Hyaluronic acid (HA) possesses excellent biocompatibility, biodegradability, and non-immunogenicity, and exhibits active targeting capability to receptors such as cluster of differentiation 44 (CD44). Therefore, HA has become an important material for the design and preparation of drug delivery carriers in recent years. HA is rich in functional groups that can be chemically modified, but different modification methods and sites can affect its biological properties. This paper summarizes and discusses the effects of chemical modification on the biological properties of HA based on the formation mechanisms of such properties, as well as the derivatization and characterization methods of HA, so as to provide some reference for rational research on chemical modification of HA.

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

OBJECTIVES: Stigma is common among community-dwelling patients with schizophrenia and has a profound negative impact on both psychiatric symptoms and quality of life. This study aims to explore the association between stigma and quality of life in this population and to examine the multiple mediating roles of anxiety and depression symptoms. METHODS: The multi-stage stratified cluster random sampling method was used to select the community-dwelling patients with schizophrenics in Chengdu, Sichuan Province, China. The questionnaire included general demographic characteristics, stigma question, the Generalized Anxiety Disorder-7 (GAD-7) scale, the Patient Health Questionnaire-9 (PHQ-9), and the 12-item Short Form Health Survey (SF-12). The SF-12 was used to measure quality of life, including physical health and mental health dimensions. A multiple mediation model was used to analyse the mediating effects of anxiety and depression symptoms together between stigma and quality of life. RESULTS: A total of 1 087 community patients with schizophrenia were included with a mean age of 50.68±12.73 years; 525 (48.30%) were male. Stigma was reported by 543 patients (49.95%). Anxiety symptoms were present in 292 patients (26.86%), and depression symptoms in 407 patients (37.44%). The physical health quality of life score was 72.01 ± 20.99, and the mental health quality of life score was 71.68 ± 19.38. Multiple mediation analysis showed that stigma directly affected quality of life, and also indirectly affected quality of life through anxiety and depression symptoms. Anxiety and depression jointly mediated 42.26% of the total effect of stigma on physical health quality of life and 47.51% on mental health quality of life. CONCLUSIONS Reducing stigma and preventing anxiety and depression symptoms in community-dwelling patients with schizophrenia can effectively improve their quality of life and support reintegration into society.
Humans ; Quality of Life ; Male ; Depression/psychology* ; Middle Aged ; Social Stigma ; Schizophrenia ; Female ; Anxiety/psychology* ; China ; Surveys and Questionnaires ; Adult ; Schizophrenic Psychology ; Independent Living ; Aged

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.
Humans ; Lysosomes/physiology* ; Autophagy/physiology* ; Nanomedicine/methods* ; Neurodegenerative Diseases/therapy* ; Animals ; Nanostructures ; Lysosomal Storage Diseases/therapy*

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease with high global prevalence and long course, which affects more than 30% of the population and seriously endangers human health. Lipid metabolism plays an important role in the occurrence and development of MASLD. An increasing number of studies have shown that active ingredients in traditional Chinese medicine can regulate lipid metabolism to improve MASLD. Due to the obvious advantages of multi-target regulation and fewer side effects, the active ingredients have shown great potential and value for application. However, the pathological mechanism of MASLD is intricate and the active ingredients of traditional Chinese medicine can improve MASLD from multiple aspects, there is currently a lack of systematic discussion on lipid metabolism. Therefore, this review focuses on lipid metabolism and reviews the latest research progress of active ingredients from traditional Chinese medicine in ameliorating MASLD from the aspects of lipid uptake, lipid synthesis, lipid oxidation, lipid secretion, etc., in order to provide more theoretical references for active ingredients of traditional Chinese medicine in regulating lipid metabolism to improve MASLD.

Objective:By reviewing and analyzing the construction practice of the National Clinical Research Center for Obstetrics and Gynecology and the relevant experience of enhancing its technological influence, this study aimed to provide effective suggestions for its subsequent high-quality development.Methods:We analyzed and summarized the core strategies and achievements of the construction of the National Clinical Research Center for Obstetrics and Gynecology.Results:Over the past decade, the National Clinical Research Center for Obstetrics and Gynecology has continuously planned research directions, conducted high-level clinical research, built a national collaborative research network, strengthened management and research platform linkage construction, and made positive contributions to leading the development of China's obstetrics and gynecology and reproductive fields.Conclusions:The sustainable development of the National Center for Clinical Research on Diseases in the future needs to balance the characteristics of overall planning, cutting-edge leadership, and flexible switching, as well as highlight the main responsibility of serving clinical technology innovation, explore interdisciplinary domestic and international exchanges and cooperation, build a high-quality talent team for clinical medical research, and coordinate with the overall layout of clinical medicine in China to ensure people′s lives and health.

Objective To examine the pattern of changes in 12 cytokines(IFN-α,IFN-γ,TNF-α,IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,and IL-17)in the cerebrospinal fluid(CSF)of patients with central nervous system(CNS)infections and their clinical significance.Methods Fifty-two patients clinically diagnosed with CNS infec-tions at our hospital were enrolled in the study.CSF was collected for CSF analysis,biochemical analysis,and cytology.Changes in the CSF levels of 12 cytokines were measured by flow cytometry.Results Only IL-5,IL-6,and IL-8 were sig-nificantly increased in the CSF,and the corresponding positive rates were 23.08%,42.31%,and 96.15%,respectively.High levels of IL-5,IL-6,and IL-8 were positively correlated with white blood cell(WBC)count and neutrophil percent-age but negatively correlated with lymphocyte percentage in the CSF.Consistent with the WBC count,IL-5,IL-6,and IL-8 levels in the CSF were significantly decreased after effective treatment.Conclusion The levels of IL-5,IL-6,and IL-8 in CSF can be used as potential markers for the diagnosis,treatment,and severity assessment of CNS infections.

Objective This study was to develop a HPLC-MS/MS method for determination of etomidate and etomidate acid in blood samples.Methods The blood samples were deproteinized with acetonitrile and supernatant was achieved by shake,sonication,centrifuge and filtration using 0.22 μm membrane.Then,supernatant was performed on an analytical column Poroshell 120 EC-C18(150 mm×3.0 mm,2.7 μm)and flowed with 0.1%formic acid(mobile phase A)and acetonitrile(mobile phase B).The gradient elution at a flow rate of 0.8 mL/min was determined using an electrospray ionization source in positive ion mode and multiple reaction monitoring mode.Results The linearities of etomidate and etomidate acid in blood samples were good within the corresponding range and the correlation coefficients(r)were over 0.9988.The limit of detection(LOD)of etomidate and etomidate acid were 19.94 and 40.25 ng/mL,and the limit of quantitation(LOQ)of them were 50 and 100 ng/mL,respectively.Moreover,matrix effects were ranged from 1.47%to 10.34%and recoveries ranged from 82.81%to 90.07%.The detection of a positive case using our method was successfully determined to be 1 138.89 and 3 126.41 ng/mL for the contents of etomidate and etomidate acid,respectively.Conclusion Our study has further confirmed that this method with simple pretreatment,little sample usage and wide linear range,can be successfully applied to the detection of forensic sciences on etomidate and etomidate acid.

Objective:To explore the effect of 8-week treadmill exercise on myocardial fibrosis in mice with T2DM and its molecular mechanism. Method:Eight m/m mice were used as the control group,and 32 db/db mice were randomly divided into control group,model group,exercise intervention group,inhibitor alone group and exercise combined with in-hibitor intervention group.Fasting blood glucose was monitored weekly.After 8 weeks,triglycerides(TG)and total cholesterol(TC)were measured.Masson staining was used to observe the degree of myocardial fibrosis,and immunofluorescence staining was used to observe the expression of Collagen Ⅰ and α-SMA.Westem Blot was used to detect the expression levels of fibrosis,inflammation,pyroptosis and p38MAPK related proteins. Result:The model group showed a significant increase in fasting blood glucose,TG and TC(P＜0.0001),Col-lagen Ⅲ(P＜0.05)and TGF-β1(P＜0.01)expression compared with control group.Compared to the model group,Masson staining in the other groups showed a significant improvement in disordered myocardial cell ar-rangement and a decrease in blue collagen fibers between the interstitial tissue and perivascular tissue;immuno-fluorescence staining also showed that the expression levels of Collagen Ⅰ and α-SMA and the expression lev-els of fibrosis-related proteins were significantly decreased in these groups.The expression levels of inflamma-tion and pyroptosis related proteins in the exercise intervention group were significantly lower than those in the model group.Compared to the model group,the phosphorylation level of p38MAPK in the exercise inter-vention group and the simple inhibitor group was significantly decreased(P＜0.05,P＜0.01),but the phosphory-lation level was not further decreased after the combined intervention.Compared to the model group,the ex-pression levels of NLRP3 and GSDMD-N in the single inhibitor group were significantly decreased(P＜0.05),and the combined intervention further inhibited the expression of Caspase-1(P＜0.05),Cleaved-Caspase-1(P＜0.05),and GSDMD-N(P＜0.001). Conclusion:Eight-week treadmill exercise can significantly improve myocardial fibrosis in db/db mice.The mechanism may reduce the phosphorylation of p38MAPK and pyroptosis of cardiomyocytes,thus improving myocardial fibrosis in db/db mice.The combination of treadmill exercise and SB203580 can further reduce py-roptosis.