of IL-18, IL-18BPa and IL-18Rα at protein level by peripheral blood CD4 + Th17 cells. The level of IL-17A in plasma was measured by Bioplex system, and its correlation with the percentage of IL-18 + Th17 cells was analyzed. Results:Compared with the healthy control group, the AR group showed increased ratios of CD4 + Th17 and IL-18 + Th17 cells ( P<0.01), decreased ratio of IL-18BPa + Th17 cells ( P<0.01), enhanced mean fluorescence intensity (MFI) of IL-18BPa ( P<0.01) and reduced MFI of IL-18Rα ( P<0.01); the nAR group showed enhanced MFI of IL-18BPa ( P<0.000 1) and reduced MFI of IL-18Rα ( P<0.000 1). The ratio of IL-18 + Th17 cells and the MFI of IL-18Rα in the AR group were higher than those in the nAR group ( P<0.05, P<0.01). House dust mite extract and Platanus pollen extract induced the expression of IL-18 and IL-18BPa by CD4 + Th17 cells of AR patients ( P<0.05). Moreover, house dust mite extract directly induced the CD4 + Th17 cells isolated from the healthy control subjects to express IL-18 and IL-18R ( P<0.05). Compared with healthy control subjects, AR patients had higher level of IL-17A in plasma and it was moderately correlated with the ratio of IL-18 + Th17 cells ( P<0.05). Conclusions:Allergens may be involved in the pathogenesis of AR by inducing blood CD4 + Th17 cells to express IL-18 and IL-18Rα.

Objective To investigate the correlation between the location of ruptured intracranial vertebral artery dissecting aneurysm (VADA)and the outcome after endovascular treatment. Methods Thirty-six patients with ruptured intracranial VADA undergoing endovascular treatment were enrolled retrospectively. According to the relationship between VADA and the location of the opening of posterior inferior cerebellar artery(PICA),they were divided into 3 groups:proximal to PICA group (n=13), distal to PICA group (n=13),and PICA involvement group (n=10). The demographic data, vascular risk factors, clinical features, imaging features, endovascular treatment mode, postoperative complications, and differece of the good outcome rate(defined as the modified Rankin scale 0-2)after 6 months of treatment were compared.Results Seven patients in the proximal to PICA group received reconstructive endovascular treatment (RET), and 6 received endovascular internal trapping(EIT);the good outcome rate was 100%(13/13).Seven patients in the distal to PICA group received RET,6 were treated with EIT;the good outcome rate was 84.6%(11/13).Four patients in the PICA involvement group received RET,and 6 received EIT,and 2 of them received contralateral vertebral artery retrograde PICA stenting combined with VADA segment and proximal vertebral artery coil embolization;the good outcome rate was 60.0%(6/10). There were significant differences in the overall outcome good rate among the 3 groups (P<0.05). The good outcome rate in the PICA involvement group was significant lower than that in the proximal to PICA group,and significantly lower than that in the proximal to PICA combined with distal to PICA group(P<0.05).Multivariate logistic regression analysis showed that only Fisher grade 3-4 was the independent risk factor for poor outcome (odds ratio 28.0, 95% confidence interval 1.71-458.82; P=0.020). Conclusions The surgical options of endovascular treatment for ruptured intracranial VADA needs to evaluate the relationship between the location of dissecting aneurysms and the PICA origin. The risk of endovascular treatment in patients with intracranial VADA involving the origin of PICA is higher and it may affect the outcome.

Sepsis is a life-threatening organ dysfunction,which is caused by the body's uncontrolled immune response to infection.Tissue masts cells(MC),derived from blood mast cell progenitors,are one of the classical effector cells in inflammatory response.MC plays an important role in sepsis via secreting a variety of inflammatory mediators and cytokines.Here,we summarized the potential roles of MC in sepsis,which is expected to provide novel ideas for the future research on the novel mechanisms of MC in sepsis.

OBJECTIVE: To analyze the prognosis of fetuses with cystic hygroma (CH) or nuchal translucency (NT) or nuchal fold (NF) thickening detected by prenatal echography. METHODS: From January 2014 to December 2015, 124 fetuses with CH and NT/NF thickening on prenatal echography were enrolled from Women's Hospital of Zhejiang University School of Medicine. The basic clinical information, ultrasonic results, pregnancy outcomes and newborn follow-ups were analyzed. The cases were grouped by prognosis and the factors affecting prognosis were analyzed with logistic regression. RESULTS: There were 85 cases of labor induction including one stillbirth and 39 cases delivered. Except one infant who died after birth, all live births survived with good prognosis. Univariate analysis showed that the gestational age at diagnosis of poor prognosis group was earlier than that of good prognosis group (<0.01); and the former group also had higher hydrops fetalis rate and additional structural anomalies rate (all <0.01). Multivariate regression analysis showed that hydrops fetalis (=90.105, <0.05) and additional structural anomalies (=61.854, <0.05) were risk factors of poor prognosis in fetuses with CH and NT/NF thickening. CONCLUSIONS Fetuses with diagnosed CH or NT/NF thickening on prenatal ultrasonography are likely to be associated with chromosomal abnormality. Early gestational weeks, hydrops fetalis and additional structural anomalies may indicate poor prognosis.
Female ; Fetus ; Humans ; Hydrops Fetalis ; etiology ; Infant, Newborn ; Lymphangioma, Cystic ; complications ; diagnosis ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy Outcome ; Prognosis ; Ultrasonography, Prenatal

Objective To investigate the effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα protein in peripheral blood CD4+Th1 cells of healthy control subjects(HC)and patients with allergic rhi-nitis(AR),and on the expressions of IL-18,IL-18BPa and IL-18Rα mRNA in the peripheral blood CD4+T cells.Methods Blood samples were collected from patients with rhinitis for negative skin prick test(AR-),rhinitis for positive skin prick test(AR+)and HC.Flow cytometry was used to evaluate the effects of allergens on the expres-sions of IL-18,IL-18BPa and IL-18Rα protein in CD4+Th1 cells.The expressions of IL-18,IL-18BPa and IL-18Rα mRNA in CD4+T cells were determined by qPCR.Results Compared with HC,increased IL-18 while de-creased IL-18BPa expressions in Th1 cells of AR-and AR+patients were observed,increased IL-18Rα expression in Th1 cells of AR+patients was also found.Additionally,allergens induced elevated expression of IL-18Rα pro-tein in Th1 cells of HC,and induced elevated mRNA expressions of IL-18,IL-18BPa and IL-18Rα in isolated blood CD4+T cells of AR+patients and HC.Conclusion Allergens may be involved in the pathogenesis of AR by inducing the expressions of IL-18 and IL-18Rα in blood CD4+Th1 cells.