Volume 138 · Issue 16 · 2025

肠道是人体消化系统的关键组成部分，不仅承担着吸收营养的重任，也是感知环境和传递信息的重要枢纽。肠上皮细胞（IECs）作为肠道的重要结构，在维持肠道环境稳定和调节生理功能方面发挥着不可或缺的作用。传统上，对IECs生理功能的研究集中在营养吸收上。最近的研究表明，IEC可能会积极地与其他器官交流。源自IECs的新型通信介质有可能为调节生理稳态开辟前所未有的途径。

嵌合抗原受体（CAR）-T细胞疗法已成为造血系统恶性肿瘤的重要治疗方式。由于CAR-T细胞疗法复杂的治疗程序及其特定的严重免疫相关不良事件，多学科整合的病例管理方法是必要的。围绕如何提高CAR-T细胞治疗的疗效和安全性，我们制定了这一共识，以建立管理和应用CAR-T细胞治疗B细胞非霍奇金淋巴瘤的多学科团队（MDT）模型的标准化方法。共识的完整版本可在补充文件http://links.lww.com/CM9/B961.中找到。

胃肿瘤代表了胃肠道病理学的重要子集。其中，胃癌是最常见的恶性肿瘤，在全球发病率中排名第五，在中国癌症相关死亡率中排名第三。^[1]内窥镜手术的日益采用导致早期胃癌（EGC）的年发病率不断上升。^[2,3]此外，胃粘膜下肿瘤（SMT）主要由间质瘤和平滑肌瘤组成，起源于非粘膜层中的突出病变，并且被检测到的频率越来越高。^[4]

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.

Ischemic stroke (IS) ranks as a leading cause of death and disability globally. The blood-brain barrier (BBB) poses significant challenges for effective drug delivery to brain tissues. Recent decades have seen the development of targeted nanomedicine and biomimetic technologies, sparking substantial interest in biomimetic drug delivery systems for treating IS. These systems are devised by utilizing or replicating natural cells and their derivatives, offering promising new pathways for detection and transport across the BBB. Their multifunctionality and high biocompatibility make them effective treatment options for IS. In addition, the incorporation of engineering techniques has provided these biomimetic drug delivery systems with active targeting capabilities, enhancing the accumulation of therapeutic agents in ischemic tissues and specific cell types. This improvement boosts drug transport and therapeutic efficacy. However, it is crucial to thoroughly understand the advantages and limitations of various engineering strategies employed in constructing biomimetic delivery systems. Selecting appropriate construction methods based on the characteristics of the disease is vital to achieving optimal treatment outcomes. This review summarizes recent advancements in three types of engineered biomimetic drug delivery systems, developed from natural cells and their derivatives, for treating IS. It also discusses their effectiveness in application and potential challenges in future clinical translation.

Microbial-derived metabolites are important mediators of host–microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.

Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database.

The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI).

The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356–128,645,155 cases), 693,444 cases (95% UI = 567,765–850,490 cases), and 17,672 cases (95% UI = 13,932–21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26–1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94–1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0–2235.14) in 1990 to 964.70 (801.26–1175.09) per 100,000 people in 2021.

Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.

Neoadjuvant therapy enhances the possibility of achieving radical resection and improves the prognosis for locally advanced gastric cancer (GC). However, there is a lack of evidence regarding the optimal extent of resection for locally advanced proximal GC after neoadjuvant therapy.

In this study, 330 patients underwent resection in Peking University Cancer Hospital, with curative intent after neoadjuvant therapy for histologically confirmed proximal GC from January 2009 to December 2022.

In this study, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). After propensity-score matching, 110 patients (71 TG and 39 PG) were included in the analysis. No significant differences between PG and TG regarding short-term outcomes and long-term prognosis were found. Specifically, PG demonstrated comparable overall survival to TG (P = 0.47). Subgroup analysis revealed that although not statistically significant, PG showed a potential advantage over TG in overall survival for patients with tumor-long diameters less than 4 cm (P = 0.31). However, for those with a long diameter larger than 4 cm, TG had a better survival probability (P = 0.81). No substantial differences were observed in baseline characteristics, surgical safety, postoperative recovery, and postoperative complications.

For locally advanced proximal GC with objective response to neoadjuvant therapy (long diameter <4 cm), PG is an alternative surgical procedure.

Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.

Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ.

This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 (COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival.

P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.

Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP.

Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo.

4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4⁺ T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo, 4-OI treatment significantly increased platelet counts in the active ITP murine model.

Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.

Gluconeogenesis is a critical metabolic pathway for maintaining glucose homeostasis, and its dysregulation can lead to glycometabolic disorders. This study aimed to identify hub biomarkers of these disorders to provide a theoretical foundation for enhancing diagnosis and treatment.

Gene expression profiles from liver tissues of three well-characterized gluconeogenesis mouse models were analyzed to identify commonly differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), machine learning techniques, and diagnostic tests on transcriptome data from publicly available datasets of type 2 diabetes mellitus (T2DM) patients were employed to assess the clinical relevance of these DEGs. Subsequently, we identified hub biomarkers associated with gluconeogenesis-related glycometabolic disorders, investigated potential correlations with immune cell types, and validated expression using quantitative polymerase chain reaction in the mouse models.

Only a few common DEGs were observed in gluconeogenesis-related glycometabolic disorders across different contributing factors. However, these DEGs were consistently associated with cytokine regulation and oxidative stress (OS). Enrichment analysis highlighted significant alterations in terms related to cytokines and OS. Importantly, osteomodulin (OMD), apolipoprotein A4 (APOA4), and insulin like growth factor binding protein 6 (IGFBP6) were identified with potential clinical significance in T2DM patients. These genes demonstrated robust diagnostic performance in T2DM cohorts and were positively correlated with resting dendritic cells.

Gluconeogenesis-related glycometabolic disorders exhibit considerable heterogeneity, yet changes in cytokine regulation and OS are universally present. OMD, APOA4, and IGFBP6 may serve as hub biomarkers for gluconeogenesis-related glycometabolic disorders.

The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE.

In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction.

The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185–0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252–0.980; P = 0.035), respectively.

Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.

致编辑：脓毒症是住院患者死亡的主要原因。^[1]器官功能障碍是脓毒症的中心特征。最常用于脓毒症诊断和治疗的顺序器官衰竭评估（SOFA）评分是基于器官功能的评估。^[2]脏器损伤的研究是目前脓毒症研究领域的热点。^[3]明确脓毒症中多器官功能障碍和死亡率的分布状况，对这些领域的进一步研究具有高度重要意义。我们设计这项研究是为了根据SOFA评分分析脓毒症患者多器官功能障碍综合征（MODS）的分布。脓毒症的诊断基于脓毒症和脓毒性休克的第三个国际共识定义。^[4]对每位患者进行重新评估，并根据原始数据进行SOFA评分。在这项调查中，纳入了eICU数据库、重症监护医学信息市场（MIMIC）-IV数据库和北京协和医院（PUMCH）收治的脓毒症患者。排除标准如下：年龄小于18岁的患者、首次入院时不是的患者以及无法进行SOFA评分的患者。PUMCH数据库中的数据收集于2013年6月8日至2022年10月12日。MIMIC是重症医学领域最大的免费临床数据库。MIMIC-IV（1.0版）是最新版本，包含2008年至2019年的数据。eICU数据库包括2014年和2015年来自208家医院的335个ICU的20多万名入院患者。我们获得了相应的证书来使用上述数据库。该方案由北京协和医院中央机构审查委员会批准（编号：I-23PJ1416）。这项回顾性分析的个人知情同意要求被免除，因为所有受保护的健康信息都是匿名的。脓毒症患者（PUMCH数据库中有2984例，eICU数据库中有12,943例，MIMIC-IV数据库中有10,150例）最终入组。基本信息和合并症见补充表1，http://links.lww.com/CM9/C490。单个系统SOFA评分≥1定义为器官功能损害，评分≥3定义为严重器官功能损害。所有分析均通过R软件（3.4.3版，R统计计算基金会，奥地利维也纳）进行。连续变量总结为中位数和四分位数间距，而分类变量表示为频率和百分比。

致编辑：慢性自发性荨麻疹（CSU）的全球患病率估计约为0.5-1%，中国约为0.75%。^[1,2]标准剂量的第二代H1抗组胺药（H1AHs）是目前CSU的首选一线治疗药物。在治疗1-2周后对H1AH反应不足的情况下，相同H1AH的剂量可增加至最大4倍，或可与其他抗组胺药联合使用。对于使用增加剂量的抗组胺药治疗2-4周后仍不耐受或无应答的CSU患者，推荐使用人源化重组抗免疫球蛋白E（IgE）单克隆抗体奥马珠单抗（每4周300 mg）作为三线治疗。^[3]

致编辑：随着抗逆转录病毒疗法（ART）将HIV转化为慢性疾病，代谢异常，特别是高血糖症，已成为HIV感染者（PLWH）的主要关注点。尽管由于ART和HIV相关因素，PLWH发生高血糖的风险更高，但在中国未接受治疗的PLWH中高血糖和糖尿病的患病率和相关因素仍未得到充分研究。本研究旨在调查2013年至2019年中国深圳市新诊断PLWH的高血糖和糖尿病患病率趋势。

致编辑：阈下抑郁（SD）通常先于重度抑郁障碍（MDD），广义地定义为在抑郁问卷上得分高于临界点，而不符合精神障碍诊断和统计手册（DSM）或国际疾病分类（ICD）标准。^[1]据估计，SD的患病率在5.3%至29.2%之间。^[2,3]此外，SD与儿童和青少年身心健康的不良结果以及不良的学业、社交和情绪结果有关。^[4]因此，通过适当的治疗来解决SD至关重要。心理干预在减少SD青少年的抑郁症状方面显示出一些影响，但面临着障碍，如难以获得、高成本和精神疾病的耻辱。^[4]数字（即基于互联网和计算机的）心理干预为解决这些障碍和促进青年心理健康护理提供了潜在的解决方案。然而，关于这些干预措施的疗效，先前的研究结果喜忧参半。对数字心理治疗项目对患有SD的青少年的疗效的现存证据进行评估，将为初级卫生保健提供重要证据。