BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

Objective To understand the current status of blood pressure variability and dyslipidemia in young and middle-aged patients with ischemic stroke, and to explore their relationship with prognosis. Methods A total of 312 young and middle-aged patients with ischemic stroke who met the inclusion criteria in Beijing Pinggu District Hospital from January 2022 to January 2025 were selected. The prognosis status [modified Rankin scale (mRS)], blood pressure variability, and blood lipids [total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were analyzed. The correlation of blood pressure variability and blood lipids levels with prognosis was explored by logistic regression analysis. Results There were 206 patients with good prognosis and 106 patients with poor prognosis. The number of patients who received diversified health education in the good prognosis group was more than that in the poor prognosis group (P<0.05). The systolic blood pressure successive variation (SV) and average real variability (ARV), and diastolic blood pressure SV and ARV were lower in the good prognosis group than those in the poor prognosis group (P<0.05). Furthermore, compared with the poor prognosis group, the good prognosis group had lower levels of TC, TG and LDL-C, while the number of patients receiving diversified health education and the level of HDL-C were higher (P<0.05). After logistic regression analysis, it was found that the levels of TC, TG, LDL-C, systolic blood pressure SV and ARV, and diastolic blood pressure SV and ARV were risk factors for poor prognosis. Conversely, receiving diversified health education and HDL-C level were protective factors for poor prognosis (P<0.05). Conclusion High blood pressure fluctuation, dyslipidemia, and lack of health education will increase the risk of poor prognosis in young and middle-aged stroke patients.

Background: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in children, with a rising incidence of macrolide resistance. Early diagnosis is crucial for reducing the disease burden; however, current diagnostic tools have limitations.We evaluated the diagnostic accuracy of serological assays and their performance based on symptom onset in children with CAP. Methods: From September 2023 to September 2024, we prospectively enrolled children with CAP, classified as M. pneumoniae pneumonia (MPP) or non-MPP, from 16 hospitals in Korea. Serological testing included chemiluminescence immunoassay (CLIA) and ELISA for detecting IgM and IgG, along with particle agglutination (PA) for total antibody measurements. Serological responses were analyzed at different times after symptom onset (0–4, 5–9, and 10–21 days). Results: Among 472 children with CAP (362 MPP, 110 non-MPP), 138 (29.2%) underwent PA testing, and 334 (70.8%) underwent IgM testing. PA at a 1:640 cutoff showed 48.0% sensitivity and 100% specificity. CLIA and ELISA showed comparable sensitivities (69.1% vs. 69.2%) and specificities (76.9% vs. 66.7%) for IgM testing. Seropositivity increased significantly with time since symptom onset (P for trend < 0.001), reaching 97.9% for IgM, 62.5% for IgG, and 94.7% for PA at 10–21 days. Conclusions The time post-symptom onset significantly influenced the diagnostic utility of serological tests for pediatric MPP, which showed limited value during the early stage of illness. These findings emphasize the importance of symptom onset-based interpretation of serological test results and their utility in complementing PCR when optimizing MPP diagnosis in children.

Extracellular vesicles (EVs) are nanosized membranous particles released by nearly all cell types, playing a crucial role in mediating cell-to-cell communication. The molecular profile of EVs often reflects that of their originating cells, rendering them valuable for therapeutic and diagnostic purposes. The kidney comprises various cell types, and urinary EVs are predominantly produced from tubular, glomerular, and urinary bladder cells. Within the nephron, EVs produced from the upper segments, such as glomerular tufts and proximal tubules, can be taken up by their downstream counterparts, thereby altering the physiology of recipient cells. Recent studies have demonstrated that this proximal-distal intra-nephron crosstalk via EVs is crucial for normal kidney physiology. Additionally, EVs from interstitial cells (e.g., fibroblasts and macrophages) have been demonstrated to mediate the exacerbation of kidney damage. This review provides up-to-date findings on the function of renal EVs during the progression of renal diseases. Furthermore, we discussed future directions to use the clinical potential of renal EVs as an early biomarker for renal disorders.

The sensitive scalp is a complex syndrome characterised by abnormal nerve sensations, such as stinging, itching, burning, and tightness, and diminished tolerance to physical or chemical stimuli that would not typically cause such unpleasant responses, with its pathology involving physical barrier destruction at the stratum corneum level, neural hyperreactivity and sensory nerve sensitization, and local immunological dysregulation and chronic low‑grade inflammation. The homeostasis of the scalp microenvironment plays a crucial regulatory role in maintaining the hair follicle growth cycle, yet this “soil” factor has long been underappreciated in hair loss research, which has traditionally centered on intrinsic follicular defects, such as genetic predisposition or androgen-driven mechanisms. In this review, we summarized the potential mechanisms underlying the imbalance in the “barrier-neural-immune” network in sensitive scalps. Sensitive scalp is further manifested as impaired skin barrier, including increased transepidermal water loss and abnormal lipid secretion. These alterations are accompanied by increased surface pH, excessive secretion of sebum rich in free fatty acids, reduced microbial diversity, and dysbiosis characterized by a reduction in Cutibacterium and an increase in Staphylococcus colonization. Mechanistically, we also analyzed how neurogenic inflammation, mediated by substances such as substance P (SP) and calcitonin gene-related peptide (CGRP), along with persistent low-grade inflammation, disrupts the microenvironment of the hair follicle stem cell niche through mechanisms involving mechanosensitive ion channels (e.g., Piezo1), oxidative stress, and cytokine cascades. When the barrier is compromised, the weakened stratum corneum may facilitate the penetration of external stimuli, sensitizing cutaneous nerve endings. Those hyperresponsive nerves then fire off neuropeptides like substance P and CGRP. These peptides activate mast cells and other immune cells via the MrgprB2 receptor, prompting degranulation and a wave of pro-inflammatory mediators that kick off neurogenic inflammation. At the same time, oxidative stress and inflammatory cytokines drive a persistent low-grade inflammation that directly damages the hair follicle stem cell niche. Physical compression from shrinking hair shafts activates Piezo1 channels, setting off calcium influx and Caspase‑3‑dependent apoptotic signaling. We primarily considered the interactions between inflammatory signaling and the sensitization of the androgen receptor (AR) pathway, as well as the inhibition of the Wnt/β‑catenin pathway, which may subsequently contribute to hair follicle miniaturization and disruption of the growth cycle. The inflammatory microenvironment appears to boost AR expression in dermal papilla cells, making them more sensitive to dihydrotestosterone (DHT). This heightened sensitivity may promote the expression of transforming growth factor-β1 (TGF-β1), TGF-β2, and Dickkopf-1 (DKK1), which suppress the Wnt/β‑catenin pathway—essential for follicle growth and regeneration—potentially accelerating follicular miniaturization and stalling the growth cycle. Coupled with direct inflammatory apoptosis, oxidative stress, and circadian disruption, these routes may collectively speed up hair follicle stem cell depletion and diffuse hair thinning. These findings point to the need for more mechanistic and translational research to test the proposed pathways and explore therapies that target the microenvironment in sensitive scalp-related hair loss. Ultimately, we hope to provide theoretical support for the intervention of hair loss by restoring the steady state of the scalp microenvironment and combining with new precision delivery technologies such as microneedles.

ObjectiveTo explore the mechanism by which Ruyan Neixiao cream （RUC） induces ferroptosis in breast precancerous lesion （BPL） cells， and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%， 2%， and 4% concentrations of Ruyanneixiao Cream transdermal solution （RUT） was assessed using cell counting kit-8 （CCK-8） and a colony formation assay. Reactive oxygen species （ROS） were measured using the DCFH-DA probe， and the levels of ferrous ions （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY^581/591 fluorescent probe. The expression of nuclear factor E₂-related factor 2 （Nrf2）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins was analyzed by Western blot. The BPL rat model was constructed using 2，2′-bis（hydroxymethyl）butyric acid （DMBA） combined with estrogen and progesterone， and the rats were treated with RUC for external application. After the 12^th cycle， the rats were euthanized， and histopathological changes in breast tissue were observed by hematoxylin-eosin （HE） staining. Fe²⁺ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2， SLC7A11， and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry （IHC） and Western blot. ResultsCompared with the matrix group， the cell viability of MCF-10AT cells in the 1%， 2%， and 4% RUT groups was significantly reduced （P<0.05） in a concentration-dependent manner， with the 24-hour half inhibitory concentration （IC₅₀） being 2.23%. Compared with the 4% RUT group， cell viability in the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the colony formation rates of MCF-10AT cells in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the cell colony formation rate of the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the levels of ROS and Fe²⁺ in the 1%， 2%， and 4% RUT groups were significantly increased （P<0.05）， while GSH levels were significantly decreased （P<0.05）， and MDA and lipid peroxidation levels were significantly increased （P<0.05）. Compared with the 4% RUT group， ROS and Fe²⁺ levels in the RUT + Fer-1 group were significantly reduced （P<0.05）， while GSH levels were significantly increased （P<0.05）， and MDA and lipid peroxidation levels were significantly reduced （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the RUT + Fer-1 group were significantly increased （P<0.05）. In the in vivo experiment， compared with the matrix group， the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved， with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group， Fe²⁺ and MDA levels in the mammary tissue of the RUC group were significantly increased （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the mammary tissue of the RUC group were significantly reduced （P<0.05）. ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway， increasing Fe²⁺ accumulation， and promoting lipid peroxidation.

ObjectiveTo explore the mechanism by which Ruyan Neixiao cream （RUC） induces ferroptosis in breast precancerous lesion （BPL） cells， and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%， 2%， and 4% concentrations of Ruyanneixiao Cream transdermal solution （RUT） was assessed using cell counting kit-8 （CCK-8） and a colony formation assay. Reactive oxygen species （ROS） were measured using the DCFH-DA probe， and the levels of ferrous ions （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY^581/591 fluorescent probe. The expression of nuclear factor E₂-related factor 2 （Nrf2）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins was analyzed by Western blot. The BPL rat model was constructed using 2，2′-bis（hydroxymethyl）butyric acid （DMBA） combined with estrogen and progesterone， and the rats were treated with RUC for external application. After the 12^th cycle， the rats were euthanized， and histopathological changes in breast tissue were observed by hematoxylin-eosin （HE） staining. Fe²⁺ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2， SLC7A11， and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry （IHC） and Western blot. ResultsCompared with the matrix group， the cell viability of MCF-10AT cells in the 1%， 2%， and 4% RUT groups was significantly reduced （P<0.05） in a concentration-dependent manner， with the 24-hour half inhibitory concentration （IC₅₀） being 2.23%. Compared with the 4% RUT group， cell viability in the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the colony formation rates of MCF-10AT cells in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the cell colony formation rate of the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the levels of ROS and Fe²⁺ in the 1%， 2%， and 4% RUT groups were significantly increased （P<0.05）， while GSH levels were significantly decreased （P<0.05）， and MDA and lipid peroxidation levels were significantly increased （P<0.05）. Compared with the 4% RUT group， ROS and Fe²⁺ levels in the RUT + Fer-1 group were significantly reduced （P<0.05）， while GSH levels were significantly increased （P<0.05）， and MDA and lipid peroxidation levels were significantly reduced （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the RUT + Fer-1 group were significantly increased （P<0.05）. In the in vivo experiment， compared with the matrix group， the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved， with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group， Fe²⁺ and MDA levels in the mammary tissue of the RUC group were significantly increased （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the mammary tissue of the RUC group were significantly reduced （P<0.05）. ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway， increasing Fe²⁺ accumulation， and promoting lipid peroxidation.

BackgroundGenetic factor plays an important role in the pathogenesis of panic disorder. Previous studies have revealed that immune system dysregulation is closely related to mental disorders such as panic disorder， while the relationship between panic disorder and immune-related gene expression remains unclear. ObjectiveTo explore the relationship between the expression of CXCL8， IL6R， JUN， PTGS2， TGFBR1， TLR2， CCR4 genes and panic disorder， providing references for the diagnosis and treatment of panic disorder. MethodsA total of 52 patients who met the diagnostic criteria for panic disorder according to the Diagnosed and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Psychosomatic Medicine Center of Sichuan Provincial People's Hospital from January 2020 to March 2021. Another 72 healthy individuals matched for age and gender from Chengdu were concurrently recruited as control group. The Panic Disorder Severity Scale （PDSS） was used to assess the severity of symptoms in panic disorder patients. Quantitative real-time polymerase chain reaction （PCR） was used to detect gene expression levels in two groups. Spearman correlation analysis was adopted to determine the correlation between PDSS score and immune-related gene expression in research group. ResultsThe expression of the JUN， PTGS2 and TGFBR1 genes were significant higher in panic disorder patients than those in control group （Z=-4.172， -2.086， -3.018， P<0.05 or 0.01）. After false discovery rate （FDR） correction for multiple testing， the differential expression of JUN and TGFBR1 genes remained statistically significant between two groups （P<0.05）. There was no significant difference in the expression of CCR4， CXCL8， IL6R and TLR2 genes between two groups （P>0.05）. Correlation analysis revealed that the expression of the JUN gene in panic disorder patients was positively correlated with PDSS score （r=0.360， P<0.01）， while the CCR4， CXCL8， IL6R， PTGS2， TGFBR1 and TLR2 genes showed no statistically significant correlation with the PDSS score （P>0.05）. ConclusionThe expression of the JUN and TGFBR1 genes may be associated with panic disorder， and the expression of the JUN gene correlated with the severity of panic disorder. ［Funded by Science and Technology Plan Project of Sichuan Provincial Department of Science and Technology （number， 2021YJ0440）］

Objective To investigate the therapeutic effects of upper limb rehabilitation robot training combined with intermittent theta burst stimulation(iTBS)on upper limb motor and neurological function in stroke patients with hemiplegia.Methods This study retrospectively consecutive enrolled 46 stroke hemiparetic patients from the Department of Rehabilitation Medicine,Nanjing Pukou People's Hospital.The patients were randomly assigned to a control group and an experimental group(23patients in each)using a random number table.Baseline data,including sex,age,disease duration,side of hemiplegia,and stroke type,were collected from patients enrolled.All patients received conventional treatment.The control group received upper limb rehabilitation robot training combined with iTBS sham stimulation(coil placed perpendicular to the skull),while the experimental group received upper limb rehabilitation robot training combined with iTBS real stimulation(coil placed parallel to the skull).Both groups underwent treatment for 3 weeks.Upper limb motor function was assessed using the Fugl-Meyer upper extremity(FMA-UE)scale and Wolf motor function test(WMFT);while neurological function was evaluated using the motor-evoked potentials(MEP)latency,amplitude,and central motor conduction time(CMCT)of the affected thumb abductor muscle.Activities of daily living were assessed using the modified Barthel index(MBI).Results(1)No significant differences in baseline data were found between the two groups(all P＞0.05).(2)Before treatment,the FMA-UE and WMFT scores in the experimental group were 27.48±7.87 and 28.22±3.87,respectively;and in the control group were 26.35±4.78 and 28.35±3.33,respectively;there were no significant differences in both FMA-UE and WMFT scores between the two groups(all P＞0.05).After 3weeks of treatment,the FMA-UE and WMFT scores in the experimental group were 40.35±8.96 and 37.74±4.11,respectively;and in the control group were 32.78±4.50 and 32.57±4.11,respectively;there were significant interaction effects of time and group(Ftime×group values of 19.613 and 31.522,both P＜0.01),main effects of group(Fgroup values of 5.401 and 5.897,both P＜0.05),and main effects of time(Ftime values of 176.516 and 211.478,both P＜0.01).(3)Before treatment,the MEP latency,amplitude,and CMCT in the experimental group were(24.39±3.56)ms,(137.77±42.67)μV,and(10.62±2.76)ms,respectively;and in the control group were(24.64±2.77)ms,(136.74±48.77)μV,and(10.73±1.84)ms,respectively,there were no significant differences between the two groups(all P＞0.05).After 3weeks of treatment,the MEP latency,amplitude,and CMCT in the experimental group were(20.39±1.83)ms,(239.91±43.70)μV,and(6.58±1.23)ms,respectively,and in the control group were(22.53±3.53)ms,(198.54±50.37)μV,and(9.19±1.60)ms,respectively,there were significant interaction effects of time and group(Ftime×group values of 7.270,15.554,and 20.110,all P＜0.05)and main effects of time(Ftime values of 76.540,256.706,and 100.629,all P＜0.01),the main effect of group for CMCT was significant(Fgroup=7.406,P＜0.01),but there were no significant difference in the main effect of group on MEP latency,amplitude between two groups(Fgroup values of 2.145,2.778,both P＞0.05).(4)Before treatment,the MBI score in the experimental group was 42.83±7.36,and in the control group was 43.91±6.56,with no significant difference between two groups(P＞0.05).After 3 weeks of treatments,the MBI score in the experimental group was 67.83±12.69,and in the control group was 54.13±5.57,there were significant interaction effects of time and group(Ftime×group=39.862,P＜0.01),main effects of group(Fgroup=8.083,P=0.007),and main effects of time(Ftime=226.241,P＜0.01).Conclusions Upper limb rehabilitation robot training combined with iTBS can improve upper limb motor function and neurological function and enhance the daily living activity ability of stroke patients.Real iTBS combined with robot training has a more significant effect than sham iTBS.

Objective To investigate the association between Helicobacter pylori(Hp)infection and the expression levels of p27,CyclinD1,matrix metalloproteinase 9(MMP-9),and related microRNAs,as well as their correlations with clinicopathological characteristics in gastric cancer(GC)tissues.Methods A total of 116 GC patients who underwent surgical resection were enrolled and classified into Hp-positive and Hp-negative groups based on Hp infection status,consisting of 76 and 40 cases,respectively.Among the Hp-positive group,patients were further categorized into good prognosis and poor prognosis subgroups according to their clinical outcomes,with 56 and 20 cases,respectively.The expression levels of p27,CyclinD1,MMP-9 proteins,as well as miR-490-3p and miR-146a in both cancerous and paracancerous tissues across the groups were compared.Additionally,the associations between the expression of these biomarkers in cancer tissues and the clinicopathological features and prognosis of Hp-positive GC patients were analyzed.Furthermore,potential risk factors contributing to poor progno-sis in Hp-positive GC patients were identified,and a predictive model was constructed to evaluate its prognostic value.Results The expression levels of p27 protein and miR-490-3p in GC tissues were significantly lower compared to those in adjacent non-cancerous tissues,whereas the expression levels of CyclinD1,MMP-9 protein,and miR-146a were significantly higher(P<0.05).In cancer tissues from the Helicobacter pylori(Hp)-positive group,the expression of p27 protein and miR-490-3p was lower than that in the Hp-negative group,while the expression of CyclinD1,MMP-9 protein,and miR-146a was higher(P<0.05).Moreover,in Hp-positive GC patients,the expression levels of p27 protein and miR-490-3p in cancer tissues were lower in those with advanced stages(Ⅲ～Ⅳ)and lymph node metastasis compared to those with early stages(Ⅰ～Ⅱ)and no lymph node metastasis(P<0.05).Conversely,the expression levels of CyclinD1,MMP-9 protein,and miR-146a were higher in patients with advanced stages and lymph node metastasis(P<0.05).Compared with the good prognosis group,the poor progno-sis group exhibited a higher proportion of advanced stages,lymph node metastasis,and elevated expression levels of CyclinD1,MMP-9 protein,and miR-146a,while the expression levels of p27 protein and miR-490-3p were reduced(P<0.05).Multivariate analysis indicated that advanced stage(Ⅲ～Ⅳ),low expression of p27 pro-tein,high expression of MMP-9 protein,and low expression of miR-490-3p were independent risk factors for poor prognosis in Hp-positive GC patients(P<0.05).The predictive model constructed for assessing the likelihood of poor prognosis in Hp-positive GC demonstrated an area under the curve(AUC)of 0.774,with a sensitivity of 80.00%and a specificity of 76.79%.Conclusions p27,CyclinD1,MMP-9 protein,miR-146a,and miR-490-3p were found to be abnormally expressed in patients with Hp-positive GC.Their expression levels were significantly associated with TNM stage and the presence of lymph node metastasis.Specifically,Stage Ⅲ～Ⅳ disease,low expression of p27 protein and miR-490-3p,and high expression of MMP-9 protein were identified as independent risk factors for poor prognosis in patients with Hp-positive GC.A predictive model based on these risk factors demonstrated favorable performance in forecasting poor clinical outcomes in this patient population.