The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

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.

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*

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.

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 To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

Objective:To establish ferroptosis-related risk characteristics, to evaluate the prognostic correlation of ferroptosis-related genes in hepatocellular carcinoma, and to explore the complex relationship between hepatocellular carcinoma, ferroptosis and immune microenvironment.Methods:The bioinformatics analysis involved obtaining ferroptosis-related differentially expressed genes (DEGs) from the GeneCards database and the cancer genome atlas database. The biological functions of ferroptosis-related DEGs were analyzed using gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment. Ferroptosis-related DEGs clusters were identified using univariate Cox regression analysis and cluster analysis, etc. The correlation between ferroptosis-related DEGs clusters and tumor immune microenvironment and tumor occurrence score was evaluated using immunopanoramic analysis and tumor-related score analysis. Based on ferroptosis-related characteristics, a ferroptosis-related characteristic spectrum and nomogram were constructed using multivariate Cox regression and correlation analysis, etc. The correlation between the risk characteristics and tumor immune microenvironment, tumor occurrence score and gene mutation were evaluated using immune panoramic analysis, tumor-related score analysis and gene mutation analysis. In the experimental verification stage, the mRNA expression levels of aurora kinase A ( Aurka), acetyl-CoA carboxylase alpha ( Acaca) and arrestin domain containing 3 ( Arrdc3) in mouse primary hepatocytes and mouse hepatoma Hepa1-6 cells were verified by real-time reverse transcription-PCR (RT-qPCR). The mRNA expression levels of AURKA, ACACA and ARRDC3 in adjacent normal tissues and tumor tissues of patients with hepatocellular carcinoma were verified by RT-qPCR. A heat map was used to show the correlation between clustering and clinical parameters, and this was analyzed using a chi-square test. Significance analysis was performed using a two-sided unpaired t test. Results:A total of 35 up-regulated genes and 19 down-regulated genes were identified. These genes were mainly involved in biological processes and signaling pathways related to ferroptosis, oxidative stress and fatty acid metabolism. A total of 14 ferroptosis-related DEGs were identified to be associated with prognosis. The clusterring effect was best when hepatocellular carcinoma patients were divided into two subgroups. The survival rate of cluster 2 was lower than that of cluster 1 ( P<0.05). There was no significant difference in the tumor immune dysfunction and exclusion (TIDE) score between cluster 2 and cluster 1 ( P=0.43). Cluster 1 exhibited higher levels of immune cell infiltration, particularly CD4 + T cells ( P<0.01). The expression levels of 10 major histocompatibility complex (MHC) molecule-related genes were higher in cluster 1. The angiogenesis activity score ( P=0.048) and stemness score ( P=0.038) of cluster 2 were increased, and the expression levels of programmed death-1 ( PDCD1) and cytotoxic T lymphocyte-associated antigen-4 ( CTLA-4) in cluster 2 (5.924±0.013 and 5.475±0.042) were higher than those in cluster 1 (4.539±0.143 and 4.372±0.176) (both P<0.05). The expression levels of AURKA, glucose-6-phosphate dehydrogenease ( G6PD), ACACA, GABA type A receptor associated protein like 1 ( GABARAPL1) and ARRDC3 were correlated with the T stage, clinical stage and survival status of hepatocellular carcinoma. The survival rate of the high-risk group was lower than that of the low-risk group with time ( P<0.01). The area under the curve of the risk characteristics at 1, 3 and 5 years was 0.797, 0.717 and 0.639, respectively. The actual survival time 1, 3, and 5 years was highly consistent with the corresponding predicted survival time. The levels of memory B cell infiltration, angiogenesis activity score and cell stemness score, programmed death-ligand 1, CTLA-4, hepatitis A virus cell receptor 2, lymphocyte activation gene 3 and PDCD1 gene expression (0.013 8±0.036 0, 0.884±0.212, 0.387±0.135, 6.273±0.228, 5.847±0.331, 8.179±0.259, 6.859±0.263 and 5.142±0.326) in the high-risk group were higher than those in the low-risk group (0.001 5±0.021 0, 0.874±0.132, 0.298±0.125, 5.866±0.132, 3.742±0.237, 7.236±0.321, 6.324±0.242 and 4.513±0.211) ( P<0.05, 0.01). The expression levels of MHC molecule-related genes in the high-risk group were also higher than those in the low-risk group ( P<0.05, 0.01), while the infiltration levels of resting mast cells, activated natural killer cells, and resting natural killer cells (0.043 2±0.135 0, 0.032 1±0.143 0 and 0.016 3±0.001 9) and the TIDE score (0.072 0±0.018 0) in the high-risk group were lower than those in the low-risk group (0.054 9±0.023 0, 0.042 7±0.017 0, 0.024 6±0.021 2 and 0.094 0±0.013 5) ( P<0.05, 0.01). The top five genes with the highest mutation frequency in the high-risk group were tumor protein P53 ( TP53, 43%), titin ( TTN, 21%), catenin beta 1 ( CTNNB1, 20%), mucin 16 ( MUC16, 18%) and piccolo presynaptic cytomatrix protein ( PCLO, 11%). The top five genes with the highest mutation frequency in the low-risk group were CTNNB1 (30%), TTN (24%), albumin ( ALB, 16%), MUC16 (15%) and PCLO (11%). The cube protein and PCLO showed the co-occurrence of gene mutations in the high-risk group, while MUC16 and axis 1 protein showed the co-occurrence of gene mutations in the low-risk group. There was no significant difference in tumor mutation burden (TMB) between the high-risk group (1.374±0.026) and the low-risk group (1.303±0.081) ( P=0.073). There was no significant difference in survival time between the high-TMB group (2.3 years) and the low-TMB group (3.8 years) ( P=0.293). The mutation rates of AURKA, G6PD, ACACA, GABARAPL1 and ARRDC3 genes (2.0%, 2.0%, 4.0%, 0.3% and 0.6%) were relatively low. The relative expression levels of Aurka, Acaca and Arrdc3 mRNA in Hepa1-6 cells (13.331±0.000, 6.619±0.000 and 1.209±0.002) were higher than those in mouse primary hepatocytes (1.000±0.000, 1.000±0.000 and 1.000±0.000) (all P<0.01). The relative expression levels of AURKA, ACACA and ARRDC3 mRNA in tumor tissues of patients with hepatocellular carcinoma (2.102±0.365, 2.476±0.351 and 11.460±9.189) were higher than those in adjacent normal tissues of patients with hepatocellular carcinoma (1.122±0.648, 0.831±0.935 and 0.852±0.171) ( P<0.05, 0.01). Conclusions:This study constructed a prognostic signature comprising five ferroptosis-related genes ( AURKA, G6PD, ACACA, GABARAPL1, and ARRDC3) that is highly correlated with clinical hepatocellular carcinoma data. This study highlights the significance of ferroptosis-related genes as prognostic markers for hepatocellular carcinoma and provides insights into the complex relationship between hepatocellular carcinoma, ferroptosis, and the immune microenvironment.

Objective To investigate the therapeutic mechanism of Shen Wu Yizhi Capsule in the treatment of post-stroke cognitive impairment(PSCI)by using network pharmacology methods and clinical trial validation.Methods A prospective trial was carried out in 90 cases of patients with PSCI admitted to Taihe Traditional Chinese Medicine Hospital Affiliated to Anhui University of Chinese Medicine from August 2022 to February 2024.The patients were randomly divided into the control group and the trial group by random number table method,with 45 cases in each group.The control group was treated with conventional treatment for PSCI,and the trial group was treated with Shen Wu Yizhi Capsule orally on the basis of treatment for the control group.The treatment course for the two groups covered 28 days.The changes of Mini-Mental State Examination(MMSE)score,Montreal Cognitive Assessment(MoCA)score,and the serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in the patients of the two groups were observed before and after treatment.Moreover,the incidences of adverse events in the two groups were recorded,thus to evaluate the safety of the treatment regimens in the two groups.And then the network pharmacological research was performed.TCMSP and literature review were used to obtain the active ingredients of Shen Wu Yizhi Capsule,GeneCards and other databases were used to obtain the PSCI disease targets,and the common targets were inputted into the STRING database to construct the PPI network.Cytoscape 3.9.0 was used to construct the network diagram of Shen Wu Yizhi Capsule-PSCI-targets,DAVID was used to perform GO and KEGG pathway enrichment analysis,and then molecular docking was used to verify the binding activity.Results(1)The results of clinical trial showed that after 28 days of treatment,the MMSE and MoCA scores of patients in the two groups were increased compared with those before treatment(P<0.05),and the increase of the scores in the trial group was significantly superior to that in the control group(P<0.05).The serum levels of TNF-α and IL-6 were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.05).During the trial,both groups of patients did not show obvious adverse reactions,with high safety.(2)The network pharmacological research of Shen Wu Yizhi Capsule yielded 92 active ingredients,803 targets,5 209 disease targets and 556 intersection targets.The core targets were AKT1,TNF,IL-6,TP53 and IL-1B,and the key compounds were deoxyharringtonine,senkyunone and genkwanin.The GO enrichment analysis obtained 1 812 GO entries,of which 154 entries were related with cellular component(CC),1 332 entries were related with biological process(BP),and 326 entries were related with molecular function(MF).The KEGG pathway enrichment analysis yielded 195 signaling pathways.The molecular docking results showed that the key compounds of Shen Wu Yizhi Capsule had good binding activities with the core targets.Conclusion The clinical efficacy of Shen Wu Yizhi Capsule in the treatment of PSCI is remarkable,and its therapeutic mechanism is probably related with multiple components through the signaling pathways such as AKT1,TNF,and IL-6.The results will provide reference for the in-depth study of Shen Wu Yizhi Capsule.