Volume 138 · Issue 10 · 2025

Collagen-based materials, renowned for their biocompatibility and minimal immunogenicity, serve as exemplary substrates in a myriad of biomedical applications. Collagen-based micro/nanogels, in particular, are valued for their increased surface area, tunable degradation rates, and ability to facilitate targeted drug delivery, making them instrumental in advanced therapeutics and tissue engineering endeavors. Although extensive reviews on micro/nanogels exist, they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials. The current review offers an in-depth look into the manufacturing technologies, drug release mechanisms, and biomedical applications of collagen-based micro/nanogels to address this gap. First, we provide an overview of the synthetic strategies that allow the precise control of the size, shape, and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials. These properties are crucial for their performance in biomedical applications. We then highlight the environmental responsiveness of these collagen-based micro/nanogels, particularly their sensitivity to enzymes and pH, which enables controlled drug release under various pathological conditions. The discussion then expands to include their applications in cancer therapy, antimicrobial treatments, bone tissue repair, and imaging diagnosis, emphasizing their versatility and potential in these critical areas. The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review, with an emphasis on the translation to clinical practice. This comprehensive review serves as a valuable resource for researchers, clinicians, and scientists alike, providing insights into the current state and future directions of collagen-based micro/nanogel research and development.

The vasculature plays a critical role in homeostasis and health as well as in the development and progression of a wide range of diseases, including cancer, cardiovascular diseases, metabolic diseases (and their complications), chronic inflammatory diseases, ophthalmic diseases, and neurodegenerative diseases. As such, the growth of the vasculature mediates normal development and physiology, as well as disease, when pathologically induced vessels are morphologically and functionally altered owing to an imbalance of angiogenesis-stimulating and angiogenesis-inhibiting factors. This review offers an overview of the angiogenic process and discusses recent findings that provide additional interesting nuances to this process, including the roles of intussusception and angiovasculogenesis, which may hold promise for future therapeutic interventions. In addition, we review the methodology, including those of in vitro and in vivo assays, which has helped build the vast amount of knowledge on angiogenesis available today and identify important remaining knowledge gaps that should be bridged through future research.

Early-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.

Tissue-resident memory T (TRM) cells are a recently defined subtype of non-recirculating memory T cells with longevity and protective functions in peripheral tissues. As an essential frontline defense against infections, TRM cells have been reported to robustly patrol the tissue microenvironment in malignancies. Accumulating evidence also implicates that TRM cells in the relapse of chronic inflammatory skin diseases such as psoriasis and vitiligo. In light of these developments, this review aims to synthesize these recent findings to enhance our understanding of TRM cell characteristics and actions. Therefore, after providing a brief overview of the general features of the TRM cells, including precursors, homing, retention, and maintenance, we discuss recent insights gained into their heterogeneous functions in skin diseases. Specifically, we explore their involvement in conditions such as psoriasis, vitiligo, fixed drug eruption - dermatological manifestations of drug reactions at the same spot, cutaneous T cell lymphoma, and melanoma. By integrating these diverse perspectives, this review develops a comprehensive model of TRM cell behavior in various skin-related pathologies. In conclusion, our review emphasizes that deciphering the characteristics and mechanisms of TRM cell actions holds potential not only for discovering methods to slow cancer growth but also for reducing the frequency of recurrent chronic inflammation in skin tissue.

传统的远程医疗使得提供诊断、咨询、监测和其他医疗服务成为可能，例如，使用视听通信技术，尽管物理距离很远。远程医疗是医疗保健的重要组成部分，尤其是在农村地区。远程医疗是进一步发展护理的重要工具。在此背景下，远程医疗的新应用领域正在不断被开发。远程医疗在医疗保健行业的数字化战略中也发挥着重要作用。

The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system.

This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China.

At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs. 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs. ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained.

In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system.

ClinicalTrials.gov, NCT03656848.

Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage.

A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate.

In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes (BRCA) mutations (BRCAm) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs. 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs. 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCAm, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively.

Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCAm, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.

T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction.

A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models.

In vitro, blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg^-1·day^-1) and Rapamycin (0.1 mg·kg^-1·day^-1) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression.

Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.

T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL.

HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse.

The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo.

This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.

The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS).

Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis.

The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls (P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS (P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity.

Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.

致编辑：在全球和中国，可用器官短缺，等待移植的名单很长。心脏（或循环）死亡（DCD）后捐献和脑死亡后捐献是广泛研究的已故供体器官捐献方法，并已成为扩大供体库的潜在方式。^[1]尽管免疫抑制疗法、抗人白细胞抗原抗体检测和移植技术的进步改善了预后，但DCD在历史上与移植后较差的临床预后相关。^[1]DCD肾移植的一个主要问题是移植物功能延迟（DGF）的高发生率。^[1]DGF与许多因素有关，包括供体或受体的年龄、性别和种族、冷缺血和热缺血时间以及出院时的钙调磷酸酶抑制剂（CNI）。^[2]众所周知，CNIs由于小动脉血管收缩而对肾脏有潜在影响，其诱导急性肾小管功能障碍。^[3]因此，考虑到与DGF相关的潜在风险，在DCD肾移植受者中使用CNIs被认为是一项临床挑战。^[4,5]已经探索了移植后延迟开始他克莫司等策略来补偿这种影响。^[3]

致编辑：天疱疮是一种罕见的自身免疫性疾病，导致皮肤和粘膜起泡，分为寻常型天疱疮（PV）和叶状天疱疮（PF），病变形成于不同的表皮水平。^[1]该病与免疫球蛋白G（IgG）自身抗体和死亡风险升高有关，超过普通人群1.7~3.0倍。^[2]尽管其具有慢性性质，但对长期结果（如完全缓解治疗（CROT）和复发）的研究仍然有限，通常受到小队列和同质治疗的限制。本研究分析了来自中国天疱疮队列的621例患者，评估了生存结果、CROT率和预后因素，以提供更好的管理策略和改善患者护理。

致编辑：靶向CD19的嵌合抗原受体（CAR）-T细胞已经转化了复发或难治性B细胞急性淋巴细胞白血病（R/R B-ALL）疗法。^[1]然而，细胞因子释放综合征(CRS)是一种严重且可能危及生命的并发症，其特征是促炎细胞因子过度释放，造成严重的、可能致命的并发症，表现为发热、恶心、疲劳，在严重的情况下，多器官衰竭。^[2,3]单细胞转录组学的进展使得复杂组织的高分辨率分析成为可能，揭示了CRS背后的细胞动力学。例如，非霍奇金淋巴瘤患者输注前CD19 CAR-T产品的单细胞蛋白分泌谱揭示了差异的细胞因子和趋化因子表达，揭示了个体CRS的可变性。^[4]尽管有这些突破，但骨髓单核细胞（BMMCs）在单细胞水平上在调节CRS结果中的作用仍未得到充分探索。本研究旨在探索BMMCs的异质性及其对抗CD19 CAR-T治疗后CRS严重程度患者间变异性的影响，这可能会影响靶向治疗策略的发展，提高CAR-T治疗的安全性和有效性。

致编辑：三分之二的孕妇在妊娠早期会出现孕期恶心和呕吐（NVP），0.3-10.8%的孕妇会出现称为妊娠剧吐（HG）的严重情况。汞会导致脱水、营养缺乏、电解质失衡和压力。NVP显著降低生活质量，导致大量孕产妇发病率，并可能导致不良妊娠结局。然而，直到最近，人们对NVP的病因和病理知之甚少。

致编辑：感音神经性听力损失(SNHL)是最普遍的听力损失形式。SNHL的发病机制仍然难以捉摸，导致大多数SNHL类型缺乏明确和有效的治疗方法。有大量证据表明炎症显著促进SNHL进展。各种有害物质损害组织和细胞，促使巨噬细胞识别这些物质和坏死物质并产生炎性介质。炎症介质通过血流转运到耳蜗，在那里它们激活常驻的巨噬细胞并刺激单核细胞浸润，从而引发耳蜗炎症。炎症引发耳蜗内的各种病理改变，主要特征是毛细胞和突触减少、螺旋神经元数量减少和血迷路屏障（BLB）完整性受损【补充图1，http：//links.lww.com/CM9/C342】。^[1]因此，探索炎症在SNHL中的作用为其治疗提供了独特的见解。

致编辑基底细胞癌（BCC）是最普遍的皮肤恶性肿瘤，在世界范围内发病率和经济负担都在增加。^[1]BCC的各种组织病理学亚型已被很好地描述，亚型确认对于根据复发风险的BCC分类至关重要。^[2]早期诊断和干预是重要的，特别是考虑到BCC侵袭性亚型的发病率比惰性亚型增加得更快。^[3]BCC的初筛主要依靠临床观察和皮肤镜检查，可以进一步辅助区分不同的组织病理学亚型。最近，人工智能（AI），特别是卷积神经网络（CNN），已经成功地应用于基底细胞癌的分类。^[4]然而，基于单模态浅色皮肤图像的模型的诊断性能是有限的，当这些模型应用于深色皮肤患者时，存在准确性受损的风险。因此，我们旨在使用中国患者的皮肤镜和临床图像微调多模态神经网络，以帮助区分基底细胞癌和常见良性肿瘤，包括黑素细胞痣（MN）、脂溢性角化病（SK）和皮肤纤维瘤（DF），并进一步预测基底细胞癌的亚型。

致编辑：云计算、大数据、人工智能的快速演进和广泛采用，显著加速了医疗机构的数字化转型。然而，这一进展导致数据泄露的发生率和成本上升，在美国，平均泄露成本约为1500万美元。^[1]此类违规行为对国家安全和公共福利构成严重威胁，凸显了医疗保健领域对强大数据保护和合规性的迫切需求。尽管先进的信息技术带来了好处，但医院在确保数据安全和合规性方面面临着巨大的挑战。为了应对这些挑战，我们提出了开发安全合规智能医院的四步解决方案，为医疗保健行业的数据保护和合规性提供了参考框架[图1A].

致编辑：据报道，糖尿病患者在感染冠状病毒疾病-2019（新冠肺炎）时患严重疾病或死亡的易感性增加。^[1]关于灭活新冠肺炎疫苗在现实环境中保护糖尿病患者免于发展为严重新冠肺炎的功效的证据有限。

作者感到遗憾的是，在“2024年中国和美国癌症统计数据比较分析”的摘要、结果和讨论部分中对新发癌症病例（修改3,246,625至4,909,585；修改2,510,597至2,491,868）和癌症死亡（修改1,699,066至2,593,882；修改640,038至633,864）的估计^[1]被错误地陈述了。