Analysis of Pathogenic Bacteria of Mooren’s Ulcer and T Lymphocyte Activation

2022 ◽  
Vol 12 (1) ◽  
pp. 28-35
Author(s):  
Yafang Zhao ◽  
Lizhi Zhang ◽  
Tao Jin ◽  
Yincong Xu ◽  
Lin Shi ◽  
...  

To analyze the distribution and types of pathogenic bacteria of Mooren’s ulcer and the activation mechanism of T lymphocytes to provide reference for the treatment of Mooren’s ulcer, 156 patients (162 eyes) who were in the hospital were rolled into the observation group. During the same period, 134 healthy people were rolled into the control group. The distribution of infectious pathogens in the observation group was identified. Then, flow cytometry was adopted to separate and detect the peripheral blood lymphocytes of patients, and RT-PCR was used to detect levels of the transcription factor T-bet, GATA-3, and Stat5 in peripheral blood mononuclear cells (PBMCs). It was found that fungal pathogens accounted for 43.59%; the bacterial infection rate was 40.38%. In the observation group, the CD4, CD8, and C25 were expressed more (P < 0.01), and the CD45 and CD45R were expressed less than the control group (P < 0.05); the proportion of Th1 cells was obviously higher (P < 0.01); the expression of T-bet and GATA-3 was obviously higher (P < 0.05), the percentage of HLA-DR in CD4+ and HLA-DR, CD-25, and CD69 in CD8+ positive cells was obviously higher (P < 0.05). In conclusion, fungal infection rate of Mooren’s ulcer is relatively high, peripheral blood T cells and their subgroups are abnormally activated, and T cell activation is related to the pathogenesis of Mooren’s ulcer.

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Xiaoyan Chen ◽  
Fan Zhu ◽  
Bin Wang ◽  
Yu Zhou ◽  
Hao Xiong ◽  
...  

Objective. To investigate the clinical effect of iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer and the effect on peripheral blood Th1/Th2 cells. Methods. A total of 136 patients with primary liver cancer from April 2017 to June 2018 were selected as subjects and randomly divided into the control group and observation group with 68 cases in each group. The control group was treated with chemotherapy, and the observation group was treated with iodine-125 seed implantation on the basis of the control group. After 3 months of treatment, the curative effect was investigated. Serum tumor markers, peripheral blood Th1/Th2 cells, and side effects and recurrence rate were compared between the two groups. Results. The levels of serum tumor markers in both groups at 3 months after treatment were lower than before treatment ( P < 0.05 ). Three months after treatment, the levels of tumor markers AFP, AFP-L3, and GP73 in the observation group were 14.61 ± 3.49 μg/L, 3.29 ± 0.41 ng/mL, and 51.24 ± 4.51 μg/L, respectively, which were lower than those in the control group, 32.53 ± 4.59 μg/L, 5.63 ± 0.63 ng/mL, and 71.52 ± 6.05 μg/L ( P < 0.05 ). At 3 months after treatment, the level of including interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) in Th1 cells of the observation group was higher than that of the control group ( P < 0.05 ), whereas the levels of IL-4, IL-6, and IL-10 in Th2 cells were lower than those in the control group ( P < 0.05 ). There was no statistical significance in the incidence of leukopenia, thrombocytopenia, and gastrointestinal reactions between the two groups ( P > 0.05 ). The recurrence rate of the observation group at 12, 24, and 36 months after treatment was lower than that of the control group ( P < 0.05 ). Conclusion. Iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer can reduce the level of serum tumor markers, improve the level of peripheral blood Th1/Th2 cells, and reduce the recurrence rate of patients without increasing the incidence of side effects, which is worthy of promoting the application of iodine-125 seed implantation.


Blood ◽  
2021 ◽  
Author(s):  
Livius Penter ◽  
Yi Zhang ◽  
Alexandra Savell ◽  
Teddy Huang ◽  
Nicoletta Cieri ◽  
...  

Relapsed myeloid disease after allogeneic stem cell transplantation (HSCT) remains largely incurable. We previously demonstrated the potent activity of immune checkpoint blockade (ICB) in this clinical setting with ipilimumab or nivolumab. To define the molecular and cellular pathways by which CTLA-4 blockade with ipilimumab can reinvigorate an effective graft-versus-leukemia (GvL) response, we integrated transcriptomic analysis of leukemic biopsies with immunophenotypic profiling of matched peripheral blood samples collected from patients treated with ipilimumab following HSCT on the ETCTN 9204 trial. Response to ipilimumab was associated with transcriptomic evidence of increased local CD8+ T cell infiltration and activation. Systemically, ipilimumab decreased naïve and increased memory T cell populations and increased expression of markers of T cell activation and co-stimulation such as PD-1, HLA-DR and ICOS, irrespective of response. However, responding patients were characterized by higher turnover of T cell receptor sequences in peripheral blood and showed increased expression of proinflammatory chemokines in plasma that was further amplified by ipilimumab. Altogether, these data highlight the compositional T cell shifts and inflammatory pathways induced by ipilimumab both locally and systemically that associate with successful GvL outcomes.


2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 26-26
Author(s):  
John Yi ◽  
Jeffrey Melson Clarke ◽  
Patrick Healy ◽  
Xiaofei F. Wang ◽  
Debra Shoemaker ◽  
...  

26 Background: Ipilimumab (Ipi) is a humanized CTLA-4 antibody that blocks binding of CTLA-4 to B7, permitting T cell activation through CD28. Phased in Ipi added to chemotherapy (C) may enhance efficacy in NSCLC. Methods: Patients with stage 2 or 3A NSCLC received neoadjuvant carboplatin AUC6 plus paclitaxel 200 mg/m2 every 21 days for 3 cycles and Ipi (10 mg/kg) was given on day 1 for cycles 2 and 3. Blood for immune profiling of circulating T cells was collected at baseline, after chemotherapy alone, and after chemotherapy plus Ipi. Tumor infiltrating lymphocytes (TIL) were derived from 7 available tumors. Polychromatic flow cytometry (PFC) analyses were performed on peripheral blood mononuclear cells (PBMC) and TIL. Objective response rates were assessed according to RECIST 1.1 criteria. Results: Of the 24 patients enrolled on this study, objective responses after 3 cycles of neoadjuvant C plus ipi included 2 PD, 8 SD, and 14 PR. Phenotypic analyses revealed that PBMC from all 24 patients were highly activated following two cycles of Ipi (cycle 3) as evidenced by significantly increased frequencies of CD28, ICOS, HLA-DR, PD-1, and CTLA-4 expressing CD4+ cells; and ICOS, HLA-DR, and CTLA-4 expressing CD8+ cells. The frequencies of Tregs were highly variable among the 24 participants. Two of the 24 participants had levels of MDSC cells above 15%. TIL contained far greater frequencies of activated CD4+ and CD8+ cells than found in the PBMC at cycle 3. Tumor associated antigen (TAA)-specific CD4+ or CD8+ cells were detected at baseline in 4 patients (24%), but their relative frequencies remained unaltered by Ipi therapy. No patients developed detectable de novo TAA reactivities while on Ipi therapy. Conclusions: Combined neoadjuvant Ipi plus chemotherapy produced significantly increased frequencies of highly activated CD4+ and CD8+ populations in the peripheral blood and the tumor microenvironment. TAA-specific CD4+ or CD8+ cells were detected in PBMC at baseline in a subset of patients. No TAA-reactive T cells were detected among the 7 TIL samples analyzed. Analysis for predictive or pharmacodynamic biomarkers is ongoing. Clinical trial information: NCT01820754.


2019 ◽  
Vol 65 (7) ◽  
pp. 971-976
Author(s):  
Wenyan Fan ◽  
Xiaoyan Li ◽  
Hongming Xu ◽  
Limin Zhao ◽  
Jiali Zhao ◽  
...  

SUMMARY OBJECTIVE To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. METHODS Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. RESULTS The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. CONCLUSIONS The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.


2020 ◽  
Vol 22 (2) ◽  
pp. 347-356
Author(s):  
A. A. Savchenko ◽  
A. G. Borisov ◽  
I. V. Kudryavtsev ◽  
A. V. Moshev

The aim of this work was to reveal the interrelations between the number of T regulatory cells (Tregs) in patients with kidney cancer (KC) and phenotype of peripheral blood monocytes and their capacities to produce ROS. Patients with KC (T3N0M0, clear cell type) were examined prior to surgical treatment. Tregs phenotype and blood monocytes were identified by flow cytometry. ROS production of purified monocytes was carried out through the determination of lucigenin- and luminol-dependent spontaneous and zymosan-induced chemiluminescence activity. It has been found that the relative number of Tregs within total lymphocyte subset in KC patients was increased if compared to control values (in KC patients — Me = 6.3%). Then the patients were divided into two groups according to the median of Tregs number (less and more than 6.3%). The most pronounced changes in the phenotype of monocytes and their chemiluminescent activity were found in KC patients with the Tregs count of less than 6.3%. Our findings suggest that low frequency of Tregs in the periphery was associated with increased relative numbers of “intermediate” and “non-classical” (“pro-inflammatory”) monocytes as it was shown on the samples from patients with KC with a low level of Tregs. According to our data, both groups of KC patients had low levels of HLA-DR expression when comparing to control group. Furthermore, both groups of patients had decreased rates of HLA-DR and CD64 co-expressing cells. Changes in the phenotype of monocytes in patients with KC were closely linked with imbalance in ROS production. Thus, the monocytes spontaneous superoxide radical (primary ROS) synthesis in KC patients with a low Treg numbers were characterized by redused NADPH-oxidase activation time and increased level of its activity if compared to patients with a high Treg rates in peripheral blood. Next, the activation index for lucigenin-dependent chemiluminescence in KC patients was reduced, as well as it was independent of circulating Tregs rates and was determined apparently by the insufficiency of metabolic reserves. Similarly, spontaneous secondary ROS production by the monocytes in KC patients was lower then in healthy controls and was also independent of circulating Tregs rates. Finally, the induced secondary ROS synthesis and activation index for their synthesis in monocytes were reduced only in patients with KC with a low number of Tregs in the blood. In general, the characteristics of the chemiluminescent reaction of monocytes in patients with KC determined the imbalance in peripheral blood monocytes primary and secondary ROS production. Monocytes in patients with KC with a low number of Tregs in the blood were characterized by more pro-inflammatory activity due to the rapid activation and intensity of the synthesis of primary ROS.


2020 ◽  
Vol 22 (5) ◽  
pp. 887-896
Author(s):  
A. A. Savchenko ◽  
A. G. Borisov ◽  
I. V. Kudryavtsev ◽  
I. I. Gvozdev ◽  
A. V. Moshev

The aim of the present study was to analyze the relationships between expression of activation and adhesion receptors on peripheral blood neutrophils, and intracellular activity of some neutrophil enzymes in patients with kidney cancer (KC). Patients and methods: the KC patients (n = 72) (T3N0M0, clear-cell type) were examined prior to surgical treatment at the Krasnoyarsk Regional Oncology Center. The diagnosis was verified histologically for all KC patients. The phenotype of blood neutrophils was studied using flow cytometry. The surface receptor expression levels of the neutrophils were evaluated by mean fluorescence intensity. NAD and NADP-dependent dehydrogenases activities in purified peripheral blood neutrophils were measured by bioluminescent method. Results: we have found that the phenotypic alterations in circulating KC patients’ neutrophils appeared along with inhibition of main intracellular metabolic processes and were closely linked with them. The features of the phenotypic imbalance in the neutrophils from KC patients were associated with a decrease in blood cells expressing adhesive (CD11b and CD62L) and functional (CD64 and HLA-DR) receptors. Moreover, the patient’s neutrophils expressed CD11b, CD16 and HLA-DR on their cell surface more intensively, than neutrophilic leukocytes from control group. These phenotypic changes in KC patients’ blood neutrophils occurred in parallel with pronounced decrease in immature cells numbers. The metabolic changes of neutrophil cytoplasmic compartment in KC patients were determined by a decrease in Glu6PDH activity (a key and initializing enzyme of the pentose phosphate cycle) and NADH-LDH (anaerobic glycolysis). Mitochondrial metabolism in neutrophils of KC patients was characterized by multidirectional changes in the activity of NAD- and NADP-dependent glutamate dehydrogenases (decreased activity of NAD-dependent and increased activity of NADP-dependent) and a decrease in NADH-MDH activity. The established features in mitochondrial enzymes activities suggest some disturbances of NAD-dependent processes that could lead to down-regulation of aerobic energy processes. We guess that the decreased activity of plastic and energy processes in blood neutrophils of KC patients could affect the receptor expression levels. By means of correlation analysis, we have found that the relationships in KC patients were determined by negative effects of NADHGDH and NADH-LDH activities upon expression of activation and adhesion receptors in blood neutrophils. Of these enzymes, only glutathione reductase activity in neutrophils from KC patients was positively linked with the CD23 and HLA-DR expression. Thus, an increase in activity of energy processes (e.g., coupling the tricarboxylic acid cycle to amino acid metabolism) in blood neutrophils from the patients with kidney cancer could stimulate expression levels of activation and adhesion receptors and potentially increase antitumor activity of neutrophils.


2021 ◽  
Vol 10 (1) ◽  
pp. 14
Author(s):  
Dalai Wuyun

<p>Objective: to investigate the effect of clinical pharmacists in ICU. Methods: 108 ICU patients from January 2018 to March 2020 were divided into the control group and the observation group, with 54 cases in each group. The control group used the previous medication route, while the observation group introduced clinical pharmacists to guide clinical medication. The infection rate and adverse reaction rate of the two groups were compared. Results: the infection rate of the observation group was 3.70%, and that of the control group was 14.81%, which was significantly lower than that of the control group (P&lt;0.05). The adverse reaction rate of the observation group was 5.56%, and that of the control group was 18.52%, which was significantly lower than that of the control group (P&lt;0.05). Conclusion: the introduction of clinical pharmacists to guide clinical medication in ICU can effectively control the infection, and reduce various adverse reactions during drug use, so as to realize the scientific and standardized use of drugs, and improve the efficiency and safety of drug use.</p>


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1045.2-1045
Author(s):  
M. Korolev ◽  
Y. Kurochkina ◽  
N. Banshhikova ◽  
V. Omelchenko ◽  
A. Akimova ◽  
...  

Background:Dendritic cells (DCs) are known to contribute to the pathogenesis of different autoimmune diseases. It is clear nowadays the role of DCs in rheumatoid arthritis (RA) but not well investigated in Axial spondylitis (AxSpA). DCs are a heterogeneous population and can be divided into groups: myeloid (mDCs) and plasmacytoid (pDCs). DCs can induce both immune response and tolerance.Objectives:To investigate the subpopulations of peripheral blood myeloid and plasmacytoid DCs in patients with early stage of RA (duration of illness up to 12 months) and AS.Methods:The study include sixty five patients with early forms of diseases including 55 patients with RA and 10 patients with AxSpA. Diagnosis RA was established according ACR/EULAR criteria (2010). Diagnosis AxSpA was established according ASAS criteria. All patients received conventional synthetic DMARDs. Thirty patients with osteoarthritis (OA) used as a control group. Analysis of the content of the B-lymphocytes, myeloid and plasmacytoid DCs was carried out by flow cytometry. B-lymphocytes, subtypes of peripheral blood DCs were characterized by the following phenotypes: myeloid DCs (CD3-CD14-CD19-HLA-DR + CD11c + CD123-), plasmacytoid DCs (CD3-CD14-CD19-HLA-DR + CD11c-CD123 +), B-lymphocytes (CD19 +). Analyses were performed before treatment and after 3 and 6 months.Results:Patients with early RA are characterized by significant evaluation of the population of myeloid DCs in comparison of patients with osteoarthritis (25.3% vs 21.5, p=0.005). Furthermore, the difference was found in the number of cells with the phenotype B-lymphocytes: 5.7% vs 3.1%, p = 0.0007). No significant differences were observed in the number of plasmocytoid DCs. After 3 and 6 month of observation we detected reducing amount of myeloid DCs 26.7% vs 20.1% vs 16.4% respectively. Disease activity according to DAS28 droped to low (4.32 to3.06, p=0.03). Patients with AxSpA are characterized a lower mDCs levels in compared with RA (19.3% vs 26.7, p=0.07). After 6 month of investigation we detected decreasing mDCs (19.3% to 14.2%, p=0.05). The percent of pDCs were constant and did not differ from the level of healthy donors.Conclusion:The data obtained indicate that early form of rheumatic diseases namely rheumatoid arthritis and axial spondylitis have the common features such as the dominance of mDCs and their decreasing in reduction of activity of disease.Disclosure of Interests:None declared


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4702-4702
Author(s):  
Xi Wang ◽  
Feifei Che ◽  
Wanjun Cao ◽  
Zichen Ye ◽  
Hong Zheng ◽  
...  

Abstract Abstract: Objective To investigate the effect of pomalidomide on the maturation of monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients. Method Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of HDs and MM patients. The generation of moDCs from monocytes in PBMCs was conducted by the incubation of 7 days in a medium consisting of RPMI 1640 medium, 5% human serum, 800U/mL GM-CSF, 500U/mL IL-4, 100U/mL penicillin and 0.1mg/mL streptomycin. During this period, the incubation system was administrated with pomalidomide at 10 µM or 1×PBS as the control group. On the 8 th day, cells were harvested, and the immunophenotyping of cells were analyzed by the flow cytometry. The CD80+CD86+ cell population in total cells is gated as DCs in the FACS analyzing system. Then, the median fluorescence intensity (MFI) of surface markers CD40 and HLA-DR as well as the proportion of CD40+ DCs and HLA-DR+ DCs in total DCs were analyzed respectively. In addition, supernatant from the incubation system with or without pomalidomide administration was collected and detected for the concentration of cytokines IL-12, TNF-α and MIP-1α. Results The proportion of CD80+CD86+ cells in total cells was higher in HD group (n=15) than in MM patient group (n=11), but there was no statistically significant difference (93.49%±6.43% vs 77.04%±27.17%, P=0.094). When analyzing all the HD-derived moDCs (n=15), pomalidomide significantly enhanced the MFI of CD40 (P=0.003) and HLA-DR (P=0.040) on moDCs when compared with the control group. Meanwhile, the proportion of CD40+ DCs (P=0.008) and HLA-DR+ DCs (P=0.032) in total DCs was significantly higher in pomalidomide group than in control group. When analyzing all MM patients-derived moDCs (n=11), pomalidomide significantly enhanced the MFI of CD40 (P=0.047) and HLA-DR (P=0.006) on moDCs when compared with the control group. Meanwhile, the proportion of HLA-DR+ DCs in total DCs was significantly higher in pomalidomide group than in the control group (P=0.000). Moreover, pomalidomide treated HD-derived moDCs (n=8) produced 192% IL-12 (P=0.020), 110% TNF-α (P=0.006) and 112% MIP-1α (P=0.055) of untreated moDCs. However, when analyzing MM patients-derived moDCs (n=10), the expression of IL-12 (P=0.458), TNF-α (P=0.377) and MIP-1α (P=0.248) from moDCs showed no significant difference between pomalidomide group and the control group. Conclusions Pomalidomide at 10 µM can promote the maturation of both HD-derived moDCs and MM patients-derived moDCs. Pomalidomide shows potential to be a DC adjuvant for DC-based therapeutic strategies, such as DC vaccine and DC cell-therapy in MM. Key words: Pomalidomide; Monocyte derived Dendritic Cells; Multiple Myeloma; DC Adjuvant Disclosures No relevant conflicts of interest to declare.


10.23856/4330 ◽  
2021 ◽  
Vol 43 (6) ◽  
pp. 235-239
Author(s):  
Artem Andriiaka ◽  
Stanislav Vydyborets

Due to the growing incidence of cancer in the world, it is becoming more relevant to study the indicators of secondary changes in blood in malignancies to use them as diagnostic and prognostic markers. The objective of the work is to conduct a morphometric analysis of peripheral blood erythrocytes in patients with iron deficiency anemia (IDA) and malignant anemia in colorectal cancer to identify specific changes and use them in a differential diagnostic practice. As the study material blood of 110 patients (58 men and 52 women) was taken. Among them 53 patients (31 women and 22 men) with IDA were examined, they formed the first (I) observation group and 57 patients (36 men and 21 women) with colorectal cancer, where the course of the underlying disease was burdened by malignant anemia second (II) observation group. The age of the patients under the survey is from 22 to 69 years. All patients were examined before any treatment was prescribed. The control group consisted of 50 healthy primary donors. Results. The data on the clinical significance of laboratory determination of morphometric changes in peripheral blood erythrocytes is highlighted in this paper. Differential-diagnostic and prognostic value of morphometric changes of erythrocytes in peripheral blood with iron deficiency anemia and anemia of malignancies is discussed. Indicators of morphometric characteristics of erythrocytes can be used in the differential diagnosis of anemia.


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