Relationship Between Peripheral Blood T Lymphocyte Subsets and Prognosis of Patients with Advanced Non-small Cell Lung Cancer Treated with Camrelizumab / 肿瘤防治研究

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Effect of intensive training on immune system cells in elite female weightlifters

SUMMARY OBJECTIVE: This study aimed to investigate the effects of intense weightlifting training on lymphocyte and natural killer cell subgroups, which are the major cells of the immune system, in elite female weightlifters. METHODS: A total of 20 elite female weightlifters were evaluated using flow cytometry before training (pre-T), immediately after training (post-T), and after a 120-min rest period (rest-T). RESULTS: Post-T and rest-T showed significant decreases in helper T (Th) and cytotoxic T compared with pre-T (p=0.045, p<0.001 and p=0.05, p<0.001, respectively). B and natural killer cells were higher in post-T and rest-T than in pre-T. The increase in B cells was significant in pre-T/rest-T (p<0.001) but not in pre-T/post-T (p=0.122). Intense training significantly increased natural killer cells in both post-T and rest-T (p<0.001). CD56bright and CD56dim natural killer cell subgroups were significantly lower in post-T and rest-T than in pre-T (p=0.005, p=0.006 and p<0.001, p=0.004, respectively). CONCLUSION: This study shows that intense weightlifting alters peripheral lymphocyte and natural killer subgroup ratios, being the first investigation in this field.

Evaluación comparativa de medición de linfocitos CD4+ por dos técnicas: estándar nacional versus test rápido de ejecución local

Antecedentes: El recuento de linfocitos CD4+ (LTCD4) es una herramienta fundamental para la evaluación y seguimiento de los pacientes que viven con VIH. En Chile, la medición de LTCD4 estandarizada es por citometría de flujo. En el sistema público se realiza en forma centralizada en tres centros. Actualmente existen tecnologías de medición rápida de recuento de LTCD4 en el lugar de atención, permitiendo optimizar la atención de pacientes con infección por VIH. Objetivo: Comparar la precisión de un test rápido de ejecución local versus la técnica estándar. Metodología: Realización de ambas técnicas en un grupo de 102 pacientes durante su control regular de salud. Resultados: El rango de variación promedio de los resultados entre las dos técnicas fue de 10%, con una concordancia en los recuentos de LTCD4 de 97% para el rango de CD4 < 200 cél/uL, de 88% para los pacientes con recuento de LTCD4 entre 200 y 349 cél/uL y de 67% en los rangos superiores. Conclusión: La técnica por test rápido es un sistema fácil de aplicar, de bajo costo, con alta concordancia con la técnica estándar, lo que debería considerarse en la atención de los pacientes que viven con VIH.

Background: The CD4+ lymphocyte cell count is an instrumental tool for the assessment and follow-up in the therapeutic management of patients living with HIV. In Chile, the standardized CD4+ lymphocyte count technique is by flow cytometry. In the public health system, it is performed centralized in 3 sites. Currently, there are technologies that allow measuring the CD4 lymphocyte count at the point of care, allowing to optimize the care of HIV-infected patients. Aim: To compare the accuracy of a point of care rapid test versus the standard technique in patients under regular care at a single HIV center. Results: The average variation of the results between the two techniques was 10%, with a 97% concordance in CD4 range values for patients with CD4 below 200 cells/uL, 88% for CD4 counts between 200 and 349 cells/uL. and 67% above that range. Conclusion: This point of care test is an easy-to-operate, low-cost system with high correlation with the standard technique and should be considered in the care of patients living with HIV.

Impact Of Integrated Yoga Practice on Immune Parameters and Quality of Life of Adult People Living With HIV: Protocol for A Randomized Open-Label Trial in Chittoor, India

Background: Yoga therapy can be a promising adjunct to antiretroviral therapy. However, evidence on the ef-fectiveness of Yoga therapy is scanty. The proposed trial will estimate the effect of integrated yoga practice for six months on immune parameters (CD4 (cluster of differentiation 4), viral load) among adult people living with HIV (PLWH) and its cost-effectiveness from the healthcare system’s perspective. Methods: In this randomized open-label parallel-group trial, 110 PLWH in stage 2 HIV, between 18 and 49 years in the intervention arm and 220 PLWH in the same stage will be recruited by block randomization. Inte-grated yoga practice will be given for six months in the intervention arm, and health education on yoga prac-tice in the control arm, besides antiretroviral therapy. After six months, the difference in immune parameters, cardio-metabolic indicators and quality of life (QOL) will be assessed. Besides, an economic evaluation will be done with sensitivity analysis. If found useful, the intervention can be tested at large scale for further confir-mation of the outcomes. Irrespective of the study's outcome, the results will be disseminated through peer-reviewed journals.

Opportunistic infections according to the CD4+ T lymphocyte count in patients with HIV at a tertiary care referral center

Opportunistic infections (OIs) have marked the prognosis in the natural course of patients with human immunodeficiency virus (HIV) infection. Objective: identifying the most common OIs and determining their relationship with the CD4+ lymphocyte count (CD4+TL) can improve our clinical practice and facilitate early diagnosis, the use of empiric treatments and prompt targeted treatment. Materials and methods: an observational, retrospective study aimed at describing the characteristics and variations of the OIs diagnosed clinically, using direct or indirect methods, which occur in patients with HIV (related to their CD4+TL count) who are admitted to a tertiary care center in Cali, Colombia. Adult patients hospitalized from January 2018 to January 2019 with a diagnosis of HIV/AIDS and a history or current diagnosis of OI were included. Individuals under the age of 18 and pregnant women were excluded. Results: a sample of 190 patients with at least one opportunistic infection was obtained, of whom 65.3% were men with a median age of 37 years (29.0-46.0), and the rest were women with a median age of 35.5 years (31.2-43.0). Eighty-three percent had a C3 classification on admission, 86% with a CD4+TL count < 200 cells/mm3. The most frequent OIs included tuberculosis, with 28.4%, pneumocystosis with 27.9% and toxoplasmosis with 27.4%. Conclusions: in our population, despite advances in and greater availability of highly-effective antiretroviral therapy, most patients with HIV are hospitalized in advanced stages with opportunistic infections, in some cases with two or more concomitant infections, and with evidence of severe virological and immunological involvement. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2327).

Bacterial dissemination in Mycobacterium tuberculosis by CD+ T-cells & proinflammatory cytokines

Background & objectives: As CD4+ and CD8+ T lymphocyte numbers decline, the conventional, localized forms of tuberculosis shift to the atypical, disseminated forms. Variations in lymphocyte and immune cell expression levels affect how tuberculosis manifests in disseminated forms. Understanding the relationship between lymphocyte counts (CD4+ and CD8+) and pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-12 and interferon, we may therefore be able to shed light on how infections spread and suggest potential biomarkers for these immune factors. Methods: In this study, 15 guinea pigs were infected with Mycobacterium tuberculosis (M.tb) H37Rv strain and grouped into three groups of five each for further investigation. Serum samples and bronchoalveolar lavage (BAL) fluid were examined for the expression of pro-inflammatory cytokines and T-cell subsets in guinea pigs infected with pulmonary tuberculosis and disseminated tuberculosis. Results: We found that M.tb escapes macrophages due to pro-inflammatory cytokine dysregulation. Despite the protective immunity created by T-cells and cytokines, M.tb bacilli may spread to other organs due to inflammation induced by these immune components. A high number of T-cells and stimulated cytokine production are involved in triggering inflammation after necrotic tissue develops and tuberculosis spreads. Interpretation & conclusions: Our findings imply that increased bacilli in the spleen at the 8th wk of infection may be caused by the overexpression of CD4+ T-cell lymphocyte subsets and cytokines that generated inflammation during the 4th wk of infection. This is a pilot study with a small sample size and less assertive inference. Larger studies would be helpful to validate the results of the present investigation.

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.

miR-146a downregulates epidermal Langerhans cell-mediated antigen presentation / 中华微生物学和免疫学杂志

Objective:To investigate the role of miR-146a in regulating the homeostasis and function of epidermal Langerhans cells (LCs).Methods:Fresh and in vitro cultured epidermal LCs were isolated and purified by flow cytometry (FCM). The expression of miR-146a in LCs was detected by quantitative PCR (qPCR). The percentages of epidermal LCs in wild-type (WT) and miR-146a conventional knockout (miR-146a cKO) mice were analyzed by FCM. The expression of major histocompatibility complex Ⅱ (MHCⅡ) and co-stimulatory molecules (CD86 and CD80) was analyzed by FCM to evaluate the effect of miR-146a on the maturation of LCs. The percentage of Dextran-FITC + LCs was detected by FCM to evaluate the effect of miR-146a on the phagocytic function of LCs. In vitro and in vivo experiments were used to analyze the ability of miR-146a-deficient and -sufficient LCs to stimulate the proliferation of CD8 + OT-ⅠT cells and CD4 + OT-Ⅱ T cells. Results:The expression of miR-146a was significantly increased in mature LCs than in the freshly isolated LCs. There was no significant difference in the number of epidermal LCs between wild-type (WT) and miR-146a cKO mice. After a 48 h culture in vitro, the expression of MHCⅡ, CD86 and CD80 in the epidermal LCs of miR-146a cKO mice was similar to that of WT mice. Moreover, miR-146a deletion had no significant influence on antigen uptake by LCs. However, miR-146a deficiency enhanced the antigen-presenting ability of LCs that could stimulate the proliferation of OVA-specific CD8 + OT-Ⅰ T cells and CD4 + OT-Ⅱ T cells. Conclusions:miR-146a had no influence on the homeostasis, maturation and phagocytosis of LCs, but enhanced the antigen-presenting function.

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.

Value of bedside high-flow continuous blood purificationcombined with Xuebijing in the treatment of severe sepsis / 中国医师进修杂志

Objective:To investigate the effect of bedside high-flow continuous blood purification (CBP) combined with Xuebijing in the treatment of severe sepsis (SS) and the influence on the patient′s coagulation-fibrinolysis index, immunity index and expression of peripheral blood Toll-like receptor 4 (TLR4).Methods:Ninety-three patients with SS who were admitted and treated in the Lianyungang First People′s Hospitalfrom January 2017 to October 2019 were selected. They were divided into the combined group (51 cases, treatment with bedside high-flow CBP and Xuebijing injection based on bundle therapy) and the control group (42 cases, treatment with Xuebijing injection based on bundle therapy). The changes in coagulation and fibrinolysis index, immunity index, biochemical index such as TLR4 before treatment and after 1 week of treatment were compared between the two groups. The incidences of complications in both groups were statistically analyzed, and the discharge time from ICU, mechanical ventilation time and 28-day mortality were recorded.Results:After 1 week of treatment, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the two groups were shortened, D-dimer (D-D) and fibrinogen (FIB) were decreased ( P<0.05); and the levels of PT and APTT in the combined group were shorter than those in the control group, the levels of DD and FIB were lower than those in the control group, there were statistical differences ( P<0.05). After 1 week of treatment, the levels of CD 4+ and CD 4+/CD 8+ ratio in both groups were increased ( P<0.05), and the levels of CD 4+ and CD 4+/CD 8+ ratio in the combined group were higher than those in the control group ( P<0.05). After 1 week of treatment, the levels of TLR4, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), blood lactate (Lac), blood urea nitrogen (BUN) and serum creatinine (Scr) in both groups were decreased ( P<0.05), meanwhile, the above indexes in the combined group were lower than those in the control group ( P<0.05). The incidence of multiple organ failure and the 28-day mortality rate in the combined group were lower than those in the control group: 3.92%(2/51) vs. 19.05%(8/42), 13.73%(7/51) vs. 30.95%(13/42), there were statistical differences ( P<0.05). The discharge time from ICU and mechanical ventilation time in the combined group were shorter than those in the control group: (12.35 ± 2.14) d vs. (14.17 ± 3.36) d, (7.12 ± 2.23) d vs. (8.51 ± 2.39) d, there were statistical differences ( P<0.05). Conclusions:Bedside high-flow CBP combined with Xuebijing injection in the treatment of SS can improve the patient′s condition, regulate the balance of coagulation and fibrinolysis, avoide the activation of coagulation, inhibite inflammatory response, reduce the expression of TLR4 in peripheral blood, improve immune function, protecte kidney function and promotethe patient′s recovery.

CCR5 Polymorphisms and its Relationship with HIV Susceptibility, Viral Load and CD4 Count in Early Antiretroviral Therapy among HIV Patients in Selangor and Terengganu

@#Introduction: Early studies have suggested the role of C-C chemokine receptor type 5 (CCR5) polymorphisms in influencing HIV pathogenesis and phenotypes, including the protection against HIV infection and delaying disease progression to AIDS. This study aimed to further determine the impact of CCR5 variants (CCR5-Δ32 and CCR5- R223Q) on HIV susceptibility, viral load suppression and CD4 recovery during highly active antiretroviral therapy (HAART) among Malaysian HIV patients. Methods: This cross-sectional study involved 182 HIV-infected who were recruited from three out-patient clinics, and 150 non-HIV subjects from Malay, Chinese and Indian ethnicities. CD4 count and viral load data at 4-6 months (t1) and 8-12 months (t2) after starting HAART were gathered from hospital records. Chi-square test was used to analyse the correlation between CCR5 variants with dependent variables. Results: Heterozygous CCR5-Δ32 and CCR5-R223Q occurred in a percentage of 0.5% (1/182) and 1.7% (3/182) among HIV patients respectively, while none of homozygous mutant for CCR5-Δ32 and CCR5-R223Q were found. CCR5-R223Q was found more frequently in non-HIV as compared to the HIV group (P=0.018). However, both polymorphisms were not found to be correlated with CD4 recovery to ≥500 cells/mm3 (P>0.05) and viral load suppression ≤50 copies/mL (P>0.05). Conclusion: CCR5-R223Q and CCR5-Δ32 alleles probably have no modifying effects on HIV susceptibility virological and immunological recoveries in the first 12 months of HAART, partially due to the low prevalence of these mutations in the studied population.

Viral selection pressure and CD4+T cell epitope in HLA-DRB1 * 11:01 of HCV infected patients / 中国输血杂志

【Objective】 HLA-DRB1 * 11:01, as a class HLA-Ⅱ gene, was reported to be associated with spontaneous clearance of HCV in Han and Li population. Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1 * 11:01 positive infected patients. 【Methods】 The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1 * 11:01 positive and negative groups in Guangdong were respectively analyzed. The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method. Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups. 【Results】 The positive selection sites (PSSs) of E1E2 and NS3 of common HCV 6a in HLA-DRB1 * 11:01 negative group were greater than those in HLA-DRB1 * 11:01 positive group. Furthermore, the number of PPSs in CD4+T cell peptide in HLA-DRB1 * 11:01 negative group were also greater than those in HLA-DRB1 * 11:01 positive group; Both groups of HCV 6a had a population growth in Guangdong, and the expansion trend of HLA-DRB1 * 11:01 negative group was significantly higher than that of HLA-DRB1 * 11 :01 positive group. Compared to HCV chronic infection group, the response rate of HCV spontaneous clearance group to five peptides (C-52 E2691-707, C-119 NS31545-1560, C-134 NS4A1669-1684, C-154 NS4B1912-1927, C-159 NS4B1929-1944) was higher. However, the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS31497-1512, C-130 NS31650-1665). When HLA-DRB1 * 11:01 typing was considered, there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1 * 11:01 positive and HLA-DRB1 * 11:01 negative groups. 【Conclusion】 This study revealed the relationship between viral selection pressure of HLA-DRB1 * 11:01 HCV infected persons and CD4+T cell antigen epitopes. At the same time, CD4+ T cell antigen epitopes of HCV pan-genotype were obtained, providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.

Enhancing the sensitivity of HIV DNA detection: a magnetic bead-based method / 中国输血杂志

【Objective】 To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). 【Methods】 Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4+ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. 【Results】 CD4+ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4+ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/106 CD4+ T cell′s respectively. 【Conclusion】 The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

Analysis of the first measurement of CD4+T lymphocyte cell counts of newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021 / 预防医学

Objective@#To investigate the level and timeliness of CD4+T lymphocyte cell (CD4 cell) counts at first measurement among newly reported HIV/AIDS cases in Taizhou City, Zhejiang Province from 2012 to 2021, so as to provide insights into improving the management of HIV/AIDS cases. @*Methods@#Demographic data and first measurement of CD4 cell counts of newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021 were collected from the HIV/AIDS Comprehensive Control System of Chinese Disease Prevention and Control Information System. The level and time of CD4 cell counts at first measurement were descriptively analyzed, and factors affecting CD4 cell counts at first measurement were identified using a multivariable logistic regression model. @*Results@#A total of 4 834 newly reported HIV/AIDS cases were recorded in Taizhou City from 2012 to 2021, including 3 889 men (80.45%), 2 005 cases at ages of 20 to 39 years (41.48%), and 2 130 farmers (44.06%). There were 1 664 cases (34.42%) with CD4 cell counts of <200/mm3 at first detection, 2 576 (53.29%) with CD4 cell counts of 200/mm3 to 499/mm3, and 594 (12.29%) with CD4 cell counts of ≥500/mm3. The proportion of CD4 cell counts of <200/mm3 showed a tendency towards a rise from 2012 to 2021 (χ2trend =4.250, P<0.001). There were 3 465 cases (71.68%) that had an interval of ≤14 days between the first detection of CD4 cell counts and confirmatory HIV test, 740 (15.31%) that had an interval of >14 to 30 days, 315 (6.52%) that had an interval of >30 to 90 days, 135 (2.79%) that had an interval of >90 to 180 days, and 179 (3.70%) that had an interval of >180 days. The proportion of an interval of ≤14 days appeared a tendency towards a rise from 2012 to 2021 (χ2trend=6.874, P<0.001). Multivariable logistic regression analysis identified women (OR=0.630, 95%CI: 0.529-0.751), age of ≥20 years (OR: 1.958 to 3.218, 95%CI: 1.216-5.412), other or unknown routes of HIV infection (OR=1.785, 95%CI: 1.100-2.896), and identification by medical institutions (OR=1.779, 95%CI: 1.497-2.114) as factors affecting CD4 cell counts of <200/mm3 at first measurement. @*Conclusions@#The timely detection of CD4 cell counts at first measurement gradually increased with year among newly reported HIV/AIDS cases in Taizhou City from 2012 to 2021; however, there were still 34.42% of cases with CD4 cell counts of <200/mm3. Gender, age, route of HIV infection, and sample source were factors affecting CD4 cell counts of <200/mm3 at first measurement.

Immunological CD4+ T-cell recovery and prognostic influencing factors in elderly HIV/AIDS patients of different genders after antiviral therapy / 中国热带医学

@#Objective　To investigate the prognostic influencing factors and recovery of CD4+ T lymphocytes in elderly HIV/AIDS patients after antiviral therapy by analyzing basic data and clinical follow-up data of elderly HIV/AIDS patients. Methods　The clinical data of 3 618 elderly AIDS patients aged ≥50 yeas who received antiretroviral therapy (ART) at HIV ART sites in Liuzhou City from 2005-2015 were collected. The data, including basic information, CD4+ T cell count, WHO clinical stage, infection route and follow-up, were retrospectively analyzed. Kaplan-Meier method was used to compare the differences in patient survival, multivariate Cox regression to analyze the independent influencing factors influencing the risk of death, and to compare the recovery of CD4+ T cell counts during follow-up of patients of different genders. Results　During the follow-up period, the 5-year cumulative survival rate up to the observation endpoint was 0.82 (female) and 0.66 (male). Multivariate logistic regression analysis showed that the risk factors affecting the effect of antiviral treatment were age (OR=1.909, 95%CI:1.474-2.464, P<0.001), body mass index (BMI) (OR=0.744, 95%CI: 0.574-0.965, P=0.026), opportunistic infections (OI) (OR=1.223, 95%CI:1.028-1.454, P=0.023), gender (OR=0.692, 95%CI:0.503-0.952, P=0.023) and baseline CD4+ T lymphocytes count (OR=0.563, 95%CI:0.429-0.739, P<0.001). Recovery of CD4+ T lymphocyte counts showed when baseline CD4+ T lymphocyte counts were less than 200 cells/mm3, older women with HIV/AIDS had higher CD4+ T lymphocytes than men at all times of ART treatment (P<0.05). Conclusions　Older women have a higher survival rate than older men after five years of antiviral therapy. Age, BMI, gender, OI and baseline CD4+T lymphocyte count may be important indicators that affect the survival of elderly HIV/AIDS patients. Older women showed better recovery of CD4+ T lymphocytes than older men during the 4-year follow-up period after ART.

Immunological effect and influencing factors of HAART on HIV/AIDS with baseline CD4 below 350 cells/mm3 / 公共卫生与预防医学

Objective To analyze the immunological effect and its influencing factors of HAART on HIV/AIDS with a baseline CD4 of less than 350 cells/mm3 in Hubei Province during 2011-2020. Methods The treatment information of people living with HIV/AIDS (PLWH) was collected through China Disease Control and Prevention Information System, and the change of CD4 mean value was analyzed by Wilcoxon sign rank sum test. Chi square test and multivariate logistic regression were used to analyze the factors influencing the immunological effect. Results The mean value of CD4 cell count at baseline was (172.78±107.65) cells/mm3 before treatment and (398.85±206.71) cells/mm3 in the fifth year after treatment. Patients with baseline CD4<50 /mm3 had the largest increase in CD4 mean value after treatment (P<0.05). Multivariate logistic regression analysis showed that Age ≥35 years, heterosexual transmission, time interval from diagnosis to treatment≥1 month, baseline CD4<50 /mm3, treatment time 7-<18 months, and drug failure were the risk factors for the success of antiviral therapy(P<0.05). Conclusion The immunological effect of HIV/AIDS antiviral therapy in Hubei Province is affected by many factors. It is necessary to strengthen the implementation of early detection and early treatment strategy and promote treatment compliance education for patients aged ≥35 years.

Advances in the study of the function of CD4+ CAR-T cell subsets in tumor therapy / 中国肿瘤生物治疗杂志

@#[摘 要] 嵌合抗原受体T（CAR-T）细胞疗法是目前治疗癌症最有效的一种免疫治疗方法，但CAR-T细胞功能障碍很大程度限制其自身对癌症治疗的效果。T细胞功能的差异以及记忆和效应T细胞的作用被证明在CAR-T细胞治疗中极为重要。CD8+ T细胞作为发挥抗癌作用的主要效应细胞一直是研究焦点，而对CD4+ T细胞的关注较少。CD4+ T细胞不仅可以通过激活CD8+ T细胞使其杀伤肿瘤细胞，还可以独立发挥抗肿瘤作用。现有研究发现，细胞因子、共刺激域和细胞代谢等因素均可影响CD4+ CAR-T细胞亚群的增殖和分化。本文主要综述了CD4+ CAR-T细胞亚群在治疗肿瘤中的重要性以及影响其增殖分化因素的研究进展，为进一步研发高效的CAR-T细胞提供新思路。

Clinical features of fundus lesions of 74 patients with acquired immunodeficiency syndrome in Shenyang / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features and factors of fundus lesions in patients with acquired immunodeficiency syndrome(AIDS)in Shenyang and the relationship between fundus lesions and CD4+T cell count.METHODS: Retrospective case study. A total of 74 cases with AIDS who were treated in the Central Hospital of Liaoning Electric Power Supply Co., Ltd., from January 2021 to December 2021 were selected. The fundus manifestation and CD4+T cell count of the patients were analyzed.RESULTS: The total detection rate of fundus lesions in AIDS patients was 58%. CD4+T cell count in the patients with fundus lesions was significantly lower than that in the patients with normal fundus [29(6, 55)/μL vs. 76(35, 103)/μL, P<0.01]. The rate of fundus lesions was the highest in the patients with CD4+T cell count ≤ 50/μL(74%). Logistic regression analysis showed that as the CD4+T cell count increased, the incidence of fundus lesions decreased(OR=0.977, 95%CI 0.964～0.991, P<0.01).CONCLUSION: Fundus lesions in AIDS patients related to CD4+T cell count. Decreasing CD4+T cell count was a risk factor of fundus lesions for AIDS patients. Routine fundus examination is important for the early diagnosis of fundus lesions in AIDS patients.