Objective To establish a method of LC-MS/MS for determining cordycepin(Cor)and 3′-deoxyinosine(3′-Deo)concentration in rat plasma,and to study their pharmacokinetics in rats.Methods Protein was precipitated with methanol using 2-chloadenosine(2-Chl)as an internal standard.The chromatography was performed on Kinetex C18(3 mm×100 mm,2.6 μm,Phenomenex,USA)with gradient elution in aqueous(5 mmol·L-1 ammonium acetate)-methanol solution as mobile phase.ESI ion source was used for mass spectrometry,and positive ion multiple reaction monitoring(MRM)was used for scanning detection.The pharmacokinetics of Cor and 3′-Deo after oral administration of Cor(10 mg·kg-1)were studied in rats.Results Cor at 0.5-100 ng·mL-1 and 3′-Deo at 1-200 ng·mL-1 had good linearity,and the lower limits of quantification were 0.5 and 1 ng·mL-1,respectively.After oral administration of Cor in rats,the plasma concentration of Cor was low,which was mainly converted into the metabolite 3′-Deo.The Cmax of Cor and 3′-Deo were(5.4±3.4)and(142.0±50.0)ng·mL-1,and AUC0-360min min were(658.4±459.3)and(18 034.9±4 981.1)ng·min·mL-1,respectively.Conclusion The method is simple,sensi-tive,and accurate,which is suitable for determining Cor and 3′-Deo concentration in plasma and the pharmacokinetic study.

[摘 要] RUNX属于转录因子家族，是哺乳动物发育过程中不可或缺的调控因子，在哺乳动物的细胞增殖、分化、谱系发育、成骨和神经形成中发挥重要作用。围绕RUNX的研究已揭示了其功能的多样性以及在肿瘤发生发展过程中的功能。RUNX家族成员在不同类型的肿瘤中具有不一的作用，与肿瘤微环境中的各组分也有不同程度的关联。RUNX家族成员可以调节肿瘤微环境中CD4+辅助性T（Th）细胞和CD8+细胞毒性T细胞（CTL）的谱系发育分化，调控组织驻留T淋巴细胞的表型、分化和存活，驱动NK细胞的增殖活化和组织驻留。RUNX家族缺失会导致MDSC的增殖和成熟活化，从而诱导肿瘤免疫抑制微环境的产生。RUNX家族成员的表达也与肿瘤微环境中肿瘤相关成纤维细胞（CAF）的浸润程度、不同免疫细胞的浸润、免疫检查点基因表达和药物敏感性显著相关，它们可作为潜在的肿瘤预后标志物和免疫治疗靶点，与CAR-T细胞疗法的联用具有很大的应用前景。本文从RUNX的基本结构和功能研究及其参与调控肿瘤免疫和微环境中各类组分的作用进展进行综述，旨在为未来以RUNX为主要靶点的肿瘤免疫治疗提供新的视角。

The gut microbiota of infants is crucial for the establishment and development of immune system tolerance and responsiveness, as well as long-term health.Breast milk, as the only recommended source of nutrition for infants under 6 months old, possesses all the necessary nutrients and functional components for their growth, development, and health promotion.Human milk oligosaccharides (HMOs), as distinctive functional components that distinguish human milk from other mammalian milk, possess natural targeting properties to reach the colorectum in its intact form and are essential for the maturation of the gut microbiota, development of the digestive system and maintenance of the immune system function in infants, providing natural protection for the digestive and immune systems of newborns.This article reviews the latest research on how HMOs affect the development of the immune system and homeostasis in infants, and focuses on the mechanism by which HMOs control the gut microbiota and influence the immune system′s response through the gut microbiota-immune axis.

[摘 要] PD-1/PD-L1抑制剂在乳腺癌免疫治疗中的应用已逐渐成为一种重要的治疗手段，然而对乳腺癌，尤其是三阴性乳腺癌（TNBC）的免疫治疗仍存在某些亟待解决的科学问题，包括PD-1/PD-L1抑制剂单药治疗的有效率欠佳，目前尚无明确的生物标志物来有效筛查治疗敏感人群，免疫相关不良反应（irAE）的发生率高。为了提高疗效和减少irAE的发生，采取以下措施是非常重要的：探讨PD-1/PD-L1抑制剂与其他药物的联合应用方案；采用纳米技术开发选择性靶向肿瘤细胞的纳米载体，降低抗肿瘤药物毒性并提高疗效；探寻开发可预测免疫治疗反应潜力的生物标志物；早期识别和诊疗irAE并建设多学科诊疗协作组（MDT）模式。随着这些措施的积极推进和问题的不断解决，PD-1/PD-L1抑制剂在乳腺癌的治疗中必将呈现出更为广阔的应用前景。

Objective:To improve the understanding of newly diagnosed multiple myeloma (NDMM) patients with bone marrow (BM) monoclonal plasma cell ratio of less than 10%.Methods:The clinical characteristics, laboratory examination, response to treatment, and prognosis of 36 NDMM patients with BM plasma cell ratio of less than 10% at Peking Union Medical College Hospital from January 2009 to December 2017 were summarized retrospectively. In the same period, other age- and gender-matched 72 NDMM patients were selected as the control group, whose BM plasma cell ratio was equal to or greater than 10%.Results:First, the patients in the study group accounted for 4.4% of the whole MM population (36/818) , among which only 11 (30.6%) were classified as International Staging System (ISS) Ⅲ, which was significantly lower than that in the control group[45 (62.5%) ] ( P=0.002) . Extramedullary disease (EMD) was more common in the study group (33.3% vs 5.6%, P<0.001) . The median quantity of serum M protein (g/L) in the less than 10% group was 1.04 (0-50.10) , which was significantly lower than that in the control group [4.50 (0-63.10) ] ( P=0.016) , similar to the median quantity of 24-h urinary light chain (510 mg vs 2800 mg, respectively, P=0.023) . Second, the median progression-free survival (PFS) times of front-line regimen in the study and control groups were 26.4 and 19.9 months, respectively ( HR=1.703, 95% CI 0.167-0.233, P=0.002) . In addition, the overall survival (OS) times were 65.8 and 46.2 months, respectively ( HR=2.626, 95% CI 0.439-0.541, P=0.058) . Third, the study group was reclassified based on the quantity of M protein. The median OS times in patients with low/high tumor load were 66.4 and 24.0 months, respectively ( HR=2.349, 95% CI 0.603-0.696, P=0.046) . The median PFS times were 33.1 and 15.5 months, respectively ( HR=1.806, 95% CI 0.121-0.399, P=0.077) . Bortezomib-based regimens did not affect the clinical outcomes. Conclusion:The subpopulation of patients with MM with BM monoclonal plasma cell ratio less than 10% has specific clinical characteristics, including an early disease stage and a lower overall tumor load. Although more patients of this minor group presented with an extramedullary disease, their response rate to the initial treatment and survival outcome are better than those of patients with BM monoclonal plasma cell ratio more than 10%.

[Abstract] Objective: To investigate the expression of chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) in breast cancer tissues and its correlation with clinicopathological features and prognosis of patients. Methods:Atotal of 136 breast cancer tissue chips (purchased from Superchip Company), including 42 pairs of matched cancer and paracancerous tissues, were used for this study. The expression level of CMTM6 in cancer and paracancerous tissues was detected by immunohistochemistry. The comparison of CMTM6 expression between breast cancer and paracancerous tissues was conducted by paired χ2 test. The relationship between CMTM6 expression in breast cancer tissues and the clinicopathological characteristics of patients was analyzed by χ2 test. Kaplan-Meier and Log rank test analyses were used to analyze the relationship between CMTM6 expression and the survival of patients, and Cox model was used to evaluate the effect of different indicators on the prognosis of patients. Results: The expression of CMTM6 in breast cancer tissues was significantly higher than that in paracancerous tissues (P<0.01). The expression of CMTM6 was correlated with pathological type of breast cancer and HER2 positivity (P<0.05). The survival time of patients in CMTM6 high expression group was significantly shorter than that of patients in CMTM6 low expression group (P<0.05). Pathological type (HR=10.374, 95%CI: 3.529-30.497, P<0.01), TNM stage (HR=4.599, 95%CI: 1.784-11.856, P<0.01), triple-negative breast cancer (HR=3.370, 95%CI: 1.055-10.761, P<0.05) and high expression of CMTM6 (HR=0.195, 95%CI: 0.073-0.518, P<0.01) were independent risk factors for prognosis of breast cancer patients. Conclusion: CMTM6 is highly expressed in breast cancer tissues, which can be used as a risk factor for prognosis evaluation of breast cancer patients.

Objective: To investigate the degree and distribution of tissue-resident CD8+ T cell (CD103+CD8+T cells) infiltration in colorectal cancer (CRC) tissues, and to analyze its relationship to patients’clinicopathological features and prognosis. Methods: Tissue chips of 88 cases of colon cancer tissues (No.HColA180Su14) and 77 cases of rectal cancer tissues (No. HRec-Ade180Sur-03) were obtained from Shanghai Outdo Biotech Co.,Ltd. Immunofluorescence staining was performed to examine the infiltration pattern and degree of CD103+CD8+T cells in the collected CRC tissues and their para-cancerous tissues. Wilcoxon rank test was used to compare CD103+CD8+T cell infiltration degree in CRC tissues and the para-cancerous tissues. Chi-square test was used to analyze the relationship between CD103+CD8+T cell infiltration in CRC and patients’clinicopathological features. Kaplan-Meier survival analysis was conducted to explore the correlation between CD103+CD8+T cell infiltration and patients’prognosis. Cox model was applied to analyze the correlation between different clinical parameters and patients’prognosis. Results: CD103+CD8+T cell infiltration presented no signifi ·cant differences between CRC and para-cancer tissues (P>0.05). Patients with distant metastasis had significantly lower CD103+CD8+T cell infiltration rate than patients without distant metastasis (P<0.01). There was no significant correlation between the infiltration of CD103+CD8+T cells and other clinicopathological features (P>0.05). Kaplan-Meier survival analysis showed that the overall survival (OS) of patients with high CD103+CD8+T cell infiltration was significantly longer than that of the patients with low infiltration (54.42% vs 25.00%, P<0.05). Multivariate Cox model analysis indicated that pathological grade (P<0.01) and high CD103+CD8+T cell infiltration (P<0.05) were independent prognostic factors for CRC. Conclusion： ：CD103+CD8+T cell infiltration in CRC is associated with patients’prognosis, suggesting that CD103+CD8+T cell plays an important role in the initiation and development of CRC.

CMTM家族作为一个新的基因家族，在免疫、生殖等系统以及多种肿瘤的发病机制中起到重要作用。CMTM家族中， CMTM1可影响细胞增殖，导致肿瘤发生；与非小细胞肺癌（NSCLC）患者的化疗耐药和预后有关。CMTM2通过AP-1、CREB通 路一定程度上影响HIV-1转录，同时在男性生殖系统中起重要作用。CMTM3等位基因失活或甲基化使其丧失对细胞增殖的负 性调控能力，是胃癌独立的预后指标。CMTM4调控细胞周期影响肿瘤细胞增殖，通过对PD-L1的协同保护参与免疫逃逸。 CMTM5在许多肿瘤中沉默表达，参与肿瘤发生发展相关的信号通路。CMTM6协同PD-L1参与免疫逃逸，是潜在的免疫治疗靶 点。CMTM7在NSCLC中通过Rab5控制EGFR-AKT信号影响肿瘤发展，且与胃癌发展相关。CMTM8通过MARVEL区域影响 EGFR和相关信号通路，调控细胞增殖、分化和凋亡等。上述重要发现，为研究肿瘤的发生发展及肿瘤基因治疗提供了新思路。

调节性T（regulatory T，Treg）细胞是一类控制体内免疫反应性的T细胞亚群，在维持机体的免疫系统稳态和调节免疫 应答方面具有重要作用，并且发现在多种肿瘤类型中以较高比例存在，被认为是产生抗肿瘤免疫应答的主要障碍。Treg细胞在 其功能状态和稳定性方面存在异质性，通过多种机制发挥免疫负调控作用，目前在自身免疫和肿瘤免疫的研究中发现，特异性调 节不同Treg细胞群体可改善免疫疗效。但是，如何更加合理有效的以Treg细胞为靶点抑制肿瘤的进展仍需进一步探索。本文就 Treg细胞在肿瘤免疫中的作用机制及治疗应用新策略展开综述。

磷脂酰肌醇蛋白聚糖3(glypican-3，GPC3)是一种锚定在细胞膜上的硫酸乙酰肝素(heparan sulfate，HS)蛋白多糖的家族成 员之一。GPC3激活经典的Wnt/β-连环蛋白(β-catenin)途径在肝癌(hepatocellular carcinoma，HCC)中表现出促癌基因的作用。尽 管GPC3在胎肝中含量丰富，在多种实体肿瘤中高表达，然而在成人正常组织中含量极少。选择靶点是肿瘤免疫治疗的关键。迄 今为止靶向GPC3的MRI、PET和近红外成像已被用于早期HCC检测。针对GPC3+实体瘤也已经开发了各种免疫治疗方案，一种 是基于抗GPC3抗体包括单克隆抗体、多肽疫苗、免疫毒素、双特异性抗体等，一种是靶向GPC3的CAR-T/NK疗法，其中部分已 进入I/II期临床试验。靶向GPC3有可能为实体瘤治疗提供新的工具。本文概述GPC3的结构、功能等生物学特性，介绍基于抗 GPC3抗体、CAR-T细胞开发的新策略，提供GPC3免疫疗法靶向实体瘤的证据。