BACKGROUND:As a degradable scaffold material for bone tissue engineering,lactic acid is widely used in tissue regeneration and repair research,and plays an important role in promoting tissue healing,new bone formation and angiogenesis. OBJECTIVE:To observe the effect of lactic acid degradation products on osteoclasts and to investigate the effects of lactic-interfered osteoclast conditioned medium on the proliferation,migration and tube-forming capacity of human umbilical vein endothelial cells. METHODS:(1)The mouse monocyte macrophage cell line RAW264.7 at logarithmic growth period was selected,and adherent cells were cultured in the osteoclast induction medium(DMEM medium with nuclear factor-κB receptor-activating factor ligand and 10%fetal bovine serum)containing different concentrations of lactic acid(0,5,10,20 mmol/L).After 5 days of culture,tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining were conducted.After 24 hours of culture,RT-PCR was used to detect the mRNA expression of tartrate-resistant acid phosphatase 5.(2)RAW264.7 cells at logarithmic growth period were selected and adherent cells were divided into two groups.Control group was cultured in the osteoclast induction medium,while experimental group was cultured in the osteoclast induction medium containing 10 mmol/L lactic acid.After 5 days of culture,the medium in each group was removed and the cells in the two groups were cultured in the serum-free DMEM medium for another 24 hours.Cell supernatant was then collected and used as the conditioned medium after mixed with an equal volume of DMEM medium containing 10%fetal bovine serum.Human umbilical vein endothelial cells at the logarithmic growth phase were taken and separately co-cultured with the conditioned medium of the control and experimental groups.The proliferation,migration and tube-forming ability of human umbilical vein endothelial cells were observed by cell counting kit-8 assay,migration assay,scratch assay and tube-forming assay.The mRNA and protein expression of angiogenesis-related genes and proteins were observed by RT-PCR and western blot. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining showed that 5 and 10 mmol/L lactic acid promoted osteoclastic differentiation of RAW264.7 cells and the promoting effect of 10 mmol/L lactate was more significant.RT-PCR results showed that the expression of tartrate-resistant acid phosphatase-5 mRNA of osteoclast-related genes was the highest when the lactic acid concentration was 5,10,and 20 mmol/L(P<0.05),especially 10 mmol/L.Compared with the control group,the proliferation,migration and tube-forming abilities of human umbilical vein endothelial cells were significantly increased in the experimental group(P<0.05).Compared with the control group,the expression levels of vascular endothelial growth factor and angiogenin 1 mRNA and protein were increased in the experimental group(P<0.05).To conclude,lactate-induced osteoclast conditioned medium could promote the angiogenesis of endothelial cells,and the mechanism may be related to the promotion of the expression of vascular endothelial growth factor and angiogenin 1.

OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Central venous access device associated skin impairment is a common complication of indwelling central venous catheters in cancer patients. To further enhance the standardization of nursing staff's practice of central venous access device associated skin impairment, a clinical nursing practice guideline for central venous access device associated skin impairment in cancer patients was developed through the Delphi expert consultation and expert meeting methods in accordance with the methodology for developing evidence-based nursing practice guidelines. Recommendations cover four aspects of management requirements, assessment, prevention, and management of central venous access device associated skin impairment, providing a practical basis for clinical healthcare professionals to make scientific decisions on central venous access device associated skin impairment.

Objective To explore the relationships between social support,positive coping,caregiver burden and family resilience of primary caregivers of first-stroke patients.Methods A questionnaire survey was conducted among 307 primary caregivers of first-stroke patients in 2 tertiary hospitals in Shanghai by convenience sampling method.Social support rating scale,simplified coping style questionnaire,Zarit caregiver burden interview,and family resilience assessment scale were used for questionnaire survey.Pearson correlation analysis and structural equation models were used for data analysis.Results A total of 288 valid questionnaires were collected,and the effective recovery rate was 93.81％.Pearson correlation analysis showed that there was a positive correlation between family resilience and social support,family resilience and positive coping,and social support and positive coping(r=0.375,0.627,and 0.277;all P＜0.01),while caregiver burden and social support,caregiver burden and positive coping,and family resilience and caregiver burden were all negatively correlated(r=-0.203,-0.343,and-0.444;all P＜0.01).The mediating effect model was constructed with positive coping and caregiver burden as mediating variables,social support as independent variables,and family resilience as dependent variables.The results showed that social support could mediate family resilience through positive coping,with a mediating effect of 0.164,accounting for 26.1％of the total effect;social support could also affect the family resilience of the primary caregivers of first-stroke patients through the partial chain mediating effect of positive coping and caregiver burden,with a mediating effect value of 0.032,accounting for 5.1％of the total effect.Conclusion Social support can predict family resilience among primary caregivers of first-stroke patients,and positive coping and caregiver burden play chain mediating roles in the impact of social support on family resilience.

Aplastic anemia is a rare and life-threatening bone marrow failure that is becoming more common and tends to affect younger individuals.Traditional Chinese medicine has a long history of preventing and treating asthenia and blood syndrome.Its treatment of aplastic anemia involves coordinated regulation through multiple components,targets,and channels.The article classifies and elaborates on the therapeutic effects of traditional Chinese medicine compounds and their components on aplastic anemia.As well as the expression of related factors from three aspects:hematopoietic stem/progenitor cells,the immune system,and bone marrow microenvironmental abnormalities.It also analyzes the frequency and meridian of commonly used drugs in traditional Chinese medicine compounds.Deficiency tonifying drugs were found to be the most frequently used treatment for aplastic anemia,which is consistent with the deficiency-based nature of the disease.The related organs affected are the liver,spleen,and kidney.This paper reviews the mechanism of aplastic anemia and the preventive and therapeutic effects of traditional Chinese medicine.The study is of great significance for the follow-up research on traditional Chinese medicine in improving aplastic anemia.

Aplastic anemia is a rare and life-threatening bone marrow failure that is becoming more common and tends to affect younger individuals.Traditional Chinese medicine has a long history of preventing and treating asthenia and blood syndrome.Its treatment of aplastic anemia involves coordinated regulation through multiple components,targets,and channels.The article classifies and elaborates on the therapeutic effects of traditional Chinese medicine compounds and their components on aplastic anemia.As well as the expression of related factors from three aspects:hematopoietic stem/progenitor cells,the immune system,and bone marrow microenvironmental abnormalities.It also analyzes the frequency and meridian of commonly used drugs in traditional Chinese medicine compounds.Deficiency tonifying drugs were found to be the most frequently used treatment for aplastic anemia,which is consistent with the deficiency-based nature of the disease.The related organs affected are the liver,spleen,and kidney.This paper reviews the mechanism of aplastic anemia and the preventive and therapeutic effects of traditional Chinese medicine.The study is of great significance for the follow-up research on traditional Chinese medicine in improving aplastic anemia.

Central venous access device associated skin impairment is a common complication of indwelling central venous catheters in cancer patients. To further enhance the standardization of nursing staff's practice of central venous access device associated skin impairment, a clinical nursing practice guideline for central venous access device associated skin impairment in cancer patients was developed through the Delphi expert consultation and expert meeting methods in accordance with the methodology for developing evidence-based nursing practice guidelines. Recommendations cover four aspects of management requirements, assessment, prevention, and management of central venous access device associated skin impairment, providing a practical basis for clinical healthcare professionals to make scientific decisions on central venous access device associated skin impairment.

Structural and functional explorations on bio-soft matter such as micelles,vesicles,nanoparticles,ag-gregates or polymers derived from traditional Chinese medicine(TCM)has emerged as a new topic in the field of TCM.The discovery of such cross-scaled bio-soft matter may provide a unique perspective for unraveling the new effective material basis of TCM as well as developing innovative medicine and biomaterials.Despite the rapid rise of TCM-derived bio-soft matter,their hierarchical structure and as-sembly mechanism must be unambiguously probed for a further in-depth understanding of their pharmacological activity.In this review,the current emerged TCM-derived bio-soft matter assembled from either small molecules or macromolecules is introduced,and particularly the unambiguous elucidation of their hierarchical structure and assembly mechanism with combined electron microscopic and spectroscopic techniques is depicted.The pros and cons of each technique are also discussed.The future challenges and perspective of TCM-derived bio-soft matter are outlined,particularly the requirement for their precise in situ structural determination is highlighted.

Astrocytes are heavily activated in Alzheimer's disease,engulfing damaged synapses,Aβ proteins,Tau proteins,apoptotic cells and other substrates.However,these substrates are difficult to degrade,accumulate as the disease progresses,and impair the phagocytosis of astrocytes.During phagocytosis,astrocytes recognize different substrates through a variety of phagocytosis receptors and partially degrade the substrates through degrad-ing enzymes and lysosomal pathways.The accumulation of Aβ and Tau proteins in astrocytes caused astrocyte im-mune and metabolic disorders,and Aβ toxicity changed after phagocytosis.In addition,astrocytes and microglia form a complementary pattern and cooperate to complete phagocytosis through interaction.Regulating the pathway of astrocyte phagocytosis and degradation is believed to be a potential novo therapeutic for clinical treatment of Alzheimer's disease.

The development of speech is a process by which the neural network structure of brain perceives, decodes, represents, and outputs input signals. At the cortical level, the classic model of speech processing proposed two pathways leading from the auditory system: the ventral stream and the dorsal stream.The ventral stream, which involved structures in the superior and middle portions of the temporal lobe, was involved in processing speech signals for perception and comprehension (speech recognition). The dorsal stream, which involved structures in the posterior frontal lobe and the posterior dorsal-most aspect of the temporal lobe and parietal operculum, had an auditory-motor integration function and was essential for speech production. However, the importance of auditory processing in central auditory nervous system(CANS) from the vestibulocochlear nerve to the auditory cortex for speech development had not been clarified.This review aims to discuss the roles and related mechanisms of the CANS in speech recognition and generation from the perspective of cognitive neuroscience, so as to provide new ideas for clinical monitoring and long-term prediction of auditory processing and speech development, and for diagnosis and treatment of clinical speech-related diseases.