Proportion Of Lymphocytes Research Articles

Hypersensitivity pneumonia diagnosed by excisional lung biopsy: a clinicopathological features of 47 cases

Objective: To analyze the clinicopathological and immunohistochemical characteristics of the hypersensitivity pneumonia (HP) cases that were diagnosed by excisional lung biopsy, to improve the diagnosis accuracy of HP. Methods: The data of 47 HP cases diagnosed by excisional lung biopsy during the last 20 years were collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2000 to June 2020. The clinicopathological features and the immunohistochemical profiles of CD3, CD4, CD8 and CD20 were analyzed using light microscopy and immunohistochemical stains. Results: The age of the patients ranged from 15 to 68 years, while the ratio of male to female was 22∶25. The main symptoms were shortness of breath and cough, and 32 cases had a history of allergen exposure. Most of the patients had restrictive impaired ventilatory function, and impaired diffusion function. The proportion of lymphocytes in bronchoalveolar lavage fluid (BALF) increased in 85.3%(29/34) of the patients, and the CD4+/CD8+ T cell ratio was not higher than 0.8 in 31.3%(10/32) of the patients. Microscopically, 59.6%(28/47) of the cases showed nonnecrotizing granuloma/giant cells in the stroma, and 40.4% (19/47) of the cases had only giant cells. Ninety-three-point six percent of the cases(44/47) had peribronchiolar metaplasia, while 70.2%(33/47) had focal cell-rich inflammation. Forty-four cases (93.6%, 44/47) had fibrosis, which was manifested as usual interstitial pneumonia-like fibrosis (47.7%, 21 cases), nonspecific interstitial pneumonia-like fibrosis (29.5%, 13 cases), purely peribronchiolar fibrosis (6.8%, 3 cases) and mixed fibrosis (15.9%, 7 cases). Immunohistochemistry showed that CD4+ T cells were fewer than CD8+ T cells in 24 cases (55.8%, 24/43) of HP. Thirty-two HP patients had follow-up data. Among them, 7 patients had improved symptoms, 12 patients were stable, and 13 patients had worsening symptoms. Conclusions: The most common type of HP diagnosed by excisional lung biopsy is chronic HP. The clinical characteristics are long course of disease, restricted ventilation disorder and impaired diffusion function with the increase of lymphocyte proportion in BALF. Nearly 1/3 of the patients have no known history of allergen contact. The degree of fibrosis in HP patients diagnosed by excisional lung biopsy is severe, and the histologic types of fibrosis varies, but the UIP-like and/or NSIP-like fibrosis is most common. The CD4+/CD8+ T cell ratio in lung tissues is less than 1 in more than half of the cases. Pulmonary fibrosis continued to increase in some of the patients with chronic HP, even after treatment.

Dysregulated proportion of intrahepatic Treg cells and Th17 along with CD8+ T lymphocytes drives disease progression after kasai biliary atresia surgery

Objective: To analyze the clinicopathological characteristics and intrahepatic immune cells infiltration condition after Kasai biliary atresia surgery. Methods: Data of 28 cases who underwent liver transplantation in the liver transplantation center of our hospital from June 2017 to March 2019 were enrolled. Of which, 20 cases were in the biliary atresia group (divided into two subgroups: 10 cases without Kasai surgery and 10 cases after Kasai surgery, and latter subsided cholestasis) and 8 cases in the control group. Clinical and pathological morphological characteristics of the groups were compared. Liver tissue sections were stained with immunohistochemistry and CD3, CD4, CD8, CD20, Foxp3, and interleukin-17A were quantitatively analyzed. Kruskal-Wallis test was used to measure the above indicators, and rank-sum test or Fisher's exact test was used to compare the count data. Results: The degree of clinical and pathological cholestasis in the biliary atresia group after Kasai surgery was significantly lower than that of the group without Kasai surgery, and the degree of liver fibrosis was also significantly reduced (P < 0.05), but there was no statistically significant difference in the degree of inflammation in the portal vein area between the two groups (P > 0.05). There was statistically significant difference in the types of immune cells infiltrated in the liver (P < 0.05). Compared with the group without Kasai surgery, the infiltration of CD3, CD8, IL-17A and Foxp3 positive cells in the portal vein area after Kasai surgery group (P < 0.05) was significantly reduced, but there was no statistically significant difference in the proportion of Foxp3/CD4 positive cells between the two groups (P > 0.05), which continued to be lower than that of the control group (P < 0.05). Compared with the non-Kasai surgery group, the proportion of Foxp3/IL-17A and Foxp3/CD8 positive cells in the portal vein area did not increase significantly after Kasai surgery group (P > 0.05), and remained lower than the control group. However, the proportion of Foxp3/IL-17A and Foxp3/CD8 positive cells was significantly reduced (P ​​< 0.05). Conclusion: Intrahepatic inflammatory cell infiltration and regulatory/effector T lymphocyte proportion dysregulation exist in patients with subsided cholestasis after Kasai biliary atresia surgery, which may be an important factor to promote the disease progression.

Associations between differential somatic cell count and milk yield, quality, and technological characteristics in Holstein cows

The aim of this study was to investigate the associations between differential somatic cell count (DSCC) and milk quality and udder health traits, and for the first time, between DSCC and milk coagulation properties and cheesemaking traits in a population of 1,264 Holstein cows reared in northern Italy. Differential somatic cell count represents the combined proportions of polymorphonuclear neutrophils plus lymphocytes (PMN-LYM) in the total somatic cell count (SCC), with macrophages (MAC) making up the remaining proportion. The milk traits investigated in this study were milk yield (MY), 8 traits related to milk composition and quality (fat, protein, casein, casein index, lactose, urea, pH, and milk conductivity), 9 milk coagulation traits [3 milk coagulation properties (MCP) and 6 curd firming (CF) traits], 7 cheesemaking traits, 3 cheese yield (CY) traits, and 4 milk nutrient recovery in the curd (REC) traits. A linear mixed model was fitted to explore the associations between SCS combined with DSCC and the aforementioned milk traits. An additional model was run, which included DSCC expressed as the PMN-LYM and MAC counts, obtained by multiplying the percentage of PMN-LYM and MAC by SCC in the milk for each cow in the data set. The unfavorable association between SCS and milk quality and technological traits was confirmed. Increased DSCC was instead associated with a linear increase in MY, casein index, and lactose proportion and a linear decrease in milk fat and milk conductivity. Accordingly, DSCC was favorably associated with all MCP and CF traits (with the exception of the time needed to achieve maximum, CF), particularly with rennet coagulation time, and it always displayed linear relationships. Differential somatic cell count was also positively associated with the recovery of milk nutrients in the curd (protein, fat, and energy), which increased linearly with increasing DSCC. The PMN-LYM count was rarely associated with milk traits, even though the pattern observed confirmed the results obtained when both SCS and DSCC were included in the model. The MAC count, however, showed the opposite pattern: MY, casein index, and lactose percentage decreased and milk conductivity increased with an increasing MAC count. No significant association was found between PMN-LYM count and MCP, CF, CY, and REC traits, whereas MAC count was unfavorably associated with MCP, CF traits, some CY traits, and all REC traits. Our results showed that the combined information derived from SCS and DSCC might be useful to monitor milk quality and cheesemaking-related traits.

Abstract OT-31-01: A phase II study to evaluate the efficacy and safety of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer: PEMBRACA trial

Abstract Background Considering the high proportion of tumor-infiltrating lymphocytes (TILs) in BRCA-related breast cancer, we expect that PD-1 pathway is highly expressed and PD-1 antagonist pembrolizumab could provide clinical activity in this kind of tumor. Furthermore, BRCA-related breast cancers are known to be more sensitive to platinum-derived drugs. Thus the association between Pembrolizumab and Carboplatin in metastatic BRCA-related breast cancer seems to be active in this setting of patients. This study will evaluate the safety and the efficacy of Pembrolizumab associated with Carboplatin in BRCA mutated or with unknown mutations metastatic breast cancer patients. Study and Statistical DesignThis is a national multicenter two-stage single arm phase II study, enrolling BRCA mutated or with unknown mutations metastatic breast cancer patients. The sample size has been estimated by using the two-stage Simon’s design. In the first stage, 20 subjects will be enrolled. If, after first stage ≤11 responses (r1) will be observed, accrual will terminate and the experimental regimen will be rejected. Otherwise if 12 or more responses will be seen then the accrual will continue to the second stage of an additional 33 subjects (total, 53 subjects). At the second stage if 33 or less responses out of 53 subjects will be observed the treatment will be rejected. With the null hypothesis (p0) being equal 0.55 with a type I (alfa) error of 0.10 (10%) and a type II (beta) error of 0.20 (power=80%) and the alternative hypothesis (p1) is 0.70, (response rate 70%), we expect to reach an overall response rate (ORR) ≥ 70% by the combination of Pembrolizumab plus Carboplatin. We also expect to reach a median Time to Progression (TTP) and Overall Survival (OS) of five and fifteen months respectively. The Disease Control Rate (DCR) will be expected as ≥ 80% by the combination of Pembrolizumab plus Carboplatin Study TreatmentCarboplatin at area under the time-concentration curve 6 (AUC 6) intravenously once every 3 weeks in combination with Pembrolizumab 200 mg intravenously every 3 weeks will be administered for six courses and then only Pembrolizumab alone will continue until occurrence of unacceptable toxicities or disease progression. Eligibility CriteriaIn order to be eligible for participation in this trial, the subject, aged ≥ 18 years, must have metastatic confirmed breast cancer, with a disease progression by radiological techniques within 12 months prior to signing informed consent, and a documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious or with unknown significance. The subject must have measurable disease based on RECIST 1.1 and have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. Prior chemotherapy with anthracyclines and taxanes has to be administered in neoadjuvant or adjuvant setting. In case of luminal tumors hormonal treatments for advanced disease can be administered before. The life expectancy must be greater than 3 months and the subject must demonstrate adequate organ function by screening labs performed within 10 days of treatment initiation. Objectives and HypothesisThe primary end-point will be the ORR, evaluated according to RECIST criteria. Secondary objectives will be the TTP, the duration of response (DOR ), the DCR, and the OS. The safety of the combination will be evaluated according to the worst toxicity grade reported throughout the whole treatment period.The Exploratory Objective will be the evaluation of ORR, TTP, DOR, and DCR based on irRECIST. Biological parameters of CD8/TILs and PD-L1 will be considered in the metastatic biopsy. Target AccrualThe first subject was enrolled in January 2019 and recruitment is ongoing. Enrollment of the first 20 subjects is expected to complete in Q2 2021. Citation Format: Laura Cortesi, Marta Venturelli, Federica Caggia, Luigi Marcheselli, Annita Gozzi, Alberto Zambelli, Valentina Guarneri, Antonino Musolino, Elena Fiorio, Giancarlo Bisagni, Andrea Rocca, Valentina Arcangeli, Elisabetta De Matteis, Sergio Rizzo, Andrea Michelotti. A phase II study to evaluate the efficacy and safety of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer: PEMBRACA trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-31-01.

Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF.

Background and AimsPatients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients.Material and MethodsBlood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions.ResultsSeveral features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion.ConclusionsGenomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.

CD3D has the Potential to be a Prognostic Factor for Endometrial Carcinoma and an Indicator of Tumor Immune Microenvironment Regulation: a Study based on TCGA Data Mining

Accumulating evidence shows that tumor immune microenvironment infiltration plays a crucial role in the occurrence and development of endometrial carcinoma (EC). At present, studying the regulation mechanism of the immune microenvironment in EC remains a challenge. We calculated the amount of immune and stromal components and the proportion of tumor-infiltrating immune lymphocytes via ESTIMATE, single-sample gene enrichment analysis (ssGSEA), and CIBERSORT computational methods. Differentially expressed genes were analyzed by protein–protein interaction network construction and univariate survival analysis. CD3D expression was negatively correlated with clinicopathological features, such as age, histological type, clinical grade, and pathological stage, but positively correlated with the survival of patients with EC. Logistic regression analysis suggested that CD3D expression could be used as a biomarker to predict EC occurrence. Gene set enrichment analysis revealed that CD3D was upregulated in the immune effect pathway. Interestingly, CD3D was downregulated in the EC pathway. EC was divided into three immune cell subsets by ssGSEA. Correlation analysis between ssGSEA and CIBERSORT showed that the infiltration level of CD8 + T cells and plasma cells in tumor-infiltrating lymphocytes was lower than that in the high-immune-score group (Immunity_H). Moreover, CD3D expression in Immunity_H was low, and the prognosis was even worse. This study demonstrated that low CD3D expression is an index of poor prognosis in patients with EC. Levels of CD3D in tumor microenvironment (TME) might be a useful indicator for predicting the prognosis of patients with EC patients.

Sex differences in immune responses to SARS-CoV-2 in patients with COVID-19.

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.

Composition of peripheral blood leukocytes and immuno-competent bodies of the cross carp “Petrovsky” in different periods of the fishing season

Crossing is an effective method of increasing agricultural production. In addition to the productive qualities of the resulting crosses, it is important to maintain and enhance their immune resistance. Breeding for immunity to pathogens of various diseases provides a decrease in economic losses and an increase in breeding efficiency. Cross “Petrovsky” (breeding achievement No. 9153820) is a reciprocal hybrid of Anish Mirror and Chuvash scaled productive carp species. It has been established that this cross is superior to the parental forms in terms of growth intensity and survival of juveniles. The work is devoted to a comparative analysis of the leukocyte composition of peripheral blood and immunocompetent organs of the carp cross “Petrovsky” in different periods of the fish-breeding season. The studies were carried out in late May and early October 2019 in the Kirya breeding farm, Chuvashia (2nd fish breeding zone). In fish, peripheral blood was sampled from the tail vein and tissues of the spleen and head kidney. Blood smears and organ-imprinted smears were taken for the study. The preparations were examined under a light microscope and the leukocyte formula was determined. The study of leukograms of immunocompetent organs and tissues of fish helps to judge the functional state and immune resistance of fish. To determine the index of the abundance of leukocytes in a peripheral blood smear, 100 visual fields were examined in different areas. This indicator allows you to record the intensity of leukopoiesis and indirectly assess the level of leukocytes in a unit of blood volume. Studies have established differences in the proportion of certain types of leukocytes and the intensity of leukopoiesis in different periods of the fish-breeding season. Fish tissues and organs differed in the proportion of lymphocytes, monocytes, and neutrophils. The obtained data can be used in carrying out selection and breeding work aimed at increasing productivity and enhancing the resistance of fish to infectious diseases.

Coronavirus disease 2019 combined with venous thromboembolism: Clinical features and prevention

Objective: To analyze the clinical characteristics and control methods of coronavirus disease 2019 (COVID-19) complicated with venous thromboembolism(VTE), and to provide scientific basis for disease prevention, diagnosis and treatment. Methods: We retrospectively studied the cases of COVID-19 complicated with VTE in Renmin Hospital of Wuhan University from January 30, 2020 to March 19, 2020, and their clinical features, results of exmaninations, treatment methods, complications, and prognosis were reviewed. Results: Among the 1 448 COVID-19 patients, 17(1.17%) were VTE positive, 60-69 years old patients were more common. The main clinical types were critical (64.7%) and severe (35.7%) types. The main clinical symptoms were lower extremity swelling (70.6%) and pain (35.7%);58.8% of the patients had a history of high risk factors related to VTE. Most VTE patients were peripheral (58.8%) and involved bilateral limbs (41.2%). The proportion of neutrophils, D-dimer and fibrin degradation products at the last examination were lower than those on admission to the hospital, while the total number and proportion of lymphocytes were higher. Of the 17 VTE cases, 64.7% received venous catheterization, 58.8% received endotracheal intubation or tracheotomy, and 2 patients received extracorporeal membrane oxygenation (ECMO). The rate of bleeding was as high as 53%, and the risk of cardiovascular and cerebrovascular accidents was very high;the prognosis of the patients was poor, and the mortality rate was 23.5%. The cure rate was 17.6%, and the improvement rate was 47.1%. Two patients were still in critically ill. Conclusion: Venous thromboembolism was common in elderly COVID-19 patients with severe types and critical types. Most patients were male and characterized by atypical symptoms, and the early active VTE risk assessment and prevention procedures should be adopted. The risk for bleeding and cardiovascular/cerebrovascular accidents was high, although most cases had good outcomes after active treatment. © 2021, Editorial Board of Medical Journal of Wuhan University. All right reserved.

Modulation of the human immune status by spinal thermal massage: a non-randomized controlled study

Thermal and massage therapies have long been used to control pain. Although spinal thermal massage (STM) has been used worldwide, its effectiveness has not been proven in a controlled clinical study. We here conducted a non-randomized controlled trial to assess the pain-relieving and immunomodulatory effects of STM in old-aged patients experiencing pain or disability. The experimental group was treated with STM five times a week for 8 weeks and rehabilitative regular care (RRC). The control group was treated with only RRC. Pain and immunological parameters were tested before treatment and after 4 and 8 weeks of treatment. The scores of three pain parameters were lowered by STM, and the differences between the groups were statistically significant at the two time points (p &lt; 0.01). Quality of life determined using the 3-level EuroQol five-dimensional questionnaire scores was significantly higher in patients in the experimental group than those in the control group. Effect sizes (ES) were in the range of medium to large in the pain-related measures (0.54–1.22). The total leukocyte counts and the proportions of lymphocytes and subsets were not significantly different between the groups, whereas the proportions of monocytes and natural killer (NK) cells were higher in the experimental group than in the control group after 8 weeks (p &lt; 0.05). The production of interleukin (IL)-4 and interferon γ in T cells was not significantly different between the groups, whereas the production of IL-2 was high in the control group. However, there was a significant increase in IFN-γ production by NK cells in the experimental group (at 4 weeks, p &lt; 0.05). ES were medium in the immunological measures (0.53–0.68). No significant difference was observed in the production of proinflammatory cytokines, IL-1β, tumor necrosis factor α, or IL-6 between the groups. In conclusion, STM treatment has a positive effect on subjective pain and quality of life. It also enhanced NK cell proportion and activity, suggesting that STM may be beneficial in the prevention of viral diseases and cancer in old-aged people.

Diagnostic efficiency of determining CXCR1, CXCR2 and hyaluronic acid blood level in non-small cell lung cancer patients

In the structure of lung cancer incidence most cases belong to non-small cell lung cancer (NSCLC) which is subdivided into two histological subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). A five-year survival rate of patients with stage I NSCLC is two times higher than in patients with stage II and more than five times higher than in stages III-IV. Currently, there are no informative blood biomarkers to diagnose early stages of NSCLC. The aim of the study was to evaluate complex determination of hyaluronic acid (HA), CXCR2 and CXCR1 levels blood of patients with AC and SCC. Blood samples from of 107 patients with SCC, 90 patients with AC, and 40 healthy people were used in this study. Concentration of HA in blood serum was determined by enzyme linked immunoassay. The level of CXCR2 and CXCR1 was determined by flow cytometry. Diagnostic parameters were determined by constructing mathematical models in the form of regression equations using the method of stepwise inclusion of predictors and subsequent ROC-analysis. Results of the study indicate that MFI CXCR1 in granulocytes, proportion of lymphocytes containing CXCR2 and concentration of HA in blood serum in stage I AC and SCC are significantly higher than in healthy people. The level of these parameter significantly increases at stage II of the disease compared to stage I and demonstrates further growth at its later stages. Based on the obtained results, regression equations were created: (i) including MFI CXCR1 in granulocytes, proportion of lymphocytes supplied with CXCR2 and HA concentration in the serum to detect stages I-II SCC (diagnostic sensitivity - 95.7%, specificity - 93.7%, threshold value - 0.59) and stages III-IV SCC (diagnostic sensitivity - 93.1%, specificity - 93.3%, threshold value - 0.64); (ii) including the proportion of lymphocytes supplied with CXCR2 MFI CXCR1 in granulocytes and CYFRA 21-1 blood level, which allows the detection of I-II stages of AC (sensitivity - 91.3%, specificity - 94.7%, threshold value - 0.61); (iii) including the proportion of lymphocytes supplied with CXCR2 and CYFRA 21-1 blood level, which allows the detection of AC stages III-IV (sensitivity - 94.6%, specificity - 91.3%, threshold value - 0.15); (iv) including the proportion of lymphocytes supplied with CXCR2 and HA level in the serum to differentiate stage II SCC from stage I (sensitivity - 94.4%, specificity - 87.5%, threshold value - 0.44) and II stage AC from stage I (sensitivity - 88.5%, specificity - 91.2%, threshold value - 0.46).

The relationship between the rs4986791 variant of the TLR4 gene and the severity of bronchial asthma in children.

Toll-like receptor 4 (TLR4) is an important receptor for lipopolysaccharide and lipid A, components of gram-negative bacteria. At present, a variant in TLR4 has been shown to be associated with asthma, but it has not been reported whether variants in TLR4 are associated with bronchial asthma in children. The objective is to determine the relationship between the rs4986791 (+1196C/T) variants of TLR4 and bronchial asthma in Chinese children. DNA extracted from peripheral blood samples was amplified and the Bi-PASA technique was carried out to identify the genotypes in 600 patients. The result showed no difference between the 1196 C/T variant of TLR4 and hemoglobin level, proportion of neutrophils and lymphocytes, leukocyte, basophil and eosinophil counts, log10IgE and hsCRP in the peripheral blood of bronchial asthmatic patients. However, the eosinophil ratio, FEV1% and FEV1/FVC level of asthma patients with the CT genotype was lower than those of patients with the CC genotype, which were 1.19 ± 0.10 and 1.67 ± 0.18 (P = 0.01), 81.25 ± 0.50 and 84.99 ± 0.65 (P < 0.0001), 81.72 ± 0.568 and 5.55 ± 0.78 (P < 0.0001), respectively. The incidence of bronchial asthma in patients with the CT genotype is higher than that in patients with the CC genotype. We analysed the influence of the two genotypes on the current medical history by multiple logistic regression, performing a comparative analysis between the two genotypes and bronchial asthma (P < 0.05). Patients with moderately persistent asthma with the CT genotype are more likely to develop severely persistent asthma compared to those with the CC genotype (P < 0.01). This comparative analysis between rs4986791 and bronchial asthma in children indicates that this variant is associated with bronchial asthma risk in Chinese children.

TNFRSF11B Remodel Immune Response in Colon Cancer Microenvironment: A Multi-Center Study

Background: Colorectal cancer is the lethal cancer in the world, due to the low tumor mutation burden and low proportion of tumor-infiltrating lymphocytes in the microenvironment of most patients, innovative immunotherapeutic approaches need to be identified. Methods: Using TCGA-COAD dataset (n = 514), we identified TNFRSF11B as a prognostic factor of colon cancer. Immunohistochemistry (IHC) dataset (n = 86), 290 single colorectal cancer cells (GSE81861) and 31 paired colon cancer transcriptional dataset were further applied to validate the function of TNFRSF11B, which was confirmed via fluorescence-activated cell sorting (FACS) analysis. Results: A risk scores system consisting of eight IRGs was constructed to predict the prognosis of colon cancer patients. Only TNFRSF11B correlated with TNM-stage, lymph node metastasis and prognosis. In our IHC dataset, High TNFRSF11B expression had a later TNM-stage, higher frequency of lymph node and lymphovascular invasion. Six genes (KRT18, ARPC5L, ACTG1, ARPC2, EZR, YWHAZ) related to pathogenic E. coli. infection were simultaneously increased with TNFRSF11B overexpression via GESA analysis. Finally, only activated memory CD4+ T cells (p =0.017) were significantly decreased in high TNFRSF11B expression group, which was supported by our FACS findings that TNFRSF11B downregulate the immune activity of central memory CD4 + T cells and effector memory CD4+ T cells (all p <0.001). Conclusion: TNFRSF11B, acts as a prognostic factor for colon cancer patient, could affect colon cancer immune response. TNFRSF11B was closely related with lymph node invasion and pathogenic E. coli. infection, which might negatively affect memory activated CD4+ T cell infiltration in colon cancer. Funding: This work was supported Joint Funds for the innovation of science and Technology, Fujian province (Grant number: 2018Y9203 to Jun-rong Zhang, 2018Y92042 to Xian-qiang Chen); Startup Fund for scientific research, Fujian Medical University (Grant number: 2019QH1016 to Ping Hou); Education Department of Fujian Province Young and middle-aged teacher education research project (Grant number: JAT190180 to Ping Hou, JT180181 to Jun-rong Zhang). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: The validation of TNFRSF11B in paraffin-embedded colorectal cancer tissues were supported by general surgery of Fujian Medical University Union Hospital from January 2013 to December 2017. The study protocol was approved by the Institutional Review Board of Fujian Medical University Union Hospital, and all patients provided written informed consent.

Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model.

High proportions of placental lymphocytes expressing DX5+/CD25+/FOXP3+/CD45+/CD4+ are beneficial to maintain immune tolerance and improve pregnancy outcomes. This study aimed to compare and evaluate the therapeutic effects of aspirin, vitamin D3 (VitD3), and progesterone on the autoimmune recurrent spontaneous abortion (RSA) model. The autoimmune RSA mouse model was constructed, and the embryo loss rate was calculated for each group. Then, primary mouse placental lymphocytes were isolated, and the expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ was detected through flow cytometry. The serum levels of anti-cardiolipin antibody (ACA), β2-GP1, CXCL6, IFN-γ, and IL-6 were measured by ELISA to evaluate the proportion of Th1 and Th2 cells. Autoimmune RSA significantly increased the embryo loss rate, which was improved by aspirin, VitD3, and progesterone treatment, and progesterone treatment had the best effect among the three treatments. The positive expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ in the VitD3 and progesterone groups was significantly higher than that in the autoimmune RSA group, and the expression was highest in the progesterone treatment group. In the plasma of autoimmune RSA mice, the ACA, β2-GP1, CXCL6, and IFN-γ levels were significantly higher and the IL-6 level was lower than the levels in control mice. All these changes could be reversed by aspirin and progesterone treatment. In conclusion, aspirin, VitD3 and progesterone treatment improved pregnancy outcomes in autoimmune RSA mice by regulating the Th1/Th2 balance and cytokines, and progesterone had the best effect of the three treatments.

Predicting Factors of Severe COVID-19 in Patients With Asthma: A Korean National Cohort Study.

As there are limited data on the disease course of and factors predicting severe coronavirus disease 19 (COVID-19) in patients with asthma, this study aims to perform a detailed analysis of the clinical course of asthmatic patients with COVID-19 and evaluate factors related to severe infection. Of the 5,628 patients confirmed with COVID-19, 128 (2.3%) had asthma. Among the 128 asthmatic patients, 32 (25%) had severe COVID-19 and 96 (75%) had non-severe COVID-19. Among asthmatic patients, those with severe COVID-19 were significantly older and had more dyspnea and fever, more comorbidities, and lower lymphocyte and platelet counts than those with non-severe COVID-19. In multivariable logistic regression analysis, chronic obstructive pulmonary disease (adjusted odds ratio [aOR], 6.49; 95% confidence interval [CI], 1.18–41.81), low lymphocyte proportion (aOR, 0.91; 95% CI, 0.86–0.97), and low platelet count (aOR, 0.99; 95% CI, 0.98–0.99) were independently associated with severe COVID-19.

The association of cortisol levels with leukocyte distribution is disrupted in the metabolic syndrome

Leukocyte glucocorticoid sensitivity (GCS) pertains to the responsivity of leukocytes to the regulating actions of glucocorticoids, such as cortisol. Impaired endocrine regulation may link the metabolic syndrome (MetS) to the development of cardiovascular disease. We tested if the physiological association between endogenous cortisol levels and peripheral leukocyte composition becomes disrupted in individuals with MetS. MetS was assessed among 689 German industrial employees. The covariance between cortisol levels and hematologic parameters (i.e., proportions of neutrophils and lymphocytes) and their ratio was explored, which has been proposed as a proxy for GCS in vivo. Cortisol level before blood collection was assessed by repeated saliva collection, and the area under the curve was calculated. Linear regression models were adjusted for potential confounders including age, gender, BMI, income, and lifestyle factors. Cortisol levels did not differ between subgroups. Participants without MetS (n = 552) showed the expected association of cortisol with hematologic parameters (β = 0.207 to 0.216; p values < 0.001). No association (β = 0.078 to 0.083; p values > 0.10) was found among those with MetS (n = 137), consistent with a reduced GCS. Analyses of separate MetS components showed that reduced GCS was associated specifically with decreased high-density lipoprotein and elevated fasting plasma glucose. Utilizing a novel statistical approach to infer GCS, this study provided first epidemiological evidence of aberrant physiological regulation of leukocyte distribution by endogenous cortisol levels among individuals with MetS. These findings underline the idea that MetS may involve disruption of endocrine-immune regulation.

Assessment of serum biochemical proϑile in breast cancer patients

Cancer occurrence and it's connected mortality on the rise and has become a significant general wellbeing concern. As of now, it is the subsequent driving reason for death around the globe. Bosom malignant growth is the world's most basic malignant growth in ladies with high mortality rate. This study was planned to evaluate the ailment movement and metastasis. The current investigation is a close, observational examination. One hundred seven female bosom disease patients over the age of 35 years were enlisted to examine varieties in serum biochemical profile of bosom malignant growth patients. In this investigation, the mean estimations of Blood urea nitrogen, Uric corrosive, White platelets and Neutrophil lymphocyte proportion were discovered to be diminished, and that of Serum creatinine, Serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, Alkaline phosphatase, Fasting glucose, neutrophils and lymphocytes were discovered to be expanded from first to fourth patterns of chemotherapy. The obtained parameters were expressed as Mean ± SD, and the parameters were compared by using paired t-test. All Biochemical parameters should be monitored after every chemotherapy cycle until the completion of a planned treatment regimen. The changes in biochemical parameters provide an opportunity to explain the degree of risk in breast cancer patients by metastasis which helps to avoid further worsening of the disease.

Immune response and intestinal microbial succession of half-smooth tongue sole (Cynoglossus semilaevis) infected with Vibrio vulnificus

This study aimed to investigate the responses of the immune system and intestinal microbiota of half-smooth tongue sole (Cynoglossus semilaevis) to Vibrio vulnificus infection. The innate immune indicators in peripheral blood and liver were measured, and the process of microbial succession monitored. Half-smooth tongue sole (length: 29.75 ± 2.63 cm, bodyweight: 116.21 ± 7.34 g) were selected to perform the pathogen challenge test. The control group (C) was intraperitoneally injected with 100 μL PBS. The inoculation amount of Vibrio vulnificus for the low-dose group (L), moderate-dose group (M), and high-dose group (H) were 1 × 104, 1 × 107, 1 × 1010 cells for each fish, respectively. A decrease and an increase in the proportions of lymphocytes and monocytes, respectively, was observed at 24 h of L, M and H. Within initial 72 h, the joint action of monocytes, neutrophils, and eosinophils to cope with the pathogen infection only occurred in H. The serum CH50 and ALP levels were significantly higher and serum lysozyme activity significantly lower in H than those observed in C at 48 h (P < 0.05). Moreover, within the initial 72 h, lysozyme activity of the liver was significantly lower (P < 0.05) in H. The intestinal microbiota shifted significantly within the initial 24 h in H and 48 h in M. The bacteria: Shewanella, Pseudoalteromonas, Acidobacteria, Firmicutes, and Actinobacteria, showed some resistance to Vibrio to a certain range. From our findings, the innate immunity in half-smooth tongue sole is not sensitive to moderate- or low-dose V. vulnificus infection. Leukocytes, ALP, and complement are primarily involved in resisting high-dose infection of V. vulnificus. A variety of intestinal microbial taxa plays a vital role in inhibiting V. vulnificus growth. In addition to bacteria from Firmicutes and Actinobacteria, bacteria from Acidobacteria are also a good probiotic option for resisting V. vulnificus.

The impact of parturition induction with cloprostenol on immunological parameters in the sow colostrum

BackgroundFarrowing induction with prostaglandin F2 analogue cloprostenol is commonly used on commercial farms to manage the timing of farrowing. When labour induction is applied, the questions arise about possible side effects of such a hormonal intervention on physiological processes connected with labour and lactation, including colostral immunity.ResultsIn this study, immune cells composition, lysozyme concentration, complement bacteriolytic activity and proinflamatory (GM-CSF2, IL-1β, IL-6, a TNFα) and anti-inflammatory (IL-4, IL-10, TGFβ1 a TGFβ2) cytokines were measured in colostrum samples from sows farrowing naturally (NP) and from sows with farrowing induced using cloprostenol administration on day 113 of gestation (IP). A significantly higher proportion of lymphocytes was found in colostrum of induced sows compared to colostrum of non-induced sows. No significant differences between NP and IP were found in complement activity, in the proportions of granulocytes, macrophages and lymphocyte subpopulations. Lower lysozyme concentration and higher IL-1β, IL-6, TGFβ1 and TNFα concentrations were found in IP sow colostrum compared to colostrum from NP sows.ConclusionsAn increased proportion of colostral lymphocytes can positively influence the cellular immunity transmission from sow to her offspring. On the other hand, a lower lysozyme concentration can adversely affect newborn’s intestinal immunity, as well as changes in cytokine concentrations can have an adverse effect on newborn piglet intestinal epithelium development and its defence function.

Medical Thoracoscopy for the Management of Exudative Pleural Effusion: A Retrospective Study.

ObjectiveThe aim of this study was to evaluate the efficacy of medical thoracoscopy in the diagnosis and treatment of exudative pleural effusion.MethodsA total of 82 patients with exudative pleural effusion underwent medical thoracoscopy under local anesthesia and mild sedation. The clinical characteristics, pleural fluid routine and biochemical tests, pleural biopsy, and outcomes were retrospectively evaluated.ResultsAmong 82 patients, the color and transparency of pleural fluid and the levels of white blood cells (WBC), lactate dehydrogenase (LDH), neutrophil proportion, lymphocyte proportion, adenosine deaminase (ADA), and glucose were different among tuberculosis (TB), malignant (M), acute and chronic inflammation (ACI), and purulent (P) cases. Furthermore, 70% of M cases had a low positive rate of exfoliated cells in the sputum and pleural fluid, and more than 90% of TB cases had low positive rates of anti-tuberculosis antibodies and acid-fast bacilli in the sputum and pleural fluid. Pleural biopsy showed that 11% of cases were M, 74.4% were TB, 11% were ACI, and 3.6% were P. Medical thoracoscopy showed that 66.7% of ACI cases had pleural adhesions, 34.4% of TB cases had moderate and 34.4% of TB cases had severe pleural adhesions, 100% of M and TB cases had pleural surface nodules and 77.8% of ACI cases had pleural surface nodules, 49.2% of TB cases showed encapsulated pleural effusion, and 33.3% of M cases showed encapsulated pleural effusion.ConclusionMedical thoracoscopy has high feasibility and accuracy in the diagnosis and treatment of exudative pleural effusion.