2025年 · 第138卷第10期

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.

Traditional telemedicine makes it possible to provide diagnosis, advice, monitoring and other medical services, for example, using audio-visual communication technologies, despite physical distance. Telemedicine is an important part of medical health care, especially in rural areas. Telemedicine is an important tool for the further development of care. Against this background, new areas of application for telemedicine are constantly being developed. Telemedicine also plays an important role in the digitalisation strategy for the health care sector.

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.

To the Editor: Globally and in China, there are shortages of available organs and long transplantation waitlists. Donation after cardiac (or circulatory) death (DCD) and donation after brain death are extensively studied methods of organ donation from deceased donors and have emerged as a potential way of enlarging the donor pool.^[1]DCD has historically been associated with worse clinical outcomes after transplant although advances in immunosuppressive therapies, anti-human leukocyte antigen antibody detection, and transplantation techniques have improved outcomes.^[1]A major concern for DCD kidney transplantation is a high incidence of delayed graft function (DGF).^[1]DGF has been associated with many factors including age, sex, and race of the donor or recipient, cold and warm ischemia times, and calcineurin inhibitor (CNI) at discharge.^[2]CNIs are known for their potential effect on kidneys due to arteriolar vasoconstriction, which induces acute tubular dysfunction.^[3]Consequently, the use of CNIs in DCD kidney transplant recipients is considered a clinical challenge given the potential risks associated with DGF.^[4,5]Strategies such as the delayed initiation of tacrolimus after transplant have been explored to compensate for this effect.^[3]

To the Editor: Pemphigus, a rare autoimmune disease, causes blistering of the skin and mucous membranes and is classified into pemphigus vulgaris (PV) and pemphigus foliaceus (PF), with lesions forming at different epidermal levels.^[1]The disease is associated with immunoglobulin G (IgG) autoantibodies and an elevated mortality risk, exceeding that of the general population by 1.7 to 3.0 times.^[2]Despite its chronic nature, studies on long-term outcomes like complete remission off therapy (CROT) and relapse remain limited, often constrained by small cohorts and homogeneous treatments. This study analyzed 621 patients from the Chinese pemphigus cohort, assessing survival outcomes, CROT rates, and prognostic factors to inform better management strategies and improve patient care.

To the Editor: Chimeric antigen receptor (CAR)-T cells targeting CD19 have transformed the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) therapy.^[1]However, cytokine release syndrome (CRS) represents a serious and potentially life-threatening complication, marked by excessive proinflammatory cytokine release, poses a severe, potentially fatal complication, manifesting as fever, nausea, fatigue, and, in severe cases, multi-organ failure.^[2,3]Advances in single-cell transcriptomics have enabled high-resolution analysis of complex tissues, uncovering the cellular dynamics underlying CRS. For example, single-cell protein secretion profiling of pre-infusion CD19 CAR-T products in non-Hodgkin lymphoma patients revealed differential cytokine and chemokine expression, shedding light on individual CRS variability.^[4]Despite these breakthroughs, the role of bone marrow mononuclear cells (BMMCs) at the single-cell level in modulating CRS outcomes has remained insufficiently explored. This study aimed to explore the heterogeneity of BMMCs and their influence on inter-patient variability in CRS severity following anti-CD19 CAR-T therapy, which may influence the development of targeted therapeutic strategies, advancing the safety and efficacy of CAR-T therapies.

To the Editor: Two-thirds of pregnant women experience nausea and vomiting during pregnancy (NVP) in their first trimester, with 0.3-10.8% of pregnant women developing a severe condition called hyperemesis gravidarum (HG). HG leads to dehydration, nutritional deficiencies, electrolyte imbalances, and stress. NVP dramatically reduces quality of life, causes substantial maternal morbidity, and can result in adverse pregnancy outcomes. However, the etiology and pathology of NVP have been poorly understood until recently.

To the Editor: Sensorineural hearing loss (SNHL) is the most prevalent form of hearing loss. The pathogenesis of SNHL remains elusive, resulting in a lack of definitive and effective treatments for most SNHL types. There is substantial evidence that inflammation significantly contributes to SNHL progression. Various injurious agents damage tissues and cells, prompting macrophages to identify these agents and necrotic material and produce inflammatory mediators. Inflammatory mediators are transported to the cochlea through the bloodstream, where they activate resident macrophages and stimulate monocyte infiltration, thereby initiating cochlear inflammation. Inflammation triggers various pathological alterations within the cochlea, primarily characterized by diminished hair cells and synapses, reduced spiral neuron numbers, and compromised blood-labyrinth barrier (BLB) integrity [Supplementary Figure 1, http://links.lww.com/CM9/C342].^[1]Thus, exploring the role of inflammation in SNHL provides distinct insights for its treatment.

To the Editor: Basal cell carcinoma (BCC) is the most prevalent skin malignancy, with an increasing incidence and economic burden worldwide.^[1]Various histopathological subtypes of BCC have been well described, and subtype confirmation is essential for BCC classification according to the risk of recurrence.^[2]Early diagnosis and intervention are important, especially considering that the incidence of aggressive subtypes of BCC is increasing faster than that of indolent subtypes.^[3]Initial screening for BCC relies mainly on clinical observation and dermoscopy, which can further assist in distinguishing between different histopathological subtypes. Recently, artificial intelligence (AI), especially convolutional neural networks (CNNs), has been successfully applied to classify BCC.^[4]However, the diagnostic performance of models based on single-modal light-skinned images is limited, with a risk of impaired accuracy when these models are applied to patients with darker skin. Therefore, we aimed to finetune a multimodal neural network using dermoscopic and clinical images of Chinese patients to assist in the differentiation between BCC and common benign tumors, including melanocytic nevus (MN), seborrheic keratosis (SK), and dermatofibroma (DF), and further predict the subtypes of BCC.

To the Editor: The rapid evolution and widespread adoption of cloud computing, big data, and artificial intelligence have significantly accelerated the digital transformation of medical institutions. However, this progress has led to a rise in the incidence and costs of data breaches, with the average breach costing approximately $15 million in the USA.^[1]Such breaches pose serious threats to national security and public welfare, underscoring the urgent need for robust data protection and compliance in healthcare. Despite the benefits of advanced information technology, hospitals face substantial challenges in ensuring data security and compliance. To address these challenges, we proposed a four-step solution for developing secure and compliant intelligent hospitals, providing a reference framework for data protection and compliance in the healthcare industry [Figure 1A].

To the Editor: Individuals with diabetes have been reported to have an increased susceptibility to severe illness or mortality when infected with coronavirus disease-2019 (COVID-19).^[1]Limited evidence exists regarding the efficacy of inactivated COVID-19 vaccines in real-world settings for protecting diabetic patients from developing severe COVID-19.

The authors regret that estimates for new cancer cases (modify 3,246,625 to 4,909,585; modify 2,510,597 to 2,491,868) and cancer deaths (modify 1,699,066 to 2,593,882; modify 640,038 to 633,864) in the abstract, results and discussion section of "Comparative analysis of cancer statistics in China and the United States in 2024"^[1]were incorrectly stated.