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 explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.

Objective To investigate the regulatory effect and molecular mechanism of circ_0044556 on the malignant biological behavior of triple negative breast cancer(TNBC)cells by targeting the miR-338-3p/bromodomain-containing protein 4(BRD4)axis.Methods The TargetScan online website was used to predict the binding sites of circ_0044556 with miR-338-3p and miR-338-3p with BRD4.Dual-luciferase reporter gene assays were performed to determine the relationship among circ_0044556,miR-338-3p,and BRD4 in MDA-MB-231 cells.Quantitative real-time PCR(qRT-PCR)and Western blotting were employed to detect the expression of circ_0044556,miR-338-3p,and BRD4 protein in human TNBC cell line MDA-MB-231 and human normal breast epithelial cells MCF-10A.MDA-MB-231 cells were divided into NC group,si-NC group(transfected with si-NC),si-circ_0044556 group(transfected with si-circ_0044556),si-circ_0044556+inhibitor NC group(transfected with si-circ_0044556 and inhibitor NC),and si-circ_0044556+miR-338-3p inhibitor group(transfected with si-circ_0044556 andmiR-338-3p inhibitor).qRT-PCR was applied to detect the expression of circ_0044556 and miR-338-3p;Western blotting was used to detect the expression of BRD4,E-cadherin,N-cadherin and Vimentin;the CCK-8 assay was applied to detect cell proliferation;flow cytometry was applied to detect cell apoptosis;and Transwell assays were used to detect cell invasion and migration.Thirty nude mice were randomly divided into NC group(tail vein injection of normal saline),si-NC group(tail vein injection of LV-NC),si-circ_0044556 group(tail vein injection of LV-circ_0044556),si-circ_0044556+inhibitor NC group(tail vein injection of LV-circ_0044556 and antiagomir NC),and si-circ_0044556+miR-338-3p inhibitor group(tail vein injection of LV-circ_0044556 and antiagomir miR-338-3p),with 6 mice per group.A xenograft tumor model was constructed by subcutaneous injection of MDA-MB-231 cells into nude mice,and tumor volume and weight were measured.Results TargetScan prediction results showed that the downstream miRNA of circ_0044556 was miR-338-3p,and the downstream target gene of miR-338-3p might be BRD4.Compared with transfecting mimic NC,transfection with miR-338-3p mimic significantly reduced the luciferase activities of WT-circ_0044556(0.34±0.03 vs.1.00±0.15,P<0.05)and WT-BRD4(0.41±0.05 vs.1.05±0.13,P<0.05)in MDA-MB-231 cells.Compared with MCF-10A cells,the expression levels of circ_0044556 and BRD4 protein in MDA-MB-231 cells were significantly increased,while the expression level of miR-338-3p was significantly decreased(P<0.05).Compared with NC group and si-NC group,the expression levels of circ_0044556,the protein expression levels of BRD4,N-cadherin,and Vimentin,and the OD450 value in MDA-MB-231 cells of si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05),the number of migrated and invaded cells was significantly reduced(P<0.05),and the expression level of miR-338-3p,the protein expression level of E-cadherin,and the cell apoptosis rate in MDA-MB-231 cells were significantly increased(P<0.05);downregulation of miR-338-3p rescued the inhibitory effect of circ_0044556 knockdown on invasion,migration,and proliferation of MDA-MB-231 cells.Compared with NC group and si-NC group,the tumor volume and weight in si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05);compared with si-circ_0044556 group and si-circ_0044556+inhibitor NC group,the tumor volume and weight in si-circ_0044556+miR-338-3p inhibitor group were significantly increased(P<0.05).Conclusion circ_0044556 may promote the malignant biological behaviors of TNBC cells through the miR-338-3p/BRD4 axis.

Objective To investigate the epidemiological characteristics of knee osteoarthritis(KOA)among military personnel in plateau regions and to explore its risk factors.Methods From July 2023 to July 2024,a multi-stage stratified cluster random sampling method was employed to survey the prevalence of KOA and related risk factors among military personnel in the northwest plateau regions of China,covering different altitudes(1500-4500 m)and geographical areas(Gansu,Qinghai,Tibet,and Xinjiang).All study subjects were divided into KOA and non-KOA groups based on the presence or absence of KOA.Variables including age,gender,body mass index(BMI),education level,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury were selected for univariate analyses between groups.Variables with P<0.05 in the univariate analyses were included in the binary multifactor logistic regression to identify risk factors for KOA.Results A total of 3000 questionnaires were distributed,and 2854 valid questionnaires were collected,with a response rate of 95.13%.The sample included 2584 males and 270 females,with 510 cases of KOA,resulting in a prevalence rate of 17.9%.Univariate analysis showed that there were statistically significant differences between KOA and non-KOA groups in terms of age,BMI,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury(P<0.05).However,no significant differences were found in gender and education level(P>0.05).Binary multivariate logistic regression analysis revealed that older age(OR=1.382,P=0.017),higher BMI(P<0.01),smoking(OR=1.929,P<0.01),higher military rank(OR=1.485,P=0.007),being a member of the Armed Police(P<0.01),longer service duration(P<0.01),higher regional altitude(OR=1.459,P<0.01),lower annual average temperature(OR=1.188,P=0.001),longer training duration(P<0.01),higher perceived training intensity(OR=2.450,P<0.01),and history of knee injury(OR=2.768,P=0.002)were independent risk factors for KOA.Conclusions Older age,overweight/obesity,smoking,higher military rank,being a member of the Armed Police,longer service duration,higher altitude,cold climate,longer training duration,higher training intensity,and history of knee injury are independent risk factors for KOA among military personnel in the northwest plateau regions of China.

Under the background of forensic medicine becoming a first-level discipline,the opportuni-ties and challenges of discipline development coexist.Starting from the actual situation and characteris-tics of local medical colleges and universities,this paper discusses the problems and solutions for the development of forensic medicine discipline from the perspective of building a regional high-level medical university.Combined with the experiences of carrying out forensic medicine education in our college,this paper supplies our thoughts and practices on improving the discipline system,enhancing the ability to serve society,perfecting the talent cultivation model and promoting forensic culture,to provide reference and inspiration for the development of forensic medicine in other universities,jointly promote the advancement of forensic medicine in China to a new stage,and contribute the wisdom and strength of forensic medical experts to the construction of a law-based China,a safe China and a healthy China.

Objective To verify the efficacy of a domestic human DNA quantification kit based on real-time fluorescence quantitative PCR in detecting the total human DNA concentration,male DNA concen-tration in mixed male/female DNA samples,the degree of DNA degradation and inhibitor tolerance.Methods Samples with different concentrations,different male/female ratios,different concentrations of inhibitors,and different degradation degrees were tested using the domestic human DNA quantification kit based on real-time fluorescence quantitative PCR.This kit was compared with a similar product on the market and was applied to the detection of DNA from real cases.Results This human DNA quan-tification kit can effectively detect human DNA as low as 0.001 65 ng/μL,and 6.25 pg/μL of male DNA in mixed samples with a male-to-female ratio of 1∶15 000.Even when the sample contains as high as 400 ng/μL of humic acid or 1 000 μmol/L of hemin alone,the DNA concentration can still be accurately detected.The degradation index can effectively characterize the degradation degree of the sample.This kit has been successfully applied in forensic practice.Conclusion This human DNA quan-tification kit is accurate and reliable in detection.It can accurately reflect the degradation of DNA and inhibitor tolerance.It has good performance in quantitative accuracy,determination of the male/female ratio in mixed samples,and inhibitor tolerance.It has application potential in forensic case examination.

Aim To observe the effect of lipopolysac-charide(LPS)induced supernatant of BV-2 cells on the inflammatory response and apoptosis of HT22 neu-rons.Methods After the concentration and time of LPS were determined by CCK-8 method,BV-2 cells were cultured with medium without LPS and medium containing LPS,the morphological changes of BV-2 microglia were observed by inverted microscope,and the CD86/CD206 ratio of BV-2 microglia was detected by immunofluorescence.Subsequently,BV-2 cell cul-ture supernatants were isolated and added to HT22 neuronal culture to observe the effect on the inflamma-tory response of HT22 neurons.The proliferation of HT22 neurons was detected by CCK-8 method and EdU method.The structural changes of HT22 neurons were observed under the microscope and examined by urani-um-lead staining.The levels of cytokines interleukin-1β(IL-1β),interleukin-10(IL-10),nuclear factor kappa-B(NF-κB)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent as-say(Elisa).Neuronal apoptosis was detected by the TUNEL method.The protein expressions of Bax,Bcl-2 and inflammatory factors were detected by Western blot.Results After induction with 1 mg·L-1 LPS,BV-2 cells exhibited increased cell body size,thicker protrusions on both side,and some cells showed de-formed protrusions,the CD86/CD206 ratio in BV-2 cells decreased,promoting the transformation of BV-2 cells from M2 type to M1 type.After treating with the culture supernatant of BV-2 cells,HT22 neuronal cell activity and proliferation were reduced,axons short-ened,and the number of cells decreased.Neuronal cell bodies were enlarged and some cells were de-formed,with damaged cell membranes,round cell nu-clei but displaced nucleoli from the normal position,swollen mitochondria with vacuoles,reduced internal ridge structures,and increased levels of inflammatory factors NF-κB,IL-1 β,and TNF-α(P＜0.05 or P＜0.01),while the anti-inflammatory factor IL-10 de-creased(P＜0.05),protein expression of the pro-apoptotic indicator Bax increased(P＜0.01),and the protein expression of the anti-apoptotic indicator Bcl-2 decreased(P＜0.05).Conclusion After induction of BV-2 cell polarization by LPS,the supernatant could inhibit HT22 neuronal cell viability,upregulate inflam-matory factor expression and promote apoptosis.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

This study aims to elucidate the role and mechanism of clematichinenoside AR(CAR) in protecting bone marrow mesenchymal stem cells(BMSCs) from hypoxia-induced apoptosis. BMSCs were isolated by the bone fragment method and identified by flow cytometry. Cells were cultured under normal conditions(37℃, 5% CO_2) and hypoxic conditions(37℃, 90% N_2, 5% CO_2) and treated with CAR. The BMSCs were classified into eight groups: control(normal conditions), CAR(normal conditions + CAR), hypoxia 24 h, hypoxia 24 h + CAR, hypoxia 48 h, hypoxia 48 h + CAR, hypoxia 72 h, and hypoxia 72 h + CAR. The cell counting kit-8(CCK-8) assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) were employed to measure cell proliferation and apoptosis, respectively. The number of mitochondria and mitochondrial membrane potential were measured by MitoTracker®Red CM-H2XRo staining and JC-1 staining, respectively. The level of reactive oxygen species(ROS) was measured with the DCFH-DA fluorescence probe. The protein levels of B-cell lymphoma-2 associated X protein(BAX), caspase-3, and optic atrophy 1(OPA1) were determined by Western blot. The results demonstrated that CAR significantly increased cell proliferation. Compared with the control group, the hypoxia groups showed increased apoptosis rates, reduced mitochondria, elevated ROS levels, decreased mitochondrial membrane potential, upregulated expression of BAX and caspase-3, and downregulated expression of OPA1. In comparison to the corresponding hypoxia groups, CAR intervention significantly decreased the apoptosis rate, increased mitochondria, reduced ROS levels, elevated mitochondrial membrane potential, downregulated the expression of BAX and caspase-3, and upregulated the expression of OPA1. Therefore, it can be concluded that CAR may exert an anti-apoptotic effect on BMSCs under hypoxic conditions by regulating OPA1 to maintain mitochondrial homeostasis.
Mesenchymal Stem Cells/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Hypoxia/drug effects* ; Homeostasis/drug effects* ; Reactive Oxygen Species/metabolism* ; Rats, Sprague-Dawley ; Membrane Potential, Mitochondrial/drug effects* ; Saponins/pharmacology* ; Caspase 3/genetics* ; Male ; bcl-2-Associated X Protein/genetics* ; Bone Marrow Cells/metabolism* ; Cell Proliferation/drug effects* ; Protective Agents/pharmacology* ; Cells, Cultured