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.

Introduction: Hypertension is common in obesity and increases cardiovascular risk. Bariatric surgery improves metabolic health, but subgroup differences in blood pressure response remain unclear. This study examined 1-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after bariatric surgery across sex, age group, and diabetes status. Methodology: This study included 32 obese adults undergoing bariatric surgery, with blood pressure measured at baseline, 6 and 12 months. Generalized estimating equation models were used to evaluate changes in SBP and DBP over time, adjusting for age, sex, surgery type, diabetes category, baseline body mass index, antihypertensive medication use, and baseline blood pressure. Interaction terms were tested to assess differences in blood pressure trajectories across subgroups. Results: Participants were predominantly female (67.4%), with a mean age of 36.9 ± 6.2 years and a mean body mass index of 40.7 ± 8.8 kg/m². Hypertension and diabetes were present in 40.6 and 31.3% of participants, respectively. There was a significant time effect for both SBP (p <0.001) and DBP (p = 0.004). At 12 months post-surgery, mean SBP decreased by 15 mmHg and DBP by 7.9 mmHg compared with baseline (both p <0.001). No significant interactions were observed between time and sex, diabetes category, or age category, indicating that blood pressure improvements were comparable across subgroups. Conclusion Bariatric surgery was associated with clinically meaningful reductions in both SBP and DBP, with similar improvement patterns observed across demographic and metabolic subgroups. These findings support the effectiveness of bariatric surgery as a strategy for blood pressure reduction and cardiovascular risk management in patients with obesity.
Blood Pressure ; Bariatric Surgery

ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized， double-blind， placebo， controlled clinical trial design was adopted， and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method， the patients were assigned into a treatment group and a control group （30 in each group， with 29 patients in the treatment group and 28 patients in the control group finally completing the trial）. The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules， and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index （PSQI）， smart bracelet sleep monitoring， epworth sleeping scale （ESS）， Mini-Mental State Examination （MMSE）， Activities of Daily Living （ADL）， and traditional Chinese medicine symptoms were scored. Furthermore， the brain-derived neurotrophic factor （BDNF） and gamma-aminobutyric acid （GABA） levels were measured. ResultsAfter 12 weeks of treatment， the total response rate of clinical efficacy assessment in the treatment group reached 89.7%， which was significantly higher than that （21.4%） in the control group （Z=-5.14， P<0.01）. After treatment， the TCM symptom scores declined in both groups （P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.01）. After treatment， the treatment group showed decreased total score and seven component scores of the PSQI scale （P<0.05， P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.05， P<0.01）. After treatment， the treatment group showed increases in the duration of deep sleep， light sleep， rapid eye movement sleep， and total sleep at night and decreases in the time to fall asleep， the number of awakenings from sleep at night， and the time for sporadic daytime naps （P<0.01）. The control group did not show significant changes in the duration of light sleep， time to fall asleep， and number of awakenings from sleep at night. Moreover， the treatment group outperformed the control group in terms of the indicators above （P<0.05， P<0.01）. After treatment， the treatment group showed decreased scores of ESS， ADL and its subscales physical self-maintenance scale （PSMS）， and Instrumental Activities of daily living scale （IADLs） and increased score of MMSE and levels of BDNF and GABA （P<0.05， P<0.01）. There was no significant difference in PSMS between the two groups， and the treatment group was significantly better than the control group in terms of the rest of the above indicators （P<0.05， P<0.01）. Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI， ESS， and ADL scores， increase the MMSE score and the expression of BDNF and GABA， effectively optimize the structure of sleep， improve the intelligence， and enhance the ability of daily life， without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.

ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized， double-blind， placebo， controlled clinical trial design was adopted， and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method， the patients were assigned into a treatment group and a control group （30 in each group， with 29 patients in the treatment group and 28 patients in the control group finally completing the trial）. The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules， and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index （PSQI）， smart bracelet sleep monitoring， epworth sleeping scale （ESS）， Mini-Mental State Examination （MMSE）， Activities of Daily Living （ADL）， and traditional Chinese medicine symptoms were scored. Furthermore， the brain-derived neurotrophic factor （BDNF） and gamma-aminobutyric acid （GABA） levels were measured. ResultsAfter 12 weeks of treatment， the total response rate of clinical efficacy assessment in the treatment group reached 89.7%， which was significantly higher than that （21.4%） in the control group （Z=-5.14， P<0.01）. After treatment， the TCM symptom scores declined in both groups （P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.01）. After treatment， the treatment group showed decreased total score and seven component scores of the PSQI scale （P<0.05， P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.05， P<0.01）. After treatment， the treatment group showed increases in the duration of deep sleep， light sleep， rapid eye movement sleep， and total sleep at night and decreases in the time to fall asleep， the number of awakenings from sleep at night， and the time for sporadic daytime naps （P<0.01）. The control group did not show significant changes in the duration of light sleep， time to fall asleep， and number of awakenings from sleep at night. Moreover， the treatment group outperformed the control group in terms of the indicators above （P<0.05， P<0.01）. After treatment， the treatment group showed decreased scores of ESS， ADL and its subscales physical self-maintenance scale （PSMS）， and Instrumental Activities of daily living scale （IADLs） and increased score of MMSE and levels of BDNF and GABA （P<0.05， P<0.01）. There was no significant difference in PSMS between the two groups， and the treatment group was significantly better than the control group in terms of the rest of the above indicators （P<0.05， P<0.01）. Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI， ESS， and ADL scores， increase the MMSE score and the expression of BDNF and GABA， effectively optimize the structure of sleep， improve the intelligence， and enhance the ability of daily life， without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Objective:To explore the effects of 4C management mode on rehabilitation and quality of life in patients with acute heart failure(AHF)in cardiovascular intensive care unit(CCU).Methods:This randomized controlled study enrolled 110 patients with AHF admitted in CCU of Guangdong Provincial Hospital of Traditional Chinese Medicine between February 2021 and February 2023.Patients were randomly divided into intervention group(n=55)and control group(n=55).Patients in the control group received routine intervention,while those in the inter-vention group received additional 4C management mode,both groups were intervened for 3 months.The indexes of cardiac function,self-efficacy,exercise tolerance,blood oxygen saturation(SpO2),mental state and quality of life were compared between the two groups.Results:Compared to those in the control group after intervention,patients in the intervention group had significantly lower interventricular septal thickness(IVST)[(9.20±0.10)mm vs.(10.30±0.17)mm,P＜0.001],left ventricular end-systolic volume index(LVESVI)[(35.21±0.74)ml/m2 vs.(39.70±1.09)ml/m2,P＜0.001],left ventricular end-diastolic volume index(LVED VI)[(45.35±0.71)ml/m2 vs.(56.76±1.48)ml/m2,P＜0.001],scores of self-rating anxiety scale(SAS)[(32.10±1.57)points vs.(45.36±1.94)points,P＜0.001],self-rating depression scale(SDS)[(35.03±1.52)points vs.(47.70±2.12)points,P＜0.001]and Minnesota living with heart failure questionnaire(MLHFQ)[(51.27±2.85)points vs.(56.46±3.53)points,P＜0.001],and significantly higher score of general self-efficacy scale(GSES)[(28.71±3.84)points vs.(20.34±1.56)points,P＜0.001],6 min walking distance(6MWD)[(428.53±5.50)m vs.(362.14±6.18)m,P＜0.001]and SpO2[(99.11±0.87)％vs.(94.23±0.73)％,P＜0.001].Conclusion:4C management mode may improve the cardiac function,self-efficacy,mental state and quality of life in patients with acute heart failure in CCU.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

Objective To observe the origin and course of the obturator artery(OA),so as to provide anatomical reference for reducing hemorrhage during pelvic surgery and pubic fracture fixation.Methods A total of 65 human hemi-pelvises specimens with intact structure were dissected to observe the origin,course and other variations of OA.Measure the length of the inner section of OA basin and the outer diameter at the origin,etc.Results OA originated from the internal iliac artery in 57 cases(87.7%),including 3 cases(4.6%)of the superior gluteal artery,5 cases(7.7%)of the inferior gluteal artery,3 cases(4.6%)of the external iliac artery and 5 cases(7.7%)of the inferior epigastric artery.OA participated in the formation of the arterial trunk in 3 cases(4.6%).The length of the pelvic segment of the OA in male and female was(50.87±15.41)mm and(51.71±14.19)mm,respectively,with no statistically significant difference between them(P>0.05).The outer diameters at the origin of the OA in male and female were(2.79±1.05)mm and(2.35±0.86)mm,and there was no statistically significant difference between them(P>0.05).Conclusion OA mainly originated from the anterior trunk of the internal iliac artery,with a few OA originated from the branches of the posterior trunk or the inferior epigastric artery,or participated in the formation of the arterial trunk.In pelvic surgery involving OA area,attention should be paid to the length of its pelvic segment and the outer diameter at the origin of OA,so as to better locate and protect blood vessels during surgery.

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.