Volume 138 · Issue 11 · 2025

自1956年首例造血干细胞移植（HSCT）以来，HSCT作为一种细胞水平的移植治疗，已经治愈了数以万计的血液病患者。^[1]HSCT主要通过清髓性条件化疗和移植物抗白血病（GVL）效应根除白血病细胞，随后的发展如供体淋巴细胞输注（DLI）和微移植作为额外的治疗方法出现。^[2]然而，传统的HSCT及相关治疗仍存在一定的局限性。首先，基于高剂量化疗/全身照射的预处理方案的肿瘤杀伤能力受到安全性问题的限制，特别是关于白血病干细胞的根除，这是患者复发的主要原因。^[3]其次，传统免疫抑制剂在预防或治疗移植物抗宿主病（GVHD）的同时，也抑制了GVL效应。仅通过免疫抑制药物控制GVHD、复发和感染难以达到理想的平衡。此外，目前没有有效的方法来解决移植后植入不良和移植相关的内皮损伤并发症。^[4]

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, highlighting the urgent need for novel preventive and therapeutic strategies. Emerging research highlights the crucial role of the gut microbiota, including bacteria, fungi, viruses, and their metabolites, in the pathogenesis of CRC. Dysbiosis, characterized by an imbalance in microbial composition, contributes to tumorigenesis through immune modulation, metabolic reprogramming, and genotoxicity. Specific bacterial species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis, along with fungal agents like Candida species, have been implicated in CRC progression. Moreover, viral factors, including Epstein-Barr virus and human cytomegalovirus, are increasingly recognized for their roles in promoting inflammation and immune evasion. This review synthesizes the latest evidence on host-microbiome interactions in CRC, emphasizing microbial metabolites, such as short-chain fatty acids and bile acids, which may act as both risk factors and therapeutic agents. We further discuss the latest advances in microbiota-targeted clinical applications, including biomarker-assisted diagnosis, next-generation probiotics, and microbiome-based interventions. A deeper understanding of the role of gut microbiome in CRC pathogenesis could pave the way for diagnostic, preventive, and personalized therapeutic strategies.

The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function—key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.

This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.

Liver cancer is one of the most common malignant tumors worldwide. Currently, the available treatment methods cannot fully control its recurrence and mortality rate. Establishing appropriate animal models for liver cancer is crucial for developing new treatment technologies and strategies. The patient-derived xenograft (PDX) model preserves the tumor’s microenvironment and heterogeneity, which makes it advantageous for biological research, drug evaluation, personalized medicine, and other purposes. This article reviews the development, preparation techniques, application fields, and challenges of PDX models in liver cancer, providing insights for the research and exploration of PDX models in diagnostic and therapeutic strategies of liver cancer.

Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021.

Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index.

In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates.

Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.

Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends.

Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson’s correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040.

Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively.

NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.

Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths.

This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate.

From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management.

The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.

Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk.

We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures.

High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity.

This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.

Increasing evidence indicates that oxidative stress and interferon γ (IFNγ)-driven cellular immune responses are responsible for the pathogenesis of vitiligo. However, the connection between oxidative stress and the local production of IFNγ in early vitiligo remains unexplored. The aim of this study was to identify the mechanism underlying the production of IFNγ by mast cells and its impact on vitiligo pathogenesis.

Skin specimens from the central, marginal, and perilesional skin areas of active vitiligo lesions were collected to characterize changes of mast cells, CD8⁺ T cells, and IFNγ-producing cells. Cell supernatants from hydrogen peroxide (H₂O₂)-treated keratinocytes (KCs) were harvested to measure levels of soluble stem cell factor (sSCF) and matrix metalloproteinase (MMP)-9. A murine vitiligo model was established using Mas-related G protein-coupled receptor-B2 (MrgB2, mouse ortholog of human MrgX2) conditional knockout (MrgB2^-/-) mice to investigate IFNγ production and inflammatory cell infiltrations in tail skin following the challenge with tyrosinase-related protein (Tyrp)-2 180 peptide. Potential interactions between the Tyrp-2 180 peptide and MrgX2 were predicted using molecular docking. The siRNAs targeting MrgX2 and the calcineurin inhibitor FK506 were also used to examine the signaling pathways involved in mast cell activation.

IFNγ-producing mast cells were closely aligned with the recruitment of CD8⁺ T cells in the early phase of vitiligo skin. sSCF released by KCs through stress-enhanced MMP9-dependent proteolytic cleavage recruited mast cells into sites of inflamed skin (Perilesion vs. lesion, 13.00 ± 4.00/high-power fields [HPF] vs. 26.60 ± 5.72/HPF, P <0.05). Moreover, IFNγ-producing mast cells were also observed in mouse tail skin following challenge with Tyrp-2 180 (0 h vs. 48 h post-recall, 0/HPF vs. 3.80 ± 1.92/HPF, P <0.05). The IFNγ⁺ mast cell and CD8⁺ T cell counts were lower in the skin of MrgB2^-/-mice than in those of wild-type mice (WT vs. KO 48 h post-recall, 4.20 ± 0.84/HPF vs. 0.80 ± 0.84/HPF, P <0.05).

Mast cells activated by MrgX2 serve as a local IFNγ producer that bridges between innate and adaptive immune responses against MCs in early vitiligo. Targeting MrgX2-mediated mast cell activation may represent a new strategy for treating vitiligo.

致编辑：妊娠是一个复杂的生理过程，在此过程中母体免疫系统耐受半同种异体胚胎在子宫内成功发育。这一时期涉及母体各器官和系统的显著变化。母胎界面由母体蜕膜组织和胚胎滋养层组成。免疫细胞占人蜕膜的40%，包括自然杀伤(NK)细胞、髓源性抑制细胞(MDSC)、巨噬细胞(M φ)、T细胞等。该界面错综复杂的免疫调节机制仍然是母胎免疫耐受研究的重点。脾脏作为人体最大的外周免疫器官，含有多种类型的免疫细胞。大量研究表明，脾脏在各种炎性疾病的发展和进展中起作用。^[1,2]理论上，由于一系列炎症事件，脾脏在怀孕期间应该会发生相应的变化；然而，缺乏关于这一主题的报道。

致编辑：根据国际疾病分类，肌肉减少症是骨骼肌质量（SMM）和功能的年龄相关消瘦，是一种独立的医学病症。由于不同的定义和人群，肌肉减少症的患病率从5%到50%不等，并且由于预期寿命的逐渐增加，预计在未来30年内将显著增加。肌肉减少症与术后并发症的高风险、低生存率、更长的住院时间、吞咽困难和出院时的身体残疾相关。关于肌肉减少症和2型糖尿病（T2DM）之间因果关系的现有研究产生了相互矛盾的结果。首先，包括血红蛋白A1c（HbA1c）（评估血糖控制的重要工具）的研究结果仍然不一致。^[1,2]第二，在探讨肌肉减少症与T2DM的关系时，应尽可能全面地考虑潜在的混杂因素。除了身体活动，吸烟状况、社会经济地位或教育程度是否在这种关系中发挥作用仍然未知。第三，由于不可避免的混杂因素和反向因果关系，很难通过观察性研究确定关系。大多数研究集中在肌肉减少症和T2DM之间的因果关系，而肌肉减少症相关特征的研究很少。鉴于缺乏有效的药物治疗和肌肉减少症的不良结果，评估肌肉减少症相关特征和T2DM之间的因果关系可能有助于开发T2DM预防、诊断和治疗的新技术。本研究旨在（1）确定英国生物库（UKB）中肌肉减少症相关特征与T2DM发病率之间的潜在相关性；（2）通过中介分析探索潜在机制。

致编辑：近期，国内出现了一种新颖的机器人手术平台——康多手术机器人（KD-SR）。如补充图1 http://links.lww.com/CM9/C379所示，KD-SR-01系统集成了开放式视觉系统，不仅使外科医生能够保持自然姿势并减轻潜在的颈部劳损，还增强了主刀外科医生与其助手之间的有效沟通。先前的研究已经证明了这种新型机器人手术系统在某些情况下令人鼓舞的结果。^[1]