[摘 要] 过继性T细胞疗法在实体瘤治疗中展现了良好的前景，成为目前肿瘤治疗领域的一大研究热点。其中，TCR-T疗法主要通过T细胞受体（TCR）与抗原肽-主要组织相容性复合体（pMHC）的特异性识别，进而激活过继性T细胞的抗肿瘤免疫反应。因此，全面解析TCR所靶向的抗原信息有助于提高TCR-T疗法在临床应用中的有效性及安全性。然而，高效、高通量的TCR抗原筛选技术的缺乏限制了TCR-T疗法的发展。近年来，随着高通量测序技术、质谱流式细胞技术和计算生物学的快速发展，研究人员开发了多种TCR抗原筛选技术用于解析TCR及其特异性识别的抗原信息。本文从抗原定向筛选、TCR定向筛选以及双向筛选三方面对TCR抗原筛选技术进行归纳总结，系统介绍其优缺点，展望TCR抗原筛选技术领域的发展前景，为未来抗原筛选技术的开发提供了新思路。

[摘 要] 目的：探讨间充质干细胞来源的外泌体（MSC-Exo）对人结肠癌CT26细胞体外增殖、迁移的影响及对放射性肠炎（RE）荷瘤小鼠模型的治疗效果及其安全性。方法：利用商品化含MSC-Exo的液体敷料产品（MSC-Exo产品），通过纳米颗粒追踪分析、透射电镜、WB法对其中的MSC-Exo进行鉴定。采用CCK-8法和Transwell小室法检测MSC-Exo产品对结肠癌CT26细胞增殖、迁移的影响。构建CT26细胞荷瘤小鼠模型，连续7 d分别给予400 μL MSC-Exo产品、MSC培养基或生理盐水灌胃，评估MSC-Exo产品在体内对肿瘤生长和小鼠生存的影响。构建RE荷瘤小鼠模型，连续7 d分别给予400 μL MSC-Exo产品、MSC培养基、生理盐水灌胃治疗，通过小肠组织H-E染色法评估MSC-Exo产品治疗RE的有效性与安全性。结果：纳米颗粒追踪分析、透射电镜、WB法的鉴定结果确证了商品化的液体敷料中含有MSC-Exo有效成分。体外研究表明，MSC-Exo产品成分不会促进结肠癌CT26细胞的增殖和迁移，具有安全性。体内研究结果发现，MSC-Exo产品的灌胃给药并不影响荷瘤小鼠的肿瘤生长和生存期，但RE荷瘤小鼠模型接受MSC-Exo产品灌胃治疗后，荷瘤小鼠血便、黏液便症状得到缓解，H-E染色结果显示小鼠肠壁组织的组织形态完整性相较于对照组有所改善，提示MSC-Exo产品对荷瘤小鼠的RE具有疗效，并且在致瘤性及肿瘤转移方面具有安全性。结论：商品化含MSC-Exo的液体敷料并不促进体外结肠癌细胞的增殖、迁移，对CT26细胞荷瘤小鼠肿瘤生长和生存期无明显影响，但对荷瘤小鼠模型的RE具有治疗作用，改善了肠道组织的损伤。

[摘 要] 目的：通过生物信息学分析以及细胞生物学实验研究角蛋白6A（KRT6A）对胰腺导管腺癌（PDAC）诊断、预后判断、免疫微环境以及PDAC细胞PANC1增殖、凋亡等生物学行为的影响。方法：通过GEPIA平台整合TCGA（The Cancer Genome Atlas）数据库与GTEx（Genotype-Tissue）数据库中的数据，分析KTRT6A在PDAC组织中的表达情况，并通过CIBERSORT工具分析KRT6A表达与PDAC组织中免疫细胞浸润的关系，然后通过GSEA方法研究与KRT6A基因表达相关的肿瘤信号通路。选取长海医院病理科保存的60例PDAC组织与癌旁组织标本进行免疫组化分析，验证KRT6A在肿瘤组织中表达情况；通过干扰RNA敲减PANC1细胞中KRT6A的表达，采用CCK-8实验以及流式细胞术检测敲减KRT6A对细胞的增殖、凋亡的影响。结果：利用TCGA与GTEx数据库数据分析发现，KRT6A在人PDAC组织中呈高表达，且与患者较差的生存期存在关联（P=0.015）。利用CIBERSORT软件以及GSEA分析发现，KRT6A高表达的PDAC组织中M2型巨噬细胞浸润性升高（P=0.034），且与Wnt通路（NES:1.7359272，P<0.05）、磷酸戊糖途径（PPP）（NES:1.5613053，P<0.05）等信号通路上调有关联（P<0.05或P<0.01）；免疫组化结果进一步验证了KRT6A在PDAC组织中呈高表达（P<0.001）。增殖和凋亡实验发现，干扰KRT6A能够显著抑制PANC1细胞的增殖（P<0.05）以及凋亡（P<0.001）。结论：KRT6A在人PDAC组织中呈高表达，敲减其表达能够抑制PANC1细胞的增殖和凋亡，具有作为PDAC诊断与预后判断新靶标的潜力。

Autoimmune pancreatitis(AIP)is an immune-mediated,special type of chronic pancreatitis,which can involve multiple organs.The clinical manifestation of AIP is complex and varied,making the diagnosis and treatment challenging.With reference to the latest guidelines and studies from both domestic and international sources,this guideline comprises 20 recommendations regarding the diagnosis,treatment,follow-up,and prognosis of AIP.The aim of this guideline is to promote the care capability and improve the outcome of patients with AIP in China.

Osteoarthritis(OA),characterized by cartilage degeneration,synovial inflammation,and subchondral bone remodeling,is among the most common musculoskeletal disorders globally in people over 60 years of age.The initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic process.Cartilage degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte metabolism.Therefore,maintaining mitochondrial homeostasis is an important strategy to mitigate OA.Mitophagy is a vital process for autophagosomes to target,engulf,and remove damaged and dysfunctional mitochondria,thereby maintaining mitochondrial homeostasis.Cumulative studies have revealed a strong association between mitophagy and OA,suggesting that the regulation of mitophagy may be a novel therapeutic direction for OA.By reviewing the literature on mitophagy and OA published in recent years,this paper elaborates the potential mechanism of mitophagy regulating OA,thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.

The endoplasmic reticulum is a key site for protein production and quality control.More than one-third of proteins are synthesized and folded into the correct three-dimensional conformation in the endoplasmic reticulum.However,during protein folding,unfolded and/or misfolded proteins are prone to occur,which may lead to endoplasmic reticulum stress.Organisms can monitor the quality of the proteins produced by endoplasmic reticulum quality control(ERQC)and endoplasmic reticulum-associated degradation(ERAD),which maintain endoplasmic reticulum protein homeostasis by degrading abnormally folded proteins.The underlying mechanisms of protein folding and ERAD in mammals have not yet been fully explored.Therefore,this paper reviews the process and function of protein folding and ERAD in mammalian cells,in order to help clinicians better understand the mechanism of ERAD and to provide a scientific reference for the treatment of diseases caused by abnormal ERAD.

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T cells. Upon antigen exposure, T cells undergo metabolic reprogramming, leading to the development of functional effectors or memory populations. However, within the tumor microenvironment (TME), metabolic stress impairs CD8 + T cell anti-tumor immunity, resulting in exhausted differentiation. Recent studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell immunotherapy. In this review, we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory conditions. Furthermore, we delved into the different metabolic switches that occur during T cell exhaustion, exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion, ultimately leading to a persistently exhausted state. Understanding the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

[摘 要] 以靶向PD-1/PD-L1和CTLA-4为代表的免疫检查点阻断治疗在实体瘤的治疗中取得了不俗疗效，但仅有不到30%的患者能够从中受益的现实表明，还存在其他免疫检查点分子介导的免疫抑制。B7H3属于免疫球蛋白超家族B7家族成员，与CTLA-4/PD-1主要表达在T细胞并介导后者的免疫抑制或耗竭不同，B7H3蛋白不仅诱导性表达在免疫细胞，还组成性高表达在多种肿瘤细胞和肿瘤相关脉管系统。B7H3不仅能够激活多条信号通路直接促进肿瘤细胞恶性表型，还可以通过重塑肿瘤免疫抑制微环境间接促进肿瘤的进展、转移和耐药。因此，基于B7H3的多项靶向抗肿瘤策略，包括特异性抗体、抗体偶联药物及CAR-T细胞等均已进入临床试验并展示出较好的应用前景。但总体而言，该领域的研究依然处于探索阶段，在相互作用受体的鉴定、降低毒性、打破耐药及联合用药策略优化等方面还面临着许多问题和挑战亟待突破。

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release.
Animals ; Mice ; Alveolar Epithelial Cells ; Pyroptosis ; Gasdermins ; Lipopolysaccharides/adverse effects* ; Tumor Necrosis Factor-alpha ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome

TET2, a member of ten-eleven translocation (TET) family as α-ketoglutarate- and Fe