Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

ObjectiveTo analyze the current research status, hotspots and future trends of the application of digital health technology (DHT) in the rehabilitation of upper limb motor function after stroke. MethodsRelevant literature on the application of DHT in upper limb motor rehabilitation for stroke patients published between January, 2015 and December, 2025 was retrieved from Web of Science Core Collection, CNKI and Wanfang database. CiteSpace 6.4.R1 was used for visualized bibliometric analysis. ResultsA total of 1 295 publications were included, comprising 454 in Chinese and 841 in English. The annual number of publications generally showed an upward trend. China ranked first in publication output in English literature. The institutions with the highest numbers of publications were Huashan Hospital Affiliated to Fudan University and Swiss Federal Institute of Technology in Zurich. Both Chinese and English keywords formed ten clustering groups. Chinese clusters mainly involved occupational therapy, neural mechanisms and home-based rehabilitation, whereas English clusters focused on virtual reality, brain-computer interfaces and machine learning. High-frequency keywords included virtual reality, brain-computer interface, machine learning and deep learning. Chinese keywords with a strong burst included rehabilitation training, while deep learning showed a strong burst in English keywords. Stroke was the most frequently cited journal. Highly cited journals covered multiple disciplines, including rehabilitation medicine, neuroscience and computer science, reflecting the interdisciplinary characteristics of this field. ConclusionResearches on DHT for upper limb motor function rehabilitation in stroke are increasing annually, focusing on core interaction technologies, neural mechanism and artificial intelligence. Future research trends may include inter-disciplinary integration of artificial intelligence with core rehabilitation technologies, neuroimaging-guided targeted interventions, optimisation of home-based rehabilitation systems, and development of multidimensional quantitative assessment models.

The disease-syndrome combination animal model in traditional Chinese medicine （TCM） andrology serves as an important bridge linking TCM theory with modern medical research， providing a key experimental platform for elucidating the 'syndrome-disease' correlation mechanism in male-specific diseases and for screening effective prescriptions. This article reviews recent progress in animal model research on common TCM andrological diseases， including prostatic diseases， sexual dysfunction， and male infertility， with a focus on analyzing the application， advantages， and disadvantages of various modeling strategies， such as immune induction， hormonal intervention， and multi-factor combination across different syndrome types. However， despite breakthroughs in model construction techniques， current research still faces several challenges， including insufficient standardization of syndrome differentiation and difficulties in quantifying TCM-specific indicators. Future studies need to optimize model evaluation systems by integrating modern technologies， in order to promote the standardization and internationalization of TCM andrology research.

BACKGROUND:Iron overload refers to excessive accumulation of iron in the body,which can cause pathological changes in various tissues.At present,the molecular mechanism and potential gene targets related to iron overload in osteoarthritis still need to be further studied and explored. OBJECTIVE:To analyze the key genes of iron overload in osteoarthritis by means of bioinformatics and verify them in animal experiments,so as to provide a new idea for preventing and treating osteoarthritis from the perspective of iron overload. METHODS:GEO database and GeneCards database were used to screen out genes associated with osteoarthritis and genes associated with iron overload.Then,the intersection of the two was taken to obtain a collection of genes commonly associated with osteoarthritis and iron overload.GO and KEGG enrichment analyses were used to screen the functions and pathways of these genes.To further investigate the interactions between these genes,a protein-protein interaction network was constructed and five computational methods of Cytoscape software were utilized to identify the Hub genes for iron overload in osteoarthritis.Finally,12 male Sprague-Dawley rats were divided into osteoarthritis group and normal group,with 6 rats in each group.A knee osteoarthritis model was established by the modified Hulth method in the osteoarthritis group.The expression of Hub genes in the knee joint of rats in each group was detected by PCR. RESULTS AND CONCLUSION:(1)A total of 51 genes associated with iron overload were identified in osteoarthritis.GO enrichment analysis showed that these genes were mainly involved in cytokine receptor binding,chemokine receptor binding,cytokine activity,growth factor receptor binding and oligosaccharide binding.(2)KEGG enrichment analysis showed that genes associated with iron overload in osteoarthritis was mainly involved in tumor necrosis factor signaling pathway and lipid and atherosclerosis signaling pathway.(3)The protein-protein interaction network was constructed,and five Hub genes of iron overload,intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6,were obtained by further analysis.Animal experiments verified that there were significant differences in the expression of the above Hub genes in the rat knee joint between the control group and the experimental group(P<0.05).(4)All these findings show that intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6 can be used as the Hub genes of iron overload in osteoarthritis,which are expected to become new targets for the prevention and treatment of osteoarthritis.

Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.

Objective To compare the screening efficacy of the Water Swallow Test and the Standard-ized Swallowing Assessment for identifying swallowing disorder risk in elderly inpatients,providing reference for selecting appropriate clinical screening tools.Methods Using convenience sampling,240 elderly inpatients admitted from March to November 2023 were enrolled.Swallowing function was evaluated using the Water Swallow Test,Standardized Swallowing Assessment,and the Eating Assessment Tool.With the Eating As-sessment Tool as the diagnostic standard,Bayes discriminant analysis and receiver operating characteristic(ROC)curves were employed to compare the screening capabilities of the Water Swallow Test and Standard-ized Swallowing Assessment for swallowing disorder risk in elderly hospitalized patients.Results A total of 240 questionnaires were distributed,and 226 valid questionnaires were recovered,with an effective recovery rate of 94.17%.The incidence of swallowing disorders in elderly patients was screened using Water Swallow Test,Standardized Swallowing Assessment,and The Eating Assessment Tool,with rates of 6.2%,31.0%,and 14.2%,respectively;The Kappa values for consistency between Water Swallow Test and The Eating As-sessment Tool,and between Standardized Swallowing Assessment and The Eating Assessment Tool were 0.381 and 0.392,respectively(both P<0.01);The areas under the ROC curves for Water Swallow Test and Standardized Swallowing Assessment were 0.839(95%CI:0.784 to 0.884)and 0.821(95%CI:0.765 to 0.869),respectively,with no statistically significant difference(Z=0.326,P=0.744);The cross validation accuracy of risk prediction for swallowing disorders was 88.5%and 77.9%,respectively;The cutoff values were 1.5 grades and 18.5 points,respectively;The sensitivity was 0.875 and 0.813,the specificity was 0.737 and 0.773,and the Youden index was 0.612 and 0.586,respectively.Conclusion Water Swallow Test and Standardized Swallowing Assessment have average ability to screen for the risk of swallowing disorders in eld-erly patients;Water Swallow Test has higher predictive efficiency for the risk of swallowing disorders,making it more suitable for screening the risk of swallowing disorders in elderly patients.

Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of 2785 person-years, resulting in an incidence density of 8007.18 per 100000 person-years, an average age of onset of (35.90±8.22) years, and an average working age of onset of (2.69±1.97) years. The incidence density in the exposure group was 128.71% higher than that in the control group, and the risk of hypertension in the exposure group was 2.115 times that of the control group. The risk of hypertension was 2.199 times higher for men than for women, 1.344 times higher for those aged 30 and above than for those under 30, 1.546 times higher for smokers than for non-smokers, and 1.750 times higher for drinking workers than for non-drinking ones. The results of Cox proportional hazards regression modeling indicated that the hazard ratio (95%CI) of hypertension among the employees exposed to dust, noise, and carbon monoxide was 2.254 (1.703, 2.982), 1.594 (1.107, 2.295), and 1.567 (1.079, 2.274), respectively, when different covariates (gender, age, smoking, and alcohol consumption) were included. The results of Log-rank test showed that there were statistically significant differences in the distribution of disease-free survival between the exposure group and the control group (P<0.05). Conclusion Occupational exposures to dust, noise, and carbon monoxide may increase the risk of hypertension among calcium carbide plant workers.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure