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.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

OBJECTIVE To provide scientific reference for perfecting the record-filing management policy of traditional Chinese medicine preparations formulated via traditional processes for medical applications （hereinafter referred to as “TCM preparations”） in medical institutions， and further promote the sound development of the research and record-filing work of such preparations. METHODS A literature review combined with cross-sectional research was carried out. We collected policy documents and preparation information related to the record-filing of TCM preparations issued by national and provincial drug administration authorities on official websites during 2018-2025. A comparative analysis was conducted on the implementation and revision of core policy documents for the registration management of TCM preparations across provinces， the scope of record-filing dosage forms， conditions for rejection of record-filing， and exemptions for registration materials. Statistical analysis on the quantity and dosage forms of record-filing preparations in each province was conducted by means of data induction and trend chart plotting， and targeted suggestions were put forward to optimize the management pathway of record-filing. RESULTS CONCLUSIONS There was obvious heterogeneity in record-filing policies among provinces. Twelve provinces refined the applicable dosage forms for record-filing， fifteen provinces supplemented conditions for rejection of record-filing （16 items in total）， and nine provinces expanded the scope of material exemptions. The number of recorded preparations presented a striking regional imbalance：Qinghai had the largest quantity of 4 269 varieties， while Hainan only had 14 varieties， with a gap of more than 300 times. The recorded preparations were mainly traditional dosage forms including pills （6 928 varieties） and powders （4 360 varieties）. Only 12 provinces formulated the provincial catalog for TCM preparations allocation. In most regions， preparation circulation was only permitted within medical consortia， leading to a low transformation rate of scientific and technological achievements of preparations. It is recommended to optimize the record-filing management pathway from three aspects： strengthening policy standardization while maintaining flexibility， streamlining record-filing procedures and documentary requirements， and reinforcing technical support and achievement transformation. These measures can reduce regional policy differences， improve work efficiency of record-filing， and advance the standardized development and clinical value transformation of hospital-made TCM preparations.

OBJECTIVE To provide scientific reference for perfecting the record-filing management policy of traditional Chinese medicine preparations formulated via traditional processes for medical applications （hereinafter referred to as “TCM preparations”） in medical institutions， and further promote the sound development of the research and record-filing work of such preparations. METHODS A literature review combined with cross-sectional research was carried out. We collected policy documents and preparation information related to the record-filing of TCM preparations issued by national and provincial drug administration authorities on official websites during 2018-2025. A comparative analysis was conducted on the implementation and revision of core policy documents for the registration management of TCM preparations across provinces， the scope of record-filing dosage forms， conditions for rejection of record-filing， and exemptions for registration materials. Statistical analysis on the quantity and dosage forms of record-filing preparations in each province was conducted by means of data induction and trend chart plotting， and targeted suggestions were put forward to optimize the management pathway of record-filing. RESULTS CONCLUSIONS There was obvious heterogeneity in record-filing policies among provinces. Twelve provinces refined the applicable dosage forms for record-filing， fifteen provinces supplemented conditions for rejection of record-filing （16 items in total）， and nine provinces expanded the scope of material exemptions. The number of recorded preparations presented a striking regional imbalance：Qinghai had the largest quantity of 4 269 varieties， while Hainan only had 14 varieties， with a gap of more than 300 times. The recorded preparations were mainly traditional dosage forms including pills （6 928 varieties） and powders （4 360 varieties）. Only 12 provinces formulated the provincial catalog for TCM preparations allocation. In most regions， preparation circulation was only permitted within medical consortia， leading to a low transformation rate of scientific and technological achievements of preparations. It is recommended to optimize the record-filing management pathway from three aspects： strengthening policy standardization while maintaining flexibility， streamlining record-filing procedures and documentary requirements， and reinforcing technical support and achievement transformation. These measures can reduce regional policy differences， improve work efficiency of record-filing， and advance the standardized development and clinical value transformation of hospital-made TCM preparations.

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: To analyze the serological characteristics of anti-Mur antibodies and investigate the distribution frequency of the Mur antigen among voluntary blood donors in Shiyan, thereby providing a basis for guiding clinical transfusion and establishing a Mur blood type database. Methods: ABO blood grouping of donors and patients was performed using an automated blood typing analyzer and the gel card method, respectively. Unexpected antibody screening and identification were performed using the saline, tube anti-human globulin, and polybrene methods. The specificity of anti-Mur antibodies was confirmed using Fisher's exact probability test. Plasma treated with 2-mercaptoethanol was used to distinguish IgM and IgG antibodies. IgM and IgG anti-Mur titers were determined by the saline tube method and the anti-human globulin tube method, respectively, at 4℃, room temperature, and 37℃. A total of 1 659 donor red blood cell samples were initially screened for the Mur antigen phenotype using three samples of human-derived anti-Mur plasma by the micro-tube method. Donors who tested positive for Mur antigen were further tested by the direct antiglobulin test (DAT); those with negative results were confirmed for Mur antigen by the gel card and polybrene methods. Results: Three blood samples were identified to contain mixed IgG and IgM anti-Mur antibodies. The titers of both IgM and IgG anti-Mur antibodies were highest at 4℃, intermediate at room temperature, and lowest at 37℃. The positive frequency of the Mur antigen among voluntary blood donors in Shiyan was 1.99% (33/1 659). Conclusion: anti-Mur antibodies were detected in both blood donors and patients in our region. The Mur antigen shows a certain distribution frequency among voluntary blood donors in Shiyan. Screening for the Mur blood type and establishing a corresponding database could enhance transfusion safety.

Objective To investigate the effects of cinnamic aldehyde(CA)on Bcl-2-associated X protein(Bax)and Bcl-2 homologous antagonist/killer(Bak)in vascular endothelial cells of diabetic ulcer wound tissues,as well as on cell apoptosis.Methods ① Forty-eight healthy SPF-grade male SD rats(5 weeks old,weighing 180～220 g)were randomly assigned to a control group(12 rats)and a diabetes group(36 rats).The diabetic model was established with an intraperitoneal injection of 50 mg/kg STZ-citrate sodium solution and high-fat diet feeding.The diabetes group was further randomly divided into Model group,CA group,and the rb-bFGF group,with 12 animals in each group.Wounds in the Con and Model groups were disinfected and topically treated with normal saline,CA group received topical application of 4 μmol/L CA in PEG 400 gel,and those of the rb-bFGF group were treated with bevacizumab gel.The wound healing rate of each group was calculated at 3,7 and 14 d after intervention.At 14 d after intervention,pathological changes in the wounds were observed with HE staining,and the expression levels of Bax and Bak were detected by Western blotting.② Human umbilical vein endothelial cell line EA.hy926 was treated with 175 mmol/L glucose for 48 h to establish a cell model of high glucose injury.The experimental cells were divided into control group,model group and CA treatment group.Cell scratch test and tube formation test were performed respectively to determine the migration ability and angiogenesis of the cells.The expression levels of Bax and Bak was detected with immunofluorescence assay,and cell apoptosis was detected by TUNEL staining.Results ①The diabetic rats in the Model group exhibited significantly higher blood glucose level(P<0.05),declined wound healing rate at 7 and 14 d after intervention(P<0.05),and enhanced expression levels of Bax and Bak(P<0.05)when compared with the control group.Pathological observation revealed that,at 14 d after intervention,accompanied with inflammatory reactions,dense infiltration of inflammatory cells,fewer new blood vessels,and continuous fluid exudation in the wound were observed in the Model group,but the control group presented complete epithelialization in full-thickness skin.Compared with the conditions in the Model group,both CA and rb-bFGF treatment improved the epithelialization process,with mature granulation tissues,showing good healing condition,promoted wound healing rate(P<0.05),and decreased the expression levels of Bax and Bak(P<0.05).② The results of cell experiments showed that the cells of the model group showed significantly reduced migration ability and tube formation ability(P<0.05),reduced protein levels of Bax and Bak(P<0.05),and lower apoptotic rate(P<0.05)when compared with the cells in the model group.Conclusion CA can inhibit the expression of apoptosis-related proteins Bax and Bak,promote the migration and tube formation of vascular endothelial cells,and inhibit the cell apoptosis under high glucose condition,which may be an important reason for its promoting wound healing in diabetic ulcer rats.

Haloacetic acids(HAAs),as a class of disinfection byproducts in drinking water,pose potential threats to human health,so the rapid,accurate and simultaneous detection of HAAs is of great significance for ensuring drinking water safety.Aiming at the challenges in HAAs detection and risk analysis,a novel method for synchronous rapid detection of seven kinds of HAAs in drinking water based on in situ derivatization technology and headspace gas chromatography was developed in this study.Through single-factor optimization experiments,the optimal reaction parameters for in situ derivatization were determined,including the type and dosage of salting-out agent,the acidity of reaction system,the amount of phase transfer catalyst,the dosage of derivatization agent,and the extraction solvent volume.Methodologic validation showed that the seven kinds of HAAs exhibited excellent linear relationships within their respective detection concentration ranges(R2>0.998).The method detection limits(MDLs)ranged from 0.04 to 0.33 μg/L,and the limits of quantification(LOQs)were between 0.14 and 1.34 μg/L.For real water samples,the average spiked recoveries of the seven HAAs ranged from 90.9%to 107.7%,with relative standard deviation(RSDs)between 1.55%and 6.49%,and the HAAs contents in all tested samples were below the limits specified in the Standards for Drinking Water Quality(GB 5749-2022)of China.This method was featured with simple operation,fast analysis speed,high sensitivity,and good accuracy,providing an efficient and reliable technical support for routine monitoring of HAAs contaminants in drinking water and showing promising application value for widespread promotion.

Objective:To analyze the respiratory virus infection status and epidemiological characteristics of influenza-like illness (ILI) cases in Shandong Province during the 2020 -2021 influenza surveillance year. Methods:According to the National Influenza Surveillance Plan (2017 version), throat swab samples of ILI cases were collected from 14 surveillance sentinel hospitals in Shandong Province. Nucleic acid was extracted from all samples. Real-time fluorescence quantitative PCR (RT-PCR) was utilized to detect six common viruses, including human metapneumovirus (HMPV), human parainfluenza virus (HPIV) types 1, 2 and 3, respiratory syncytial virus (RSV), and adenovirus (ADV). Subsequently, the obtained detection results were analyzed.Results:A total of 2 386 specimens were collected, with a detection rate of 24.22% (578). Six viruses were detected, with detection rates of 6.75% (162 cases) for HMPV, 5.87% (140 cases) for RSV, 3.56% (85 cases) for HPIV3, 3.14% (75 cases) for HPIV2, 2.98% (71 cases) for HPIV1, and 2.77% (66 cases) for ADV. There was no significant difference in detection rates between genders, but a notable variation among different age groups ( P<0.001). The highest detection rate was observed in individuals aged 0-4 years (31.94%), followed by those aged≥60 years (26.06%). The prevalence of six viruses showed a monthly variation, with the detection rate of HMPV being higher in December and HPIV1 being higher in February. HPIV2, HPIV3, RSV, and ADV had higher detection rates in November. The co-detection rate of multiple viruses was 0.80%, with RSV being the most common pathogen involved in co-detection, primarily in individuals aged 0-4 years. Conclusion:The detection of six multiple pathogens in ILI cases in Shandong Province is dominated by HMPV, RSV and HPIV3. The prevalence of respiratory viruses varies by age and time.