Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

The chronicity of infectious diseases is an important field in the collaborative research of traditional Chinese and Western medicine. The warm disease theory of pathogen invading nutrient and blood aspects in traditional Chinese medicine （TCM） takes the struggle between healthy Qi and pathogenic Qi and cementation of Yin as the core pathogenesis， providing a unique theoretical framework for explaining the common pathology of infectious chronic diseases. This theory originated from Yin-Yang interaction in the Internal Classic and was enriched with WU Youke's theory of intruding pathogen interacting and lingering in blood vessels and YE Tianshi's theory of long-term illness entering collaterals. Combining the theory with modern medical knowledge， our team has condensed the dynamic pathogenesis model of deficiency （nutrient and blood aspects） and excess （pathogen） interacting in the blood collaterals of Yin aspect， the core feature of which is the four-dimensional interactions of cause （pathogen characteristics）， location （three Yin locations of diseases）， nature （deficiency and excess）， and potential （transmission trend）. The common pathology of infectious chronic diseases is reflected in interactions. That is， the interactions between nutrient and blood deficiency （immune exhaustion and metabolic disorder） and pathogen excess （pathogen persistence and fibrous hyperplasia） in the liver collaterals （Jueyin）， kidney collaterals （Shaoyin）， lung collaterals （Taiyin） and other blood collaterals of Yin aspect form the pathological damage characterized by immune inflammatory response-continuous tissue damage with excessive repair. Taking the inheritance and innovative development of classics as the main line， this paper systematically discusses the scientific connotation of the theory of pathogen invading nutrient and blood aspects and the paths of inheritance and innovation and clarifies the original significance of this theory in the chronic development of infectious diseases. Furthermore， taking clinical diseases as an example， this paper reflects the guiding value of this classical theory in the modern diagnosis and treatment of infectious diseases with integrated traditional Chinese and Western medicine and the application potential of this theory in solving complex medical problems through the construction of the innovative paradigm of precise diagnosis and treatment with integrated traditional Chinese and Western medicine.

ObjectiveBased on the regulation of macrophage M2 polarization， this study aims to explore the molecular mechanism and action targets of the Qijia Rougan prescription and its key effector ingredients in anti-fibrosis， thereby providing a basis and reference for the development of new drugs for hepatic fibrosis. MethodsA rat model of hepatic fibrosis was established by subcutaneous injection of 40%CCl₄， followed by oral administration of Qijia Rougan granules. The volume of collagen fibers was detected using Masson staining， the fibrosis markers Collagen Ⅰ and α-SMA were detected using immunohistochemistry， the proportion of M2 macrophages was detected by flow cytometry. The expression levels of M2 macrophage phenotype markers CD163 and CD206 were detected using immunofluorescence double staining. Western blot was used to detect the levels of the transforming growth factor-β （TGF-β）， platelet derived growth factor subunit B （PDGFB）， interleukin-10 （IL-10）， phosphorylated Janus kinase 1 （p-JAK1）， and phosphorylated signal transducer and activator of transcription 6 （p-STAT6）. Real-time fluorescent quantitative PCR was used to detect the relative expression levels of JAK1， STAT6， Arginase 1（Arg1）， and Fizz1. Based on the theory of serum pharmacology， liquid chromatography-mass spectrometry and WENN analysis were used to obtain the active ingredients of Qijia Rougan prescription. Molecular docking and molecular dynamics simulation were performed to analyze the effector ingredients and their targets. The identified effector ingredients were interfered with IL-4-induced M2 polarization of RAW264.7 macrophage in vitro to validate the targets. ResultsQijia Rougan prescription significantly reduced the content of fibrosis markers α-SMA and Collagen Ⅰ， as well as collagen fiber content （P<0.05）. It decreased the proportion of M2 macrophages and the levels of related cytokines IL-10， TGF-β and PDGFB， and up-regulated the levels of p-JAK1 and p-STAT6 （P<0.05）. A total of 1 214 compounds were identified from Qijia Rougan prescription， medicated serum and blank serum， and 29 ingredients were finalized by Venn analysis， including 15 blood-entry prototypes and 14 drug metabolites. Molecular docking showed that enoxolone and berberine bound more strongly to JAK1， with binding free energies of -9.6 kcal·mol^-1（1 cal≈4.184 J） and -9.1 kcal·mol^-1， respectively. Molecular dynamics simulations showed that JAK1-enoxolone and JAK1-berberine exhibited stable simulation trajectories within 100 ns， with essentially identical conformations and high protein overlap before and after simulation. Their binding free energies were -25.18 5.0.81 kcal·mol^-1 and -27.39 7.0.85 kcal·mol^-1， respectively. The number of hydrogen bonds formed between JAK1 and enoxolone ranges from 0 to 5， and most of the time can be maintained at 2-3. In vitro intervention with enoxolone or berberine significantly reduced p-JAK1 and p-STAT6 levels （P<0.05）. ConclusionQijia Rougan prescription inhibits M2 macrophage polarization in hepatic fibrosis. Enoxolone and berberine are the key effector ingredients of Qijia Rougan prescription to inhibit macrophage M2 polarization through targeting JAK1 and modulating the JAK1/STAT6 signaling pathway， thereby ameliorating hepatic fibrosis. This study provides a basis for prescription optimization， clinical application and new drug development， as well as a reference for monolithic anti-hepatic fibrosis research.

A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.

ObjectiveTo conduct sarcopenia-related screening and assessment among community-dwelling elderly patients with type 2 diabetes mellitus (T2DM) in Changning District of Shanghai, to analyze the current status and influencing factors of suspected sarcopenia in this population, and to provide references for the early prevention and treatment of sarcopenia. MethodsUsing a stratified random sampling method, elderly T2DM patients under management in the Chronic Disease Health Management System of Changning District in Shanghai were selected as the study subjects. Patients were screened for sarcopenia and underwent related health examinations according to the Chinese Expert Consensus on Diagnosis and Treatment of Sarcopenia in the Elderly (2021). Self-designed questionnaires were used to collect basic information, lifestyle habits and health status, and the Montreal Cognitive Assessment (MoCA) was employed to evaluate cognitive function. ResultsAmong 758 elderly patients with T2DM [average age: (72.19±6.19) years old], 214 patients were identified as having suspected sarcopenia,accounting for 28.23%. The proportion of suspected sarcopenia was higher in females (30.94%) than in males (24.08%) (χ²=4.20, P=0.040), and higher in older patients (χ²=22.26, P<0.001). Higher proportions of suspected sarcopenia were also observed among patients who followed a vegetarian diet (39.77%) (χ²=73.28, P=0.011), had diabetic foot (59.09%) (χ²=10.65, P=0.001), reported feeling fatigued most of the time (37.11%) (χ²=4.33, P=0.037), or had mild cognitive impairment (χ²=3.95, P=0.047). The duration of T2DM in the suspected sarcopenia group [(12.86±10.07) years old] was longer than that in the non-sarcopenia group [(9.73±8.63) years old] (t=3.79, P<0.001), and the average body mass index (BMI) in the suspected sarcopenia group [(22.17±2.45) kg⋅m^-²)] was lower than that in the non-sarcopenia group [(25.11±3.26) kg⋅m^-²)] (t=-11.41, P<0.001). Multivariate logistic regression analyses showed that older age (OR=1.08, 95%CI:1.047‒1.110) and longer duration of T2DM (OR=1.02, 95%CI:1.005‒1.043) were associated with a higher risk of suspected sarcopenia in elderly T2DM patients. Female elderly T2DM patients had a higher risk of suspected sarcopenia (OR=1.89, 95%CI:1.310‒2.733) than males, and those with diabetic foot (OR=3.66, 95%CI:1.341‒9.990) had a higher risk than those without diabetic foot. ConclusionThe proportion of elderly T2DM patients with suspected sarcopenia was relatively high. In community-based integrated health management, healthcare providers should pay more attention to elderly T2DM patients who are older, have longer disease duration, are female, or have diabetic foot, so as to identify risks early and implement targeted comprehensive interventions and health management.

Mammalian male germline development depends on a specialized gonadal somatic microenvironment. However, itsin vitro reconstruction remains challenging. Major barriers include the generation of appropriate supporting-cell lineages, organized tissue architecture, and culture conditions that sustain germ-cell maturation. Yoshino et al. established a mouse pluripotent stem cell-derived testicular organoid model. This model reconstitutes the sex-determining region Y (Sry)-SRY-box transcription factor 9 (Sox9)‑mediated sex-determination program and generates testicular somatic cell-like cells (TesLCs). When assembled with primordial germ cell-like cells (PGCLCs), TesLCs formed seminiferous tubule-like structures and supported male germline progression toward prospermatogonia and germline stem cell-like cells (GSCLCs). After transplantation into infertile recipient testes, organoid-derived GSCLCs produced fertilization-competent sperm and generated fertile offspring. The major significance of this work extends beyond sperm production. It integrates sex determination, germ-cell fate transition, and testicular niche self-organization into an experimentally tractable organoid system. This commentary discusses the technical strategy, sex-determination mechanism, value of testicular niche reconstruction, and translational limitations of this study. It also highlights its implications for in vitro gametogenesis, male infertility modeling, and reproductive medicine.

With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Naval hospitals,the backbone of naval health service system,are the key to build a world-class naval health service system.On the basis of the requirements of military transformation and high-quality development of public hospitals,this paper summarized five aspects of high-quality development of naval hospitals,including directions and regulations,support and contribution of combats,efficiency,sustainable development momentum,and the expansion of service functions.It is very important to strengthen the top-level design and policy support for naval hospitals,to improve the level of governance and innovation,and to find the right target for the naval hospital construction in naval health service system reform.