ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

ObjectiveTo construct and validate a clinical prediction model for inflammatory remission outcomes in rheumatoid arthritis （RA） patients with liver and kidney deficiency syndrome treated with Bushen Zhiwang Decoction （补肾治尪汤， BZD） based on metabolomics. MethodsA prospective cohort study was conducted， enrol-ling 60 RA patients with liver and kidney deficiency syndrome. All patients were treated with BZD and conventional-dose oral conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） for 12 months. Clinical data were collected， and the change in disease activity score in 28 joints （DAS28） after treatment compared with baseline （△DAS28） was used as the primary outcome and grouping criterion. Peripheral blood samples were collected before treatment to analyze plasma metabolites. Differential analysis and least absolute shrinkage and selection operator （LASSO） regression were used to preliminarily screen differential metabolites， followed by machine learning algorithms to further identify a core metabolite combination. Based on the expression levels of the core metabolite combination， a novel metabolite index， namely the metabolomics-based inflammatory remission score （Met-IRS）， was calculated using standar-dized metabolite values， and its clinical applicability was evaluated. A clinical prediction model was constructed by integrating clinical characteristics and Met-IRS， and the model performance was assessed. ResultsAmong the 60 patients， those with △DAS28 ≥ 0.27 were assigned to the high inflammatory remission group， while those with △DAS28 ＜ 0.27 were assigned to the low inflammatory remission group， with 30 cases in each group. Compared to the low inflammatory remission group， the high inflammatory remission group showed a higher frequency of methotrexate use and a lower positive rate of rheumatoid factor （RF） （P＜0.05）. Seven core metabolites were identified as the optimal combination， including mangiferic acid， fatty acid-hydroxy fatty acid ester 40∶6， fatty acid-hydroxy fatty acid ester 18∶0， fatty acid-hydroxy fatty acid ester 36∶1， glucosylceramide， lysophosphatidylcholine 22∶5， and pregnanetriol ketone. The calculated Met-IRS comprehensively reflected the characteristics of differential metabolites and demonstrated clinical applicability. Met-IRS was significantly higher in the high inflammatory remission group than in the low inflammatory remission group， and was positively correlated with high inflammatory remission outcomes （P＜0.05）. Based on the variables Met-IRS， methotrexate use， leflunomide use， and RF positivity， a clinical prediction model for inflammatory remission in RA treatment （Cj-RTRM） was constructed. Model performance evaluation demonstrated that the model had good clinical predictive ability， with an area under the receiver operating characteristic curve （AUC） of 0.880， sensitivity 0.967， specificity 0.700 and Youden's index 0.667. ConclusionThe clinical prediction model Cj-RTRM constructed based on the metabolomics-based inflammatory remission score Met-IRS can effectively predict clinical inflammatory remission outcomes in RA patients treated with BZD and accurately identify the advantageous population for this treatment. This model provides guiding evidence for dynamic inflammation monitoring， targeted management， and identification of populations with advantages in traditional Chinese medicine.

Objective To construct and compare logistic regression and decision tree models for predicting systemic inflammatory response syndrome (SIRS) in patients with type B aortic dissection (TBAD) after interventional surgery. Methods A retrospective analysis was conducted on clinical data of TBAD patients at Peking University Shenzhen Hospital from 2020 to 2024. The patients were divided into a SIRS group and a non SIRS group based on whether SIRS occurred within 24 hours after surgery. Multivariate logistic regression was used to analyze the influencing factors of SIRS occurrence in TBAD intervention patients, and a decision tree model was constructed using SPSS Modeler to compare the predictive performance of the two models. Results A total of 742 patients with TBAD were included, including 579 males and 163 females, aged 27-97 (58.85±10.79) years. Within 24 hours after intervention, a total of 506 patients developed SIRS, with an incidence rate of 68.19%. Logistic regression analysis showed that the extensive involvement of the dissection, the surgical time≥2 hours, PET coated stents implanted, serum creatinine, white blood cell count, C-reactive protein, monocyte (MONO), neutrophil count levels elevated, estimated glomerular filtration rate and decreased albumin levels were independent risk factors for SIRS (P<0.05). The decision tree model selected a total of 10 explanatory variables and 6 layers with 37 nodes, among which MONO was the most important predictor. The area under the decision tree model curve was 0.829 [95%CI (0.800, 0.856)], which was better than the logistic regression model's 0.690 [95%CI (0.655, 0.723)], and the difference was statistically significant (P<0.001). Conclusion The incidence of SIRS after TBAD intervention is high, and the decision tree model has better predictive performance than logistic regression. It can identify high-risk patients with higher accuracy and provide a practical tool for early clinical intervention.

Objective To evaluate the predictive value of pathological tumor cell proportion size(PTS)and invasive lesion classification for recurrence of stage Ⅰ lung adenocarcinoma(LUAD).Methods A total of 160 patients who underwent stage Ⅰ LUAD resection in the hospital from February 2019 to February 2022 were retrospectively enrolled.According to PTS,the patients were divided into a high proliferation group(n=76)and a low proliferation group(n=84).According to the invasive lesion classification,the patients were divided into adenocarcinoma in situ(AIS)group(n=58),minimally invasive adenocarcinoma(MIA)group(n=52)and invasive adenocarcinoma(IAC)group(n=50).Cox proportional hazards regression was used to analyze the influencing factors of recurrence of stage Ⅰ LUAD.Kaplan-Meier was used to analyze the disease-free sur-vival(DFS)of each group,and the statistical power of variable factors was analyzed by receiver operating characteristic(ROC)curve.Results There were significant differences in mean tumor diameter,nodule type,margin condition,spread through air spaces(STAS),TNM stage,maximum tumor diameter,degree of differ-entiation,lymph node metastasis and proliferation cell nuclear antigen(Ki-67)proliferation index among pa-tients with different PTS(P＜0.05).STAS was a risk factor for DFS in patients with different PTS(P＜0.05),and the difference in DFS among patients with different PTS was statistically significant(P＜0.05).DFS in the low proliferation group was higher than DFS in the high proliferation group.PTS combined with STAS had a better efficacy in predicting stage Ⅰ LUAD recurrence[area under the curve(AUC)was 0.748].There were significant differences in mean tumor diameter,nodule type,margin condition,STAS,TNM stage,maximum tumor diameter,degree of differentiation,lymph node metastasis and Ki-67 proliferation index a-mong patients with different invasive lesions(P＜0.05).Margin condition and STAS were risk factors for DFS in patients with different invasive lesion types(P＜0.05).There was a significant difference in DFS be-tween patients with different invasive lesion types(P＜0.05),DFS in AIS group＞DFS in MIA group＞DFS in IAC group.The type of invasive lesions and margin condition combined with STAS had a good predictive value for stage Ⅰ LUAD recurrence(AUC was 0.784).Conclusion Different PTS combined with STAS can predict the recurrence of stage Ⅰ LUAD.Different invasive lesions combined with margin condition and STAS also have important predictive value for the recurrence of stage Ⅰ LUAD.

Diabetic retinopathy(DR),as one of the most common microvascular complications in patients with diabe-tes mellitus(DM),has a complex and multifaceted etiology that involves multiple factors.The unique characterization of DR in genomics,epigenomics,transcriptomics,proteomics,and metabolomics has opened new avenues for the exploration and development of novel therapeutic strategies for this disease.However,the inherent limitation of single-omics approa-ches is that they can only analyze the biological and molecular mechanisms underlying the disease from a single dimension,which makes it difficult to comprehensively capture the complex nature of DR.With the rapid advancement of high-throughput sequencing technology,multi-omics joint analysis combines the advantages of different histological techniques and can explore the pathogenesis of DR from multiple dimensions and levels.This paper aims to comprehensively review the latest progress of multi-omics technologies in revealing the pathogenesis of DR and its complex molecular mechanisms and thoroughly explore the new opportunities,current challenges,and future development prospects of multi-omics tech-nologies for DR research.

Occupational heavy metal exposure has become a critical issue in China's high-quality economic development within the field of occupational health. Current occupational exposure now extends beyond traditional contaminants like lead and mercury to include emerging materials such as rare earth elements, forming a dual pollution pattern that combines both conventional and novel pollutants. These substances can damage multiple bodily systems including the nervous and respiratory systems, imposing significant disease burdens on working populations. This paper examines the mechanisms of traditional heavy metals' toxicity, highlighting their distinct indirect neurotoxic effects compared to previous understanding. It analyzes exposure pathways and multi-system toxicological effects of rare earth elements, clarifying current gaps in their toxicology research and standardization efforts while identifying future research directions. The study aims to provide theoretical references for improving occupational heavy metal exposure prevention systems, thereby laying the foundation for safeguarding workers' health and addressing new challenges in modern occupational health.

Objective:To investigate the application value of dermoscopy and reflectance confocal microscopy (RCM) in identifying field cancerization in actinic keratosis (AK) in the elderly.Methods:A retrospective analysis was conducted on clinical, dermoscopic, and RCM features of elderly (> 60 years old) patients, who were confirmedly diagnosed with AK and had complete medical records at Shanghai Skin Disease Hospital from January 2022 to December 2023.Results:A total of 132 elderly patients with AK were included. Dermoscopy showed brownish-gray pseudonetwork pigment patterns, follicular horn plugs, irregular branched vessels, and rosette signs in AK lesions. Histopathological examination in 51 patients revealed that 47 (92.16%) were confirmedly diagnosed with AK. Field cancerization was observed in 106 patients (80.3%), among whom 66 (62.26%) had irregular branched vessels, 88 (83.02%) predominantly exhibited brownish-gray pseudonetwork pigment patterns, and 83 (78.30%) showed scattered brown pigment networks/fingerprint-like patterns. Post-treatment follow-up of 63 patients showed varying degrees of changes in vascular and pigment structures by dermoscopy, with significant reductions in follicular horn plugs and superficial yellow-white scales or keratin masses. RCM examinations in 41 AK patients all showed disordered arrangements of keratinocytes presenting as atypical honeycomb patterns, with atypical cells in the AK lesions; in the field cancerization areas of 20 patients, RCM revealed keratinocytes disorderedly arranged in an irregular honeycomb pattern, with some keratinocytes exhibiting mild atypia. Thirty-four AK patients underwent dynamic RCM monitoring before and after 1, 3 and 6 months of ALA-PDT treatment, which showed gradual regularization of arrangements of keratinocytes and reduction of atypical cells, as well as reappearance of atypical keratinocytes upon recurrence.Conclusions:The incidence of field cancerization was relatively high in elderly AK patients. Dermoscopy and RCM are helpful for the early identification of AK and field cancerization, especially in patients with multiple lesions and with difficulties in multi-site biopsy.