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 identify the structure of the complementarity determining region (CDRs), the V(D)J rearrangement and somatic hypermutational characteristics of the heavy and light chains of a red blood cell blood group-specific monoclonal antibody. Methods: The hybridoma cell line secreting human IgM κ monoclonal anti-P antibody was used as the research object. Total RNA was extracted from cultured monoclonal cell line, and cDNA was obtained by reverse transcription PCR (RT-PCR) using random hexamers primers. It was then amplified and sequenced using primers specific for variable regions of the immunoglobulin heavy and light chains encoding the anti-P antibody. The sequences were aligned against the NCBI database using online Immunoglobulin BLAST (Ig-BLAST) tool. Results: The study determined the structure of the CDRs and framework regions (FRs) of the variable regions of human monoclonal anti-P immunoglobulin, as well as the characteristics of V(D)J rearrangement. Moreover, the closest VH, VD, and VJ germline alleles for the heavy chain and VL and VJ germline alleles for the light chain were also identified. The IgH gene rearrangment pattern of the monoclonal anti-P was IGHV6-1 * 01—IGHD5-18 02—IGHJ4 02 and IgL gene was IGκV1-12 01—IGκJ3 01. Nine base mutations occurred within the germline gene IGHV6-1 01 in variable region of heavy chain, whereas 5 base mutations were found in the germline gene IGκV1-12 01 in variable region of light chain, respectively. Conclusion: This study characterized the CDR structure in monoclonal antibody cell line targeting the high-frequency red blood cell P antigen, and provided a foundation for the construction of recombinant antibody expressing plasmids and transfomation of the immunoglobulin type.

OBJECTIVE To confirm trigger items for adverse drug reaction （ADR） induced by bevacizumab， to identify and analyze the occurrence of related ADR， and to establish a predictive model for severe adverse reaction （SAR） caused by this drug. METHODS Based on the global trigger tool （GTT） theory， and referencing the GTT White Paper， drug package inserts and relevant literature， trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items， electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects （divided into training and test sets at a ratio of 7∶3）， candidate feature variables were selected from 39 related variables using the Boruta algorithm， and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features， Logistic Regression， Extreme Gradient Boosting， Light Gradient Boosting Machine， Random Forest， and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve （AUC） of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations （SHAP） method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined， comprising 17 laboratory indicators， 13 clinical manifestations， and 8 intervention measures. In total， 483 patients with positive trigger items were included， and 318 patients with bevacizumab-induced ADR were identified， including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% （708/1 625） and 63.84% （318/483）， respectively. Bevacizumab-induced ADR involved 7 systems/organs， with the hematological system being the most frequently involved （64.15%）. The Boruta algorithm selected 7 vari ables： serum potassium， hematocrit， albumin-to-globulin ratio， prealbumin， hypertension history， age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR （OR＝0.234， P ＝0.002）， while a history of hypertension （OR＝2.642， P ＝0.006） and increased age （OR＝1.040， P ＝0.025） were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC， F1 score and recall rate （0.761， 0.447， 0.607）， compared to other models. SHAP evaluation results indicated that variables such as serum potassium， hematocrit， and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR， whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.

BackgroundCurrently， the incidence of depression among teenagers is on the rise， and the related academic problems are becoming increasingly serious. Short video addiction has a negative impact on teenagers' emotional issues and academic achievements. However， few studies have explored the relationship between this addiction and the learning burnout of teenagers with depression， and even fewer have focused on the role paths of impulsivity and coping disposition in this process. ObjectiveTo explore the relationship between short video addiction and learning burnout in adolescent patients with depression， as well as the pathway of impulsivity and coping disposition， so as to provide references for the intervention of learning burnout in adolescent patients with depression. MethodsA total of 191 adolescent patients who were hospitalized at The Affiliated Brain Hospital of Guangzhou Medical University from December 2024 to April 2025 and met the diagnostic criteria for depression according to the International Classification of Diseases， tenth edition （ICD-10） were selected consecutively. The Short Video Addiction Measurement Scale （SVAMS）， the Brief Barratt Impulsiveness Scale （BBIS）， the Simplified Coping Style Questionnaire （SCSQ）， and the Adolescent Student Burnout Inventory （ASBI） were used for assessment. Pearson correlation analysis was employed to examine the correlations of the scores of each scale. Model 6 of the SPSS macro Process 4.2 was employed to analyze the chained mediation pathway of impulsivity and coping disposition between short video addiction and learning burnout. ResultsA total of 173 cases （90.58%） of adolescent patients with depression completed the valid questionnaire survey. Correlation analysis showed that SCSQ coping disposition score was negatively correlated with the SVAMS score， the BBIS score， and the ASBI score （r=-0.282， -0.341， -0.431， P<0.01）， the SVAMS score was positively correlated with the BBIS score and the ASBI score （r=0.339， 0.262， P<0.01）， and the BBIS score was positively correlated with the ASBI score （r=0.486， P<0.01）. The pathway analysis showed that the direct effect of short video addiction on learning burnout was not statistically significant， but the total effect and the indirect effect were statistically significant. The effect values were 0.275 （95% CI： 0.207–0.343） and 0.193 （95% CI： 0.143–0.246）， respectively， with the indirect effect accounting for 70.18%. Impulsivity and coping disposition both played independent mediating roles between short video addiction and learning burnout， with effect values of 0.122 （95% CI： 0.090–0.156） and 0.054 （95% CI： 0.032–0.079）， accounting for 44.36% and 19.64% of the total effect， respectively. The chained mediation effect of impulsivity and coping disposition was significant， with an effect value of 0.017 （95% CI： 0.011–0.026）， accounting for 6.18% of the total effect. ConclusionAlthough short video addiction does not directly affect learning burnout in adolescent patients with depression， it may indirectly influence learning burnout through independent and chain paths of impulsivity and coping disposition. ［Funded by Guangzhou Key Clinical Specialty （Clinical Medical Research Institute）］

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 compare the effects of manual acupuncture(MA),electroacupuncture(EA),and moxibustion on knee joint cartilage morphology,serum inflammatory factors interleukin(IL)-6 and IL-10,matrix metalloproteinase 13(MMP13),and intestinal flora composition in knee osteoarthritis(KOA)model rats.Methods:Forty male specific-pathogen-free Sprague-Dawley rats aged seven weeks were randomly divided into a normal group(n=8)and a KOA modeling group(n=32).The KOA model was established using sodium iodoacetate induction.The KOA modeling rats were further randomly divided into a model group,an MA group,an EA group,and a moxibustion group,with 8 rats in each group.In the MA,EA,and moxibustion groups,interventions targeting the right Futu(ST32)and Zusanli(ST36)were performed for 15 min,once every other day,for 14 sessions.The normal and model groups were bundled on the self-made fixation frame for 15 min.The rat knee joint diameter was measured on the 8th day of adaptive feeding,after successful modeling,and after the 14th intervention.Lequesne behavioral scoring was performed after successful modeling and after the 14th intervention.After the 14th intervention,hematoxylin-eosin(HE)staining and Masson staining were performed with the cartilage sections of the right knee joint.The pathomorphological changes of the rat joint cartilage were observed and quantified by Mankin's score.Enzyme-linked immunosorbent assay was used to detect the rat serum levels of IL-6,IL-10,and MMP13.Additionally,16S rDNA sequencing was used to detect the composition of rat fecal flora.Results:Compared to the normal group,the right knee joint diameter and the Lequesne score were significantly increased in the model group(P<0.01).Compared to the model group,the right knee joint diameter and the Lequesne score of rats in the MA,EA,and moxibustion groups were significantly reduced(P<0.01),with no significant differences among the three intervention groups(P>0.05).HE staining and Masson staining revealed disordered cartilage structure in the model group,which was improved following interventions in the MA group,EA group,and moxibustion group.Mankin's score was significantly higher in the model group versus the normal group(P<0.05)while significantly lower in the MA,EA,and moxibustion groups versus the model group(P<0.05).Serum analysis showed elevated IL-6 and MMP13 levels and reduced IL-10 level in the model group versus the normal group(P<0.05).Compared to the model group,the serum IL-6 level was significantly reduced(P<0.05),and the IL-10 level was significantly increased(P<0.05)in the MA,EA,and moxibustion groups,but without statistical differences among the three intervention groups(P>0.05);moreover,the MMP13 level in the moxibustion group was significantly lower than that in the model group(P<0.05).The alpha diversity analysis of intestinal flora showed no statistical difference in the number of operational taxonomic units(OTUs)and alpha diversity index among groups(P>0.05).Intestinal flora beta diversity analysis revealed significant differences among groups(P<0.05).Intestinal flora composition analysis showed significantly increased relative abundance of Lactobacillus(P<0.05)and significantly decreased relative abundance of Eubacterium_coprostanoligenes(P<0.05)in the model group compared to the normal group;compared to the model group,the relative abundances of Firmicutes,Lactobacillus,and Romboutsia in the MA,EA,and moxibustion groups were significantly reduced(P<0.05);the relative abundance of Bacteroidetes and Lachnospiraceae_NK4A136 in the MA group increased significantly(P<0.05);Bacteroidetes and Ruminococcaceaae_UGC-005 increased significantly in the moxibustion group(P<0.05).Conclusion:MA,EA,and moxibustion effectively reduced knee joint swelling,improved cartilage tissue morphology,optimized intestinal flora composition,down-regulated expression levels of serum pro-inflammatory factors IL-6 and MMP13,and increased expression level of anti-inflammatory factor IL-10 in KOA rats.Among them,moxibustion exhibited the most obvious regulatory effect on inflammatory factors.

Objective To analyze the effect of Shufeng Tongqiao decoction combined with methylprednisolone tablets in patients with chronic sinusitis and nasal polyp(CRSwNP)after operation.Methods A total of 104 patients with CRSwNP underwent endoscopic nasal surgery were prospectively selected,and patients were randomly divided into the hormone group(n=52,postoperative methylprednone tablets)and the study group(n=52,postoperative combined treatment with Shufeng Tongqin Decoction).After removal and shedding,50 cases were included in the hormone group,and 49 cases were included in the study group.The curative effect,lung wind-heat syndrome score,nasal mucosa recovery(assessed by Lund-Kennedy score system)and nasal mucosa remodeling were compared between the two groups.Serum levels of human β-defensin(HBD)-2 and high mobility group protein B1(HMGB1)were detected by enzyme-linked immunosorbent assay.Results The total control rate was higher in the study group than that of the hormone group(95.92%vs.80.00%,P＜0.05).At 12 weeks after surgery,the lung meridian wind heat syndrome scores,Lund-Kennedy scores and serum HMGB1 level were lower than before surgery in both groups(P＜0.05),and the study group was lower than the hormone group(P＜0.05).At 12 weeks after surgery,the epithelial injury grading was better in the study group than that in the hormone group(P＜0.05),and the basement membrane thickness was thinner than that in the hormone group(P＜0.05).Conclusion The joint of Shufeng Tongqiao decoction and methylprednisolone tablets has a better effect on postoperative CRSwNP patients,and it can greatly improve the levels of serum hBD-2 and HMGB1,effectively inhibit nasal mucosal remodeling,and greatly improve the recovery of nasal mucosa.

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

Objective:To assess the impact of urban-rural health insurance integration on the non-agricultural employment of rural labor in China.Methods:Using CHFS data(2011-2019)and a DID model,this study analyzed the impact on non-agricultural employment probability and quality(wage income,job stability)and examined the effect of different integration models.Results:The integration of urban and rural health insurance significantly increases the probability and quality of non-agricultural employment among rural labor.This effect operates through three key mechanisms:easing household liquidity constraints,improving health-related human capital,and expanding job search scope.Moreover,the"unified urban-rural tier"model proves more effective than the"one-system-multi-tiers"model in promoting non-agricultural employment and enhancing job quality.Conclusion:The integration positively contributes to improving rural labor allocation efficiency and mobilizing surplus rural labor capacity.Policy recommendations include accelerating the adoption of the"unified urban-rural tier"model and further refining the urban-rural resident health insurance system.