Combining single-cell RNA sequencing and population-based studies reveals hand osteoarthritis-associated chondrocyte subpopulations and pathways

Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.

Aldehyde dehydrogenase activity helps identify a subpopulation of murine adipose-derived stem cells with enhanced adipogenic and osteogenic differentiation potential

AIM To identify and characterize functionally distinct subpopulation of adipose-derived stem cells(ADSCs).METHODS ADSCs cultured from mouse subcutaneous adipose tissue were sorted fluorescence-activated cell sorter based on aldehyde dehydrogenase(ALDH) activity, a widely used stem cell marker. Differentiation potentials were analyzed by utilizing immunocytofluorescece and its quantitative analysis.RESULTS Approximately 15% of bulk ADSCs showed high ALDH activity in flow cytometric analysis. Although significant difference was not seen in proliferation capacity, the adipogenic and osteogenic differentiation capacity was higher in ALDHHi subpopulations than in ALDHLo. Gene set enrichment analysis revealed that ribosome-related gene sets were enriched in the ALDHHi subpopulation. CONCLUSION High ALDH activity is a useful marker for identifying functionally different subpopulations in murine ADSCs. Additionally, we suggested the importance of ribosome for differentiation of ADSCs by gene set enrichment analysis.

Early Changes of Peripheral Blood Lymphocyte Subpopulations in Patients with Occupational 2,4-dinitrophenol Poisoning

2,4-dinitrophenol （DNP）, an organic compound which frequently used in industry, is considered to have high toxicity. This study aimed to investigate the early changes of lymphocyte subpopulations in patients with occupational 2,4-DNP poisoning. Totally 9 patients with acute occupational 2,4-DNP poisoning and 30 healthy volunteers as control were enrolled. The patients received immediately comprehensive supportive treatments, including large-dose glucocorticoid and repeated hemoperfusion （HP）. The ratio of CD4＋/CD8＋ T cells were significantly higher in patients upon admission compared to healthy controls （P 〈 0.01）; however, counts of total lymphocytes, CD3＋, CD3＋CD4＋, CD3＋CD8＋, B （CD19＋）, and natural killer （NK） cells （CD16＋CD56＋） were significantly reduced （all P 〈 0.001）. The NK cell count was negatively correlated with initial plasma 2,4-DNP concentration （r = -0.750, P = 0.026）. Thus, acute occupational 2,4-DNP poisoning was accompanied by immediate complex immune cell reactions, especially NK cells might play important role in severe 2,4-DNP poisoning.

Olfactory ensheathing cells for spinal cord repair: crucial differences between subpopulations of the glia

OECs for spinal cord repair： Is repairing the iniured spinal cord by olfactory ensheathing cell （OEC） transplantation pos- sible？ A recent human trial in which a paralysed man regained some function after transplantation of partially purified OECs suggests that this therapy may be a successful approach （Ta- bakow et al., 2014）. In another human trial in which olfactory mucosa lamina propria was transplanted, patients recovered some motor and sensory function （Wang et al., 2015）. While these results show promise, it is clear that improvements are needed to provide patients with increased functional output. Strategies to improve the therapeutic use of OECs may include improving the purification of the OECs used for transplantation, using them in combination with growth factors to combat the inhibitory environment and improve anon growth, the use of nerve bridges, advanced physiotherapy and the use of exo- skeleton robotics to reinforce functional connections. Of all these approaches, it is probably is primarily addressed to ensure crucial that the purity of OECs consistency in outcomes.

Hypertonic saline resuscitation maintains a more balanced profile of T-lymphocyte subpopulations in a rat model of hemorrhagic shock

Objective: To investigate the potential and early effect of hypertonic saline resuscitation on T-lymphocyte sub- populations in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was established in 18 Sprague-Dawley (SD) rats. The rats were randomly divided into Sham group, HTS group (hypertonic saline resuscitation group) and NS group (normal saline resuscitation group). Each group contained 6 rats. The CD4+ and CD8+ subpopulations of T-lymphocytes in peripheral blood were detected respectively before shock and after resuscitation by double antibody labelling and flow cytometry. Results: In the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the CD4+ lymphocytes of peripheral blood in HTS and NS groups markedly increased. Small volume resuscitation with HTS also induced peripheral CD8+ lymphocytes to a certain extent, whereas NS resuscitation showed no effect in this respect. Consequently, compared with Sham and HTS groups, CD4+/CD8+ ratio of peripheral blood in NS group was obviously increased, and showed statistically differences. Conclusion: In this model of rat with severe hemorrhagic shock, small volume resuscitation with HTS is more effective than NS in reducing immunologic disorders and promoting a more balanced profile of T-lymphocyte subpopula- tions regulating network.

Flow cytometric characterizations of leukocyte subpopulations in the peripheral blood of northern pig-tailed macaques （Macaca leonina）

Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques(M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer(NK) cells, monocytes, and the expression levels of activation or differentiation related molecules(CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of Ig D and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques(M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques.

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection.METHODS: A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. SerumHBV DNA load was assessed by quantitative real-time polymerase chain reaction.RESULTS: CD8+ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8+ T-cells than CD4+ T-cells (36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P < 0.01), whereas the peripheral blood in patients at the immune-inactive carrier stage and in normal controls contained less CD8+ T-cells than CD4+ T-cells (28.09 ± 5.64 vs 36.85 ± 6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P < 0.01). ANOVA linear trend test showed that CD8+ T-cells were signif icantly increased in patients with a high viral load (39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P < 0.001), while CD4+ T-cells were signif icantly increased in patients with a low HBV DNA load (37.45 ± 6.14, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly signif icant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3+, CD4+ and CD8+ cells and CD4+/CD8+ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION: Differences in peripheral T-cell subpopulation profi les can be found in different clinical stages of chronic HBV infection. T-cell impairment is signifi cantly associated with HBV load.

Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

AIM:To investigate the peripheral T-lymphocyte subpopulation profile,and its correlations with hepatitis B virus(HBV) replication level in chronic HBV-infected(CHI) individuals with normal liver function tests(LFTs) . METHODS:Frequencies of T-lymphocyte subpopu-lations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection,and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis. RESULTS:CHI individuals had significantly decreased relative frequencies of CD3+,CD4+ subpopulationsand CD4+/CD8+ ratio,and increased CD8+ subset percentage compared with uninfected individuals(all P < 0.001) . There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations(ANOVA linear trend test P < 0.01) . The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers,and those having gained infection before the age of 8 years. In multiple regressions,after adjustment for age at HBV infection and status of maternal HBV infection,log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations,whereas the effect of HBeAg was not significant. CONCLUSION:HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.

MINIMUM ATTRIBUTE CO-REDUCTION ALGORITHM BASED ON MULTILEVEL EVOLUTIONARY TREE WITH SELF-ADAPTIVE SUBPOPULATIONS

Attribute reduction is an important process in rough set theory.Finding minimum attribute reduction has been proven to help the user-oriented make better knowledge discovery in some cases.In this paper,an efficient minimum attribute reduction algorithm is proposed based on the multilevel evolutionary tree with self-adaptive subpopulations.A model of multilevel evolutionary tree with self-adaptive subpopulations is constructed,and interacting attribute sets are better decomposed into subsets by the self-adaptive mechanism of elitist populations.Moreover it can self-adapt the subpopulation sizes according to the historical performance record so that interacting attribute decision variables are captured into the same grouped subpopulation,which will be extended to better performance in both quality of solution and competitive computation complexity for minimum attribute reduction.The conducted experiments show the proposed algorithm is better on both efficiency and accuracy of minimum attribute reduction than some representative algorithms.Finally the proposed algorithm is applied to magnetic resonance image(MRI)segmentation,and its stronger applicability is further demonstrated by the effective and robust segmentation results.

Changes of T lymphocyte subpopulation and its relationship with Modified Bobath score in index stroke

Objective To analyze the correlation of changes of T lymphocyte subpopulation and Modified Bobath index in acute stroke.Method Peripheral blood CD3+,CD4+,CD8+,CD16+56+ and ratio of CD4+/CD8+ were measured using bicolor fluorescent monclonal antibody and flow cytometry and compared with those of 23 healthy controls. Simultaneously,relationship between modified Bobath index and changes of T lymphocytes subpopulation was analyzed.Result Compared with healthy controls, peripheral blood percent of CD3+,CD4+ of subjects with acute stroke was marked lower,which was positively correlated with modified Bobath index.Conclusion Immune response is involved in development of acute cerebrovascular diseases.Improving immune function is important for prevention and treatment of cerebrovascular diseases.

Correlation of Quantitative Changes in Bone Marrow Lymphocyte Subpopulations with Some Rhabdomyosarcoma Prognosis Factors in Children

Rationale: The known prognosis factors for rhabdomyosarcoma (RMS) in children do not always explain the unsatisfactory outcome of treatment. Changes in the subpopulation composition of Bone Marrow (BM) effector cells during the development of RMS may indicate new directions for the search for prognostic factors and points for the impact of targeted therapy. Purpose: To identify correlations between quantitative changes in the levels of subpopulations of T, B and NK-lymphocytes of BM and known risk factors for RMS in children. Objects: The study included 31 patients. The main group included 16 patients with RMS, average age—6.8 ± 1.0 years, while children 1 - 10 years old—13 (81.3%), over 10 years old—3 (18.8%) people, girls and boys were 8 people each. The embryonic variant of RMS was established in 10 (62.5%) cases, the alveolar variant—in 4 (25%) cases, in two patients (12.5%), the histological variant was not established. In 12 (75%) patients, an unfavorable localization of the RMS (parameningeal, extremities, prostate, bladder) was revealed, in 4 patients (25%), the localization of the tumor was regarded as favorable. Patients with T2b—13 (81.2%) and T2a—2 (12.5%) stages prevailed. Regional and distant metastases were detected in 10 (52.6%) patients. The comparison group included 15 children in whom the presence of malignant neoplasia was excluded, the average age was 8.4 ± 1.5 years, 11 boys (73.7%) and 4 girls (26.3%). Methods: All patients underwent morphological (myelogram counting) and immunological (quantitative analysis of lymphocytic subpopulations) bone marrow studies. Immunophenotyping in all patients was carried out by direct immunofluorescence using a triple fluorescent label. Results: Significant differences in the levels of subpopulations of BM T-lymphocytes were found when comparing the values of the main group, distributed by localization and histological variant, with the data obtained in the control group of patients. For example, the percentage of CD3+ T cells with the co-stimulatory molecule CD28+ was significantly higher in patients with parameningeal RMS (p = 0.010). Conclusion: Each clinical group of patients has its own individual immunological characteristics. The results obtained by us can be considered indicative and regarded as starting points for further study of the peculiarities of the subpopulation composition of BM in patients with RMS.

T Lymphocyte Subpopulations in Normal Pregnancies and Those Complicated by Eclampsia in Kaduna State, Nigeria

Background: Eclampsia, the occurrence of generalized convulsion(s) in association with signs of preeclampsia [PE] (hypertension and proteinuria) in pregnancy has remained a significant public threat in Nigeria, contributing to maternal and perinatal morbidity and mortality. This study was a comparative cross-sectional study conducted in some selected hospitals in Kaduna State, between April 2014 and November 2015. Subjects and Methods: Blood (3 mls) was collected into an ethylenediaminetetraaccetic acid (EDTA) vacutainer tube from third trimester women diagnosed with eclampsia (EC;n = 38) and healthy pregnant controls (PC;n = 38)—age and parity matched and healthy non-pregnant controls (NPC;n = 38)—age matched. T Cell subpopulations and Complete Blood Count levels were measured by Sysmex, Auto blood analyzer and flow cytometry respectively. Participants with smear positive malaria, seropositive for human immunodeficiency virus (HIV), any other clinical infection or refused consent were excluded from this study. Data obtained were analyzed using analysis of variance (ANOVA) and Post Hoc test. A p-value of less than 0.05 was considered to be significant. Result: Overall, results showed a depressed (mean ± Standard deviation (SD): CD3+ T cell (65.6 ± 15.5%;1225.5 ± 401.5 cell/μL), CD4+ T cell (36.1 ± 8.7%;657.1 ± 189.9 cell/μL), and a low CD4/CD8 value in women with EC (1.4 ± 0.5) and PC (1.5 ± 0.3) compared to NPC (1.9 ± 0.6) control (p < 05), while the total white blood cell count, and differential percentage neutrophils count were noted to be elevated among the eclamptic women (9.8 ± 4.9 × 109/L;70.3 ± 12.0%) compared to PC (6.9 ± 3.6 × 109/L;64.6 ± 8.1%) and NPC (5.6 ± 2.0 × 109/L;48.5 ± 10.7%), p < 0.05. Conclusion: Eclampsia was associated with significantly depressed CD3+ and CD4+ T lymphocyte, and increased percentage differential neutrophil counts.

Analysis of Peripheral T-Lymphocyte Subpopulations in Patients with Early Syphilis by Flow Cytometry

Objective: To study the cellular immunity function of patients with early syphilis and the effects on immune modifiers Esberitox N or IFN. Methods: T-lymphocyte subpopulations of the peripheral blood in 44 patients with syphilis and 40 healthy controls were examined by flow cytometry. Results: The number of CD4+ cells and the CD4+/CD8+ ratio in patients with syphilis were found to be significantly lower than those in the control (P<0.01), while the number of CD8+cells was higher than that in the control (P<0.01). The CD4+/CD8+ ratio in those with active disease was lower than that in those who had been cured (P<0.05). The CD4+ count and the CD4+/CD8+ ratio in those treated with antibiotics alone(Penicillin G or Cephalosporins) were lower than those treated with both antibiotics and immunomodulators (P<0.05). Conclusions: Cellular immunity in the patients with early syphilis was prominently suppressed, and treatment with immunomodulators may be helpful for the recovery of cellular immunity of these patients.

金匮肾气丸联用cART对HIV-1感染者的疗效及不良反应分析

获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)的主要治疗方法为联合抗逆转录病毒治疗(combined antiretroviral therapy,cART),但部分患者由于免疫功能重建不全和不良反应,可能出现药物性肝损伤、消化功能下降、神经系统毒性和代谢紊乱等,严重影响了抗病毒疗效和患者生存质量,已成为AIDS治疗领域的瓶颈[1]。部分国家资助的中医药防治AIDS科研课题提出正虚(主要为肾虚)是AIDS发生发展的内在病理基础,以肾气与肾阴肾阳的功能下降为主要特征[2-3]。补肾制剂可能是缓解人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染患者病情和不良反应的可靠方式。金匮肾气丸是由地黄、山药、茯苓、牡丹皮、山茱萸、牛膝、泽泻等多味中药制成的综合制剂[4],具有温补肾阳、化气行水的作用。本研究首次采用金匮肾气丸与cART联用治疗HIV-1感染者,比较了金匮肾气丸与cART联用、单用cART对HIV-1感染者抗病毒疗效和不良反应的差异,试图为探索HIV-1感染者治疗的新途径提供参考。

人脐带间充质干细胞的异质性探讨及基于单细胞RNA测序结果的亚群分析

目的探讨人脐带间充质干细胞(hUCMSCs)的异质性,并基于单细胞RNA测序结果进行亚群分析。方法选择两株由郑州奥博细胞医学实验室有限公司提供的hUCMSCs(分别命名为hUCMSCs-1和hUCMSCs-2),通过实时荧光定量聚合酶链反应(qPCR)进行干性基因[性别决定区Y-box 2(Sox2)、Nanog]检测。对hUCMSCs进行成骨诱导,3 d后检测成骨基因碱性磷酸酶(Alp)的表达,7 d后进行碱性磷酸酶染色,14 d后进行茜素红染色。对两株hUCMSCs进行成软骨诱导,21 d后检测成软骨基因二型胶原(COL2A1)的表达。用10 ng/mL白细胞介素-1β(IL-1β)刺激大鼠软骨细胞24 h,与hUCMSCs-1和hUCMSCs-2共培养后,检测软骨细胞合成代谢基因蛋白聚糖(ACAN)和分解代谢基因基质金属蛋白酶3(MMP3)的表达。对hUCMSCs-1进行单细胞RNA测序,并根据功能进行亚群分组,通过生物信息学分析方法描绘各个亚群标志基因热图、富集的信号通路。结果两株hUCMSCs的Sox2、Nanog、Alp、COL2A1表达水平差异有统计学意义(P<0.05)。在成骨诱导7 d后,hUCMSCs-1的碱性磷酸酶染色程度深于hUCMSCs-2。在成骨诱导14 d后,茜素红染色结果显示,hUCMSCs-1钙结节数量多于hUCMSCs-2。经IL-1β干预后,软骨细胞与两株hUCMSCs共培养后的MMP3表达水平差异有统计学意义(P<0.05),但ACAN表达水平差异不显著(P>0.05)。基于单细胞RNA测序结果,hUCMSCs-1可分为C1、C2、C3三个功能亚群。C1亚群的信号通路在细胞外基质受体相互作用上富集,与软骨细胞合成代谢相关;C2亚群信号通路在细胞衰老和凋亡上富集,与细胞的自我更新相关;C3亚群信号通路在DNA复制和减数分裂上富集,与细胞周期相关。结论不同个体来源的hUCMSCs存在异质性,其在成骨、成软骨和抗分解代谢能力方面可能存在差异。通过单细胞RNA测序可较好地根据hUCMSCs的功能特性对其进行分群,有助于提高间充质干细胞治疗的临床疗效。

血清CAR LMR T淋巴细胞亚群与多发性骨髓瘤患者预后的相关性分析

目的:探讨血清C反应蛋白与白蛋白比值(CAR)、淋巴细胞/单核细胞比值(LMR)、T淋巴细胞亚群与多发性骨髓瘤(MM)患者预后的相关性。方法:选取2020年1月至2022年1月诊治的105例多发性骨髓瘤患者作为研究对象,设立为观察组,同期选取75例健康体检者设立为对照组。根据MM患者治疗后随访2年是否出现复发或死亡分为预后不良组(n=34)和预后良好组(n=71),对比血清CAR、LMR、T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))。采用Logistic回归分析CAR、LMR、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)对MM患者预后的影响。采用ROC曲线模型分析CAR、LMR、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、T淋巴细胞亚群综合参数预测MM患者预后的AUC值、敏感度和特异度。结果:观察组的CAR、CD8^(+)高于对照组,而LMR、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)低于对照组(P<0.05)。预后不良组的CAR、CD8^(+)高于预后良好组,而LMR、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)低于预后良好组(P<0.05)。二元Logistic回归分析显示,CAR、CD8^(+)升高和LMR、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)下降会对MM患者预后产生影响(P<0.05)。ROC曲线分析显示,CAR、LMR、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、T淋巴细胞亚群综合参数预测MM患者预后的AUC值分别为(0.637、0.792、0.726、0.767、0.669、0.750、0.853,P<0.05)。结论:血清CAR、LMR、T淋巴细胞亚群在MM患者中呈异常表达趋势,检测其变化有利于为评估MM患者的预后提供重要参考。

外周血CD8+效应记忆T细胞对脓毒症诊断的价值评估

目的探讨CD8+T细胞各亚群在脓毒症诊断的价值。方法前瞻性选择2021年3月—2022年3月陆军军医大学大坪医院ICU收治的脓毒症和非脓毒症患者各30例作为研究对象。男性40例,女性20例;年龄29~70岁,平均55.4岁。创伤患者16例(包括道路交通伤7例,高处坠落伤5例,挤压伤3例,锐器伤1例)。采集患者入ICU后第1、3、5天外周血,用流式细胞仪检测T淋巴细胞及CD8+T细胞各亚群的比例,采用资料测量方差分析比较两组间差异,并采用两组间多重比较方法比较特定时间点两组间差异,单因素Logistic回归分析其与脓毒症发生相关的亚群;受试者工作特征(ROC)曲线评估其对脓毒症的诊断效能;Pearson检验分析其与脓毒症患者严重程度的相关性。结果脓毒症患者入ICU第1、3、5天的CD3+T淋巴细胞的比例显著低于非脓毒症患者[(54.32±16.44)%vs.(67.13±12.90)%、(59.42±14.49)%vs.(68.12±12.95)%、(58.81±17.47)%vs.(69.68±10.87)%,P均<0.05];进一步分析发现脓毒症患者入ICU第1、3、5天的CD8+效应记忆T细胞亚群的比例也显著低于非脓毒症患者[(25.45±10.55)%vs.(39.51±12.59)%、(27.38±11.19)%vs.(39.81±14.24)%、(28.56±12.38)%vs.(38.97±12.89)%,P均<0.05]。此外,脓毒症患者入ICU第3天的CD4+T淋巴细胞及CD8+Naive T细胞亚群的比例显著高于非脓毒症患者[(64.88±10.94)%vs.(57.51±13.49)%、(22.85±17.00)%vs.(14.47±7.32)%,P均<0.05];Logistic回归分析显示CD3+T淋巴细胞比例、CD8+效应记忆T细胞亚群比例、血浆降钙素原(PCT)及CRP水平是患者发生脓毒症的独立危险因素。ROC曲线分析显示,血浆PCT水平与CD8+效应记忆T细胞亚群比例联合诊断脓毒症的ROC曲线下面积(AUC)为0.890(0.775~0.995)。结论CD8+效应记忆T细胞的比例及血浆PCT水平二者联合对脓毒症诊断具有较好的效能。