This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Background: Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear. Objective: To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells. Methods: A rosacea-like mouse model was induced by LL37 in both Mas-related G-proteincoupled receptor B2 conditional knockout (MrgprB2 −/− ) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2’-deoxyuridine incorporation assays.The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining. Results: LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 −/− mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization. Conclusion BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.

Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.

Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.

The development mode of public hospitals has shifted from scale expansion to improving quality and efficien-cy,and specialized operation and management is an important means to improve the performance of surgical departments.Howev-er,at present,there is a gap in the performance appraisal of specialized operators,requiring the hospital to formulate a specific and accurate performance appraisal plan for the management department.Taking hospital Z as an example,based on post value(IPE),this paper analyzes the idea of its performance appraisal plan in detail,and analyzes the specific application of its per-formance allocation with specialized operation assistant as an example.Based on IPE,the responsibility,rank and performance distribution coefficient of hospital management positions can effectively solve the difficulties that the total work and quality of hos-pital management departments are difficult to quantify,and also provide some reference for the formulation of performance apprais-al plan of specialized operation staff in public hospitals.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

The main chemical components of Allii Macrostemonis Bulbus and components in serum were analyzed and identified rapidly and precisely by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technique in this study.The compounds were identified based on the relative molecular mass,fragmentation ions,and retention time of chromatographic peaks.A total of 36 kinds of chemical components were identified from Allii Macrostemonis Bulbus,including 28 kinds of saponins,3 kinds of amino acids,2 kinds of flavonoids,one kind of organosulfur compound,one kind of nucleoside,and one kind of hormone-lipid compound.In addition,8 kinds of compounds of Allii Macrostemonis Bulbus were identified from the serum.Based on the intersection compounds of which detected in serum and screened out by TCMSP platform database,by using targeted network pharmacology and molecular docking technology,a"drug-component-target-pathway"association network was constructed.Naringenin,quercetin,macrostemonoside E and 25(R)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostan-3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranoside were screened as the main active constituents of Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.In addition,adenosine 5′-monophosphate-activated protein kinase(AMPK),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA)and matrix metallopeptidase 9(MMP9)were the key action targets for Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.Molecular docking was performed using the main pharmacodynamic components and key action targets.The results indicated that all the four active components showed strongly bound to AMPK.This suggested that the regulation of lipid metabolism might be the key mechanism of Allii Macrostemonis Bulbus in antihyperlipidemic effect.This study provided a data reference for the research on the pharmacodynamic components of Allii Macrostemonis Bulbus,and provided a basis for the improvement of quality standard of Allii Macrostemonis Bulbus.

Objective To observe the clinical efficacy of ZHU's scalp acupuncture combined with Danzhi Xiaoyao San in the treatment of tinnitus of liver constraint transforming into fire type.Methods A total of 70 patients with tinnitus of liver constraint transforming into fire type were randomly divided into treatment group and control group,35 cases in each group.The treatment group was treated with ZHU's scalp acupuncture combined with Danzhi Xiaoyao San,and the control group was treated with Yinxingye Tablets and Mecobalamin Tablets.The course of treatment was three weeks.After three weeks of treatment,the clinical efficacy of the two groups was evaluated,and telephone follow-up was conducted at three and six months after the end of treatment to evaluate the clinical efficacy.The changes of Tinnitus Evaluation Scale(TEQ)Score and Self-Rating Anxiety Scale(SAS)score were observed before and after treatment in the two groups.The changes of Tinnitus Handicap Inventory(THI)scores were compared before and after treatment between the two groups.The safety and adverse reactions of the two groups were evaluated.Results(1)After treatment,the total effective rate of the treatment group was 88.57%(31/35),and that of the control group was 62.86%(22/35),and the therapeutic efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the TEQ,SAS,and THI scores of the two groups were significantly improved(P＜0.01),and the treatment group was significantly superior to the control group in improving TEQ,SAS,and THI scores,and the differences were statistically significant(P＜0.05).(3)At the 3-month follow-up after the end of treatment,the overall effective rate was 85.71%(30/35)in the treatment group and 60.00%(21/35)in the control group.At the 6-month follow-up after the end of treatment,the overall effective rate was 82.86%(29/35)in the treatment group and 54.29%(19/35)in the control group.At the 3-and 6-month follow-up after the end of treatment,the efficacy of the treatment group was superior to that of the control group,and the differences were statistically significant(P＜0.05).(4)No obvious adverse reactions were seen in the two groups of patients,and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion ZHU's scalp needling combined with Danzhi Xiaoyao San for the treatment of tinnitus of liver constraint transforming into fire type can significantly improve the tinnitus symptoms of patients,with high safety,no adverse reactions,and remarkable efficacy.