Diagnostic and prognostic value of peripheral blood CD4+T lymphocytes for hepatocellular carcinoma recurrence after liver transplantation / 中华检验医学杂志

Objective:To investigate the clinical value of peripheral blood T lymphocytes in the diagnosis and prognosis of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation.Methods:The clinical and laboratory data of 50 HCC patients, who received liver transplantation and were followed up in the Liver transplantation Center of Beijing Youan Hospital from January 2014 to December 2016, were retrospectively analyzed. The differences on clinical laboratory indicators and five-year survival were compared between HCC recurrence group ( n=29) and non-recurrence group ( n=21). Spearman correlate analysis was used to analyze the correlation between clinical laboratory indicators and HCC recurrence after liver transplantation. Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of CD4+T lymphocytes in HCC recurrence after liver transplantation. Kaplan-Meier survival curve was used to compare the survival time of patients with different CD4+T lymphocytes levels post liver transplantation. Results:Compared to non-recurrence group, the level of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, albumin, lymphocytes, alpha-fetoprotein, protein induced by vitamin K deficiency or antagonist-Ⅱ, CD3+, CD4+and CD8+T lymphocytes were significantly different (all P<0.05). The median recurrence time after liver transplantation was 13.0 (6.0, 24.0) months, and the mortality rate was 100%. The 5-year mortality rate was 0 in the non-recurrence group. During 5-year follow-up, the median survival time of patients in the HCC recurrence group was 18.0 (9.0, 36.0) months, which was significantly lower than that of non-recurrence group [60.0 (60.0, 60.0) months, ( P<0.05)]. Compared with non-recurrence group, the CD3+, CD4+, and CD8+T lymphocytes were significantly lower in the recurrence group (all P<0.05). Spearman correlate analysis showed that HCC recurrence after liver transplantation was negatively correlated with the CD3+, CD8+and CD4+T lymphocytes ( r=-0.43, -0.38, -0.44, all P<0.05). ROC analysis showed that CD4+T lymphocytes at cutoff of≤265.50 cells/μl was valuable for the diagnosis of HCC recurrence after liver transplantation (specificity 100%, sensitivity 48.30%). Survival curve analysis showed that the survival time was significantly lower in the CD4≤265.50 cells/μl group [15.0 (10.0, 36.8) months] than that in the CD4>265.50 cells/μl group [53.0 (19.5, 60.0) months] ( P<0.05). Conclusion:There is a significant negative correlation between CD4+T lymphocytes and HCC recurrence after liver transplantation. CD4+T lymphocytes at cutoff value of≤265.50 cells/μl is valuable for the clinical diagnosis and prognosis evaluation of HCC recurrence after liver transplantation.

Study on the relationship between intestinal flora analysis and CD4 +T lymphocyte subsets in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To explore the characteristics of intestinal microbiota in patients with systemic lupus erythematosus (SLE), and further explore the relationship between microbiota and CD4 +T lymphocyte subsets and disease activity. Methods:Fecal samples were collected from 96 patients with SLE, and 96 sex- and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing. Flow cytometry was used to detect peripheral CD4 +T lymphocyte subsets of Th1, Th2, Th17 and Treg cells. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4, Systemic lupus erythematosus disease activity index(SLEDAI) for each patient were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and Pearson′s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples. Results:The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs ( P<0.01). Bacterial diversity estimators, including the Shannon ( P<0.01) and Simpson′s ( P<0.01) indices, were also significantly lower in SLE. Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HC, 24 species of bacteria were significantly different in SLE patients at the genus level ( P<0.05). Moreover, there was a significant positive correlation between CRP and Coprococcus ( r=0.30, P=0.014), C4 and Corynebacterium ( r=0.31, P=0.013) and Faecalibacterium( r=0.25, P=0.048), Hemoglobin and Morganella( r=0.41, P=0.001), as well as SLIDA and Corynebacterium( r=0.25, P=0.047). In terms of lymphocyte subsets, there was significant positive correlation between B cells, Treg cells and Eubacterium eligens group, as well as CD8 +T, CD4 +T, NK cells and Corynebacterium. In additional, Th1 was positively correlated with Shigella Escherichia coli ( r=0.52, P=0.008), and Th2 was positively correlated with Dielma ( r=0.51, P<0.001). Conclusion:The abundance and diversity of intestinal flora in SLE patients were significantly reduced, and the differentially expressed bacteria were closely related to the CD4 +T lymphocyte subsets and disease activity indicators of patients.

Investigation on the incidence of IRIS in HIV patients with TB infection and its relationship with Th17/Treg, CD4 + T lymphocyte levels / 中国医师杂志

Objective:To investigate the incidence of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV (HIV) and tuberculosis (TB) infection, and analyze the relationship between Th17/Treg cytokines, CD4 + T lymphocytes and IRIS. Methods:HIV patients with TB infection admitted to Public Health Clinical Center of Chengdu from June 2020 to June 2022 were divided into IRIS group (31 cases) and non IRIS group (93 cases) according to whether IRIS occurred after highly active antiretroviral therapy (HAART). The Demography data, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was conducted to investigate the influencing factors of IRIS in HIV patients with TB infection.Results:There was no significant difference in Demography data between the two groups ( P>0.05). There was a statistically significant difference in the history of opportunistic infection between the IRIS group and the non IRIS group (χ 2=5.194, P<0.05). The levels of HIV RNA, interleukin (IL)-17, and IL-23 in the IRIS group were higher than those in the non IRIS group (all P<0.05). The levels of the γ interferon (IFN- γ), the transforming growth factor-β (TGF- β) and baseline CD4 + T lymphocyte count were lower than those in the non IRIS group (all P<0.05). The results of multivariate logistic regression analysis showed that IL-17 ( OR: 1.266, 95% CI: 1.095-1.464), IL-23( OR: 1.384, 95% CI: 1.120-1.710), and TGF- β( OR: 0.589, 95% CI: 0.436-0.797) were influencing factors for the occurrence of IRIS in HIV patients with TB infection (all P<0.05). Conclusions:For patients with high IL-17 levels, high IL-23 levels, and low TGF- β level of HIV complicated with TB infection, clinical prevention and control should be carried out as soon as possible to prevent the occurrence of IRIS.

Expression Level and Significance of Tim-3 in CD4+ T Lymphocytes in Peripheral Blood of Patients with Coronary Heart Disease

Abstract Objective: To investigate the expression level and significance of T cell immunoglobulin and mucin-domain containing molecules-3 (Tim-3) and interleukin-7 (IL-7) in CD4+ T lymphocytes in peripheral blood of patients with coronary heart disease (CHD). Methods: 75 patients with CHD treated at our hospital were selected and classified as mild group (25 cases), moderate group (25 cases) and severe group (25 cases), according to the severity of illness. Twenty-five healthy volunteers who underwent a physical examination at our hospital during the same period were selected as the control group. The expression level of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients in four groups was detected by flow cytometry and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression level of IL-7 in peripheral blood serum was measured by enzyme-linked immunosorbent assay (ELISA). Correlation analyses of Tim-3 and IL-7, Tim-3 and disease severity and IL-7 and disease severity were performed, respectively. Results: Flow cytometry and qRT-PCR demonstrated that the expression of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients with CHD increased with the aggravation of the disease. ELISA showed that the tendency of IL-7 expression in peripheral blood serum was consistent with the expression of Tim-3, and the expression of Tim-3 had a positive correlation with IL-7. The expression levels of both Tim-3 and IL-7 were positively correlated with the Gensini score. Conclusion: The expression of Tim-3 and IL-7 in peripheral blood of patients with CHD was upregulated and increased with the aggravation of CHD.

Avaliação do perfil bioquímico, hematológico e imunológico em pacientes com diagnóstico recente para HIV de um Centro de Referência em Santarém, Pará, Brasil / Evaluation of the biochemical, hematological and immunological profile in patients with a recent diagnosis of HIV in Santarém Reference Center, Pará, Brazil

Introdução: Alterações hematológicas, bioquímicas e imunológicas podem estar presentes no paciente infectado pelo HIV, no momento do diagnóstico, antes ou depois de iniciar com os antirretrovirais. Objetivo: Analisar o perfil bioquímico, hematológico e imunológico de pacientes com diagnóstico recente para HIV. Método: O estudo avaliou 321 prontuários de pacientes recém diagnosticados com a infecção pelo HIV. A coleta de dados envolveu informações sociodemográficas (data de nascimento, idade, sexo, escolaridade, estado civil, vínculo empregatício e procedência), clínicas (data do diagnóstico para a infecção pelo HIV, situação de imunodeficiência e tipo de exposição), bioquímicas (glicose, triglicerídeos, colesterol total e frações), hematológicas (hemoglobina e plaqueta) e imunológicas (linfócitos T CD4+ e carga viral). Os dados foram analisados por estatística descritiva e inferencial, adotando-se p<0,05. Resultados: Notou-se predominância do sexo masculino (67%), faixa etária de 18-27 anos (39,9%), solteiros (58,6%) e com 32% dos pacientes apresentando Aids. Das variáveis analisadas, o sexo masculino apresentou, em relação às mulheres, maior quantidade de hemoglobina e menores valores para contagem de linfócitos T CD4+, glicose e colesterol total (p<0,05). Além disso, ressalta-se que 69% da amostra apresentou alguma alteração lipídica, 96% tinha carga viral detectável e 29% apresentou linfócitos T CD4+ <200 cel/mm3. Conclusão: Pessoas vivendo com o HIV, no momento do diagnóstico, podem apresentar alterações imunológicas, hematológicas e bioquímicas, tornando imprescindível a avaliação, acompanhamento e orientação multiprofissional, tanto antes como posterior introdução dos antirretrovirais, a fim de evitar futuros agravos a saúde. [au]

Introduction: Hematological, biochemical, and immunological alterations may already be present in HIV-infected patients at the time of diagnosis or before, or after starting antiretroviral therapy. Objective: Analyze the biochemical, hematological, and immunological profile of patients with a recent diagnosis of HIV. Method: The study evaluated 321 medical records of patients newly diagnosed with HIV infection. Data collection involved sociodemographic (date of birth, age, gender, education, marital status, employment relationship, and origin), clinical (date of diagnosis for HIV infection, immunodeficiency status, and type of exposure), biochemical (glucose, triglycerides, total cholesterol, and fractions), hematological (hemoglobin and platelet) and immunological (CD4+ T lymphocytes and viral load) information. Data were analyzed by descriptive and inferential statistics, adopting p<0.05. Results: There was a predominance of males (67%), aged 18-27 years (39.9%), single (58.6%), and 32% of patients had AIDS. Of the variables analyzed, males presented higher amounts of hemoglobin and lower values for CD4+ T lymphocyte count, glucose, and total cholesterol in relation to females (p<0.05). In addition, it is noteworthy that 69% of the sample presented a lipid alteration, 96% had a detectable viral load, and 71% had CD4+ T lymphocytes <200 cells/mm3. Conclusion: People living with HIV, at the time of diagnosis, may present immunological, hematological, and biochemical alterations, making multidisciplinary evaluation, follow up, and guidance essential, both before and after the introduction of antiretroviral therapy, in order to avoid future health problems. [au]

Analysis of interleukin 1 receptor-associated kinase 1, disease activity and CD4 + T cell subsets in peripheral blood of rheumatoid arthritis patients / 中华风湿病学杂志

Objective:To explore the expression level of interleukin-1 receptor-associated kinase-1 (IRAK1) in the peripheral blood of rheumatoid arthritis (RA) patients and analyze its relevance between disease activity and CD4 + T cell subsets. Methods:① The concentration of IRAK1 in the peripheral blood of 77 RA patients and 24 healthy controls were detected by enzyme linked immunosorbent assay (ELISA). ② The demo-graphic and clinical data of the RA group including disease activity score with 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CD4 + T cell subsets in peripheral blood. ③Independent sample t test or Mann-Whitney U test were used to compare the differences between the two groups. Spearman rank correlation test and multiple linear regression were used to analyze the correlation between IRAK1 expression level and clinical data. Results:① The IRAK1 level of the peripheral blood of RA patients was significantly higher than in the normal controls ( P<0.001). ② Compared to normal controls, the peripheral blood of the RA group, the absolute numbers and proportion of regulatory T (Treg) cells were decreased ( P<0.001), the absolute numbers and proportion of helper T (Th) 17 and the ratio of Th17/Treg were increased. Moreover, the ratio of Th17/Treg was also increased. ③ With the increase of disease activity in RA patients, the expression of IRAK1 also increased. The expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR, number of joints involved and DAS28, and had statistically significant difference between the two groups ( r=0.23, P<0.05; r=0.24, P<0.05; r=0.27, P<0.05). Meanwhile, it was sign-ificantly negatively correlated with the percentage of Treg ( r=-0.27, P<0.05), and was significantly positively correlated with the ratio of Th17/Treg ( r=0.23, P<0.05) . However, there was no significant correlation with the ratio of Th1/Th2( P>0.05). Furthermore, multiple stepwise regression analysis showed that the expression of IRAK1 in the peripheral blood of RA group was positively correlated with ESR and the number of joints involved ( β=0.34, P=0.019; β=0.27, P=0.004), and it was inversely correlated with percentage of Treg ( β=-0.23, P=0.047, R2=0.219). Conclusion:IRAK1 expression in the peripheral blood of RA patients is up-regulated and correlated with disease activity. The decrease of Treg and the imbalance of Th17/Treg caused by high expression of IRAK1 may be one of the main factors for the occurrence and development of RA. Interfering the expression of IRAK1 may be a potential new target for RA treatment.

Effectiveness of antiretroviral therapy for the first time on HIV/AIDS patients in Jiangyin / 公共卫生与预防医学

Objective To analyze the effect of HIV/AIDS patients receiving antiretroviral therapy (ART) for the first time in Jiangyin, and to provide a reference for further improvement of Jiangyin's AIDS antiretroviral treatment. Methods The historical cards and related information in the treatment management database of Jiangyin City's cases who received ART for the first time from 2005 to 2019 were collected and statistically analyzed. The changes in viral load and CD4+ T lymphocytes (CD4 cells) before and after treatment were compared. Results Among 652 patients receiving ART, 507 cases (77.76%) were successful in virological treatment. The median natural change rate of annual average CD4 cell count was 90.8 cells/μL/year (χ2=37.915, P2=10.713, P<0.05; H =10.394, P<0.05) and different baseline CD4 count layers. The results showed that age and baseline CD4 value were the influencing factors of treatment effect. Conclusion Age and baseline CD4 value can affect the effect of ART treatment. The older the age and the lower the baseline CD4 value, the worse the virological efficacy and the recovery effect of CD4 cells. It is suggested that the infected patients should be involved in ART in time, which is conducive to shorten the time of initial treatment and further improve the effect of antiviral treatment.

Expression and relevance of long non-coding RNA MIAT in CD4+T cells in peripheral blood of gastric cancer patients / 中华检验医学杂志

Objective:To explore the expression of long-chain noncoding RNA (lncRNA) and myocardial infarction-associated transcription (MIAT) in Leukocyte differentiation antigen (CD)4+T cells in peripheral blood of gastric cancer patients and its value of clinical application.Methods:Peripheral blood CD4+T cells were collected from 124 patients with gastric cancer, 90 benign gastric diseases patients and 80 healthy controls enrolled in Taizhou People′s Hospital from January 2019 to April 2021. The expression levels of MIAT and N6-methyladenosine(m6A) binding to MIAT promoter in CD4+T cells were detected by real-time fluorescent quantitative polymerase chain reaction (qPCR) and Chromatin immunoprecipitation (ChIP)-qPCR, respectively. Spearman test was used to analyze the correlation between MIAT and clinicopathological features, as well as between MIAT and regulatory T cell levels. The receivor operating characteristic curve (ROC) of the subjects was used to evaluate the MIAT expression level in the auxiliary diagnostic value of gastric cancer.Results:The relative expression levels of MIAT in the gastric cancer patients, the benign gastric diseases patients, and the healthy controls were 2.849 (2.131, 4.062), 1.511 (0.916, 1.855) and 0.963 (0.729, 1.432), respectively. The difference among the three groups was statistically significant ( H=158.25, P<0.001). The relative expression level of MIAT in the gastric cancer patients was significantly higher than the levels in the benign gastric diseases patients and healthy controls. The difference was statistically significant ( Z=100.63, 145.14, P<0.001). The binding activity of m6A to MIAT promoter in patients with early stage (stage Ⅰ and Ⅱ) and end stage (stage Ⅲ and Ⅳ) gastric cancer was 8.590±1.483 and 4.274±0.425, respectively. The difference was statistically significant ( t=6.255, P=0.002). Furthermore, the binding activity of m6A to MIAT promoter in the gastric cancer patients was significantly lower than that in patients with benign gastric diseases (17.267±3.106) and healthy controls (27.637±3.945) ( t=-7.331,-12.832, P<0.001). The relative expression of MIAT in CD4+T cells in peripheral blood of the gastric cancer patients had no significant difference in age(χ2=0.000, P=1.000), gender(χ2=0.000, P=1.000), CEA (χ2=0.648, P=0.421) and CA199(χ2=1.554, P=0.213), but had significant difference with tumor size expression(χ2=9.443, P<0.01), TNM stage(χ2=23.571, P=0.002) and lymph node metastasis (χ2=45.248, P<0.01). In addition, there was a significant positive correlation between the relative expression of MIAT in CD4+T cells and Treg level ( r2=0.76, P<0.001). The diagnostic efficacies of MIAT in CD4+T cells, CEA and CA199 in the gastric cancer patients were analyzed by ROC curve. When compared with patients with benign gastric diseases, the areas under the curve were 0.879, 0.635 and 0.611, respectively. When compared with healthy patients, the areas under the curve were 0.953, 0.784 and 0.598, respectively. Conclusions:The level of MIAT in CD4+T cells in peripheral blood of patients with gastric cancer is significantly higher than the levels in patients with benign gastric diseases and the healthy controls, which may be related with the decreased activity of m6A binding to the promoter of MIAT. The level of MIAT in CD4+T cells may be a relevant biomarker for the diagnosis and prognosis of gastric cancer.

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Criptococosis meníngea en un paciente con linfopenia T-CD4+ idiopática / Cryptococcal meningitis in a patient with idiopathic CD4+ T lymphopenia

RESUMEN La infección por el virus de la inmunodeficiencia humana es el factor de riesgo principal para desarrollar criptococosis meníngea; sin embargo, existe una entidad poco conocida, la linfopenia T-CD4+ idiopática, que genera un inexplicable déficit de células T-CD4+ circulantes predisponiendo a variadas complicaciones, entre ellas la infección por gérmenes oportunistas. Presentamos el caso de un paciente con criptococosis meníngea secundaria a una linfopenia T-CD4+ idiopática, que a nuestro conocimiento es el primer caso reportado en el Perú. Esta enfermedad debería considerarse en pacientes negativos para el virus de inmunodeficiencia humana, que cursen con infecciones infrecuentes del sistema nervioso central, ya que la evolución, manejo y pronóstico podrían ser distintos en pacientes con esta condición.

ABSTRACT Infection with the human immunodeficiency virus (HIV) is the main risk factor for developing cryptococcal meningitis. However, there is a poorly known entity, idiopathic CD4+ T-cell lymphopenia, which leads to an unexplainable CD4+ circulating T-cell deficit, predisposing patients to many complications, including infections caused by opportunistic microorganisms. We present the case of a patient with cryptococcal meningitis secondary to idiopathic T-CD4+ lymphopenia, which, as far as we know, is the very first case of its kind reported in Peru. This entity should be considered in patients negative for HIV infection developing non-common infections of the central nervous system, since outcome, management, and prognosis may be different in patients with this condition.

Infección por citomegalovirus en púrpura de Henoch-Schönlein del anciano como complicación y factor perpetuador de la enfermedad. Reporte de caso / Cytomegalovirus infection and Henoch-Schönlein purpura in the elderly as a complication and factor that perpetuates the disease. Case report

RESUMEN La púrpura de Henoch-Schönlein en el adulto es un reto diagnóstico. Su baja incidencia y su sintomatología poco específica configuran un cuadro clínico que puede pasar desapercibido en diversas ocasiones o solaparse bajo el peso de diferentes sospechas diagnósticas. La púrpura de Henoch-Schönlein no es un cuadro de espectro único. Se considera un grupo de enfermedades de manifestación heterogénea con un eje patogénico común dado por el hallazgo de inflamación de la pared en vasos de pequeño calibre mediada por complejos inmunes. Este es el caso de un paciente de 70 arios quien cursa con un cuadro compatible con púrpura de Henoch-Schönlein, de inicio tardío, caracterizada por su difícil manejo y constantes recaídas. a pesar del uso cuidadoso de las pautas terapéuticas establecidas por los consensos actuales. En este paciente se documentó, de forma concomitante, una infección por citomegalovirus que al recibir tratamiento permitió el control adecuado de síntomas. Adicionalmente, este paciente presentaba una linfocitopenia que parecía ser secundaria a la infección viral.

ABSTRACT Henoch-Schönlein purpura in the adult is a diagnostic challenge. Its low incidence and its unspecific symptomatology in this age group, establish a clinical chart that can be ignored on several occasions. Henoch-Schönlein purpura is considered a group of diseases of heterogeneous manifestation with a common pathogenic axis: the finding of inflammation of the wall of the small calibre vessels, mediated by immune complexes. The case is presented of a 70-year-old patient with a difficult to treat Henoch-Schönlein purpura, with constant relapses despite the use of the therapeutic guidelines established in the current guidelines. In this patient, a concomitant cytomegalovirus infection was documented that, after receiving treatment, allowed adequate control of symptoms. Additionally, this patient also had a lymphocytopenia that was secondary to cytomegalovirus.

Preliminary study on the causes of anemia in newborns delivered by human immunodeficiency virus infected mothers / 中华传染病杂志

Objective:To investigate the causes of anemia in newborns delivered by human immunodeficiency virus (HIV) infected mothers.Methods:This was a retrospective study. Forty-two newborns delivered by HIV infected mothers during January 2010 and May 2019 in Beijing Ditan Hospital Affiliated to Capital Medical University were selected. According to the hemoglobin levels of newborns on the days of their birth, newborn cases were divided into two groups, anemia group and non-anemia group. The clinical data including gestational ages, birth weight, maternal anemia status during pregnancy, using of antiviral drugs during pregnancy, percentages of HIV RNA positivity in early pregnancy/pre-treatment and before delivery, maternal percentage of different CD4 + T lymphocyte counts in early pregnancy/pre-treatment and before delivery between two groups were compared. The efficacies of relative indicators for prediction of anemia in newborns were evaluated by the area under receiver operating characteristic curve (AUROC). Differences between groups were compared by chi-square test. Results:Among 42 cases of newborns, 14 cases were in anemia group and 28 cases in non-anemia group. There were no statistical differences in gestational ages, birth weight, maternal anemia status during pregnancy and positive percentage of HIV RNA before delivery between two groups ( χ2=2.211, 1.025, 1.362 and 3.783, respectively, P=0.283, 0.763, 0.181 and 0.092, respectively). In anemia group, 11 mothers took zidovudine during pregnancy, which was 12(42.86%) in non-anemia group. The difference was statistically significant ( χ2=4.359, P=0.037). Eight cases of mothers with HIV RNA positive in early pregnancy/pre-treatment in the anemia group, which was 11(39.29%) in the non-anemia group. The difference was statistically significant ( χ2=6.490, P=0.011). The number of CD4 + T lymphocyte count ≤500/μL was 13 in early pregnancy/pre-treatment in anemia group, which was 20(71.43%) in the non-anemia group. The difference was statistically significant ( χ2=16.396, P<0.01). The number of CD4 + T lymphocyte ≤0.28 was 13 in early pregnancy/pre-treatment in the anemia group, which was 19(67.86%) in the non-anemia group ( χ2=19.908, P<0.01). The number of CD4 + T lymphocyte count ≤500/μL was 14 before delivery, which was 15(53.37%) in the non-anemia group ( χ2=9.536, P=0.008). The number of CD4 + T lymphocyte ≤0.28 before delivery was 14 in anemia group, which was 15(53.37%) in the non-anemia group ( χ2=9.750, P=0.006). According to the receiver operating characteristic curve results, the AUROC, optimal cut-off value, sensitivity and specificity of CD4 + T lymphocyte count before delivery in predicting neonatal anemia were 0.708, 476.0/μL, 100.0% and 50.0%, respectively. The AUROC, optimal cut-off value, sensitivity and specificity of maternal CD4 + T lymphocyte percentage before delivery in predicting neonatal anemia were 0.719, 0.275, 100.0% and 53.6%, respectively. Conclusion:Low CD4 + T lymphocyte level in HIV-infected mothers before delivery, HIV positive in early pregnancy/pre-treatment and using of zidovudine during pregnancy may be associated with neonatal anemia.

Screening of differentially expressed genes in CD4 + T cells in peripheral blood of 45 leprosy patients / 中华皮肤科杂志

Objective:To detect the mRNA expression profile of CD4 + T cells in the peripheral blood of leprosy patients, and to screen and identify genes that may be closely related to the pathogenesis of leprosy. Methods:From July 2018 to May 2020, 45 leprosy patients were collected from Hunan Province, and 45 healthy volunteers from Health Examination Center of Changsha Central Hospital. CD4 + T cells were isolated from peripheral blood samples by using magnetic beads, and then RNA was extracted. Solexa sequencing was performed to screen differentially expressed genes between 6 patients and 6 healthy controls, who were randomly selected from the above subjects. Differentially expressed genes were defined as those with a fold change greater than 2 and a P value below 0.05, and then Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed. Real-time fluorescence-based quantitative PCR was conducted to verify the gene expression. Results:Genetic screening revealed 4 831 newly-discovered transcripts with protein-coding potential. Eight differentially expressed genes were screened out between the two groups. Among them, the mRNA expression of CXCL8, PPBP, RPS18 and IL-1β genes was up-regulated, while the mRNA expression of RNH1, RPL39, RPL15 and AMBRA1 genes was down-regulated. Verification results of real-time fluorescence-based quantitative PCR were consistent with the above-mentioned genetic screening results. KEGG analysis showed that the differentially expressed genes between leprosy patients and healthy controls were mainly enriched in mitochondrial autophagy, autophagy-related pathways and human papillomavirus infection pathways.Conclusion:Down-regulated mRNA expression of AMBRA1 and RNH1 genes and up-regulated mRNA expression of CXCL8, PPBP and IL-1β genes were identified in patients with leprosy, which may be involved in the pathogenesis of leprosy through the mitochondrial autophagy pathway and chemokine-mediated signaling pathway, respectively.

Caracterización de las manifestaciones otorrinolaringológicas en pacientes con infección por VIH/Sida en la ciudad de Cartagena / Characterization of the otorrinolaringological manifestations in patients with HIV/AIDS infection in the city of Cartagena

Introducción: en Colombia, la incidencia por virus de inmunodeficiencia humana (VIH) ha ido en aumento; la ciudad de Cartagena tiene una de las más altas del país. Las manifestaciones otorrinolaringológicas en personas con VIH se estiman entre un 20%-80%, lo que genera un gran impacto en la calidad de vida. Objetivo: determinar las características epidemiológicas y las manifestaciones otorrinolaringológicas en un grupo de personas con VIH/Sida de la ciudad de Cartagena. Metodología: diseño observacional descriptivo de corte transversal y prospectivo. Se recolectó información de pacientes con VIH de la ciudad de Cartagena, que asistieron a dos centros médicos. Se les aplicó un cuestionario para obtener datos epidemiológicos, signos y síntomas otorrinolaringológicos, así como un examen físico otorrinolaringológico completo. Resultados: se incluyeron 150 pacientes en el estudio, con una media de edad de 31 años, 59,3% del género masculino y 40,7% del femenino. El antecedente patológico no otorrinolaringológico más frecuente fue la coinfección por sífilis en un 10%; el otorrinolaringológico fue la sinusitis y la candidiasis oral, cada uno con un 3,3%. El 73% de los pacientes manifestó alteración otorrinolaringológica en el momento de la evaluación. Las más frecuentes fueron las otológicas, con el 39,9% de los pacientes. Además, se observó una relación estadísticamente significativa entre los conteos de CD4 y hallazgos como disfonía en laringe (p = 0,045). Conclusiones: las manifestaciones otológicas fueron las más frecuentes en nuestro medio y se encontró una relación entre el conteo de CD4 y las manifestaciones laríngeas de la enfermedad.

Introduction: In Colombia, the incidence of the disease has been increasing and Cartagena has the highest numbers of the country. Otorhinolaryngological manifestations in people with HIV/AIDS are estimated between 20%-80% generating a great impact on quality of life. Objective: To determine the epidemiological characteristics and otorhinolaryngological manifestations in a group of people with HIV / AIDS in the city of Cartagena. Methodology: Observational, descriptive, cross-sectional and prospective design. Information was collected from patients with HIV from the city of Cartagena who attended 2 medical centers, a questionnaire was applied to obtain epidemiological data, otorhinolaryngological signs and symptoms, as well as a complete otorhinolaryngological physical examination. Results: 150 patients were included in the study, with a mean age of 31 years, 59.3% male and 40.7% female. The most frequent non-otorhinolaryngological pathological antecedent was syphilis coinfection in 10% and otorhinolaryngological, sinusitis and oral candidiasis each with 3.3%. 73% of the patients at the time of the evaluation manifested otorhinolaryngological alteration, the otological ones being the most frequent with 39.9% of the patients. Furthermore, a significant relationship was observed between CD4 counts and findings such as laryngeal dysphonia (p = 0.045). Conclusions: The otological manifestations were the most frequent in our environment and a relationship was found between the CD4 count and the laryngeal manifestations of the disease.

Detection of autophagy in peripheral CD4+ T lymphocytes and skin lesions of patients with herpes zoster / 中华皮肤科杂志

Objective To observe changes in expression of autophagy proteins in peripheral CD4+ T lymphocytes and the epidermis of skin lesions,as well as generation of autophagy vesicles in epidermal cells in skin lesions of patients with herpes zoster,and to explore the relationship between varicella-herpes zoster virus (VZV) infection and autophagy.Methods Totally,35 patients with herpes zoster were enrolled from Department of Dermatology,General Hospital of Southern Theater Command of PLA between December 2017 and December 2018,including 20 males and 15 females.Their age ranged from 18 to 79 (59.23 ± 9.27) years,pain duration was 5.14 ± 2.28 days,and lesion duration (from the onset of the lesion to the clinic visit) was 3.45 ± 1.77 days.Flow cytometry was performed to determine the expression of autophagy proteins including microtubule-associated protein 1 light chain 3B (LC3B),Beclin-1 and p62 in peripheral blood CD4 + T lymphocytes of these patients.Thirty healthy adults served as control group.Lesional skin tissues were obtained from 12 patients with herpes zoster,and perilesional normal skin tissues of the same patient served as the control.Immunohistochemical study was conducted to determine the expression of autophagy proteins LC3B,Beclin-1 and p62 in epidermal tissues,and transmission electron microscopy to observe the generation of autophagy vesicles in epidermal cells.Two independent-sample t-test was carried out for intergroup comparison.Results The expression rates of autophagy proteins LC3B and Beclin-1 in peripheral CD4 + T lymphocytes were significantly higher in the herpes zoster group (61.23％ ± 7.61％,35.84％ ± 4.22％,respectively) than in the control group (36.56％ ± 4.27％,15.34％ ± 1.89％,respectively;t =15.75,24.56 respectively,both P ＜ 0.01),while the expression rate of p62 (5.75％ ± 0.67％) was significantly lower in the herpes zoster group than in the control group (10.03％ ± 1.15％,t =18.65,P ＜ 0.01).Among the 12 patients with herpes zoster,the expression levels of LC3B and Beclin-1 in the epidermis were significantly higher in the skin lesions than in the perilesional normal skin tissues (t =2.86,4.58,P ＜ 0.05),but the expression level of p62 was significantly lower in the skin lesions than in the perilesional normal skin tissues (t =2.43,P ＜ 0.05).Transmission electron microscopy showed formation of autophagy vesicles containing virus particles in epidermal cells in the skin lesions of 12 patients with herpes zoster,and vesicle counts were significantly higher in the skin lesions than in perilesional normal skin tissues (t =9.67,P ＜ 0.01).Conclusion The autophagy level was elevated in peripheral CD4+ T lymphocytes and epidermis of skin lesions of patients with herpes zoster.

Change and clinical significance of T helper 9 cells in previously untreated patients with chronic hepatitis C / 临床肝胆病杂志

ObjectiveTo investigate the changes of T helper 9 (Th9) cells, interleukin-9 (IL-9), and related transcription factors in previously untreated patients with chronic hepatitis C, as well as their association with clinical indices. MethodsA total of 29 previously untreated patients with chronic hepatitis C who attended Hainan Provincial People’s Hospital from December 2018 to July 2019 were enrolled, and 15 healthy individuals were enrolled as healthy controls. The patients with chronic hepatitis C received sofosbuvir/velpatasvir antiviral therapy for 12 weeks, and then plasma and peripheral mononuclear cells (PBMCs) were isolated. Flow cytometry was used to measure the percentage of CD3+CD4+IL-9+ Th9 cells in PBMCs; ELISA was used to measure the plasma level of IL-9; quantitative real-time PCR was used to measure the relative mRNA expression of IL-9 and the transcription factors PU.1 and Foxo1 in PBMCs. The t-test or the paired t-test was used for comparison between two groups, and a Pearson correlation analysis was used to investigate correlation. ResultsCompared with the healthy controls, the previously untreated chronic hepatitis C patients had significantly lower percentage of peripheral Th9 cells (0.92%±0.14% vs 1.14%±0.21%, t=4.31, P＜0.001) and plasma IL-9 level (248.2±66.97 pg/ml vs 309.02±88.48 pg/ml, t=2.63, P=0.012). The previously untreated chronic hepatitis C patients had significantly lower relative mRNA expression of IL-9 and PU.1 than the healthy controls (t=20.67 and 23.21, both P＜0.001), while there was no significant difference in the relative mRNA expression of Foxo1 between the previously untreated chronic hepatitis C patients and the healthy controls (P＞0.05). In the previously untreated chronic hepatitis C patients, the percentage of peripheral Th9 cells, IL-9 level, and mRNA expression of IL-9 and PU.1 were negatively correlated with HCV RNA (r=-0.46, -0.38, -0.52, and -0.41, all P＜0.05), but they were not correlated with the level of alanine aminotransferase (all P＞0.05). Sofosbuvir/velpatasvir antiviral therapy achieved virologic response in 29 chronic hepatitis C patients, and the percentage of peripheral Th9 cells and the mRNA expression of PU.1 after antiviral therapy were significantly higher than those at baseline (t=2.20 and 6.52, both P＜0.05), while there were no significant changes in the plasma level of IL-9 and the relative mRNA expression of IL-9 from baseline to after treatment (both P＞0.05). ConclusionChronic hepatitis C virus infection may suppress the activation of Th9 cells, suggesting that Th9 cells might be involved in the chronicity of hepatitis C virus infection.

Effects of interleukin-35 on the balance of helper T cell 17/regulatory T cell in peripheral blood of patients with oral lichen planus / 中华口腔医学杂志

Objective@#To investigate the effects of exogenous interleukin (IL)-35 on the balance of helper T cell 17 (Th17) and regulatory T cell (Treg) in peripheral blood of patients with oral lichen planus (OLP).@*Methods@#Totally 12 peripheral blood samples of OLP patients (OLP group, one male and 11 female, 26-68 years old; four cases of reticular OLP and eight cases of erosive OLP) were collected from patients of Department of Oral Mucosal Specialist of the Affiliated Hospital of Guizhou Medical University from October to December 2016. During the same period, thirteen normal peripheral blood samples were collected from the Physical Examination Center of the Affiliated Hospital of Guizhou Medical University (normal control group, one male and 12 female, 20-68 years old). The peripheral blood mononuclear cells (PBMC) were extracted in sterile condition and CD4+ T cells were sorted by flow cytometry (FCM). Quantitative real-time PCR (qPCR) technique was used to detect the mRNA expression levels of retinoid-related orphan nuclear γt (RORγt) and forkhead box3 (Foxp3). The CD4+ T cells were divided into experimental group and control group. The CD4+ T cells of experimental group were cultured in vitro by adding rhIL-35, and the CD4+ T cells of control group were cultured with the same volume of phosphate buffered saline (PBS). After the completion of the culture, the cells were collected. The expression levels of the same factors were detected by qPCR.@*Results@#The expression [M(Q25, Q75)] of Foxp3 [0.15 (0.09, 0.30)] and RORγt mRNA [1.04 (0.45, 2.15)] in the CD4+ T cells of OLP were significantly higher than those in normal control group [0.04 (0.02, 0.06), 0.10 (0.05, 0.11)] (Z=-4.134, P<0.01; Z=-3.699, P<0.01). The ratio of ROR γt/Foxp3 mRNA in OLP group [6.22(3.67, 15.34)] was higher than that in normal control group [2.50 (1.24, 5.23)] (Z=-2.665, P=0.007). In the CD4+ T cells of OLP patients, the expression of Foxp3 mRNA in the experiment group [0.40 (0.21, 1.22)] was higher than that in the control group [0.15 (0.11, 0.26)](Z=-2.510, P=0.012), and the expression of ROR γt mRNA between two groups showed no significant difference (P>0.05). The ROR γt/Foxp3 mRNA ratio [3.44 (1.55, 8.16)] of the experiment group was lower than that in the control group [6.22 (4.43, 12.21)] (Z=-2.746, P=0.006).@*Conclusions@#There was a Th17/Treg imbalance with predominated by Th17 cells in the peripheral blood of patients with OLP. Exogenous rhIL-35 had an immunomodulatory effect on the balance of Th17/Treg.

Detection of autophagy in peripheral CD4+ T lymphocytes and skin lesions of patients with herpes zoster / 中华皮肤科杂志

Objective@#To observe changes in expression of autophagy proteins in peripheral CD4+ T lymphocytes and the epidermis of skin lesions, as well as generation of autophagy vesicles in epidermal cells in skin lesions of patients with herpes zoster, and to explore the relationship between varicella-herpes zoster virus (VZV) infection and autophagy.@*Methods@#Totally, 35 patients with herpes zoster were enrolled from Department of Dermatology, General Hospital of Southern Theater Command of PLA between December 2017 and December 2018, including 20 males and 15 females. Their age ranged from 18 to 79 (59.23 ± 9.27) years, pain duration was 5.14 ± 2.28 days, and lesion duration (from the onset of the lesion to the clinic visit) was 3.45 ± 1.77 days. Flow cytometry was performed to determine the expression of autophagy proteins including microtubule-associated protein 1 light chain 3B (LC3B) , Beclin-1 and p62 in peripheral blood CD4+ T lymphocytes of these patients. Thirty healthy adults served as control group. Lesional skin tissues were obtained from 12 patients with herpes zoster, and perilesional normal skin tissues of the same patient served as the control. Immunohistochemical study was conducted to determine the expression of autophagy proteins LC3B, Beclin-1 and p62 in epidermal tissues, and transmission electron microscopy to observe the generation of autophagy vesicles in epidermal cells. Two independent-sample t-test was carried out for intergroup comparison.@*Results@#The expression rates of autophagy proteins LC3B and Beclin-1 in peripheral CD4+ T lymphocytes were significantly higher in the herpes zoster group (61.23% ± 7.61%, 35.84% ± 4.22%, respectively) than in the control group (36.56% ± 4.27%, 15.34% ± 1.89%, respectively; t = 15.75, 24.56 respectively, both P < 0.01) , while the expression rate of p62 (5.75% ± 0.67%) was significantly lower in the herpes zoster group than in the control group (10.03% ± 1.15%, t = 18.65, P < 0.01) . Among the 12 patients with herpes zoster, the expression levels of LC3B and Beclin-1 in the epidermis were significantly higher in the skin lesions than in the perilesional normal skin tissues (t = 2.86, 4.58, P < 0.05) , but the expression level of p62 was significantly lower in the skin lesions than in the perilesional normal skin tissues (t = 2.43, P < 0.05) . Transmission electron microscopy showed formation of autophagy vesicles containing virus particles in epidermal cells in the skin lesions of 12 patients with herpes zoster, and vesicle counts were significantly higher in the skin lesions than in perilesional normal skin tissues (t = 9.67, P < 0.01) .@*Conclusion@#The autophagy level was elevated in peripheral CD4+ T lymphocytes and epidermis of skin lesions of patients with herpes zoster.

Relationships between phenotype and function of blood cd4+ t-cells and ascending thoracic aortic aneurysm: an experimental study

Abstract Introduction: Non-familial ascending thoracic aorta dilation and aneurysms (TAAs) are silent diseases in elderly patients. Histopathology revealed that functionally polarized infiltrating CD4+ T-cells play a key role in aortic wall weakening. Objective: To evaluate the possible associations between phenotype and cytokine production of circulating CD4+ T-lymphocytes and the presence of TAA in patients with aortic valve disease (AVD). Methods: We studied blood samples from 10 patients with TAA and 10 patients with AVD. Flow cytometry was used to quantify: a) CD4+ T-lymphocytes surface expression of CD25, CD28, and chemokine receptors (CCR5, CXCR3, CX3CR1); b) fractions of in vitro stimulated CD4+ T-cells producing cytokines (interferon gamma [IFN-γ], interleukin [IL]-17A, IL-21, IL-10); c) CD4+CD25highFoxP3+ regulatory T-cells (Treg) fraction. Enzyme-linked immunosorbent assays (ELISA) were performed for cytokines (IFN-γ, IL-6, IL-10, IL-17A, IL-23, transforming growth factor beta [TGF-β]) and chemokines (RANTES, CX3CL1). Results: The total CD4+CD28±CD4+/CX3CR1+ T-cells fraction was higher (P=0.0323) in AVD (20.452±4.673) than in TAA patients (8.633±2.030). The frequency ratio of CD4+ T-lymphocytes producing IFN-γ vs. IL-17A+IL-21 cytokine-producing CD4+ T-cells was higher (P=0.0239) in AVD (2.102±0.272) than in TAA (1.365±0.123) patients. The sum of CD4+CD28±CD4+/CX3CR1+ T-cells correlated positively with values of the previous cytokine ratio (P=0.0002, R=0.732). The ratio of CD4+CD28±CD4+/CX3CR1+ T-cells vs. Treg was higher (P=0.0008) in AVD (20.859±3.393) than in TAA (6.367±1.277) patients. Conclusion: Our results show that the presence of TAA in subjects with AVD is associated with imbalance between phenotypic and cytokine-producing subsets of circulating CD4+ T-lymphocytes, prevalently oriented towards a pro-fibrotic and IFN-γ counteracting effect to functional polarization.

Expression of miRNA-148a-3p in CD4+ T lymphocytes in peripheral blood of patients with psoriasis vulgaris and its clinical significance / 中华皮肤科杂志

Objective To determine the expression of miRNA-148a-3p in CD4+ T lymphocytes in peripheral blood of patients with psoriasis vulgaris,and to explore its role in occurrence of psoriasis vulgaris.Methods Totally,20 patients with psoriasis vulgaris and 20 healthy controls were enrolled from Guangzhou Institute of Dermatology between July 2017 and April 2018.Peripheral venous blood samples were obtained from these subjects,and CD4+ T lymphocytes were isolated from these peripheral blood samples by magnetic cell sorting system.Real-time quantitative PCR (RT-PCR) was performed to determine the expression of miRNA-148a-3p in CD4+ T lymphocytes in the peripheral blood.Potential target genes of miRNA-148a were predicted by using bioinformatics software,and verified by using a dual-luciferase reporter system.Western blot analysis was conducted to determine the protein expression of Bcl-2 interacting mediator of cell death (Bim,the potential target gene of miRNA-148a-3p) in the CD4+ T lymphocytes of the subjects.Statistical analysis was carried out with SPSS 20 software by two sample-t test for comparing the means of normally distributed data,and by Pearson correlation analysis for analyzing the correlation of two variables.If the data were not normally distributed,Mann Whitney U test was used for comparing means between two groups,and Spearman correlation analysis for analyzing the correlation of two variables.Results The miRNA-148a-3p expression in the CD4+ T lymphocytesin the psoriasis vulgaris group (18 cases,5.61 ± 1.66) was significantly higher than that in the healthy control group (12 cases,1.00 ± 0.26;U =12,P ＜ 0.05),and was positively correlated with the psoriasis area severity index (PASI) score (r =0.93,P ＜ 0.001).Bim was predicted to be one of the potential target genes of miRNA-148a-3p by bioinformatics software,which was also verified by using a dual-luciferase reporter system.The protein expression of Bim in the CD4 + T lymphocytes was significantly lower in the psoriasis vulgaris group (11 cases,0.69 ± 0.07) than in the healthy control group (8 cases,0.93 ± 0.06;t =4.38,P ＜ 0.01),and the protein expression of Bim in the patients with psoriasis vulgaris was negatively correlated with PASI score (r =-0.774,P ＜ 0.01).Conclusion miRNA-148a-3p is overexpressed in CD4+ T cells in the peripheral blood of patients with psoriasis vulgaris,which may regulate the protein expression of Bim,leading to abnormal activation of CD4+ T cells,and then participate in the occurrence and development of psoriasis.