Allergic diseases exhibited the characteristics of latent concealment and dynamic transmutation， which highly align with the pathogenic features of "latency and transformative change" described in the theory of latent pathogens. Based on the "latent pathogens with transformative potential" theory， this paper systematically explored the mechanisms of occurrence， transmission， and outcome of allergic diseases. It proposed that the insufficiency of kidney essence is the root cause enabling pathogens to lurk internally， leading to disease onset due to deficient healthy qi and lurking pathogens； the dysfunction of sanjiao serves as the pathway for pathogen stagnation， driving multi-system transmission； the accumulation of phlegm， stasis， and toxins constitutes the predicament of a protracted course， ultimately resulting in intractable pathological entanglement. Accordingly， a tiered intervention strategy is formulated，i.e. during the latency period， treatment should tonify the kidney and replenish essence to consolidate the foundation and halt the tendency of pathogens to lurk internally； during the transmission period， treatment should regulate sanjiao to intercept disease transmission and curb multi-system proliferation； during the protracted period， treatment should purge phlegm and resolve stasis to eliminate stubborn lesions， and break the vicious cycle of chronic accumulation and damage.

ObjectiveTo observe the effect and therapeutic effect of Kaixuan Jiedu core prescription （KXJD） on skin homing of Th17 cells in the mouse model of imiquimod （IMQ） combined with restraint stress-induced psoriasis-like skin damage， and to explore its potential mechanism from the perspective of neuro-immune axis. MethodsThirty male C57BL/6J mice were randomly allocated into five groups （n=6）： Control， model （IMQ）， restraint stress model （IMQ+RS）， KXJD， and methotrexate （MTX）. The mouse model of psoriasis-like skin damage was established by 5% IMQ combined with restraint stress. At the same time of modeling， each treatment group was treated with corresponding doses of drugs， and the control， IMQ， and IMQ+RS groups were treated with the same amount of normal saline by gavage once a day for 5 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the skin tissue and Baker scoring was performed. Serum levels of interleukin-1β （IL-1β） and angiopoietin-2 （Ang-2） were measured by enzyme-linked immunosorbent assay （ELISA）. The levels of matrix metalloproteinase-9 （MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， C-C motif chemokine ligand 20 （CCL20）， and C-C motif chemokine receptor 6 （CCR6） in the skin tissue were determined. Immunohistochemistry （IHC） was employed to determine the protein expression of cutaneous lymphocyte-associated antigen （CLA）， integrin α_E （CD103）， cytokeratin 10 （CK10）， and nuclear factor-kappa B （NF-κB） in the skin. Immunofluorescence double staining （DIF） was adopted to detect the expression and co-localization of vascular endothelial cadherin （VE-cadherin） and platelet-endothelial cell adhesion molecule （CD31）， CCR6， CD103， substance P （SP）， calcitonin gene-related peptide （CGRP）， and protein gene product 9.5 （PGP9.5） in the skin tissue. Real-time PCR was employed to quantify the mRNA levels of IL-10， IL-17A， and IL-23. ResultsCompared with the control group， the IMQ group and IMQ+RS group showed significant inflammatory cell infiltration， abnormal proliferation of epidermal cells， keratinization and other pathological changes in the skin tissue， and a significant increase in Baker score， elevated levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in the skin lesions， upregulated expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA， and IL-23 mRNA in the skin lesions， and downregulated expression of TIMP-1 and IL-10 mRNA. In addition， the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， SP and PGP9.5 co-localization， and CGRP and PGP9.5 co-localization were increased （P<0.05）. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ+RS group， KXJD and MTX significantly alleviated the pathological damage of skin lesions， significantly decreased the Baker score， lowered the levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in skin lesions， downregulated the expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA and IL-23 mRNA in skin lesions， and upregulated the expression of TIMP-1 and IL-10 mRNA. Furthermore， KXJD and MTX reduced the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， CGRP and PGP9.5 co-localization， and SP and PGP9.5 co-localization （P<0.05）. ConclusionKXJD can significantly ameliorate the psoriasis-like skin damage induced by IMQ combined with restraint stress in mice by regulating the neural-immune axis and inhibiting the skin homing of Th17 cells.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Objectives:To evaluate the incidence of neurological complications following left ventricular assist device(LVAD)implantation and to investigate related risk factors.Methods:A retrospective analysis was conducted on 151 patients who underwent LVAD implantation at Fuwai Hospital between June 2017 and September 2024.Clinical characteristics and postoperative survival outcomes were compared between patients with and without neurological complications.Results:Neurological complications occurred in 21 patients(13.9%)postoperatively,15 cases were ischemic strokes,5 cases were symptomatic intracranial hemorrhages or subarachnoid hemorrhages,and 1 case was transient ischemic attack(TIA).The total incidence of neurological complications was 0.08 events per person-year(EPPY),ischemic stroke was 0.06 EPPY and hemorrhagic stroke was 0.02 EPPY.Compared with patients without neurological complications,patients with neurological complications had a higher proportion of preoperative aortic regurgitation and tricuspid regurgitation,lower triglyceride levels,a lower rate of concurrent left atrial appendage resection and a higher rate of concurrent aortic valve replacement surgery.Multivariate cox regression analysis revealed that higher preoperative triglyceride levels(HR=0.21,95%CI:0.08-0.56,P=0.002)were associated with neurological complications.The median follow-up time was 508.0(186.5,931.5)days,12 out of 15 cases of ischemic stroke experienced no long-term sequelae,while 3 patients had varying degrees of residual deficits.All 5 patients with hemorrhagic stroke died,with 2 deaths directly attributed to hemorrhage.Kaplan-Meier survival curve analysis indicated that patients with neurological complications had a significantly lower survival rate(log-rank P=0.005).Conclusions:Neurological complications after LVAD implantation are predominantly ischemic strokes.Although less frequent,hemorrhagic strokes are associated with worse outcomes.Higher preoperative triglyceride levels is associated with neurological complications.

Objective:This study aimed to investigate the value of myocardial contrast echocardiography(MCE)in the prognostic assessment of patients undergoing revascularization for acute anterior ST-segment elevation myocar-dial infarction(STEMI).Methods:A total of 234 patients with acute anterior STEMI who underwent percutaneous coronary intervention(PCI)and completed MCE admitted in Dongguan People's Hospital between July 1st 2019 and October 1st 2021 were included.According to presence of major adverse cardiovascular events(MACE)during 6 months,patients were divided into no MACE group(n=188)and MACE group(n=46).General data and MCE indexes were compared between the two groups.Multivariate Logistic regression analysis was employed to analyze influencing factors for MACE in patients with acute anterior STEMI after PCI.Receiver operating characteristic(ROC)curve was applied to analyze predictive value of MCE indexes for MACE in patients with acute anterior STE-MI after PCI.Results:Compared with patients in no MACE group,those in MACE group had significant higher proportion of previous myocardial infarction,D-dimer,C reactive protein,B-type natriuretic peptide,creatine kinase isoenzyme MB(CK-MB),incidence of T-wave inversion and ST-segment resolution amplitude(P＜0.05 or＜0.01).MCE showed that compared with those in no MACE group,those in MACE group had significant lower left ventricular ejection fraction(LVEF)[(52.54±7.66)％ vs.(55.98±10.04)％],and significant higher wall motion score index(WMSI)[(1.22±0.13)vs.(1.17±0.15)]and contrast score index(CSI)[(1.54±0.32)％vs.(1.16±0.21)％](P＜0.05 or＜0.01).Multivariate Logistic regression analysis revealed that previous myocar-dial infarction,C-reactive protein,CSI and T-wave inversion were independent risk factors for MACE in patients with acute anterior STEMI after PCI(OR=13.790～6601.747,P＜0.05 or＜0.01).ROC curve indicated that CSI had good predictive value for MACE in patients with acute anterior STEMI after PCI,the area under curve(AUC)was 0.874(95％CI 0.825～0.914)and optimal cutoff point was 1.33％.Conclusion:Myocardial contrast echocardiography plays an important role in prognostic assessment of patients undergoing revascularization for acute anterior STEMI.

Objective:To investigate the immunological mechanism by which grifola frondosa extract improves colonic tissue inflammation in rats with ulcerative colitis(UC)through the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)signaling pathway.Methods:Forty male SD rats were randomly divided into five groups:blank group,model group,sulfasalazine treatment group(SASP group),grifola frondosa extract treatment group(GF group),and sulfasalazine combined with grifola frondosa extract treatment group(SASP+GF group).UC model was established using a 3%dextran sulfate sodium(DSS)free drinking method.After one week,each treatment group received sulfasalazine 0.3 g/(kg·d),grifola frondosa extract 10 mg/(kg·d),and combination of both drugs by gavage.During the experiment,the general condition of the rats was observed,the disease activity index(DAI)score was re-corded and the protein content and positive expression levels of SPHK1,S1P,tumor necrosis factor receptor-associated factor 2(TRAF2)and TNF-α in rat colon tissue were detected by immunohistochemistry.mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in rat colon tissue were measured by RT-qPCR and Western blot.Results:Compared with the blank group,the general condition of the model group rats were poor,the DAI score was significantly increased,and the protein positive expres-sion,mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in colon tissue were significantly increased(P<0.01).Compared with the model group,the general condition of the rats in each treatment group improved significantly,the DAI score was decreased(P<0.01),and the positive expression of each target protein was significantly reduced(P<0.01),especially in the GF group and SASP+GF group;the mRNA and protein expression levels of SPHK1 and TRAF2 were reduced to varying degrees(P<0.01 or P<0.05),while the mRNA and protein expression levels of S1P and TNF-α only decreased significantly in the GF group and SASP+GF group(P<0.01).Compared with the SASP group,the GF group only showed a decrease in SPHK1 protein expression,TNF-α mRNA,and protein expression levels,while the SASP+GF group showed significant reductions in all targets(P<0.01 or P<0.05).Compared with the GF group,the SASP+GF group showed significant reductions in SPHK1 protein positive expression and content,S1P mRNA expression levels,and TNF-α protein content(P<0.05 or P<0.01).Conclusion:Grifola frondosa extract may alleviate co-lonic tissue inflammation in rats with UC by inhibiting the activation of the SPHK1/S1P pathway,restoring intestinal mucosal barrier function,and improving symptoms of UC.

Objective:To observe the effect of modified autologous skull defect repair in patients with traumatic brain injury and its influence on neurological function and living ability.Methods:104 patients with traumatic brain injury who were admitted to our hospital from March 2022 to August 2024 were included,they were divided into Group A[37 cases,poly ether ether ketone(PEEK)skull defect repair],Group B(35 cases,traditional titanium mesh skull defect repair),and Group C(32 cases,modified autologous skull defect repair).Perioperative indicators,neurological function,activity of daily living,quality of life,satisfaction,and incidence of postoperative complications were compared among three groups.Results:There were no differences in the operation time,operation blood loss and postoperative hospital stay among the three groups(P＞0.05).The hospitalization costs of Group A,Group B and Group C decreased successively(P＜0.05).Activity of Daily Living(ADL)scores at 3 and 6 months after surgery increased among three groups,while National Institutes of Health Stroke Scale(NIHSS)scores decreased(P＜0.05).There was no significant difference in physiological function,social function,psychological function,and material life among the three groups at 6 months after surgery(P＞0.05).The overall satisfaction rate in Group C was higher than that of Group A and Group B(P＜0.05).The overall incidence of complications in Group C was lower than that in Group A and Group B(P＜0.05).Conclusion:PEEK,traditional titanium mesh,and modified autologous skull are used in skull defect repair,operation time,operation blood loss and postoperative hospital stay are comparable,they can also reduce neurological function damage,improve living ability,and enhance the quality of life of patients,however,PEEK is relatively expensive,the satisfaction of traditional titanium mesh is low,andincidence of postoperative complications are relatively high.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Aim To explore the potential mechanisms underlying therapeutic effects of cordycepin in asthma by utilizing network pharmacology,molecular docking,and in vitro cellular validation.Methods The thera-peutic targets associated with asthma and the drug tar-gets of cordycepin were systematically identified through comprehensive database searches.An overlap analysis of the two gene sets was performed,followed by the construction of a protein-protein interaction(PPI)network and topological analysis to identify the core targets.The core targets were subjected to Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway a-nalysis and Gene Ontology(GO)enrichment analysis,and a drug-target-pathway network was constructed.To validate the interaction between cordycepin and core targets,molecular docking and molecular dynamics sim-ulations were conducted.Subsequently,the pharmaco-logical effects and underlying mechanisms of cordyce-pin were validated in vitro using Beas-2B cells,emplo-ying Cell Counting Kit-8(CCK-8)assay and quantita-tive real-time reverse transcription PCR(RT-qPCR).Results A total of 438 potential targets of cordycepin were identified,113 of which overlapped with asthma-related therapeutic targets.Topological analysis based on the PPI network revealed 22 core targets.Using KEGG enrichment analysis,165 significantly enriched pathways were identified,including the TNF and HIF-1 signaling pathways.Molecular docking analysis re-vealed high binding affinities between cordycepin and select core targets,which further corroborated by mo-lecular dynamics simulations.In vitro experiments showed that after cordycepin pretreatment,the upregu-lation of MAPK1,HIF1A,MTOR,MYC,IL10,and JUN mRNA was significantly rescued in HDM-stimulated Beas-2B cells.Conclusions Cordycepin exerts anti-asthmatic effects by targeting MAPK1 and other key molecules,thereby providing a scientific foundation for its further development and clinical application.

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.