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.

ObjectiveTo investigate the therapeutic effect of Biejiajian Pills on rats with carbon tetrachloride （CCl₄）-induced hepatic fibrosis and its mechanism based on the bile acid （BA）-short-chain fatty acid （SCFA） metabolic axis. MethodsThe method of CCl₄ induction was used to establish a rat model of hepatic fibrosis， and 32 male Sprague-Dawley rats were randomly divided into control group， model group， Biejiajian Pills group （2.2 g/kg）， and silymarin group （43.19 mg/kg）， with 8 rats in each group. All rats except those in the control group were given intraperitoneal injection of CCl₄ （diluted with corn oil at a ratio of 4∶6， 2 mL/kg） to induce a model of hepatic fibrosis for 8 consecutive weeks， and the rats in the drug administration groups were given the corresponding drug by gavage. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBil）， and albumin （Alb）； chloramine-T colorimetry was used to measure the content of hydroxyproline （HYP） in liver tissue； HE staining and Masson staining were used to observe liver histopathological changes； UPLC-MS/MS and GC-MS were used to measure the levels of BAs and SCFAs. The Shapiro-Wilk test and the Levene test were performed for all data to determine normality and homogeneity of variance； a one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of Ishak score between groups， and the Dunn’s test was used for further comparison between two groups. The Benjamini-Hochberg method was used for multiple comparison correction in the screening of differentially expressed metabolites in metabolomics data. The variable importance in projection （VIP） values were obtained in combination with the orthogonal partial least squares-discriminant analysis （OPLS-DA） model， and metabolites with VIP>1 and P<0.05 were selected as significantly differentially expressed metabolites between groups. The robustness of the OPLS-DA model was evaluated through 200 permutation tests， and the main parameters of the model were reported， including the interpretation rate of the model for categorical variables （R²Y） and the predictive ability of the model （Q²）. A Spearman’s rank correlation analysis was performed. ResultsThe results of staining showed ordered arrangement of hepatocytes in the Biejiajian Pills group， with significant alleviation of inflammatory cell infiltration and collagen fiber deposition. Compared with the control group， the model group had significant increases in the serum levels of TBil and HYP and a significant reduction in the serum level of Alb （all P<0.05）. Compared with the control group， the Biejiajian Pills group had significant increases in the serum levels of AST， ALT， TBil， and HYP and a significant reduction in the serum level of Alb （all P<0.05）， and the silymarin group had significant increases in the serum levels of ALT， TBil， and HYP and a significant reduction in the serum level of Alb （all P<0.05）. Compared with the model group， the Biejiajian Pills group had significant reductions in the serum levels of ALT， AST， TBil， and HYP （all P<0.05）， and the silymarin group had significant reductions in the serum levels of ALT， TBil， HYP， and AST and a significant increase in the serum level of Alb （all P<0.05）. Mechanism studies showed that compared with the control group， the model group had significant reductions in the levels of taurolithocholic acid， tauro-α-muricholic acid， taurocholic acid， glycodeoxycholic acid， taurohyocholic acid， chenodeoxycholic acid， glycohyodeoxycholic acid， 7，12-diketolithocholic acid， taurochenodeoxycholic acid， and glycochenodeoxycholic acid and significant increases in the levels of hyodeoxycholic acid， norcholic acid， β-muricholic acid， and cholic acid （all P<0.05）. Compared with the model group， the Biejiajian Pills group had significant increases in the levels of the protective BAs taurolithocholic acid， chenodeoxycholic acid， taurocholic acid， taurohyocholic acid， and taurodeoxycholic acid and significant reductions in the levels of tauro-α-muricholic acid， tauro-β-muricholic acid， taurohyodeoxycholic acid+tauroursodeoxycholic acid， α-muricholic acid， glycoursodeoxycholic acid， and norcholic acid （alll P<0.05）. As for SCFAs， compared with the model group， the Biejiajian Pills group had significant increases in the levels of acetic acid， propionic acid， isobutyric acid， butyric acid， isopentanoic acid， pentanoic acid， and hexanoic acid （all P<0.05）. Compared with the model group， the silymarin group had significant reductions in the levels of taurolithocholic acid， tauro-α-muricholic acid， norcholic acid， glycocholic acid， deoxycholic acid， tauro-β-muricholic acid， taurodeoxycholic acid， taurohyodeoxycholic acid+tauroursodeoxycholic acid， and α-muricholic acid and significant increases in the levels of taurocholic acid and chenodeoxycholic acid， as well as significant increases in the levels of the SCFAs acetic acid， propionic acid， pentanoic acid， and hexanoic acid （all P<0.05）. The correlation analysis showed that the metabolism of BAs and SCFAs was correlated with the changes in serum indicators. ConclusionBiejiajian Pills can alleviate CCl₄-induced hepatic fibrosis in rats by regulating the BA/SCFA metabolic axis.

OBJECTIVE To explore the clinical efficacy of Suyin Jiedu Prescription in the treatment of Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type and its effect on serum Klotho and inflammation levels.METHODS A total of 102 patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type who met the inclu-sion criteria were randomly divided into a treatment group and a control group,51 cases in each group;a total of 84 cases were comple-ted,including 44 cases in the control group and 40 cases in the treatment group.The control group was given conventional Western medicine basic treatment,and the treatment group was given Suyin Jiedu Prescription on the basis of the control group treatment.The treatment course of both groups was 16 weeks.The levels of renal function indexes[hemoglobin(Hb),serum albumin(Alb),urea ni-trogen(BUN),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),24 h urine protein(UTP)]and TCM syndrome scores were observed in the two groups before and after treatment.The levels of serum Klotho,tumor necrosis factor α(TNF-α)and interleukin 18(IL-18)were detected by ELISA.The clinical efficacy between the two groups after treatment was compared.RE-SULTS After treatment,BUN and Scr levels of the two groups of patients were significantly decreased(P<0.05),eGFR was signifi-cantly increased(P<0.05,P<0.01),the treatment group was better than the control group(P<0.05);the TCM syndrome scores of the two groups were significantly decreased(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05,P<0.01);the serum Klotho level in the treatment group was significantly increased(P<0.05),the IL-18 level was significantly de-creased(P<0.01),and the serum Klotho,TNF-α,and IL-18 levels in the treatment group were better than those in the control group(P<0.05,P<0.01).The total clinical effective rate in the treatment group was higher than that in the control group(P<0.01).CONCLUSION Suyin Jiedu Prescription can effectively improve renal function and relieve clinical symptoms in patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type,which may be related to increasing Klotho level and reducing inflammation in the body.

Objective To explore the incidence and its influencing factors of transient severe motion(TSM)in the arterial phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI.Methods The databases of China National Knowledge Network(CNKI),VIP,Wanfang,PubMed,and Embase were searched for studies on the incidence and influencing factors of TSM,and the search time was from the establishment of the databases to October 2024.Meta-analysis was performed via Stata 17.0 software.Results A total of 30 papers(33 studies)were finally included,totaling 12 565 patients.Meta-analysis results showed that the incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI was 13.0％.The risk factors for TSM included age[odds ratio(OR)=1.03;95％confidence interval(CI)1.02-1.05;P＜0.001),chronic obstructive pulmonary disease(COPD)(OR=4.21;95％CI 1.76-10.09;P=0.001),and moderate-to-severe pleural effusion(OR=3.34;95％CI 1.69-6.63;P=0.001),while a previous usage history of Gd-EOB-DTPA(OR=0.56;95％CI 0.39-0.81;P=0.002)was a protective factor of TSM.Conclusion The incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI is relatively high.Age,COPD,moderate-to-severe pleural effusion are risk factors for TSM,while the previous usage history of Gd-EOB-DTPA is a protective factor for TSM.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.