Identificación del alelo HLA B*57: 01 en una población militar, de Lima-Perú / Identification of the allele HLA B*57: 01 in a military population, from Lima-Peru

El alelo HLA B*57:01 es un marcador genético asociado con la hipersensibilidad al fármaco anti-retroviral abacavir (ABC) y su frecuencia en la población peruana todavía es desconocida. El objetivo fue identificar el alelo HLA B*57:01 en una población militar de Lima, Perú. Se reclutaron 43 personas viviendo con VIH (PVV) quienes aceptaron participar a través de un consentimiento informado. La detección del alelo HLA B*57:01 se realizó mediante RPC en tiempo real (RT-PCR). Asimismo, se determinó la carga viral (CV), el recuento de linfocitos CD4 y la genotipificación del VIH. Se identificaron dos casos positivos al alelo HLA B*57:01 (4,7%). Además, uno de ellos presentó múltiples mutaciones de resistencia a los anti-retrovirales (ARV), incluyendo ABC. Se demostró por primera vez en el Perú la presencia del alelo HLA B*57:01.

The HLA B*57:01 allele is a genetic marker associated with hypersensitivity to the antiretroviral Abacavir (ABC) and its frequency in the Peruvian population is still unknown. The objective was to identify the HLA B*57:01 allele in a military population from Lima, Peru. Forty three people living with HIV (PLWH) were recruited, who agreed to participate through informed consent. Detection of the HLA B*57:01 allele was performed by real-time PCR (RT-PCR). Likewise, viral load (VL), CD4 lymphocyte count and HIV genotyping were determined. Two cases positive for the HLA B*57:01 allele (4.7%) were identified. In addition, one of them had multiple resistance mutations to antiretrovirals (ARVs), including ABC. The presence of the HLA B*57:01 allele was demonstrated for the first time in Peru.

Expression and significance of CD4+T cell subtypes and their associated inflammatory factors in NE-FE-COPD patients / 重庆医学

Objective To investigate the expression of CD4+T cell subtypes and related inflammatory factors in patients with neutrophil-predominant frequent acute exacerbation chronic obstructive pulmonary disease(NE-FE-COPD).Methods COPD patients who were treated in the hospital from March 2019 to March 2021 were selected as the research objects.According to different phenotypes,they were divided into the infrequent exacerbator COPD group(IECOPD group,n=11),the eosinophilic dominant frequent acute plus severe COPD group(Eos-FE-COPD group,n=13),and the neutrophil dominant frequent exacerbator COPD group(NE-FE-COPD group,n=15).Patients with normal lung function and smoking history＞10 packs/year were the control group(CTRL group,n=9).Bronchoalveolar lavage fluid(BALF)was collected from each group,and the expression of CD4+T cell subtypes and inflammatory factors were detected by flow cytometry.The correlation between BALF and lung function and the frequency of acute exacerbation was ana-lyzed.CD4+CD28nullT cells and CD4+CD28+T cells were co-cultured with human airway epithelial cells(hAECs)and divided into co-culture group and Control group.The damage of hAECs was observed by immu-nofluorescence staining,and the mRNA and protein expression levels of ZO-1 and occludin were detected by RT-qPCR and Western blot.Results The proportion of CD4+CD28nullT cells and IL-1β level in BALF in the NE-FE-COPD group were higher than those in the CTRL group,the IE-COPD group,and the Eos-FE-COPD group,and the difference was statistically significant(P＜0.05).The proportion of CD4+CD28nullT cells and IL-1βlevel were negatively correlated with lung function(P＜0.05),and positively correlated with acute ex-acerbation frequency(P＜0.05).Compared with the Control group,hAECs tight junctions were damaged in the co-culture group,and mRNA and protein expression levels of ZO-1 and occludin decreased,with statistical significance(P＜0.05).Conclusion CD4+CD28nullT cells and IL-1β may be involved in the occurrence and de-velopment of NE-FE-COPD.

Relationship between serum CD4+/CD8+T lymphocyte ratio combined with MRA and recurrence of cerebral infarction / 国际检验医学杂志

Objective To investigate the correlation and predictive effect of serum CD4+/CD8+T lympho-cyte ratio combined with magnetic resonance angiography(MRA)on recurrence of cerebral infarction.Meth-ods A total of 153 patients with acute cerebral infarction admitted to the Zhenjiang First People's Hospital from January 2021 to February 2022 were selected.CD4+/CD8+T lymphocyte ratio of patients was deter-mined,vascular stenosis score and collateral circulation filling score were evaluated by MRA.The patients were followed up for 1 year,including 34 patients with recurrent cerebral infarction as recurrent cerebral in-farction group,107 patients without recurrent cerebral infarction as the non-recurrent cerebral infarction group,12 patients were excluded due to other causes of loss of follow-up,and the receiver operating character-istic(ROC)curve for using the indicators to predict the recurrent cerebral infarction was drawn.Results The CD4+/CD8+T lymphocyte ratio in recurrent cerebral infarction group was significantly higher than that in non-recurrent cerebral infarction group(P<0.05).Vascular stenosis score and collateral circulation filling score in recurrent cerebral infarction group were lower than those in non-recurrent cerebral infarction group(P<0.05).The recurrence of cerebral infarction was correlated with CD4+/CD8+T lymphocyte ratio,vascu-lar stenosis score and collateral circulation filling score(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of CD4+/CD8+T lymphocyte ratio,vascular stenosis score,and collateral circulation filling score to predict recurrent cerebral infarction was 0.975,0.889,and 0.935,respectively,and the AUC of recurrent cerebral infarction was 0.994 when combined with the three factors.The AUC of cerebral infarction recurrence was significantly higher than that of each index alone.Conclusion Serum CD4+/CD8+T lympho-cyte ratio combined with MRA vascular stenosis score and collateral circulation filling score have high efficacy in the diagnosis of recurrent cerebral infarction,which have predictive value for recurrent cerebral infarction.

The value of peripheral blood sIL-2R,CD4+/CD8+and TNF-α in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis / 国际检验医学杂志

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.

Predictive value of lactate/albumin ratio,interleukin-6 and CD4+T lymphocyte count in the short-term prognosis of severe pneumonia and sepsis / 新乡医学院学报

Objective To investigate the predictive value of lactate/albumin ratio(LAR),interleukin-6(IL-6)and CD4+T lymphocyte count in 28-day mortality in patients with severe pneumonia and sepsis.Methods A total of 73 patients with severe pneumonia and sepsis admitted to the Respiratory Intensive Care Unit(RICU)of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2022 to June 2023 were enrolled and divided into the survival group(n=43)and the death group(n=30)according to their 28-day outcomes.The clinical data of the patients were collected from their electronic medical records,including age,gender,comorbidities with hypertension,diabetes,and coronary artery heart disease(CHD),as well as sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,mean arterial pressure(MAP),confusion,uremia,respiratory rate,blood pressure,age ≥65 years(CURB-65)score,total bilirubin(Tbil),serum creatinine(Scr),platelet count(PLT),white blood cell(WBC)count,procalcitonin(PCT),and C-reactive protein(CRP)at admission to RICU.On the 1st,3rd,and 7th day after admission to RICU,the patients'arterial blood was drawn,and the lactate level was detected by a fully automated blood gas analyzer.The peripheral venous blood was drawn,and the serum albumin and IL-6 levels were detected by enzyme-linked immunosorbent assay,and the CD4+T lymphocyte subset count was measured by flow cytometry.The LAR of patients on the 1st,3rd and 7th day was calculated.The clinical data of the patients and the LAR,IL-6 level and CD4+T lymphocyte count on the 1st,3rd,and 7th day were compared between the two groups.The influencing factors of 28-day mortality in patients with severe pneumonia and sepsis were analyzed by logistic regression,and the predictive value of each influencing factor on the 28-day mortality in patients with severe pneumonia and sepsis was evaluated by the receiver operating characteristic(ROC)curve.Results There was no significant difference in gender,age,proportions of comorbidities with hypertension,diabetes and CHD,length of stay in RICU,and Tbil,MAP,PLT,Scr,WBC,PCT and CRP at admission to RICU(P＞0.05).The APACHE Ⅱ and CURB-65 scores of the patients in the death group were significantly higher than those in the survival group(P＜0.05).On the 1st,3rd and 7th day,the CD4+T lymphocyte count in the death group was significantly lower than that in the survival group,while the SOFA score was significantly higher than that in the survival group(P＜0.05).On the first day,there was no significant difference in the LAR and IL-6 level be-tween the death group and the survival group(P＞0.05).However,on the 3rd and 7th day,the LAR and IL-6 level in the death group were significantly higher than those in the survival group(P＜0.05).The LAR,IL-6 level and SOFA score on the 3rd and 7th day in the survival group were significantly lower than those on the 1st day,and these indicators on the 7th day were sig-nificantly lower than those on the 3rd day(P＜0.05);the CD4+T lymphocyte count on the 3rd and 7th day was significantly higher than that on the 1st day(P＜0.05),while it showed no significant difference on the 7th and 3r day(P＞0.05).The IL-6 level on the 7th day in the death group was significantly lower than that on the 1st and 3rd day(P＜0.05),while there was no significant difference in IL-6 level on the 1st day compared with the 3r day(P＞0.05);moreover,there was no significant difference in LAR,CD4+T lymphocyte count and SOFA score between each time point(P＞0.05).Pearson correlation analy-sis showed that on the 3rd day,the LAR and IL-6 level were significantly positively correlated with the SOFA score in patients with severe pneumonia and sepsis(r=0.385,0.394;P＜0.05).On the 7th day,the LAR and IL-6 level were also significantly positively correlated with the SOFA score(r=0.418,0.402;P＜0.05).On the 3 rd and 7 th day,CD4+T lymphocyte count was significantly negatively correlated with the SOFA score(r=-0.451,-0.454;P＜0.05).Logistic regression analysis showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day,and the IL-6 level and CD4+T lym-phocyte count on the 7th day were the influencing factors for 28-day mortality in patients with severe pneumonia and sepsis(P＜0.05).The ROC curve showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day and the combination of the three,IL-6 level and CD4+T lymphocyte count on the 7th day and the combination of the two had certain predictive value for the 28-day mortality in patients with severe pneumonia and sepsis(P＜0.05).The area under the ROC curve(AUC)of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day combined to predict 28-day mortality in patients with severe pneumonia and sepsis was 0.891,and the AUC of APACHE Ⅱ score for predicting 28-day mortality in pa-tients with severe pneumonia and sepsis was 0.769.The AUC values of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.795,0.757 and 0.770,respective-ly,and the AUC values of IL-6 level and CD4+T lymphocyte count on the 7th day and their combination for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.743,0.802 and 0.888,respectively.Conclusion The 3-day LAR,IL-6 level and CD4+T lymphocyte count,and the 7-day IL-6 level and CD4+T lymphocyte count after admission are re-lated to the 28-day mortality in patients with severe pneumonia and sepsis.The combined LAR,IL-6 level and CD4+T lympho-cyte count on the 3rd day can better assess the severity and prognosis of patients.

Effects of allergens on the expression of IL-18, IL-18-binding protein a and IL-18 receptor α by peripheral blood CD4 + Th17 cells of patients with allergic rhinitis / 中华微生物学和免疫学杂志

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

Role of clearance of exogenous myelin antigen in experimental autoimmune encephalomyelitis / 中华微生物学和免疫学杂志

Objective:To investigate the role of the clearance of exogenous myelin antigen in experimental autoimmune encephalomyelitis (EAE).Methods:EAE was induced in C57BL/6J mice by subcutaneous immunization with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) or FITC-MOG 35-55. The concentration of exogenous myelin antigen was assessed by analyzing the proliferation of the transferred CFSE-labeled mT/mG-2D2 CD4 + T cells in spleen tissues. The release of exogenous myelin antigen from the inoculation sites was analyzed by immunohistochemistry and flow cytometry. HE staining was used to investigate the mechanism underlying the rapid clearance of exogenous myelin antigen. The role of the clearance of exogenous myelin antigen in EAE was investigated by comparative analysis of EAE induced by subcutaneous immunization in the back and footpads, and analyzing the therapeutic effect of soluble MOG 35-55. Results:The proliferation of mT/mG-2D2 CD4 + T cells in mice was enhanced on day 2 than on day 7 after immunization [(52.6±6.8)% vs (18.5±4.9)%, P<0.01]. There was no significant difference in the proliferation of mT/mG-2D2 CD4 + T cells between EAE mice (day 13) and naive mice [(4.4±1.5)% vs (2.5±1.4)%, P=0.11]. Immunohistochemistry and flow cytometry showed that MOG 35-55 was released and engulfed by CD11b + cells at the inoculation sites, and no more MOG 35-55 was released at the onset of EAE. HE staining showed that granuloma that formed surrounding the antigen emulsion during EAE development prevented antigen release from the emulsion, completely isolating the antigen from the peripheral immune system. The incidence of EAE was relatively low in mice immunized via footpads, which was related to the sustained release of MOG 35-55, but had no direct relation to CD4 + regulatory T cells. Continuous intraperitoneal injection of soluble MOG 35-55 could prevent and treat EAE. Conclusions:Exogenous myelin antigen has been completely cleared in EAE mice, and the occurrence of EAE depends on the clearance of the myelin antigen.

Effects of breastfeeding on immune response of CD4+T lymphocytes in infants / 中国儿童保健杂志

【Objective】 To explore the effects of breastfeeding on the immune response of CD4+T lymphocytes in infants in non-inflammatory state, and to analyze the immunomodulatory significance of the whole composition of breast milk. 【Methods】 A retrospective cohort study was conducted. From January to September 2022, six-month-old infants who took physical examination in the Child Healthcare Department of Changzhou Children′s Hospital Affiliated to Nantong University, were selected based on inclusion criteria, and were divided into breastfeeding group (n=33) and formula feeding group (n=27) based on their feeding patterns. Flow cytometry was used to detect the percentage of CD4+ T cells, including helper T cell (Th) 1, Th2, Th17, regulatory T cell (Treg), and the levels of related cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17 in peripheral blood. The differences in these indicators between the two groups were compared. 【Results】 Compared with the formula feeding group, the breastfeeding group showed significantly higher percentages of Th1(t=3.038), Treg (t=2.088). The ratio of Th1 to Th2(Z=2.756), IL-10(Z=2.297) and IFN-γ (Z=2.076) in the peripheral blood of the breastfeeding group were also significantly higher. Conversely, the breastfeeding group had significantly lower percentage of Th17(Z=2.704) and IL-17A (t=2.187) (P<0.05). There was no significant difference the percentage of Th2, as well as in the levels of IL-2, IL-4, IL-6 and TNF-α between the two groups (P>0.05). 【Conclusions】 Breastfeeding has a regulatory effect on the immune response of infant CD4+ T lymphocytes. It promotes the development of Th1/Th2 towards Th1 and the immunomodulatory effect of Treg. Moreover, it inhibits the Th17 type immune response. These findings suggest that the complete composition of breast milk contributes to the development and maturation of infant immune system, enhancing immune defense and immune tolerance.

Effects of Jiawei Jingqin Decoction （加味荆芩汤） on Inflammatory and Immune Responses in Rosacea Model Mice / 中医杂志

ObjectiveTo investigate the potential mechanisms of Jiawei Jingqin Decoction （加味荆芩汤） in the treatment of rosacea. MethodsFifty 8-week-old female BALB/c mice were randomly divided into normal control group， model group， and Jiawei Jingqin Decoction low， medium， and high-dose groups， with 10 mice in each group. Except for the normal control group， mice in the other groups were injected with 40μl of antimicrobial peptide LL-37 at a concentration of 320 μmol/L on the back， repeated once every 12 hours for a total of 4 injections， to induce the rosacea mouse model. The mice in the normal control group were injected with 40 μl of PBS solution at the same time. After successful modeling， the mice in the Jiawei Jingqin Decoction low， medium， and high-dose groups were orally administered Jiawei Jingqin Decoction at doses of 4.35， 8.71， and 17.42 g/（kg·d） respectively， while the mice in the normal control group and the model group were orally administered 20 ml/（kg·d） of normal saline. All groups were treated once daily for 5 days. The changes in skin lesions were observed， and the erythema area was measured and scored. Skin tissue at the injection site was collected for histopathological examination using HE staining， and the number of mast cells was detected using toluidine blue staining. The levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in the skin lesion tissues were measured using the ELISA method. The mRNA expression levels of key factors in the innate immune response pathway of rosacea disease mechanism， including Toll-like receptor 2 （TLR2）， downstream molecules serine protease kallikrein 5 （KLK5） and matrix metalloproteinase 9 （MMP-9）， as well as related inflammatory factors （IL-1β， IL-6， TNF-α）， and adaptive immune CD4+ T cell-related factors interferon-gamma （INF-γ） mRNA were detected using RT-qPCR. Immunohistochemical staining was performed to detect the protein expression of KLK5， MMP-9， and the number of CD4+ T-positive cells. Western blot analysis was used to determine the protein expression levels of CD4+ T cell-related factors including IFN-γ， CC chemokine receptor 5 （CCR5）， signal transducer and activator of transcription 1 （STAT1）， signal transducer and activator of transcription 3 （STAT3）. ResultsThe skin at the injection site on the back of mice in the normal control group appeared normal without any skin lesions or erythema， and histopathological examination showed no infiltration of inflammatory cells. The model group had significantly higher erythema scores and larger erythema areas compared to the normal control group （P＜0.05）， and histopathological examination revealed a significant infiltration of inflammatory cells， with some signs of deep connective tissue damage. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a significant decrease in erythema scores and erythema areas （P＜0.05）， as well as a reduction in inflammatory exudates and inflammatory cell infiltration. However， the Jiawei Jingqin Decoction low-dose group did not show significant difference （P＞0.05）， but there was a slight reduction in inflammatory cell infiltration compared to the model group. When compared to the normal control group， the rosacea skin tissues of the model group showed an increase in the number of mast cells， levels of IL-1β， IL-6， TNF-α， mRNA expression of IL-1β， IL-6， TNF-α， TLR2， INF-γ， KLK5， MMP-9， protein expression of KLK5， MMP-9， and the number of CD4+ T-positive cells （P＜0.05）. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a decrease in the number of mast cells， levels of IL-1β， mRNA expression of IL-1β， TNF-α， and the number of CD4+ T-positive cells. The Jiawei Jingqin Decoction high-dose group showed a decrease in IL-6， TNF-α levels， mRNA expression of IL-6， TLR2， INF-γ， MMP-9， protein expression of MMP-9， KLK5， and the number of CD4+ T-positive cells， as well as a decrease in IFN-γ and STAT1 protein expression （P＜0.05） compared to the Model group. ConclusionJiawei Jingqin Decoction has significant improvement effect on the skin symptoms of roseacne in a mouse model. Its mechanism might be related to regulating skin immune inflammatory reactions， thereby reducing the release of pathogenic factors and inflammatory factors.

DKK1 blockade improves anti-tumor immune response by promoting Th1 type polarization of CD4+ T cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨恶性肿瘤中Dickkopf-1（DKK1）表达对CD4+ T细胞极化的影响及其作为肿瘤免疫治疗靶点的潜在价值。方法：利用生物信息学方法分析DKK1在多种类型肿瘤组织和癌旁组织中的表达水平，分析DKK1表达与肿瘤患者预后及肿瘤微环境免疫浸润间的相关性。利用流式细胞术检测DKK1蛋白对CD4+ T细胞表型变化的影响。构建黑色素瘤B16F10细胞小鼠皮下移植瘤模型，观察阻断DKK1对小鼠移植瘤生长和移植瘤组织中免疫细胞浸润与表型的影响。结果：DKK1 mRNA表达水平在多种肿瘤组织中显著高于癌旁组织，DKK1高表达与多数肿瘤患者的不良预后相关且在多数肿瘤中DKK1对CD4+ T细胞抗肿瘤免疫应答功能有重要负性调节作用（P<0.05或P<0.01）。流式细胞术检测结果显示，DKK1蛋白刺激可显著降低CD4+ T细胞中T-bet、IFN-γ及CD107a表达水平（均P<0.01）。在小鼠皮下黑色素瘤模型中发现，阻断DKK1可以显著抑制小鼠移植瘤的生长（P<0.01），有效改善抗肿瘤免疫应答，表现为Th1细胞（T-bet+ CD4+）占比显著升高（P<0.001），效应性CD8+ T细胞（CD44+ CD62L-）占比显著升高（P<0.01），Th2细胞（GATA3+ CD4+）与Treg细胞占比显著下降（均P<0.01）。结论：阻断DKK1可有效促进CD4+ T细胞向Th1型极化，DKK1具有作为肿瘤免疫治疗靶点的潜在价值。

Effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test in screening for latent tuberculosis infection among HIV/AIDS patients / 预防医学

Objective@#To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients.@*Methods@#From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed.@*Results@#A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05).@*Conclusion@#The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.

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.

Analysis and Correlation between Peripheral Adiponectin and CD4+T Cell Subsets in Patients with Acute Gouty Arthritis / 医学研究杂志

Objective To compare the difference of peripheral blood adiponectin and CD4+T cell subsets between patients with a-cute gouty arthritis and healthy controls,to explore the correlation between adiponectin and serum uric acid,disease activity,CT4+T cell subsets and some cytokines in patients with gout.Methods The clinical data(including general data,neutrophils,erythrocyte sedimen-tation rate,C-reactive protein,blood uric acid,CT4+T cell subsets and some cytokines)of acute gout group(n=90)and healthy con-trol group(n=72)were collected.The level of adiponectin in peripheral blood of two groups were detected,and the differences of adi-ponectin and CD4+T cell subsets between the two groups were compared;the correlation between adiponectin and clinical data was ana-lyzed.Results The levels of serum adiponectin in the acute gout group were significantly lower than those in the healthy control group(P＜0.001),and the levels of Th2,Thl7,Th17/Treg were significantly higher than those in the healthy control group(P＜0.05),while the levels of Treg and Th1/Th2 were significantly lower than those in the healthy control group(P＜0.05).In the acute gout group,adiponectin was negatively correlated with neutrophil,erythrocyte sedimentation rate and C-reactive proten(r=-0.244,P＜0.05;r=-0.311,P＜0.05;r=-0.506,P＜0.001),there was no correlation with serum uric acid.In acute gout group,adiponectin was posi-tively correlated with Th1 and Th1/Th2(r=0.252,P＜0.05;r=0.218,P＜0.05).In acute gout group,adiponectin in peripheral blood was positively correlated with interleukin-2(IL-2),interleukin-4(IL-4)and interleukin-10(IL-10)(r=0.323,P＜0.05;r=0.377,P＜0.05;r=0.359,P＜0.05).There was a negative correlation between interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)(r=-0.265,P＜0.05;r=-0.299,P＜0.05).Multiple linear regression analysis showed that adiponectin in the acute gout group was negatively correlated with erythrocyte sedimentation rate,C-reactive protein,IL-6 and TNF-α(BESR=-12.541,P=0.003;BCRP=-8.256,P=0.024;BIL-6=-15.907,P=0.037;BTNF-α=-79.770,P=0.040),but positively correlated with Th1(BTh1=2.959,P=0.006).Conclusion The levels of adiponectin in the peripheral blood of patients with acute gouty arthritis were decreased,the levels of Th2 and Th17 were increased,and the levels of Treg were decreased.The decrease of adi-ponectin was related to the immunological disorder and inflammation in the patients with acute gouty arthritis.

Study on lipidomics of CD4+T cells in mice with diabetic kidney disease / 中国免疫学杂志

Objective:To investigate the lipidomics differences of CD4+T immune cells in diabetic kidney disease(DKD)mice,and screen out the differential metabolites with biological significance.Methods:CD4(L3T4)MicroBeads immunomagnetic beads were used to isolate CD4+T immune cells from spleen of BKS.Cg-Dock7m+/+Leprdb/J mice with spontaneous DKD;the purity of CD4+T cells were identified by flow cytometry.The non-targeted lipidomics of CD4+T cells were detected by LC-MS/MS,and the differ-ential metabolites were analyzed.Results:A total of 463 metabolites were detected by LC-MS.PCA and OPLS-DA analysis showed that the metabolic components were significantly separated;twenty-four differential metabolites were screened out.KEGG and enrich-ment analysis showed that the differential metabolites involved in the disorder of glycerol phospholipid metabolism.Conclusion:Phos-pholipid metabolism of CD4+T cells is closely related to the occurrence of DKD.Phospholipid metabolism targeting DKD CD4+T cells in DKD may be a new direction of DKD treatment.

Immune response and antitumor effects of HCA587/MAGE-C2 protein formu-lated with CFA and CpG / 中国免疫学杂志

Objective:To investigate ability of HCA587/MAGE-C2 protein combined with different adjuvants inducing antigen-specific immune response and antitumor effects in mice model.Methods:C57BL/6J mice were immunized with HCA587 protein com-bined with Freund's complete adjuvant(CFA)/Freund's incomplete adjuvant(IFA)and different doses of CpG ODN 1826(CpG),cellular and humoral immunity levels induced by different schemes were compared.ELISpot was used to evaluate frequency of IFN-γ-producing splenocytes.HCA587-specific antibodies were detected by ELISA.Intracellular cytokine staining(ICCS)analysis was mea-sured by flow cytometry.A tumor-bearing animal model was created by subcutaneously injection of B16-HCA587 tumor cells into right flank of C57BL/6J mice,which was treated with strategy with the strongest cellular and humoral immune response in immune compari-son protocol.Vernier calipers were used to measure tumor volume,and Log-rank test was used to analyze survival curve.Results:HCA587 protein combined with CFA and 50 μg CpG elicited strongest specific IFN-γ-secreting splenocytes and anti-HCA587 anti-bodies,which induced highest IFN-γ+CD4+T cells(P<0.05).In tumor treatment model,HCA587 protein combined with CFA and 50 μg CpG significantly inhibited tumor growth(P=0.026),while Log-rank test showed no significant effect on survival(P>0.05).Conclusion:HCA587 protein vaccine formulated with CFA and 50 μg CpG causes a significant cellular and humoral immune response and partial antitumor effect in mice model,providing new experimental data for preclinical research of tumor antigen protein vaccine.

miR-155/GATA3/CD4+T cell pathway regulates pathogenesis of allergic rhinitis / 中国免疫学杂志

Allergic rhinitis(AR)is a type Ⅰ allergic reaction,which mediated by immunoglobulin E immediately when an individual with a special constitution is exposed to a same allergen for second time,whose pathogenesis has not been clarified yet,and closely related to genes,immune cells and cytokines.Pathogenesis of AR become more deeper and more accurate due to rapid develop-ment of molecular biology and second-generation gene sequencing technology.Current studies have found that miR-155 and transcrip-tion factor GATA3 have important regulatory effects on occurrence and development of AR,then affect dominant differentiation of CD4+T lymphocytes and proliferation of ILC2.This article discusses and reviews pathogenesis of AR,which mainly focuses on miR-155/GATA3 pathway and effects of related upstream genes and downstream regulatory substances.

Research progress of microRNA-mediated immune function of CD4+T cells subsets in immune thrombocytopenia / 中国免疫学杂志

MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.

Correlation between interleukin-2 receptor and CD4+/CD8+ on the activity of lupus nephritis / 中国现代医生

@#Objective To investigate the correlation between serum interleukin-2 receptor(IL-2R),CD4+/CD8+ and disease activity in patients with lupus nephritis(LN).Methods A total of 38 patients with LN who were treated in Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from March 2021 to December 2022 were enrolled in LN group,and 40 healthy persons who underwent physical examination in the hospital during the same period were included in healthy control group.General clinical data,systemic lupus erythematosus disease activity index(SLEDAI)and pathological classification were collected.LN patients were divided into active group and inactive group according to SLEDAI score,and the difference of clinical indicators between two groups was compared.Results The hemoglobin(Hb),platelet count,albumin(ALB),complement C3 and C4 in LN group were significantly lower than those in healthy control group,the positive rates of antinuclear antibody and anti-double strand DNA antibody(anti-ds-DNA antibody),serum creatinine(SCr)and C-reactive protein were significantly higher than those in healthy control group(P<0.05).The ALB of active group was significantly lower than that of inactive group,and IL-2R,erythrocyte sedimentation rate,24h urinary protein quantity and anti-ds-DNA antibody positive rate were significantly higher than those of inactive group(P<0.05).Serum IL-2R levels in LN patients were positively correlated with SLEDAI,SCr,blood urea nitrogen and 24h urinary protein quantity,and negatively correlated with Hb and complement C3(P<0.05).Conclusion Serum IL-2R can be used as an indicator to judge the degree of LN activity and provide a basis for the judgment of clinical disease activity.

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.