ObjectiveTo explore the effects and mechanism of the modified Danggui Yinzi on "itch-anxiety" model rats of chronic urticaria （CU）. MethodsThe 36 SPF-grade 6-8-week-old female SD rats were randomly divided into a blank control group，a model group，a positive control group，a low-dose modified Danggui Yinzi group，a medium-dose modified Danggui Yinzi group，and a high-dose modified Danggui Yinzi group. A "itch-anxiety" model was established by intraperitoneal injection of a suspension of sodium chloride and aluminum hydroxide and ovalbumin，combined with chronic unpredictable emotional stress stimulation. After successful modeling，rats in each group were administered drugs by gavage. The positive control group was given intragastric administration of the drug solutions of cetirizine and fluoxetine （2.08 mg·kg^-1·d^-1 fluoxetine， 2 mg·kg^-1·d^-1 cetirizine）， the low-，medium-，and high-dose modified Danggui Yinzi groups were administered traditional Chinese medicine at 1.44，2.88， 5.76 g·kg^-1， respectively，while the blank control group and model group were given an equal volume of normal saline. All interventions lasted for 15 days. Behavioral changes were evaluated by the elevated plus-maze test （detecting the percentage of entries into the open arms （OE%），the percentage of time spent in the open arms （OT%），and the total number of entries into the open and closed arms （TNE）），the open-field test （detecting total activity，average movement speed，and latency to enter the central area），and scratching behavior observation. Pathological changes of skin tissues were observed by hematoxylin-eosin （HE） staining and toluidine blue staining，while those of amygdala tissues were observed by HE staining，Nissl staining，and immunofluorescence detection of ionized calcium-binding adapter molecule-1 （Iba-1）. The content of immunoglobulin E （IgE），interleukin-33 （IL-33），histamine in serum and glutamate in the amygdala was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of striatal-enriched protein tyrosine phosphatase （STEP），N-methyl-D-aspartate receptor subunit 2B （NR2B）， calmodulin-dependent protein kinase Ⅱ （CaMKⅡ），phosphorylated CaMKⅡ （p-CaMKⅡ），mitogen-activated protein kinase （MAPK），phosphorylated MAPK （p-MAPK），nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB），phosphorylated NF-κB （p-NF-κB），and postsynaptic density protein-95 （PSD-95） in the amygdala. ResultsCompared with the blank control group，the model group rats showed obvious anxiety-like behaviors （decreased OE%，OT%，and TNE，reduced total activity，slower average movement speed，and prolonged latency to enter the central area），increased scratching times，obvious skin inflammation and mast cell degranulation，severe amygdala tissue damage，increased glutamate content in the amygdala，and elevated levels of IgE and IL-33 in serum. The expression of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala increased，while the expression of PSD-95 protein decreased （P<0.05）. Compared with the model group，the modified Danggui Yinzi group of each dose had increased OE%，OT%，TNE，total activity，and average movement speed，shortened latency to enter the central area， reduced scratching times，alleviated skin inflammation and mast cell degranulation，relieved amygdala tissue damage，decreased glutamate content in the amygdala，and reduced levels of IgE and IL-33 in serum. Moreover，compared with the model group，the low -，medium-，and high-dose modified Danggui Yinzi groups showed decreased expression levels of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala，and increased expression of PSD-95 protein. There was a significant dose-effect relationship，with the high-dose group showing the most significant regulatory effect （P<0.05）. ConclusionThe modified Danggui Yinzi has a therapeutic effect on "itch-anxiety" model rats of CU. Its mechanism may be related to regulating glutamate metabolism in the amygdala，modulating the STEP/NR2B/CaMKⅡ/MAPK/NF-κB pathway，and regulating the expression of PSD-95.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

Objective To investigate the status and predictive factors of future acute exacerbation of asthma in adults. Methods Adult patients with asthma who were admitted to the hospital from March 2023 to July 2025 were selected. Based on the acute exacerbation status after follow-up, the patients were categorized into acute exacerbation group (n=107) and control group (n=245). The clinical data, pulmonary function [peak expiratory flow (PEF) and forced expiratory volume in the 1st second/forced vital capacity (FEV₁/FVC)] and health status [asthma control questionnaire (ACQ), Morisky medication adherence scale (MMAS-8), short form 36-item health survey (SF-36)] of the study subjects were collected. The correlation between the indicators and acute exacerbation was explored by logistic regression analysis, and the predictive efficiency was evaluated by ROC curve. Results The age, smoking history, asthma course, allergen exposure and ACQ in the acute exacerbation group were higher than those in the control group, while the average monthly family income, glucocorticoid treatment, PEF, FEV₁/FVC, MMAS-8 and SF-36 were lower (P<0.05). Multivariate logistic regression suggested that ACQ score, glucocorticoid treatment, MMAS-8 score, FEV₁/FVC, PEF and smoking history were the influencing factors of acute asthma exacerbation (P<0.05). ROC analysis revealed that the diagnostic efficiency of combined prediction was the highest (AUC=0.965), with sensitivity of 0.944 and specificity of 0.857 (P<0.05). Conclusion It is necessary to pay more attention to the medication compliance and asthma control level of patients, and integrate multi-dimensional information such as smoking history, pulmonary function and treatment conditions to accurately identify patients with high-risk acute exacerbation and implement targeted intervention measures.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Objective To develop a method for rapidly identifying Clostridioides difficile(C.difficile)and de-termining high-producing toxin strains,conduct clinical evaluation.Methods The loop-mediated isothermal amplifi-cation(LAMP)method was used to identify C.difficile based on the tcdC,tcdA,and tcdB genes.The sensitivi-ty,specificity,and overall consistency of the detection method were evaluated.Results Feces specimens from 499 hospitalized patients suspected of C.difficile-associated diarrhea were detected,with C.difficile detection rate of 12.8％(64/499),out of which the detection rate of toxin-producing C.difficile was 10.8％(54/499).The sensi-tivity,specificity,positive predictive value,and negative predictive value of the detection method for tcdA were 87.2％,98.9％,89.1％,and 98.6％,respectively,and 88.2％,99.6％,90.0％,and 98.73％for tcdB,respec-tively.The total toxin levels of different strains were different,but the average toxin production level of A+B+strains(1.79 μg/mL)was higher than those of A-B+strains(0.72 μg/mL)and A-B-strains(＜0.10 μg/mL).Conclusion The portable high-throughput LAMP detection method can rapidly and efficiently identify C.difficile and determine high-producing toxin strains.

This study was analyzed the spatial-temporal distribution and aggregation characteristics of Yersinia pestispositive host animals and vector pathogens in marmot natural foci in the Qilian-Altun mountains,Gansu Province,to provide a scientific basis for precise plague prevention and control.Y.pestissurveillance data for marmot natural foci in Qilian-Altun Mountains of Gansu Province from 2014 to 2023 were obtained from the Disease Control and Prevention Center of Gansu Province.Origin 2024 software was used for data visualization and presentation.Global and local spatial autocorrelation analyses and trend analyses were conducted in ArcGIS 10.8 software,with townships as the spatial scale.Cumulatively,440 strains of Y.pestis were isolated from the natural marmot foci in the Qilian-Altun mountainsof Gansu Province from 2014 to 2023.Most strains was isolated from marmots(345 strains,78.41%),and the remainder were isolated from vectors.Temporal distribution analysis indicated that the highest number of detected bacteria was reported in July and August(both 121 strains,27.50%).Regional distribution analysis revealed that Aksai County reported the highest number of detected bacteria(255 strains,57.95%).Global spatial autocorrelation analysis showed a spatially clustered distribution of the number of bacteria detected annually in the townships containing natural foci,except in2014,2016,and 2021-2023.The strongest spatial clustering was observed in 2020(Moran's I=0.521 2,Z=14.397 0,P<0.001).Local spatial autocorrelation analysis indicated a"high-high"aggregation area in the natural foci every year from 2014 to 2023,primarily in Hongliuwan Town of Aksai County and Dangchengwan Town of Subei County.The distribution of the"low-low"aggregation area was essentially consistent with the low activity area of the Yersinia pestisepidemic.The trend in annual total bacterial count gradually increased from east to west,and peaked in the western part of the epidemic focus.Clear spatial aggregation characteristics of the number of Y.pestis were detected in the marmot natural foci in the Qilian-Altun mountains at the townshiplevel as a whole in Gansu Province from 2014 to 2023.The aggregation area was mainly in the western section of Qilian Mountain to the Altun mountain section of the epidemic source area.Monitoring and prevention and control efforts should be focused in this key area,with prevention and control measures tailored to the local conditions,and classified guidance to decrease the risk of plague occurrence and spread.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective:To investigate the application value of exercise rehabilitation mode based on cardiopulmonary exercise testing(CPET)in the treatment and rehabilitation of coronary heart disease(CHD).Methods:This ran-domized controlled study enrolled 260 CHD patients admitted in Hai'an People's Hospital between January 2021 and June 2022.They were divided into control group(n=130,routine nursing)and intervention group(n=130,addi-tional exercise rehabilitation training nursing).After 6-month intervention,scores of Heart Health-Self-Effica-cy and Self-Management(HH-SESM)scale,Chinese Quality of Life Questionnaire for Cardiovascular Patients(CQQC),peak oxygen uptake(VO2peak),percentage of peak oxygen uptake in predicted maximum(VO2peak％Pred),peak metabolic equivalent(peak Mets),cardiac function indexes,and incidence of adverse events were com-pared between two groups.Results:After intervention,compared with patients in control group,those in interven-tion group had significant higher scores of HH-SESM[(76.57±5.88)points vs.(64.51±5.16)points]and CQQC[(111.66±7.93)points vs.(84.16±6.96)points],VO2peak[(1.41±0.11)L/min vs.(1.19±0.26)L/min],VO2peak％Pred[(59.32±3.51)％vs.(51.27±3.11)％],peak Mets[(7.89±1.86)vs.(5.22±1.16)],6MWD[(473.53±18.12)m vs.(354.27±23.11)m],and significant lower serum N-terminal pro brain natri-uretic peptide(NT-proBNP)[(5.13±2.17)pg/ml vs.(13.81±2.22)pg/ml],cardiac troponin Ⅰ(cTnⅠ)[(2.90±0.51)ng/ml vs.(4.76±1.32)ng/ml](P＜0.001 all).Intervention group had significant lower incidence of adverse events comparing to control group(3.85％vs.13.85％,P=0.005).Conclusion:Exercise rehabilitation treatment based on cardiopulmonary exercise test could effectively improve self-efficacy and self-management,quality of life,cardiopulmonary function and reduce risk of adverse events in patients with coronary heart disease.