ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Neuropathic pain （NP） is a chronic pain syndrome resulting from injury， inflammation， or dysfunction of the somatosensory nervous system. Its pathogenesis is complex and intimately associated with peripheral sensitization and maladaptive neuroplasticity within the central nervous system. The core clinical manifestations， including spontaneous pain， allodynia， and paresthesia， severely compromise patients’ quality of life and pose substantial challenges to clinical management. Endoplasmic reticulum stress （ERS）， a critical cellular defense mechanism against disrupted intracellular homeostasis， is primarily initiated and modulated through three canonical branches of the unfolded protein response （UPR）： the protein kinase RNA-like endoplasmic reticulum kinase （PERK） pathway， the inositol-requiring transmembrane kinase/endonuclease 1α （IRE1α） pathway， and the activating transcription factor 6 （ATF6） pathway. These signaling cascades play a pivotal role in the pathological progression of NP. Traditional Chinese medicine （TCM） exhibits unique advantages in the treatment of NP. Leveraging its hallmark characteristics of multi-target， multi-pathway， and holistic regulation， TCM can systematically modulate the ERS signaling network to inhibit neuronal apoptosis， attenuate neuroinflammatory infiltration， and rectify autophagic dysfunction， ultimately promoting the repair and regeneration of damaged neural tissue. This review systematically summarizes the core role of ERS in the occurrence and development of NP. It focuses on the latest research progress regarding ERS pathway modulation in NP amelioration by representative TCM interventions， including potential core bioactive components （e.g.， tanshinoneⅡ_A， catalpol， and formononetin）， classic and empirical compound formulas （e.g.， Huangqi Guizhi Wuwu decoction， Compound Qiying granules， and Tangluoning）， and TCM external therapies （e.g.， electroacupuncture， moxibustion with seed-sized moxa cone， and acupotomy）. Through an in-depth analysis of the functional characteristics and mechanisms of these TCM interventions， particularly their bidirectional regulation and multi-target synergy， this review aims to provide a solid theoretical foundation for further optimizing TCM-based strategies for NP prevention and treatment and to delineate future directions for clinical translation of related research achievements and targeted drug development.

Objective To explore the cost-benefit of computerized tomography perfusion imaging(CTP)in guiding endovascular treatment of patients with large vessel occlusion associated with delayed time window.Methods A total of 365 patients with great vascular occlusive stroke associated with delayed time window(6-24 h),who were admitted to the Tangshan Municipal Workers' Hospital of China to receive endovascular treatment from January 2016 to February 2022,were enrolled in this study.Based on whether the patient received CTP imaging guidance or not,the treatment cost and benefit of different treatment strategies were analyzed.Modified Rankin scale(mRS)was used to evaluate the patient's postoperative 3-month and 12-month neurological functions.The decision tree-Markov model was used to make cost-benefit analysis.Probability sensitivity analysis(PSA)was used to assess the influence of parameter uncertainty.Results The operation cost of CTP-guided endovascular treatment of large vessel occlusion was 1 526.87 Chinese yuan.According to the calculation method of disease and sequelae burden,it could bring direct burden of 1 089.23 Chinese yuan,direct+indirect burden of 3 204.85 Chinese yuan and direct+indirect+intangible burden of 5 083.07 Chinese yuan.Each Chinese yuan could get 0.178 8,0.231 8 and 0.263 4 earnings,respectively.The therapeutic cost of CTP-guided endovascular treatment of great vascular occlusive stroke was 26 689.13 Chinese yuan,producing 2.065 quality-adjusted life-year(QALY)for each patient,while the therapeutic cost and QALY of non-CTP-guided endovascular treatment were 33 299.07 Chinese yuan and 1.776 QALY respectively.PAS-analyzed incremental cost-benefit ratio(ICER)and incremental net monetary benefit(iNMB)were 22 592.82 and 7 846.43 respectively.At the cost-benefit threshold of ￥50 000/QALY,the probability that CTP guidance could get cost-benefit was up to 90.0％.The tornado chart analysis of one-way sensitivity analysis revealed that the initial mRS distribution guided by CTP had the greatest influence on iNMB,followed by the cost input in the first three months after operation.Conclusion For patients with great vascular occlusive stroke associated with delayed time window,CTP-guided endovascular treatment has high cost-benefit and effect value.

Objective To investigate the relationship between platelet to lymphocyte ratio(PLR)and low-density lipoprotein cholesterol(LDL-C)/high-density lipoprotein cholesterol(HDL-C)ratio with the degree of carotid artery stenosis,neurological deficits,and prognosis in elderly pa-tients with ischemic stroke and carotid artery stenosis.Methods A total of 186 elderly patients diagnosed with ischemic stroke and carotid artery stenosis admitted in our hospital from June 2021 to June 2024 were enrolled in this study.The PLR and LDL-C/HDL-C ratio were collected,and then with median split,they were divided into high and low PLR groups(both 93 cases),and high and low LDL-C/HDL-C groups(both 93 cases).General clinical data were compared between the two pairs of groups.Multivariate logistic regression analysis was used to identify the factors influencing the severity of carotid artery stenosis,neurological deficits,and prognosis.Kendall's Tau-b correlation analysis was employed to assess the relationship of PLR and LDL-C/HDL-C with the degree of carotid artery stenosis and prognosis.Pearson correlation analysis was conduc-ted to evaluate the association of PLR and LDL-C/HDL-C with neurological deficits.Results Sta-tistically differences were observed in the degree of carotid artery stenosis and prognosis between the high and low PLR groups(P＜0.01).The NIHSS score was significantly higher in the high PLR group(P＜0.01).Similar differences were noted between the high and low LDL-C/HDL-C groups in terms of degree of carotid artery stenosis and prognosis(P＜0.01).The NIHSS score was obviously higher in the high LDL-C/HDL-C group(P＜0.01).Multivariate logistic regression analysis showed that PLR and LDL-C/HDL-C were risk factors for the degree of carotid artery stenosis,neurological deficits and prognosis in elderly patients with carotid artery stenosis after ischemic stroke(OR=3.842,95％CI:2.551-5.328,P=0.000;OR=3.604,95％CI:2.402-5.407,P=0.000;OR=2.956,95％CI:1.955-4.471,P=0.000;OR=3.463,95％CI:2.506-4.785,P=0.000;OR=2.878,95％CI:1.991-4.160,P=0.000;OR=3.785,95％CI:2.483-5.768,P=0.000).Kendall's Tau-b correlation analysis showed that PLR and LDL-C/HDL-C were positively correlated with the degree of carotid artery stenosis and the prognosis in these eld-erly patients(P＜0.05).Pearson correlation analysis indicated that PLR and LDL-C/HDL-C were positively correlated with the NIHSS score in the patients(P＜0.05).Conclusion For the elderly ischemic stroke patients with carotid artery stenosis,PLR and LDL-C/HDL-C are related to the prognosis,and can be used to help assess the severities of carotid artery stenosis and neurological deficits.

Objective:This study utilizes data from the 2021 Chinese Longitudinal Healthy Longevity and Happy Family Survey(CLHLS-HF)to examine the current status of Long-Term Care Insurance(LTCI)implementation and to identify the factors influencing whether disabled elderly individuals receive formal care services.The study aims to provide policy recommendations to enhance the effectiveness and equity of the system.Methods:In this cross-sectional study, a sample of 1 447 older participants with dependency, residing in LTCI pilot areas and meeting the inclusion criteria from the 2021 CLHLS-HF, was selected.Chi-square tests and binary logistic regression analyses were employed to explore the factors influencing the receipt of formal care by dependent older individuals.Results:Among the 1 447 participants, there were 496 males with an average age of 92 years(SD 9)and 951 females with an average age of 95 years(SD 9). Of these, 701 received formal care.The logistic regression analysis revealed that factors influencing the receipt of formal care included urban residence( OR=2.237, 95% CI: 1.675-2.987, P<0.001), residing in the eastern region( OR=2.907, 95% CI: 1.747-4.837, P<0.001), living in the western region( OR=3.132, 95% CI: 1.816-5.501, P<0.001), having no children( OR=2.478, 95% CI: 1.108-5.540, P=0.027), and the degree of disability, with severe disability being more likely to receive care compared to mild( OR=0.497, 95% CI: 0.388-0.637, P<0.001)and moderate disabilities( OR=0.589, 95% CI: 0.433-0.801, P=0.001). Conclusions:Dependent older individuals in the eastern and western regions, particularly those without children or with severe disabilities, are more likely to receive formal care through the LTCI system.However, there are substantial inequities in LTCI coverage among individuals with varying degrees of disability.To enhance the effectiveness of the LTCI system, greater efforts should be directed towards economically disadvantaged regions and older individuals with mild to moderate disabilities, thereby ensuring better protection for the disabled population.