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.

Dry eye （DE） is a prevalent multifactorial disease of the ocular surface， clinically characterized by tear film homeostasis imbalance accompanied by related ocular surface symptoms. Specifically， the tear film is a thin liquid layer of tears covering the cornea and conjunctiva through blinking， while tear film homeostasis serves as the foundation for maintaining normal ocular surface structure and function. Insufficient tear secretion and excessive tear film evaporation lead to tear hyperosmolarity and the production of inflammatory mediators， disrupting tear film homeostasis and subsequently forming DE. Additionally， cascade reactions are triggered， resulting in a "vicious cycle of DE" that exacerbates the disease severity and prolongs its duration. Therefore， for DE treatment， it is crucial to restore tear film homeostasis and terminate this vicious cycle. Traditional Chinese medicine （TCM）， which differentiates and treats DE based on systemic conditions， often achieves favorable therapeutic outcomes， offering additional treatment options for DE. Studies have demonstrated that TCM can alleviate DE by regulating tear film homeostasis and terminating the vicious cycle. This review systematically summarizes recent basic experimental research in China and abroad on TCM in alleviating DE by regulating tear film homeostasis， aiming to provide a theoretical basis for clinical treatment and an insight for research design.

ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

ObjectiveTo construct a competency model for "dual-qualified" teachers in vocational undergraduate rehabilitation therapy programs based on the World Health Organization's rehabilitation competency framework (RCF) and relevant domestic and international standards, and explore the training pathways for rehabilitation therapy teachers in China. MethodsLiterature analysis and comparative research methods were employed to systematically review RCF, physiotherapist-education-framework-FINAL, the Minimum-Standards-for-the-Education-of-Occupational-Therapists, and the "dual-qualified" teacher standards in vocational education for China. Focusing on the characteristics of vocational undergraduate talent cultivation, it took the integration of the "educator-clinical rehabilitation therapist" dual roles as its starting point, combining rehabilitation industry competence with educator standards as its basic principle, and using RCF as its foundational dimension. It then integrated advanced competency dimensions required of vocational undergraduate teachers to form a dimensional framework. Following the systematic curriculum development concept of the work process, the core activities of each dimension were designed by combining, improving and expanding the concept integration method, and describing the ability characteristics in a graded and progressive manner, to construct a model. ResultsThis model was guided by the core concepts of three types of values ​​and four types of professional beliefs. Vertically, it encompassed 28 activities across eight competency dimensions, including teaching practice, rehabilitation practice, digital literacy, professionalism, learning and development, management and leadership, applied research, and social service. Horizontally, it encompassed 53 corresponding competency characteristics across three advanced levels (beginner, intermediate and advanced). ConclusionThis model, through its vertical dimension design and horizontal progressive development, clearly describes the advancement of vocational undergraduate rehabilitation therapy teachers from newly hired teachers to backbone teachers and professional leaders. It not only aligns with the general requirements of the national standards for "dual-qualified" teachers in higher vocational colleges in China, but also incorporates an international perspective on rehabilitation education and practice, and possesses the characteristics of vocational undergraduate education that integrates multiple abilities and roles. At the theoretical level, it provides core theoretical support for establishing standardized and internationalized "dual-qualified" teacher standards for vocational undergraduate rehabilitation therapy programs in China; at the practical level, it serves as an "action map" for teacher professional development, assessment and evaluation, providing a key reference for constructing a systematic high-end skilled rehabilitation talent training system.

ObjectiveTo construct a competency model for "dual-qualified" teachers in vocational undergraduate rehabilitation therapy programs based on the World Health Organization's rehabilitation competency framework (RCF) and relevant domestic and international standards, and explore the training pathways for rehabilitation therapy teachers in China. MethodsLiterature analysis and comparative research methods were employed to systematically review RCF, physiotherapist-education-framework-FINAL, the Minimum-Standards-for-the-Education-of-Occupational-Therapists, and the "dual-qualified" teacher standards in vocational education for China. Focusing on the characteristics of vocational undergraduate talent cultivation, it took the integration of the "educator-clinical rehabilitation therapist" dual roles as its starting point, combining rehabilitation industry competence with educator standards as its basic principle, and using RCF as its foundational dimension. It then integrated advanced competency dimensions required of vocational undergraduate teachers to form a dimensional framework. Following the systematic curriculum development concept of the work process, the core activities of each dimension were designed by combining, improving and expanding the concept integration method, and describing the ability characteristics in a graded and progressive manner, to construct a model. ResultsThis model was guided by the core concepts of three types of values ​​and four types of professional beliefs. Vertically, it encompassed 28 activities across eight competency dimensions, including teaching practice, rehabilitation practice, digital literacy, professionalism, learning and development, management and leadership, applied research, and social service. Horizontally, it encompassed 53 corresponding competency characteristics across three advanced levels (beginner, intermediate and advanced). ConclusionThis model, through its vertical dimension design and horizontal progressive development, clearly describes the advancement of vocational undergraduate rehabilitation therapy teachers from newly hired teachers to backbone teachers and professional leaders. It not only aligns with the general requirements of the national standards for "dual-qualified" teachers in higher vocational colleges in China, but also incorporates an international perspective on rehabilitation education and practice, and possesses the characteristics of vocational undergraduate education that integrates multiple abilities and roles. At the theoretical level, it provides core theoretical support for establishing standardized and internationalized "dual-qualified" teacher standards for vocational undergraduate rehabilitation therapy programs in China; at the practical level, it serves as an "action map" for teacher professional development, assessment and evaluation, providing a key reference for constructing a systematic high-end skilled rehabilitation talent training system.

ObjectiveTo construct a competency model for "dual-qualified" teachers in vocational undergraduate rehabilitation therapy programs based on the World Health Organization's rehabilitation competency framework (RCF) and relevant domestic and international standards, and explore the training pathways for rehabilitation therapy teachers in China. MethodsLiterature analysis and comparative research methods were employed to systematically review RCF, physiotherapist-education-framework-FINAL, the Minimum-Standards-for-the-Education-of-Occupational-Therapists, and the "dual-qualified" teacher standards in vocational education for China. Focusing on the characteristics of vocational undergraduate talent cultivation, it took the integration of the "educator-clinical rehabilitation therapist" dual roles as its starting point, combining rehabilitation industry competence with educator standards as its basic principle, and using RCF as its foundational dimension. It then integrated advanced competency dimensions required of vocational undergraduate teachers to form a dimensional framework. Following the systematic curriculum development concept of the work process, the core activities of each dimension were designed by combining, improving and expanding the concept integration method, and describing the ability characteristics in a graded and progressive manner, to construct a model. ResultsThis model was guided by the core concepts of three types of values ​​and four types of professional beliefs. Vertically, it encompassed 28 activities across eight competency dimensions, including teaching practice, rehabilitation practice, digital literacy, professionalism, learning and development, management and leadership, applied research, and social service. Horizontally, it encompassed 53 corresponding competency characteristics across three advanced levels (beginner, intermediate and advanced). ConclusionThis model, through its vertical dimension design and horizontal progressive development, clearly describes the advancement of vocational undergraduate rehabilitation therapy teachers from newly hired teachers to backbone teachers and professional leaders. It not only aligns with the general requirements of the national standards for "dual-qualified" teachers in higher vocational colleges in China, but also incorporates an international perspective on rehabilitation education and practice, and possesses the characteristics of vocational undergraduate education that integrates multiple abilities and roles. At the theoretical level, it provides core theoretical support for establishing standardized and internationalized "dual-qualified" teacher standards for vocational undergraduate rehabilitation therapy programs in China; at the practical level, it serves as an "action map" for teacher professional development, assessment and evaluation, providing a key reference for constructing a systematic high-end skilled rehabilitation talent training system.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective: To analyze the association between altitudes and nutritional status of children and adolescents, and to explore the moderating effects of dietary behaviors and physical activity, so as to provide a scientific basis for developing lifestyle interventions tailored to local conditions. Methods: From September to November 2023, physical examinations and questionnaire surveys were conducted among children and adolescents aged 7-17 in two autonomous regions, Inner Mongolia and Xizang, with a final sample of 156 511 participants by the stratified cluster random sampling method. Height and weight were measured to calculate body mass index (BMI). Sociodemographic characteristics, dietary behaviors, and physical activity were collected via questionnaires, while the altitude of each participant s school was obtained using Amap. Logistic regression was performed to examine the relationship between altitudes and nutritional status. Interaction terms and stratified analyses were applied to assess the moderating effects of dietary behaviors and physical activity. Restricted cubic spline (RCS) were used for visualization. Results: In 2023, the prevalence of wasting and overweight/obesity among children and adolescents in Xizang were 9.7% and 9.0%, respectively, compared to 2.9% and 22.0% in Inner Mongolia. Logistic regression analysis results showed that for every 1 km increase in altitude, the risk of wasting increased, while the risk of overweight/obesity decreased ( OR =1.43, 0.19, both P <0.05). The results of the stratified analysis showed that compared to those living at altitudes <1 km, children and adolescents with healthy diets showed no significant association between altitudes (1-<2 and 2-<3 km) and wasting ( OR =1.22, 0.75, both P >0.05), whereas significant associations were observed at 3-<4 and ≥4 km altitudes ( OR =2.25, 2.89, both P <0.05). In contrast, unhealthy dietary groups showed statistically significant associations across altitudes ( OR =1.18-4.04, all P <0.05), consistent with RCS results. No moderating effects were observed for physical activity on the altitude wasting association or for dietary behaviors and physical activity combined on the altitude overweight/obesity association ( P interaction =0.63, 0.10, 0.53). Conclusion Healthy dietary behaviors play a critical role in improving the nutritional status of children and adolescents and reducing regional disparities, providing a scientific foundation for public health policy formulation and implementation.