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 assess renal oxygen metabolism and iron deposition in type 2 diabetes mellitus(T2DM)patients using a combination of blood oxygen level-dependent(BOLD)and mDixon Quant techniques.Methods Clinical data of 58 T2DM patients from Tianjin First Central Hospital(September 2022-December 2023)were prospectively collected.According to urinary albumin-to-creation ratio(ACR),patients were divided into the normal albuminuria(NAU,ACR＜30 mg/g,n=35)group and the microalbuminuria(MAU,30 mg/g≤ACR＜300 mg/g,n=23)group.Thirty-three healthy volunteers were included as the control group during the same period.All participants underwent renal BOLD and mDixon Quant MRI to obtain cortical and medullary apparent relaxation rate(R2*)values.The differences of general data and image parameter values were compared between groups.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic efficacy of relevant parameters for early renal function changes.Results There were significant differences in body weight,estimated glomerular filtration rate(eGFR)and ACR between the control group,the NAU group and the MAU group(P＜0.01).The R2* value in renal cortex was lower than that in renal medulla(P＜0.01)in the same group.Apart from R2* value of BOLD renal cortex,which showed no significant difference between the three groups(P＜0.05),and the differences in the other parameters were statistically significant(P<0.05).When distinguishing between the control group and the NAU group,the NAU group and the MAU group,as well as between the control group and the early-stage T2DM(NAU+MAU)group,the combined two-sequence approach demonstrated higher area under the curve(AUCs)than any single sequence alone,with AUC value of 0.892(95%CI:0.809-0.975),0.785(95%CI:0.666-0.904)and 0.841(95%CI:0.756-0.926),respectively.Conclusion The combination of BOLD imaging with mDixon Quant enables noninvasive and quantitative assessment of alterations in renal oxygen metabolism and iron content in early-stage T2DM patients.The diagnostic performance of this combined approach surpasses that of individual methods.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Objective To assess renal oxygen metabolism and iron deposition in type 2 diabetes mellitus(T2DM)patients using a combination of blood oxygen level-dependent(BOLD)and mDixon Quant techniques.Methods Clinical data of 58 T2DM patients from Tianjin First Central Hospital(September 2022-December 2023)were prospectively collected.According to urinary albumin-to-creation ratio(ACR),patients were divided into the normal albuminuria(NAU,ACR＜30 mg/g,n=35)group and the microalbuminuria(MAU,30 mg/g≤ACR＜300 mg/g,n=23)group.Thirty-three healthy volunteers were included as the control group during the same period.All participants underwent renal BOLD and mDixon Quant MRI to obtain cortical and medullary apparent relaxation rate(R2*)values.The differences of general data and image parameter values were compared between groups.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic efficacy of relevant parameters for early renal function changes.Results There were significant differences in body weight,estimated glomerular filtration rate(eGFR)and ACR between the control group,the NAU group and the MAU group(P＜0.01).The R2* value in renal cortex was lower than that in renal medulla(P＜0.01)in the same group.Apart from R2* value of BOLD renal cortex,which showed no significant difference between the three groups(P＜0.05),and the differences in the other parameters were statistically significant(P<0.05).When distinguishing between the control group and the NAU group,the NAU group and the MAU group,as well as between the control group and the early-stage T2DM(NAU+MAU)group,the combined two-sequence approach demonstrated higher area under the curve(AUCs)than any single sequence alone,with AUC value of 0.892(95%CI:0.809-0.975),0.785(95%CI:0.666-0.904)and 0.841(95%CI:0.756-0.926),respectively.Conclusion The combination of BOLD imaging with mDixon Quant enables noninvasive and quantitative assessment of alterations in renal oxygen metabolism and iron content in early-stage T2DM patients.The diagnostic performance of this combined approach surpasses that of individual methods.

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 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.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Objective:To investigate the expression of ephrin type-A receptor 2 (EPHA2) in psoriatic lesions and its effect on the proliferation and differentiation of normal human epidermal keratinocytes (NHEKs) .Methods:The GDS4602 dataset from the Gene Expression Omnibus (GEO) database was analyzed to determine EPHA2 gene expression changes in psoriatic lesions. Skin tissue samples were collected from 3 psoriasis patients and 3 healthy controls, and EPHA2 expression was determined in the skin tissues by immunofluorescence staining. Twelve female BALB/c mice were randomly divided into 3 groups (4 mice in each group) : a normal control group (receiving no treatment), an imiquimod group (topically treated with 62.5 mg of imiquimod 5% cream), and an imiquimod + ALWⅡ-41-27 group (topically treated with 62.5 mg of imiquimod 5% cream, followed by intraperitoneal injections of the EPHA2 inhibitor ALWⅡ-41-27 at a dose of 20 mg·kg -1·d -1) ; after 6 days of treatment, dorsal skin samples were harvested for hematoxylin-eosin (HE) staining, immunofluorescence staining was performed to determine the expression of EPHA2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of the nuclear proliferation antigen Ki67, involucrin (Ivl), loricrin (Lor), and keratin 10 (Krt10). In vitro cultured NHEKs were divided into a control group (receiving no treatment), an M5 group (treated with 10 ng/ml M5 cytokines [including interleukin-17A, interleukin-22, interleukin-1α, oncostatin M and tumor necrosis factor-α]), an ALWⅡ-41-27 group (treated with 1 μmol/L ALWⅡ-41-27), and an M5 + ALWⅡ-41-27 group (treated with 10 ng/ml M5 and 1 μmol/L ALWⅡ-41-27) ; after 24 hours of treatment, the 5-ethynyl-2′-deoxyuridine (EdU) assay was performed to assess cellular proliferative activity, Western blot analysis to determine the expression of EPHA2, ERK and their phosphorylated proteins, and qPCR to determine the mRNA expression of KI67, IVL, LOR, and KRT10. One-way analysis of variance, Dunnett's T3 test, two-independent-sample t test, and paired t test were used for statistical analysis. Results:GEO database analysis revealed upregulated EPHA2 expression in psoriatic lesions compared with normal skin tissues from healthy controls ( t = 21.07, P < 0.001). Immunofluorescence staining showed increased EPHA2 expression in skin tissues from psoriasis patients and mouse models of psoriasis compared with those from healthy controls and normal control mice, respectively (both P < 0.01). In the animal experiments, the imiquimod group showed thicker epidermis, increased Ki67 mRNA expression, decreased mRNA expression of Ivl, Lor, and Krt10, and elevated p-ERK1/2 expression compared with the normal control group and imiquimod + ALWⅡ-41-27 group (all P < 0.05). In the cell experiments, the M5 group showed an increased proportion of EdU-positive cells (35.61% ± 1.18% vs. 24.83% ± 0.60% and 12.49% ± 1.52%, t = 8.12, 12.00, P = 0.015, 0.001, respectively), increased KI67 mRNA expression, and decreased mRNA expression of IVL, LOR, and KRT10 compared with the control group and M5 + ALWⅡ-41-27 group (all P < 0.05) ; Western blot analysis revealed that the expression levels of EPHA2, p-EPHA2, and p-ERK1/2 in NHEKs were significantly higher in the M5 group than in the control group and M5 + ALWⅡ-41-27 group (all P < 0.05), but there was no significant difference in the ERK1/2 protein expression among groups ( P > 0.05) . Conclusion:EPHA2 expression was upregulated in psoriatic lesions, which may promote keratinocyte proliferation and inhibit its differentiation, possibly via the ERK pathway.