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.

Aim To investigate the interventional effects of polysaccharides from Dicliptera chinensis(L.)Juss.(DCP)on acute liver failure(ALF)in-duced by lipopolysaccharide(LPS)combined with D-galactosamine(D-GalN)in mice,and on LPS-induced inflammatory responses in RAW264.7 cells,based on the TLR-4/MyD88/NF-κB signaling pathway.Meth-ods Mice were randomly divided into the control,model,silymarin,DCP low,medium,and high dose groups,and toxicity test groups.After 10 consecutive days of treatment,ALF models were established by in-jecting mice with LPS+D-GalN.Additionally,an in-flammatory response model was established by stimula-ting RAW264.7 cells with LPS.Results Biochemical assays showed that compared with the model group,the medium-and high-dose DCP groups exhibited de-creased serum ALT,AST,ALP,TBIL,and γ-GT activi-ties(P＜0.05),reduced levels of ROS,MPO and MDA in liver(P＜0.05),increased activities of SOD,GSH-Px,CAT,and elevated T-AOC levels(P＜0.05).ELISA revealed lower levels of ICAM-1,VCAM-1,IL-6,IL-1β,and TNF-α in liver(P＜0.05).HE staining indicated reduced inflammatory cell infiltration and improved hepatocyte necrosis in liv-er after DCP administration.The use of DCP alone showed no significant organ toxicity.qRT-PCR and Western blot results indicated that DCP inhibited the expression of key factors in TLR-4/MyD88/NF-κB sig-naling pathway(P＜0.05).Cell validation experi-ments also confirmed that this pathway was inhibited by DCP.Conclusion DCP alleviates ALF primarily by inhibiting oxidative stress and blocking the activation of the TLR-4/MyD88/NF-κB signaling pathway.

Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)％vs.(36.9±3.2)％],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P＜0.05 or＜0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)％vs.(45.1±0.9)％]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P＜0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

Objective:To observe the early efficacy of intense pulsed light(IPL)combined with non-ablative fractional laser(NAFL)in preventing postoperative pathological scar formation and intervention of inflammatory factors.Methods:93 patients with postoperative pathological scar formation who were admitted to our hospital from March 2022 to September 2024 were selected,they were divided into control group A(silicone gel treatment,n=31),control group B(NAFL on the basis of control group A,n=31)and study group(IPL on the basis of control group B,n=31)using the random number table method.The clinical efficacy,simple quality of life scale(SF-36),vancouver scar scale(VSS),inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)],and adverse reactions among three groups were compared.Results:The clinical total effective rate in the study group were higher than those in the control group A and control group B(P＜0.05).SF-36 increased sequentially and VSS decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).CRP,IL-6,and TNF-α decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).There was no significant difference in the incidence of adverse reactions among the three groups(P＞0.05).Conclusion:IPL combined with NAFL in preventing postoperative pathological scar formation,can effectively reduce scar formation,reduce inflammatory factors levels,improve patients' quality of life,and be safe and reliable.

Objective:To observe the early efficacy of intense pulsed light(IPL)combined with non-ablative fractional laser(NAFL)in preventing postoperative pathological scar formation and intervention of inflammatory factors.Methods:93 patients with postoperative pathological scar formation who were admitted to our hospital from March 2022 to September 2024 were selected,they were divided into control group A(silicone gel treatment,n=31),control group B(NAFL on the basis of control group A,n=31)and study group(IPL on the basis of control group B,n=31)using the random number table method.The clinical efficacy,simple quality of life scale(SF-36),vancouver scar scale(VSS),inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)],and adverse reactions among three groups were compared.Results:The clinical total effective rate in the study group were higher than those in the control group A and control group B(P＜0.05).SF-36 increased sequentially and VSS decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).CRP,IL-6,and TNF-α decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).There was no significant difference in the incidence of adverse reactions among the three groups(P＞0.05).Conclusion:IPL combined with NAFL in preventing postoperative pathological scar formation,can effectively reduce scar formation,reduce inflammatory factors levels,improve patients' quality of life,and be safe and reliable.

Objective To understand the current status of work-related musculoskeletal disorders (WMSDs) among operating room doctors,thereby analyzing its effect on mental health. Methods A total of 1013 doctors in the operating rooms of 30 hospitals in 24 provinces from September to December 2022 were selected by cross-sectional survey method. The domestic musculoskeletal disease questionnaire was used to investigate the occurrence of WMSDs in operating room doctors,the symptom check list-90 (SCL-90) was used to evaluate the psychological status of operating room doctors,the relationship between WMSDs related items and SCL-90 scores was analyzed,the correla-tion between the rest time of each shift and SCL-90 factors was analyzed by Pearson method,and the influencing factors of mental health of operating room doctors were analyzed by multivariate Logistic regression.Results A total of 1100 questionnaires were distributed and 1013 valid questionnaires were recovered,with an effective rate of 92.10％. The incidence of WMSDs among operating room doctors in the past 1 year was 95.06％. The body parts with incidences of WMSDs from high to low were as follows:waist (36.92％),neck (35.54％),shoulder (33.56％),and upper back (32.77％). In the past 1 year,the SCL-90 scores and total scores of patients with musculoskeletal pain in various body parts,keeping the same back posture for a long time while work,bending the back at the same time of turning frequently while working,bowing the head for a long time while working,and bending the knee for a long time while working were significantly higher than those who were without the above conditions (P<0.05). Shorter rest time of each shift and longer periods of keeping the same back posture were the risk factors for the development of mental illness in operating room doctors. Conclusion The incidence of WMSDs in operating room doctors is high,which can influence the mental health of operating room doctors. Therefore,operating room doctors should avoid keeping the same back posture for a long time,bending the back at the same time of turning frequently,bowing the head for a long time,and bending the knee for a long time while working,and increase the rest time of each shift,in order to improve the mental condition of the operating room doctors.

OBJECTIVE To investigate the effects of Chuangling Ye(CLY)on diabetic foot ulcer(DFU)model mice based on the nuclear factor erythroid 2-related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)pathway and explore its potential mechanism.METHODS In animal experiments,streptozotocin(STZ)-induced diabetic mice with full-thickness skin defects were divided into control,model,positive control(recombinant human epidermal growth factor,rhEGF),and CLY low-and high-dose groups(n=10).After 14 days of intervention,wound healing rate was measured.Serum inflammatory factors(IL-6,TNF-α,IL-1β)were detected by ELISA,while oxidative stress markers(SOD,MDA,GSH)and tissue ferrous iron(Fe2+)levels were measured by colorimetric assays.Mitochondrial ultrastructure was observed via transmission electron microscopy(TEM).Nrf2,SLC7A11,and GPX4 expression in wound tissues were analyzed by qPCR and Western blot.In cell experiments,a high glucose(HG)-induced ferroptosis model in human umbilical vein endothelial cells(HUVECs)was established and divided into control,HG,CLY,and CLY combined with pathway inhibitors(ML385,Erastin,RSL3)groups.CCK-8 was used to detect cell via-bility,FerroOrange was used to detect Fe2+content,DCFH-DA and C11-BODIPY 581/591 probes were used to detect intracellular ROS and lipid ROS content,and Western blot was used to detect the expression of proteins such as Nrf2/SLC7A11/GPX4.RESULTS Animal experiments showed that compared with the model group,the wound healing rate in the low-and high-dose CLY groups was significantly improved(P<0.01);the serum IL-6,IL-1β,and TNF-α levels were significantly decreased(P<0.01);the MDA con-tent was significantly reduced(P<0.01),and the SOD activity and GSH content were significantly restored(P<0.05).Colorimetric a-nalysis showed that the low-and high-dose CLY significantly reduced the abnormally elevated Fe2+levels in DFU wounds(P<0.05,P<0.001).Electron microscopy showed that the mitochondrial cristae structure was improved in the low-and high-dose groups.qPCR showed that high-dose CLY upregulated the expression levels of Rno-Nfe2l2(Nrf2),Rno-Slc7a11,Rno-Gpx4,and Rno-Acsl4 mR-NA,and inhibited the expression level of Rno-Acsl4 mRNA(P<0.001).Western blot results showed that CLY upregulated the expres-sion of Nrf2,SLC7A11,GPX4,and FTH1 in DFU wound tissues(P<0.01),while downregulated the level of ACSL4(P<0.01).Cell experiments showed that treatment with CLY increased the survival rate of high glucose-stimulated HUVECs(P<0.001).However,the protective effect of CLY was significantly inhibited after the addition of ML385,Erastin,or RSL3(P<0.01).Treatment with CLY significantly decreased the Fe2+content(P<0.001),which was reversed by ML385,Erastin,or RSL3.The levels of ROS and lipid ROS were also significantly reduced(P<0.001),while the addition of ML385,Erastin,or RSL3 partially weakened the antioxidant effect of CLY.Western blot results showed that CLY significantly upregulated the expression of Nrf2、SLC7A11 and GPX4(P<0.001)and downregulated the expression of 4-HNE and COX2(P<0.01),and ML385,Erastin,or RSL3 could reverse this protective effect.CONCLUSION CLY promotes DFU healing by activating the Nrf2/SLC7A11/GPX4 pathway to inhibit ferroptosis,mitigate oxidative stress,and suppress inflammation,providing a novel therapeutic target for DFU.

Objective:To systematically analyze the impact of various physician payment methods on medical service delivery behavior and outcomes.Methods:Based on the scoping review method,2 255 documents related to"physician","compensation","payment method",and"physician behavior"were retrieved from Web of Science,CNKI,VIP,and WanFang databases,and finally 70 studies were included based on scientific screening standards and process.Results:Fee-for-service encourages physicians to deliver an adequate volume of services but is susceptible to overtreatment;salary and capitation assist in controlling costs but can lead to insufficient service provision;the advantages of DRG/DIP in the quantity and quality of medical services weaken as the patient's condition worsens.Mixed payment methods can effectively balance the quantity and cost of medical services,while pay-for-performance is generally outstanding in improving quality.Conclusions:It is difficult for a single payment method to achieve the optimization of medical service delivery behavior and outcomes.A mixed payment system that integrates multiple payment methods with quality incentives must be established urgently.At the same time,it is recommended to deepen the reform of the mechanism for converting medical insurance balance into physician compensation,fully implement the allocation autonomy of public hospitals,and accelerate the establishment of a mixed physician payment method that is coordinated with medical insurance payment and performance appraisal.

Aim To explore the mechanism of Yangxin decoction in the treatment of chronic heart failure(CHF)based on network pharmacology and animal ex-periments.Methods The database was used to screen Yangxin decoction,a network of"drug-compo-nent-disease-target"was established,and the obtained targets were enriched and analyzed.The CHF model of rats was replicated by abdominal aortic ligation.After the administration,the general condition,body weight and heart weight of the rats were observed,and the he-modynamic changes,echocardiography indicators and left ventricular mass index were measured.HE staining was used to observe the morphological changes of myo-cardial tissue.Serum IL-1 β,IL-18,TNF-α and BNP were detected by ELISA.The expressions of NLRP3,caspase-1,ASC and NF-κB p65 proteinswere detected by Western blot.Results Enrichment analysis showed that the potential regulatory pathways of Yangx-in decoction in the treatment of CHF involved NOD-like signaling pathway,NF-κB signaling pathway,etc.The results of animal experiments showed that the body weight,left ventricular diastolic diameter and left ven-tricular systolic diameter of the rats in the administra-tion group decreased(P＜0.05),the left ventricular mass index,ejection fraction and short axis narrowing rate increased(P＜0.05),the pathological morphology of myocardial tissue was reduced,and the levels of IL-1 β,IL-18,TNF-α,BNP,NLRP3,caspase-1,ASC and NF-κB p65 decreased(P＜0.05).Conclusions The mechanism of Yangxin decoction in the treatment of CHF rats may be related to inhibiting the activation of NLRP3 inflammasome signaling pathway and reduc-ing the inflammatory response.