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.

ObjectiveDonkey hide is the sole legally designated raw material for the preparation of the traditional Chinese medicine Ejiao. The quality stability of donkey hide during preservation directly determines the efficacy and safety of Ejiao. This study focuses on the dynamic succession of microbial communities during the preservation of donkey hides from different origins, aiming to clarify the correlation between microbial biodiversity difference and the degradation profiles of hide collagen and critical biochemical components, thereby providing a theoretical foundation for developing targeted preservation strategies based on microbial regulation. MethodsDonkey hides originating from four different regions were subjected to an accelerated microbial aging assay to simulate the spoilage process. The microbial community succession was analyzed using high-throughput sequencing. Microstructure changes and pore structure characteristics were assessed by scanning electron microscopy and mercury intrusion porosimetry, respectively. Additionally, the content of major components, including lipids, proteins, and sugars were determined by biochemical methods. ResultsAfter 96 h of aging, the collagen fiber structure in Africa donkey hides (ADH) exhibited significant degradation and collapse, followed by Xinjiang donkey hides (XDH). Instead, the microstructure of Dong’e black donkey hides (DDH) and Peru donkey hides (PDH) remained relatively intact. The porosities of DDH, XDH, PDH, and ADH increased from 27.9%, 15.7%, 30.3%, and 46.2% to 36.5%, 52.6%, 42.8%, and 57.7%, respectively, during the aging process, which suggested that the originally compact fiber structure was disrupted by microbial aging. Fourier transform infrared spectrometer analysis revealed the amide bands in XDH exhibited relatively weak intensity, and no collagen amide I band was observed in ADH. Meanwhile, the lipid and protein contents decreased in all four types of donkey hides, indicating that these components served as the primary nutrient sources for the growth of microorganism. Notably, the most severe collagen degradation was observed in XDH and ADH. A substantial increase was detected in the total soluble sugar in PDH aging solution and hydroxyproline in the ADH aging solution, respectively. These results indicated that donkey hides exhibit distinct patterns of structural degradation and nutrient utilization. Furthermore, the viable cells number of donkey hides increased sharply after 48 h of aging. Metagenomic analysis revealed that the relative abundance of Euryarchaeota in ADH, PDH and XDH declining from initial 93.19%, 97.73% and 30.08% to 0.79%, 1.43% and 0.02% after 96 h, respectively. Conversely, a significantly increase was observed in the abundance of Bacillota, with a marked increase in ADH, peaking at 92.75%. Additionally, the abundance of Pseudomonadota in PDH increased from 0.10% to 87.84%, suggesting that Bacillota and Pseudomonadota may be key factors exacerbating donkey hide spoilage. Unlike the other three types of donkey hides, the dominant bacterial phylum in DDH shifted from Pseudomonadota to Bacteroidota, characterized by a substantial abundance increase of Bacteroidota from 0.13% to 44.22%. ConclusionRegional variation in origin significantly influence the microbial aging of donkey hides, leading to distinct patterns of structural deterioration and differential nutrient utilization. Therefore, implementing origin-specific preservation strategies, through the precisely controlling environmental factors to suppress harmful phyla such as Bacillota and Pseudomonadota, is crucial for enhancing the storage quality of donkey hides.

Objective To analyze the clinical characteristics and risk factors of extreme thrombocytosis caused by piperacillin sodium and tazobactam sodium injection, and provide reference for medical treatment and pharmaceutical care of such patients. Methods Extreme thrombocytosis of a patient treated with piperacillin sodium and tazobactam sodium injection was found by clinical pharmacists, who participated in clinical diagnosis and treatment by analyzing of the adverse drug reaction, optimization of the medical treatment and pharmaceutical care. Results After correlation analysis, the patient's extreme thrombocytosis was likely to be an adverse reaction caused by the piperacillin sodium and tazobactam sodium injection. The medication was immediately discontinued, and antiplatelet therapy with aspirin was administered. Two weeks later, the patient's platelet count had significantly decreased compared to before. Conclusion Clinical pharmacists participated in patients’ clinical diagnosis and treatment, carried out pharmaceutical care and assisted physicians in adjusting treatment plans, which ensured the safety and effectiveness of patients' clinical drug therapy.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objective:To investigate the miRNA-mRNA regulatory network in a rat model of Tourette syndrome(TS)using transcriptomic technology and to screen key signaling pathways and potential traditional Chinese medicine(TCM)candidates for intervention.Methods:A TS rat model was established using iminodipropionitrile(IDPN).RNA sequencing was performed to identify differentially expressed miRNAs and mRNAs in the brain tissues of TS rats.Bioinformatics analysis was applied to construct interaction networks,and network pharmacology was further employed to screen potential TCM compounds.Results:After 7 days of IDPN modeling,the model group exhibited motor and stereotypical behavioral changes,with behavioral scores greater than 3 points.Hema toxylin-eosin(HE)staining revealed irregular neuronal nuclear morphology,uneven chromatin distribution,nuclear pyknosis,and increased glial cell density.KEGG enrichment analysis identified key pathways:calcium signaling pathway,neuroactive ligand-receptor interaction,p53 signaling pathway,ECM-receptor interaction,and TGF-β signaling pathway.miR-125a-3p,miR-106-3p,and miR-760-3p were identified as pivotal miRNAs.Potential TCM candidates included Ajuga decumbens,Acanthopanax bark,Codonopsis pilosula,Stephania japonica,Os Draconis,Notopterygium root,Siraitia grosvenorii,Zanthoxylum nitidum root,Morinda officinalis,and Corydalis yanhusuo.Conclusion:The miRNAs miR-106-3p,miR-125a-3p,and miR-760-3p may mediate TS pathogenesis by altering critical signaling networks,including the calcium signaling pathway,neuroactive ligand-receptor interaction,and ECM-receptor interaction pathways,leading to neuroimmune inflammation and dopaminergic system dysregulation.TCM compounds such as Corydalis yanhusuo and Ajuga decumbens may exert therapeutic effects through multi-component synergistic regulation of these miRNAs and downstream pathways.

Objective To analyze the CT manifestations of high altitude pulmonary edema(HAPE)to provide radiological evidence for its early and accurate diagnosis.Methods Totally 200 HAPE patients clinically confirmed at some hospital from April 2021 to April 2024 were enrolled into a study group,and 56 individuals undergoing health examinations at the hospital's physical examination center between January and June 2023 were included into a control group.Examinations were carried out with a United Imaging uCT528 40-slice spiral CT scanner.The patients in the study group were observed in terms of HAPE staging,the extent of pulmonary involvement,CT manifestations of different stages including location,distribution,density and morphology of pulmonary lesion.The diameters of the main pulmonary arteries and ascending aortas of the subjects in the two groups were measured,and the ratios of the two diameters were calculated.SPSS 25.0 software was used for statistical analysis.Results In the study group,there were 26 cases(13.0%)at early stage,105 ones at progression stage(52.5%),32 ones at critical outbreak stage(16.0%)and 37 ones at resolution and absorption stage(18.5%),and there were 35.5%with unilateral lung involvement and 64.5%with bilateral involvement.At early stage,HAPE chest CT manifestations included increased and thickened bilateral bronchovascular bundles,widened main pulmonary artery lumen and faint ground-glass opacity in lungs;at progression stage,HAPE chest CT manifestations revealed multiple cloud-like or patchy areas of increased density within lungs;at critical outbreak stage,CT scanning indicated diffuse patchy opacities and consolidation in lungs,white lung-like changes could be found in some severe cases,and bronchial air signs were shown within affected segments in some ones with severer signs in the right lung than in the left lung;at resolution and absorption stage the CT manifestations were similar to those at early stage,with lesions completely resolving after treatment.The study group had the diameters of the main pulmonary arteries greater while the diameters of the ascending aortas less than those of the control group,and the ratios of the diameters of the two diameters in the study group were higher than those in the control group,with the differences being statistically significant(all P<0.05).Conclusion Chest CT is an important examination method for the early diagnosis of HAPE and clarification of its clinical staging,which directly reflects the pulmonary pathological changes in HAPE patients and helps doctors fully understand the disease progression.

Aim To investigate the effect of Zhenwu decoction on inflammation,oxidative stress and apopto-sis of human glomerular epithelial cells(HGEC)in-duced by lipopolysaccharide(LPS)based on Nrf2/HO-1 signaling pathway,and to explore the underlying mechanism.Methods HGEC were treated with LPS(1.0 mg·L-1)for 24 h to construct an oxidative damage model.On this basis,2.5％,5％and 10％Zhenwu decoction-containing serum were added to the low,medium and high dose groups of Zhenwu decoc-tion,and a normal group was set up.The changes of cell activity were assessed by MTT method and LDH method.The contents of TNF-α,IL-6,IL-10,SOD,CAT,GSH-Px,ROS and MDA in each group were de-tected by ELISA.The apoptosis of each group was de-tected by flow cytometry.The mRNA and protein ex-pressions of Bax,Bcl-2,caspase-3,caspase-9 and Nrf2/HO-1 pathway were detected by RT-qPCR and Western blot,respectively.Results Compared to the normal group,the model group of HGEC exhibited increased levels of inflammatory cytokines,enhanced oxidative stress response and aggravated apoptosis;after inter-vention with various doses of Zhenwu decoction,the in-flammatory levels in HGEC were reduced,oxidative damage and apoptosis were effectively ameliorated,and the mRNA and protein expression levels of the Nrf2/HO-1 signaling pathway were upregulated.Conclu-sions Zhenwu decoction can protect HGEC from LPS-induced inflammation and oxidative damage and im-prove apoptosis.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Objective To explore the factors affecting the coefficient of variation(CV)of glucose in type 2 diabetes mellitus(T2DM)patients based on real-time dynamic glucose monitoring system.Methods A total of 354 patients with T2DM hospitalized in the Department of Endocrinology of Jiangsu Shengze Hospital were enrolled in this study from March 2023 to March 2024 and divided into two groups:the glycemic variability(GV,CV>36%)group(n=118)and the glucose stable(GS,CV≤36%)group(n=236).The clinical data of the two groups were compared,and the influencing factors for CV>36%were analyzed.Results The DM duration and HbA1c were higher(P<0.05),while BMI,visceral fat area,subcutaneous fat area(SFA),FC-P,serum uric acid(SUA),and TG were lower in the GV group than in the GS group(P<0.05).Spearman correlation analysis showed that CV was positively correlated with diabetes duration and HbA1c(P<0.05),and negatively correlated with FC-P,SFA and SUA(P<0.05).Logistic regression analysis showed that DM duration,HbA1c,SFA,FC-P and SUA were the influencing factors for GV.Scatter plot analysis showed that there was a linear trend between CV level and log HbA1c and log SFA in T2DM patients.CV level increased with the increase of log HbA1c,and decreased with the increase of log SFA.ROC curve analysis showed that the area under the curve(AUC)of FC-P was 0.703(95%CI:0.640～0.765,P<0.001)for predicting GV in T2DM patients,and the cut-off value was 1.095 ng/ml.The AUC of SUA was 0.622(95%CI:0.555～0.688,P<0.001)for predicting GV,and the cut-off value was 280.5 μmol/L.Conclusions The DM duration,HbA1c,SFA,FC-P and SUA are important factors for GV,and FC-P and SUA have predictive value for GV.

The knowledge and experience of medical practitioners in the diagnosis and treatment of diseases throughout history are mostly reflected in the description and analysis of relevant clinical events.The diagnosis and treatment thinking and cognitive reasoning process among the knowledge has dynamic and complex characteristics in time and space.However,the current exploration of ancient doctors' diagnosis and treatment experience of diseases and syndromes is mainly focuses on the academic evolution of the entire historical time line,and lacks the exploration of the concept of time and its medical relevance in ancient books.It mainly focuses on entity knowledge,and lacks the presentation of temporal dynamic cognitive logic.Moreover,the research primarily focuses on the study of specific terms in ancient Chinese medicine books,without fully covering ancient medical events.To address this issue,this research proposes to construct the evolution model of diagnosis and treatment experience based on time-series dynamic perspective:according to the time series of diagnosis and treatment events,it covers the time system module,the"coming disease"module,the"already sick"module,and the"after sick"module,which involves the dynamic risk assessment of disease occurrence by ancient medical practitioners,the grasp of the dynamic evolution of the already sick state and the treatment plan,and the dynamic health plan for the after sick state.