Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

ObjectiveTo analyze the literature related to traditional Chinese medicine （TCM） pharmacology of Institute of Chinese Materia and Medica， China Academy of Chinese Medical Sciences （hereinafter referred to as "Institute of Chinese Materia and Medica"）， and evaluate the research status， development trend， influence of discipline members， and patent technology of this field. MethodThe papers from 2002 to 2024 in the databases of CNKI and Web of Science （WOS） were searched， whose first authors or corresponding authors are from the Institute of Chinese Materia and Medica， and CiteSpace 6.3.R6 was adopted for visual analysis of the annual number of publications and keywords. Additionally， the total number of published papers， citation times， and other measurement parameters of discipline members of TCM pharmacology in the institute were counted. After obtaining the h index， the academic track was calculated， and the academic influence of discipline members was quantitatively evaluated from the aspects of the academic track T and highly cited papers. Meanwhile， patent data from 2005 to 2024 of TCM pharmacology in the studied institute were retrieved from the HimmPat patent database， and Excel 2022 and Origin 2021 were utilized to conduct visual analysis on the overall patent application trend and technology composition. ResultIn the past 20 years or more， the annual publication of academic papers has been on the rise generally， and the key words include "animal model"， "mechanism of action"， "network pharmacology" and so on. The studies focus on the innovative methods of TCM pharmacological mechanisms， basic research on TCM prevention and treatment of major non-infectious diseases， and the prevention and treatment of respiratory viral diseases. The academic track T of the discipline members of TCM pharmacology in the Institute of Chinese Materia and Medica is positive， with sound personal influence. In recent years， the patent application trend has increased significantly， mainly concentrating on A61K patents and G01N subcategories， and IPC large-group analysis shows that the main technical applications are mainly in A61K36， A61K31， and other fields. ConclusionTCM pharmacology in the institute develops steadily and the academic influence of the discipline members is still sound， with fruitful patent achievements. In the future， research on pharmacological discipline innovation and new drug research and development can be enhanced， and multidisciplinary integration studies should be carried out to promote TCM modernization.

Objective:To explore the mediating role of aging attitude and anxiety in the relationship between self-worth and depression among the elderly.Methods:From July to August 2022, a total of 536 elderly people in Shijiazhuang University for the Elderly were surveyed by the elderly self-worth scale, generalized anxiety disorder-7(GAD-7), attitudes to aging questionnaire(AAQ) and patient health questionnaire(PHQ-9). SPSS 26.0 software was used for descriptive statistics and correlation analysis.AMOS 24.0 was used to construct an intermediation model, and Bootstrap method was used for mediating effect testing.Results:(1)The score of self-worth was 101.00 (92.00, 112.00), the score of aging attitude was 92.00 (83.00, 101.75), the score of anxiety was 2.00(0, 6.00), and the score of depression was 2.00 (0, 5.00). (2)Self-worth was positively correlated with aging attitude ( r=0.67, P<0.01), while negatively correlated with anxiety ( r=-0.45, P<0.01) and depression ( r=-0.48, P<0.01). The aging attitude was negatively correlated with anxiety ( r=-0.41, P<0.01) and depression ( r=-0.41, P<0.01). Anxiety was positively correlated with depression ( r=0.71, P<0.01). (3)The indirect effect of aging attitude between self-worth and depression in the elderly was -0.016, accounting for 19.75% (-0.016/-0.081)of the total indirect effect.The indirect effect of anxiety between self-worth and depression in the elderly was -0.045, accounting for 55.56%(-0.045/-0.081) of the total indirect effect.The chain mediating effect of aging attitude and anxiety between self-worth and depression in the elderly was -0.020, accounting for 24.69%(-0.020/-0.081) of the total indirect effect. Conclusion:Aging attitude and anxiety play a chain mediating role between self-worth and depression in the elderly.

Objective:To investigate the protective effect of naringenin on acute lung injury related with sepsis; To discuss its possible mechanism.Methods:Totally 30 male SD rats were randomly divided into sham-operation group, model group, naringin low-, medium- and high-dosage groups, with 6 rats in each group. The sepsis-related acute lung injury model was established by cecal ligation and puncture in all groups except the sham-operation group. After modeling, naringin low-, medium- and high-dosage groups were given naringin 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively for gavage, while the sham-operation group and the model group were given the same volume of distilled water by gavage, once a day, for 2 days. Pathological changes in lung tissue were observed using HE staining. The levels of 1L-1, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) were measured by ELISA; the expression of TNF-α in lung tissue was detected by immunofluorescence histopathology; the expressions of TGF-β1, TGF-βR1 and Smad2 were detected by Western Blot. An agonist group and a naringin plus agonist group were set up, with 6 mice in each group, and the expressions of TGF-β1 and Smad2 protein in the lung tissue of each group were detected by immunohistochemical staining to verify the effect of naringin on the expressions of TGF-β1 and Smad2 protein.Results:Compared with the model group, the pathological injury of lung tissue in naringin groups were obviously alleviated, and the levels of IL-1β, IL-6 and IL-18 in BALF decreased ( P<0.01), the protein expressions of TNF-α, TGF-β1, TGF-βR1 and Smad2 in lung tissue decreased ( P<0.01 or P<0.05). Further verification found that the expressions of TGF-β1 and Smad2 in the agonist group increased ( P<0.01), while the expressions of TGF-β1 and Smad2 in the naringin agonist group decreased ( P<0.01). Conclusion:Naringin can reduce the inflammatory response in the lung of the rats to protect against sepsis-related acute lung injury, and its protective effect could be related to the inhibition of the TGF-β1/Smad2 signaling pathway.

OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.

BACKGROUND: Insufficient angiogenesis and the lack of skin appendages are critical challenges in cutaneous wound healing. Stem cell-fabricated cell sheets have become a promising strategy, but cell sheets constructed by a single cell type are inadequate to provide a comprehensive proregenerative microenvironment for wound tissue. METHODS: Based on the communication between cells, in this study, bone marrow mesenchymal stem cells (BMSCs) and hair follicle stem cells (HFSCs) were cocultured to fabricate a composite cell sheet (H/M–CS) for the treatment of fullthickness skin wounds in mice. RESULTS: Experiments confirmed that there is cell–cell communication between BMSCs and HFSCs, which enhances the cell proliferation and migration abilities of both cell types. Cell–cell talk also upregulates the gene expression of proangiogenic-related cytokines in BMSCs and pro-hair follicle-related cytokines in HFSCs, as well as causing changes in the properties of secreted extracellular matrix components. CONCLUSIONS Therefore, the composite cell sheet is more conducive for cutaneous wound healing and promoting the regeneration of blood vessels and hair follicles.

Objective:To explore the phenotype and mechanism of ferroptosis in steatosis liver ischemia reperfusion injury (IRI) and elucidate the mechanism of targeted inhibition of ferroptosis down-regulating steatosis liver IRI.Methods:First, 20 mice are divided into 2 group according to the different feeding mode: Normal chow diet(NCD group, n=10)and high fat diet(HFD group, n=10). The fatty liver constructs are successful as verified by laboratory tests for relevant indicators and oil red staining.NCD and HFD mice were randomized into two groups sham and IRI.The expression of glutathione peroxidase 4(Gpx4)in liver tissues of each group is detected by Western blot.Morphological phenotypes of mitochondria in liver tissue are observed by transmission electron microscope.Accordingly, it was determined whether ferroptosis occurred in mouse liver IRIs.NCD(n=30)and HFD(n=30)are further randomized into 3 groups: sham(n=10), IRI(n=10)and inhibitor(IRI-fer-1 group, n=10). The serum contents of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)are detected by ALT/AST kits.Hematoxylin-eosin(HE)stain is employed for detecting the degree of liver injury; immunohistochemistry(IHC)and enzyme-linked immunosorbent assay(ELISA)for detecting the levels of inflammatory factors and inflammatory cell infiltration.Similarly, primary hepatocytes from NCD/HFD mice are extracted and the occurrence of ferroptosis is verified by detecting C11-BODIPY(581/591)by fluorescent stain after hypoxia-reoxygenation(H/R).Results:As compared with NCD-IRI group, Gpx4 protein expression declined obviously in HFD-IRI group while serum ALT/AST level spiked markedly( P<0.01). IHC staining of 4-HNE is positive, mitochondrial specific damage is more pronounced and inflammatory infiltration became enhanced.As compared with IRI group, serum level of ALT/AST dropped obviously and infiltration of inflammatory cells and secretion of inflammatory factors are blunted markedly in IRI-fer-1 group( P<0.01). Conclusions:A high degree of ferroptosis and severe inflammatory response during fatty liver IR are features of distinguishing steatosis liver IRI from ordinary liver IRI.Targeted inhibition of ferroptosis lowers inflammation and damage during IR in steatosis liver.

Objective : To investigate whether NaHS，a hydrogen sulfide donor，can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc －/ GPX4 signaling pathway in ferroptosis． Methods : Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis，which was divided into Control group，LPS group and LPS + NaHS group．The kits were applied to detect the changes of cardiomyocyte viability，Fe2 + ，LDH and CK-MB，determine the levels of oxidative stress indexes GSH and MDA，detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes， and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. Results: Compared with the Control group，H9c2 cell viability decreased，Fe2 + concentration increased ，GSH ，MDA and ROS levels increased，mitochondrial JC-1 monomer increased ，expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased，and cell damage increased after LPS stimulation (P＜0. 05) ．Compared with the LPS group，NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration，decreased the level of LPS-induced oxidative stress in H9c2 cells ，and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P＜0. 05 ) ． Conclusion The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc －/ GPX4 signaling pathway in fer- roptosis.

Objective:To know the clinical characteristics, seasonal pattern and influencing factors of atypical depression(AD) patients.Methods:A total of 203 depressed outpatients of Peking University Sixth Hospital from January 2021 to August 2021 were included.They were assessed with demographic questionnaire, inventory of depressive symptomatology self-report(IDS-SR30) and seasonal pattern assessment questionnaire(SPAQ). According the score of IDS-SR30, all patients were classified as atypical depression(AD) and non-atypical depression(non-AD). The data were analyzed by t-test, non-parametric test and Logistic regression using SPSS 26.0 software. Results:The prevalence of AD among depressed patients was 36.0% (95% CI=29.3%-42.6%). The IDS-30 score of the AD group was (41.59±10.59), and IDS-30 score of the non-AD group was (36.08±13.17), and the difference between the two groups was statistically significant ( t=3.062, P<0.05). The global seasonal score of the AD group was 6 (3, 9), and 17.8% of the AD group had seasonal pattren.The global seasonal score of the non-AD group was 5 (3, 8), and 14.6% of the non-AD group had seasonal pattern.There was no significant difference in the global seasonal score and the proportion of seasonal pattern between the two groups ( Z=0.389, χ2=0.359, P>0.05). Depression patients who were females ( β=1.08, OR=2.95, 95% CI=1.32-6.59, P<0.05), low self-evaluation ( β=0.82, OR=2.27, 95% CI=1.12-4.59, P<0.05)and psychomotor retardation ( β=0.93, OR=2.54, 95% CI=1.33-4.85, P<0.05) were more likely to be diagnosed as AD, and depression patients having mood variation ( β=-0.94, OR=0.39, 95% CI=0.19-0.81, P<0.05) were more likely to be diagnosed as non-AD. Conclusion:Women, low self-evaluation, psychomotor retardation and unobvious mood variation can predict and help to diagnose atypical depression in depressed patients.

Objective:To analyze the influencing factors of community hospice care service needs of the elderly based on structural equation model.Methods:A multi-stage sampling method was used to survey 564 elderly people from 40 community health service centers in four districts of Chaoyang District in Beijing from September to November 2020 with a self-designed questionnaire. The survey content included three dimensions: tendency characteristics (population characteristics, health beliefs), enabling resources and demand factors. The chi-square test and rank sum test were used to analyze the influencing factors of the community hospice care needs of the elderly. At the same time, based on Anderson theory, structural equation model was used to analyze the action path and effect size of the influencing factors.Results:Registered residence, occupation, understanding of community elderly care services, recognition of community medical convenience, recognition of community health services in reducing family burden, recognition of community health services in improving their own health, understanding of community hospice care services, mean monthly income of their families, degree of income satisfaction, self-paid medical expenses of the previous year, living status, acceptance of community medical expenses, satisfaction with the number of community medical staff, self-assessment of health status, whether the elderly was ill in the last two weeks and the number of chronic diseases and etc affected the needs of the elderly for community hospice care services (all P<0.05). In the three dimensions of Anderson model, enabling resources had a direct effect, and could also be affected by demand factors indirectly, the total effect value was 0.404; demand factors had direct impact, and the effect value was 0.193; propensity characteristics exerted impact indirectly through enabling resources and demand factors, and the total effect value was 0.176. Among them, the acceptance of community health service fees in the enabling resource dimension has the greatest impact (FL=0.535), the number of chronic disease in the demand factor dimension had the greatest impact (FL=1.018), and the recognition of community health service in reducing family burden in the propensity characteristic dimension had the greatest impact (FL=0.612) (all P<0.05). Conclusions:There are various factors and action paths that affect the needs of community hospice care services for the elderly. Among them, the acceptance of community health service fees, the number of chronic disease, and the recognition of community health service in reducing family burden have a greater impact.