At present,malignant tumor diseases occur frequently and increase year by year.Traditional chemoradiotherapy methods are expensive,have serious toxic and side effects,and are easy to reduce patient tolerance.Natural medicines have advantages of multiple targets,high selectivity and low toxicity and side effects in process of anti-tumor,and are one of important sources of anti-tumor drugs.As a polypeptide substance,lactoferrin has a strong anti-tumor effect and plays a huge role in field of nano-drug delivery.Receptors of lactoferrin are widely expressed on surface of various cancer cells.In addition to its strong anti-tumor effect,it is also widely used to modify nanocarriers.In this paper,anti-tumor mechanism of lactoferrin is reviewed,and the latest research progress of using lactoferrin as an anti-cancer drug delivery carrier is also introduced.

With the rapid advancement and iterative development of new artificial intelligence technologies, there remains a regulatory vacuum in corresponding governance measures among governments worldwide. Simultaneously, a technological and governance gap exists between developing countries and developed economies. In response, the World Health Organization (WHO) has released "Ethics and Governance of Artificial Intelligence for Health: Guidance on Large Multi-Modal Models" to assist governments in strengthening governance capabilities in this field. This paper provides an in-depth analysis of the Guidance, aiming to identify challenges and risks associated with the application of multimodal large models in healthcare. Guided by ethical principles for advancing health through artificial intelligence, the paper examines the three-tier governance framework and recommendations outlined in the Guidance. Additionally, it evaluates the current state of AI governance in China, offering insights and reference points for improving AI governance in China′s healthcare sector.

Objective To investigate programmed death including necroptosis,apoptosis,autophagy,ferroptosis,and pyroptosis in bone marrow megakaryocytes of mice during sepsis and its impact on platelet production capacity and coagulation function in mice.Methods C57BL/6J mice were randomly divided into a sham operation group(sham group)and a sepsis model group(CLP group).Peripheral blood platelets and coagulation function were measured by abdominal aortic blood sampling at 24 h postoperatively in both sham and CLP groups.After the mice were sacrificed,long bones of both lower limbs were taken,and bone marrow megakaryocytes were extracted using megakaryocyte separation solution and immunomagnetic bead separation.Laser confocal microscopy was used to observe the activation of programmed death-related marker molecules in mouse bone marrow megakaryocytes.Flow cytometry was used to detect programmed death rate,platelet production phenotype,and platelet surface markers(CD41,CD42b,CD61)of megakaryocytes.Western blotting was used to detect the expression of programmed death-related proteins in megakaryocytes.Results Compared with the sham group,the CLP group showed significant decreases in the number of platelets during acute sepsis(24 h)(P<0.000 1),significant increases in platelet distri-bution width(PDW)and mean platelet volume(MPV)(P<0.01),significant prolonging of thrombin time(TT),prothrombin time(PT),and activated partial thromboplastin time(APTT)(P<0.000 1,P<0.001,P<0.01),and significant reduction in fibrinogen(Fib)(P<0.000 1).Compared with the Con/sham group,the LPS/CLP group exhibited significant increases in the platelet production phenotype of megakaryocyte,the number of PLP in the supernatant,and the expression levels of platelet surface markers(CD41,CD42b,CD61).The rates of megakaryocyte necroptosis/apoptosis,pyroptosis,and ferroptosis were significantly elevated at 24 h post-CLP surgery.Laser confo-cal microscopy showed significant activation of LC3,P-MLKL,Caspase-1,and Fe2+in megakaryocytes of mice after CLP surgery.Western blotting results revealed that the CLP group exhibited a significant increase in the activa-tion rate of necroptosis-related protein P-MLKL(P<0.001),a significant increase in the cleavage of pyroptosis-related proteins GSDMD and GSDMD-N(P<0.01,P<0.001,respectively),a significant increase in the expres-sion of ferroptosis-related protein ACSL4(P<0.01),and a significant decrease in the expression of GPX4(P<0.01)compared to the sham group.Additionally,the CLP group demonstrated significant increases in the expression of apoptosis-related protein Bax,the cleavage of autophagy-related protein LC3B-Ⅱ,and the expression of P62(P<0.05,P<0.001,P<0.001,respectively).Inhibition of apoptosis with programmed cell death inhibitors decreased platelet production function of megakaryocyte,while inhibition of necroptosis and pyroptosis had limited effects on platelet production function of megakaryocyte.Inhibition of ferroptosis and autophagy enhanced platelet production function of megakaryocyte.Conclusion Significant programmed death of megakaryocytes was observed during the acute phase of sepsis(24 h).Among those megakaryocytes,apoptosis is an important mechanism for the differentia-tion of platelet production phenotype and increased platelet production capacity of megakaryocyte.Overactive autophagy and ferroptosis in megakaryocytes lead to megakaryocyte dysfunction,which is an important mechanism for coagulation abnormalities in sepsis.

With the rapid advancement and iterative development of new artificial intelligence technologies, there remains a regulatory vacuum in corresponding governance measures among governments worldwide. Simultaneously, a technological and governance gap exists between developing countries and developed economies. In response, the World Health Organization (WHO) has released "Ethics and Governance of Artificial Intelligence for Health: Guidance on Large Multi-Modal Models" to assist governments in strengthening governance capabilities in this field. This paper provides an in-depth analysis of the Guidance, aiming to identify challenges and risks associated with the application of multimodal large models in healthcare. Guided by ethical principles for advancing health through artificial intelligence, the paper examines the three-tier governance framework and recommendations outlined in the Guidance. Additionally, it evaluates the current state of AI governance in China, offering insights and reference points for improving AI governance in China′s healthcare sector.

Objective To investigate programmed death including necroptosis,apoptosis,autophagy,ferroptosis,and pyroptosis in bone marrow megakaryocytes of mice during sepsis and its impact on platelet production capacity and coagulation function in mice.Methods C57BL/6J mice were randomly divided into a sham operation group(sham group)and a sepsis model group(CLP group).Peripheral blood platelets and coagulation function were measured by abdominal aortic blood sampling at 24 h postoperatively in both sham and CLP groups.After the mice were sacrificed,long bones of both lower limbs were taken,and bone marrow megakaryocytes were extracted using megakaryocyte separation solution and immunomagnetic bead separation.Laser confocal microscopy was used to observe the activation of programmed death-related marker molecules in mouse bone marrow megakaryocytes.Flow cytometry was used to detect programmed death rate,platelet production phenotype,and platelet surface markers(CD41,CD42b,CD61)of megakaryocytes.Western blotting was used to detect the expression of programmed death-related proteins in megakaryocytes.Results Compared with the sham group,the CLP group showed significant decreases in the number of platelets during acute sepsis(24 h)(P<0.000 1),significant increases in platelet distri-bution width(PDW)and mean platelet volume(MPV)(P<0.01),significant prolonging of thrombin time(TT),prothrombin time(PT),and activated partial thromboplastin time(APTT)(P<0.000 1,P<0.001,P<0.01),and significant reduction in fibrinogen(Fib)(P<0.000 1).Compared with the Con/sham group,the LPS/CLP group exhibited significant increases in the platelet production phenotype of megakaryocyte,the number of PLP in the supernatant,and the expression levels of platelet surface markers(CD41,CD42b,CD61).The rates of megakaryocyte necroptosis/apoptosis,pyroptosis,and ferroptosis were significantly elevated at 24 h post-CLP surgery.Laser confo-cal microscopy showed significant activation of LC3,P-MLKL,Caspase-1,and Fe2+in megakaryocytes of mice after CLP surgery.Western blotting results revealed that the CLP group exhibited a significant increase in the activa-tion rate of necroptosis-related protein P-MLKL(P<0.001),a significant increase in the cleavage of pyroptosis-related proteins GSDMD and GSDMD-N(P<0.01,P<0.001,respectively),a significant increase in the expres-sion of ferroptosis-related protein ACSL4(P<0.01),and a significant decrease in the expression of GPX4(P<0.01)compared to the sham group.Additionally,the CLP group demonstrated significant increases in the expression of apoptosis-related protein Bax,the cleavage of autophagy-related protein LC3B-Ⅱ,and the expression of P62(P<0.05,P<0.001,P<0.001,respectively).Inhibition of apoptosis with programmed cell death inhibitors decreased platelet production function of megakaryocyte,while inhibition of necroptosis and pyroptosis had limited effects on platelet production function of megakaryocyte.Inhibition of ferroptosis and autophagy enhanced platelet production function of megakaryocyte.Conclusion Significant programmed death of megakaryocytes was observed during the acute phase of sepsis(24 h).Among those megakaryocytes,apoptosis is an important mechanism for the differentia-tion of platelet production phenotype and increased platelet production capacity of megakaryocyte.Overactive autophagy and ferroptosis in megakaryocytes lead to megakaryocyte dysfunction,which is an important mechanism for coagulation abnormalities in sepsis.

Severe burns and trauma frequently lead to the skin barrier disruption and development of moist burn wound, which can trigger sepsis, septic shock, and even death. Immunodysfunction is closely associated with poor prognosis. In-depth research on the mechanisms of natural and adaptive immune dysfunction can help reveal the essence of the disease. Currently, elucidating the underlying mechanisms of immune dysfunction has become a critical research priority. Such investigations may provide fundamental insights into disease pathogenesis. Besides, accurate immune function assessment holds significant value for early detection of immune dysfunction, judgment of the severity of the condition, precise prediction of the prognosis, and guidance of clinical treatment. Implementing immunomodulatory treatment based on the pathophysiological mechanisms and evaluation results is a necessary approach to restoring the immune function, reducing mortality rate, and improving the prognosis of the patients with sepsis following severe burns and trauma. To this end, the authors systematically examined the characteristics and mechanisms of immune dysfunction, immune assessment as well as classification, and corresponding therapeutics in sepsis following severe burns and trauma, thereby providing a reference for the development of precise diagnosis and treatment strategies for immune dysfunction management.

At present,malignant tumor diseases occur frequently and increase year by year.Traditional chemoradiotherapy methods are expensive,have serious toxic and side effects,and are easy to reduce patient tolerance.Natural medicines have advantages of multiple targets,high selectivity and low toxicity and side effects in process of anti-tumor,and are one of important sources of anti-tumor drugs.As a polypeptide substance,lactoferrin has a strong anti-tumor effect and plays a huge role in field of nano-drug delivery.Receptors of lactoferrin are widely expressed on surface of various cancer cells.In addition to its strong anti-tumor effect,it is also widely used to modify nanocarriers.In this paper,anti-tumor mechanism of lactoferrin is reviewed,and the latest research progress of using lactoferrin as an anti-cancer drug delivery carrier is also introduced.

Severe burns and trauma frequently lead to the skin barrier disruption and development of moist burn wound, which can trigger sepsis, septic shock, and even death. Immunodysfunction is closely associated with poor prognosis. In-depth research on the mechanisms of natural and adaptive immune dysfunction can help reveal the essence of the disease. Currently, elucidating the underlying mechanisms of immune dysfunction has become a critical research priority. Such investigations may provide fundamental insights into disease pathogenesis. Besides, accurate immune function assessment holds significant value for early detection of immune dysfunction, judgment of the severity of the condition, precise prediction of the prognosis, and guidance of clinical treatment. Implementing immunomodulatory treatment based on the pathophysiological mechanisms and evaluation results is a necessary approach to restoring the immune function, reducing mortality rate, and improving the prognosis of the patients with sepsis following severe burns and trauma. To this end, the authors systematically examined the characteristics and mechanisms of immune dysfunction, immune assessment as well as classification, and corresponding therapeutics in sepsis following severe burns and trauma, thereby providing a reference for the development of precise diagnosis and treatment strategies for immune dysfunction management.

Active immunotherapy for cancer aims to treat disease by inducing effective cellular immunity and humoral immunity.Research on virus-like particles(VLPs)vaccines has made tremendous progress in recent years,dramatically reducing morbidity and mortality from some infectious diseases.VLPs are nanoparticles self-assembled from one or more structural proteins,with highly ordered repeat sequences and good immunogenicity,which can induce strong cellular immune and humoral immune responses.VLPs can overcome immunosuppressive state of tumor microenvironment,break self-tolerance,and trigger strong cytotoxic T lymphocyte activity,which is critical for both viral clearance and destruction of cancer cells.This article mainly reviews current research progress of VLPs-based cancer vaccines and potential defects of VLPs as vaccine carriers in development of cancer vaccines.