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.

Objective To compare the diagnostic performance of three breast MRI measurement methods—RECIST 1.1,the optimal method,and three-dimensional(3D)volumetric assessment—in assessing the efficacy of neoadjuvant chemotherapy(NAC)in breast cancer patients,with the objective of identifying the most clinically practical approach.Methods A total of 110 breast cancer patients who underwent NAC followed by surgical treatment between 2019 and 2023 were included in the study.Breast magnetic resonance imaging(MRI)was conducted within one week before and after the completion of NAC.Tumor response was evaluated using RECIST 1.1 criteria,widely recognized as the optimal method,as well as 3D volume measurement.Pathological response was determined according to the Miller-Payne grading system.Sensitivity,specificity,accuracy,and the area under the receiver operating characteristic curve(AUC)were computed and compared using the DeLong test.Results The AUC values for RECIST 1.1,the optimal method,and 3D volumetric assessment were 0.768,0.795,and 0.883,respectively.The 3D volumetric assessment exhibited significantly better discriminative performance(P＜0.05),with the highest sensitivity(98.9％),specificity(77.8％),and accuracy(95.5％).Additionally,the optimal method demonstrated superior performance over RECIST 1.1 across multiple parameters.Conclusions 3D volumetric mea-surement demonstrates superior performance compared to RECIST 1.1 and the optimal method in evaluating the response to NAC,offering a more accurate and comprehensive assessment tool.Additionally,the optimal method shows advantages over RECIST 1.1 and may serve as a practical alternative in settings where 3D software is not available.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To analyze the trend of the health literacy level of Chinese residents from 2012 to 2023 and predict the health literacy level from 2024 to 2027.Methods:The study collected data on the health literacy surveillance of Chinese residents from 2012 to 2023. The Joinpoint regression model was used to calculate the average annual percent change (AAPC) and analyze the trend. The interrupted time series analysis with Prais-Winsten transformed generalized least squares estimation was employed to investigate the impact of the"Healthy China 2030" policy on residents′ health literacy levels. Joinpoint regression, autoregressive integrated moving average model and grey forecasting models were established to select the optimal model for forecasting health literacy levels from 2024 to 2027.Results:The results showed that the health literacy level of Chinese residents increased from 8.80% in 2012 to 29.70% in 2023 (AAPC=11.65%, P<0.05). The health literacy level of urban and rural residents increased from 11.79% and 7.13% in 2012 to 33.25% and 26.23% in 2023, respectively (AAPC=9.57% and 12.60%, both P<0.05). Rural (1.59% per year) saw a lower average annual increase than urban (1.79% per year), widening the urban-rural health literacy gap. All aspects of health literacy, including basic knowledge and concepts, healthy lifestyles and behaviors, and health skills, showed an upward trend. The literacy level of six health issues—safety and first aid, scientific health views, health information, infectious disease prevention, chronic disease prevention, and basic medical care—also exhibited rising trends. Interrupted time series analysis indicated a significant further increase in the health literacy level of Chinese residents after the implementation of the "Healthy China 2030" policy, with the growth rate increasing from 0.615% per year before implementation to 2.655% per year afterwards. The Joinpoint regression model showed superior predictive performance compared to autoregressive integrated moving average model and grey forecasting models. The prediction results suggested a continued upward trend in the health literacy level from 2024 to 2027, reaching 32.68%, 35.62%, 38.84%, and 42.34%, respectively. Conclusion:From 2012 to 2023, the overall and various aspects of health literacy among Chinese residents show a continuous upward trend. This study predicts that the level of residents′ health literacy will continue to rise by 2027.

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.