ObjectiveTo investigate whether Bushen Huoxue prescription improves embryo implantation through regulating exosomal miRNA to enhance maternal-fetal interface communication based on Bushen Huoxue therapy. MethodsIn the animal experiment， all the rats （except for the blank group） were administered hydroxyurea （450 mg·kg^-1） via gavage for 10 d， as well as epinephrine （0.3 mg·kg^-1） and mifepristone （5.5 mg·kg^-1） via subcutaneous injection for 7 d to establish an implantation disorder model of kidney deficiency and blood stasis type. The Bushen Huoxue prescription （BSHX） groups were administered the prescription at different doses （7.30 g·kg^-1 for the high-dose group， 3.65 g·kg^-1 for the medium-dose group， and 1.83 g·kg^-1 for the low-dose group） via gavage. The dydrogesterone group was administered the corresponding medicine （2.63 mg·kg^-1） via gavage. After intervention for 10 days， uterine histopathological changes were observed via hematoxylin-eosin （HE） staining. Mucin （MUC1）， forkhead box protein O1 （FoxO1）， and homeobox A10 （HoxA10） expression levels were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Cell experiment selected primary endometrial epithelial cells （EEC） and trophoblast cells （TC） as research subjects. Exosome-free medicated serum was prepared by ultracentrifugation and cultured in complete medium. Exosomes were isolated from cell supernatants by ultracentrifugation for cross-co-culture. After 48 h， migration and invasion abilities were assessed by scratch and Transwell assays. Sequencing was then performed on EEC-origin exosomal miRNA. ResultsThe model rats exhibited thin endometrium， along with reduced blood vessels， glandules， and pinopode numbers. BSHX improved endometrial morphology and increased pinopode numbers. MUC1， FoxO1， and HoxA10 expressions were downregulated in the model rats， while these parameters were upregulated after BSHX medium- and high-dose intervention. In the cell experiment， after exosome-free medicated serum intervention for 24 h， migration and invasion abilities were enhanced in the BSHX groups （P<0.01）. In EEC-origin exosomal miRNA sequencing， gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses revealed enrichment in biological processes （gastrulation， neuronal differentiation， alongside cell development and regeneration）， involving the mitogen-activated protein kinase （MAPK）， FoxO1， Wnt， mammalian target of rapamycin （mTOR）， and tumor necrosis factor （TNF） signaling pathways. ConclusionBSHX promotes embryo implantation by improving endometrial receptivity via regulating exosomal miRNA. These findings provide potential targets for exosomal miRNA-based assisted reproductive strategies and a novel theoretical basis for infertility treatment by traditional Chinese medicine.

Cardiovascular disease remains a significant factor leading to patient mortality and influencing outcomes during the perioperative period.Dexmedetomidine is an α2-adrenergic receptor agonist with functions such as analgesia,sedation,and anti-anxiety.This review summarizes various types of findings regarding dexmedetomidine in myocardial ischemia/reperfusion injury and conducts in-depth discussions on the corresponding mechanisms of the results,aiming to further clarify the potential cardioprotective effects of dexmedetomidine in patients with heart diseases.

With the increasing difficulty of traditional chemical drug research and development,peptide drugs have gradually become a hot spot in drug research and development due to their advantages of high specificity,significant efficacy,easy metabolism and low toxicity.This review systematically expounds the physicochemical properties,main advantages and limitations of peptide drugs,and summarizes the currently common strategies for structural modification and delivery.It focuses on the application and target of approved peptide drugs in various diseases such as diabetes,cancer,bacterial and viral infections,multiple sclerosis,and osteoporosis.Furthermore,the research analyzes the challenges in the research and development of peptide drugs,including poor in vivo stability,low bioavailability,and limited routes of administration.It also discusses the prospects of new technologies based on molecular modification,nanodelivery systems,and computer-aided design.In summary,peptide drugs have shown unique advantages in multi-field therapy,but they still need to break through bottlenecks in preparation,delivery and drug resistance to provide new ideas and directions for future precision therapy.

Rho proteins and the Rho-associated protein kinase(ROCK)signaling pathway are cruci-al components of intracellular signaling cascades.Rho proteins,which belong to the small GTPase family,play a pivotal role in regulating essential elements of the cytoskeleton within cells.ROCK functions as a downstream effector protein kinase of Rho,modulating various biological processes,including cell morphology,migration,and proliferation.Recent studies have underscored the signifi-cance of the ROCK signaling pathway in the replication of a diverse group of viruses.Furthermore,it has been discovered that some viruses disrupt cellular contraction,adhesion,and migration through the Rho/ROCK pathway,subsequently influencing the immune response triggered by vi-ral infections and affecting the tight junctions between cells.This article primarily reviews the re-search progress regarding the Rho/ROCK signaling pathway and its key signaling molecules,Rho and ROCK,in terms of their activation and regulation of viral replication and tight junction pro-teins between cells.

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective:To systematically summarize, describe, and evaluate the evidence related to convex baseplates use in adult ostomy patients through an evidence map, in order to identify research gaps and future directions.Methods:A systematic search was conducted in Chinese and English databases, including China National Knowledge Infrastructure, Wanfang Data, VIP, and PubMed, and others, from database inception to September 2024. Randomized controlled trials and quasi-experimental studies on convex baseplates use in adult ostomy patients were included. Literature quality was assessed using the Cochrane Handbook 5.1.0 bias risk assessment tool and the critical appraisal tool for quasi-experimental studies from the Joanna Briggs Institute Centre for Evidence-Based Healthcare. Based on the PICO principle [participant (P) , intervention (I) , comparison (C) , outcome (O) ] , an evidence mapping coding system was extracted and developed by integrating relevant guidelines and consensus. Data extraction and coding were performed using EPPI-Reviewer software, and key evidence characteristics and literature quality were presented using bubble charts.Results:A total of eight randomized controlled trials and six quasi-experimental studies were included. Most of the 14 studies had a high risk of bias. The target populations for interventions were divided into two categories: prevention and treatment. The main complications involved stoma skin-mucosal separation, stoma peristomal dermatitis, and stoma height issues. The main outcome measures included baseplate seal integrity, wound healing, complication rates, clinical symptoms, adverse events, patient acceptance, and quality of life.Conclusions:Most of the studies on convex baseplates has focused on enterostomy patients. The majority of studies have a high risk of bias, and the number of studies is limited. Further clarification is needed on the selection criteria for convex baseplates with different characteristics, and the clinical application effects of convex baseplates urgently need further evaluation.

Objective:To explore the difficulties and needs of wound ostomy incontinence specialist nurses when applying convex baseplates, with the aim of providing a basis for standardizing ostomy care.Methods:Purposeful sampling was used to select 13 wound ostomy incontinence specialist nurses from tertiary hospitals in Hebei, Jilin, Hunan, Beijing, and Tianjin for semi-structured interviews between November and December 2024. Content analysis was used to analyze the data.Results:Two main themes were identified: application dilemmas and application needs. Application dilemmas included four subthemes: insufficient understanding of convex baseplate characteristics, unclear indications and contraindicated populations, lack of unified standards for assessment timing, and inadequate awareness of health education. Application needs included two subthemes: urgent need for related evidence-based evidence and a desire for clinical guidelines and expert consensus.Conclusions:Currently, wound ostomy incontinence specialist nurses in China face challenges in understanding the characteristics of convex baseplates, scope of application, identifying contraindications, determining the optimal timing for application assessment, and providing patient education. Administrators should develop clinical application standards for convex baseplates based on these challenges. Furthermore, researchers should develop relevant clinical guidelines or expert consensus for convex baseplate application in China, providing a basis for the standardized use of ostomy care products.

Objective To explore the scheme for the deployment and withdrawal of the surgical module of the new-type tent hospital system.Methods A set of standardized scheme for deploying and withdrawing the surgical module of the new-type tent hosital system was proposed and implemented in terms of labor division,operation precedure,operation technique and precaution.The operating time,number of operational errors and number of equipment damages were recorded for each of the five deployment and withdrawal operations before and after the program was executed,and the team members'immediate heart rate,percentage of maximum heart rate(MHR)and rating of perceived exercise(RPE)at the end of the operation were recorded after the program was implemented.SPSS 26.0 software was used for statistical analysis.Results The standardized scheme had the deployment time shortened from(85.15±11.430)min to(58.23±8.513)min,withdrawal time decreased from(65.36±9.369)min to(48.92±7.129)min,with the differences being statistically significant(P＜0.05);the numbers of operatio-nal errors and equipment damages were both reduced when compared with those before the implementation of the schemce;the immediate heart rate of the team members at the end of the operation ranged from 43 to 157 beats/min,with an average value of 151.1 beats/min,the individual MHR percentages were from 75％to 87％,with an average value of 81.1％,and the RPE scores were from 14 to 17,with an average value of 15.3,which all could be categorized as moderate-operation intensity.Condusion The standardized deployment and withdrawal scheme for the surgical module meets the needs of actual combat and training assessment,and thus is worthy promoting in medical institutions equipped with the surgical module of the new-type tent hosital system.[Chinese Medical Equipment Journal,2025,46(2):74-79]