OBJECTIVE To screen out the pharmacodynamic substances of Cistanches Herba aqueous extracts, explore the basis of the pharmacodynamic substances and their mechanism of action in the treatment of diabetic nephropathy(DN), based on the spectral relationship between the mass spectral peak areas of different elution sites of Cistanches Herba aqueous extracts and their anti-DN effects. METHODS UPLC-Orbitrap-MS/MS technique was used to characterise the chromatographic peaks; MTT method was used to detect the effects of different elution sites of Cistanches Herba aqueous extract on the proliferation of high glucose and high fat HK-2 cells; grey correlation analysis and partial least squares method were used to analyse the spectral relationship between mass spectrometry peak area and anti-DN activity. MTT method was used to determine the anti-DN activities of the individual components of Cistanches Herba aqueous extract; biochemical kit and ELISA were used to determine the levels of oxidative indicators(SOD, GSH-P) and inflammatory factors(IL-1β, TNF-α, TGF-β); Western blotting was used to detect the expression of apoptosis-related proteins. RESULTS UPLC-Orbitrap-MS/MS technique speculated and identified 72 common compounds; In Cistanches Herba aqueous extracts, water, 20% ethanol, and 40% ethanol-eluted sites differentially increased the proliferation rate of HK-2 cells in a high-sugar, high-fat environment; Partial least squares and grey correlation analyses showed that the constituents of the aqueous extracts of Cistanches Herba with greater anti-DN contributions were 8-epideoxymatricinic acid, geniposidic acid, pinoresinol, betaine and syringin, et al. MTT assay reveals that 8-epi-deoxystrychnic acid and geniposidic acid had significant proliferative effects on HK-2 cells in a high glucose and high fat environment; Biochemical kit and ELISA showed that 8-epideoxystrychnic acid and geniposidic acid were able to up-regulate the activity of SOD and GSH-Px, and at the same time they had an inhibitory effect on the expression of inflammatory factors IL-1β, TNF-α and TGF-β. Western blotting results showed that 8-epideoxystrychnic acid and geniposidic acid were able to down-regulate and up-regulate the markers of dermal mesenchymal transition: α-SMA, Collagen Ⅰ and E-cadherin, and they could exert anti-DN effects by inhibiting the PI3K-Akt pathway. CONCLUSION The two compounds, 8-epideoxystrychnic acid and geniposidic acid, which are screened by the spectroeffective relationship of anti-DN among the many chemical constituents contained in Cistanches Herba, can affect oxidative stress, inflammation and epithelial-mesenchymal transformation of renal tubular cells by inhibiting the PI3K-Akt signalling pathway, and improve renal pathology, degree of fibrosis and renal function, which will be useful for the in-depth study of aqueous extracts of Cistanches Herba in the treatment of DN.

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease that is difficult to diagnose clinically, and finding appropriate biomarkers to assist in the diagnosis and prognosis monitoring of IPF can improve the proportion of early diagnosis and timely treatment of these patients and improve the quality of life of patients

Objective:The combined diagnosis models was constructed with the test indicators and its application value in the clinical evaluation of patients with interstitial lung disease was evaluated.Methods:Methodology development and validation. A total of 101 patients with idiopathic pulmonary fibrosis (IPF) and 107 patients with non-IPF interstitial lung disease admitted to China-Japan Friendship Hospital from 2022 to 2023 were collected, and 98 healthy people were collected during the same period. The population in each group was divided into modeling group (180 cases) and validation group (126 cases) by complete randomization. Serum samples and clinical test results were collected. The test indicators included white blood cell count, lymphocyte count, monocyte count, hemoglobin concentration, highly sensitive C-reactive protein, Krebs von den Lungen 6, total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, adenosine deaminase, neuron-specific enolase, alpha-fetoprotein, carcinoembryonic antigen, cytokeratin 19 fragment, carbohydrate antigen 15-3, gastrin releasing peptide precursor, squamous cell carcinoma antigen and interleukin 1 (IL-1), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α, interferon-α, interferon-γ. Multiple collinearity test, univariate and multivariate logistic regression were performed for the included test indicators in each group, and nomograms were established and validated by receiver operating characteristic (ROC) curves, calibration curves and clinical decision curves.Results:By comparing interstitial lung disease to healthy people, carbohydrate antigen 15-3 ( OR=1.285, 95% CI 1.178-1.402), IL-6 ( OR=1.128, 95% CI 1.011-1.258), adenosine deaminase ( OR=1.465, 95% CI 1.261-1.702), and Krebs von den Lungen-6 ( OR=1.013, 95% CI 1.008-1.017) were independent risk factors for interstitial lung disease. Based on these four indexes, the nomogram model was constructed. The AUCs of the combined diagnosis model in the modeling group and validation group were 0.967(95%CI 0.941-0.993)and 0.948(95% CI 0.911-0.984), respectively.Decision curve analysis showed that the net benefit of the combined diagnosis model in diagnosing IPF was higher than that of a single indicator within the threshold range of 0.01-1. In the comparison of IPF and non-IPF interstitial lung disease, alpha-fetoprotein ( OR=1.403, 95% CI 0.975-2.019) and squamous cell carcinoma antigen ( OR=0.531, 95% CI 0.321-0.878) were independent risk factors for IPF. The AUCs of the combined diagnosis model in the modeling group and validation group were 0.703 (95% CI 0.597-0.81) and 0.642 (95% CI 0.528-0.757), respectively. Through calibration curve and clinical decision curve verification, it was found that it had a certain value in the differential diagnosis of IPF. Conclusions:Carbohydrate antigen 15-3, IL-6, adenosine deaminase and Krebs von den Lungen 6 are risk factors of interstitial lung disease, which can be used to construct a combined diagnostic model for the diagnosis of interstitial lung disease. Alpha-fetoprotein and squamous cell carcinoma antigen are risk factors of IPF, which can be used to construct a combined diagnostic model to distinguish IPF from non-IPF interstitial lung disease and assist clinical diagnosis of IPF.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease that occurs mostly in the middle-aged and eldly people, with a short median survival and cannot be cured, and the etiology is still unclear. Currently, it is believed that the pathogenesis is related to cellular aging, and abnormal cellular aging leads to the failure of damaged alveolar epithelial cells that cannot be repaired normally, which promotes the occurrence of pulmonary fibrosis. Senescence-associated secretory phenotype (SASP), SASP affects pulmonary fibrosis through different signaling pathways in IPF patients, and this article reviews the expression level and mechanism of existing SASP in IPF patients.

OBJECTIVE To investigate the effects and mechanism of luteolin on osteogenic repair of bone defects. METHODS The targets and potential pathways of luteolin in the treatment of bone defects were screened by network pharmacology method， and then the top 2 targets were selected by Hub gene screening for molecular docking verification， with binding energy as the evaluation standard. In vitro experiments were conducted on rat bone mesenchymal stem cells （BMSC） and rat umbilical vein endothelial cells （RUVEC）. Phenotypic validation was performed using alkaline phosphatase staining， alizarin red S staining， and in vitro angiogenesis experiments. Western blot assay was used to detect the protein expressions of phosphatidylinositol 3 kinase （PI3K） and protein kinase 1 （Akt1）， so as to validate the mechanism of luteolin on osteogenic differentiation of BMSC and angiogenesis of RUVEC in vitro. RESULTS The results of network pharmacology showed that the effects of luteolin on vascular formation and bone repair in bone defects were mainly related to Akt1， SRC， estrogen receptor 1， epidermal growth factor receptor， cyclooxygenase 2， matrix metalloproteinase 9 targets， and were closely related to PI3K-Akt signaling pathway. The results of molecular docking showed that luteolin binding to Akt1 and SRC proteins was stable. The results of in vitro experiments showed that luteolin could significantly improve the expressions and activities of alkaline phosphatase in BMSC， increased the number of calcium salt deposits and calcified nodules， and promoted calcification of BMSC. Compared with luteolin 0 μmol/L group， the angiogenesis ability of RUVEC was enhanced significantly in luteolin 1， 10 μmol/L groups， the length of blood vessels and the protein expressions of PI3K and Akt1 were significantly increased （P＜0.05 or P＜0.01）； the higherthe concentration， the better the effect. CONCLUSIONS Luteolin may play a role in promoting angiogenesis and bone repair at the fracture site by activating PI3K/Akt signaling pathway and promoting the protein expressions of PI3K and Akt1.

Objective:To compare and analyze the clinical curative effect and safety of chemoembolization with drug-loaded microspheres of different particle sizes (D-TACE) for the treatment of hepatocellular carcinoma.Methods:Clinical data of 281 cases with hepatocellular carcinoma treated with drug-loaded microspheres-transarterial chemoembolization (TACE) were retrospectively analyzed. According to the different particle sizes of drug-loaded microspheres, they were divided into 100~300 μm (small particle size) and 300~500 μm (large particle size) group. Tumor response rate and complication conditions at 1, 3, and 6 months after chemoembolization were compared. The overall survival time of the two groups were analyzed. Quantitative data conformed to normal distribution and homogeneity of variance were compared using t-test, while other with Wilcoxon signed rank-sum test. Qualitative data were compared using χ2 test. Kaplan-Meier method was used for survival analysis, and the differences in survival were analyzed using Log-rank test. P＜0.05 was considered as statistically significant. Survival curves and histograms were drawn using GraphPad Prism9.1 software. Results:The complete remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 31.25%, 30.15%, and 42.45% and 18.25%, 15.79% and 24.74%, respectively, and the differences were statistically significant between groups (P 1 month=0.012, P 3 month=0.009, P 6 month=0.008, P＜0.05). The objective remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 88.19%, 76.99%, and 70.75% and 81.02%, 72.81% and 53.60%, respectively. Six months after surgery, the small particle size group (objective response rate = 70.75%) was significantly higher than the large particle size group (objective response rate=53.6%, P=0.012). The disease control rates of the small particle size group were 95.14%, 83.33%, and 74.53%, while large particle size group were 91.24%, 81.58%, and 64.95%, respectively, with no statistically significant difference between the two groups. However, the incidence of postoperative biliary tumors (6.20%) was significantly higher in the small-size than large-size group (0.70%), and the difference was statistically significant ( P＜0.05, P=0.03). There were no statistically significant differences between other adverse events such as post-embolization syndrome, liver abscess, and myelosuppression. The median survival time of the small and large particle size groups was 31.8 months and 20.5 months, respectively, but the difference was not statistically significant ( P=0.182). Conclusions:In the treatment of hepatocellular carcinoma with D-TACE, the short-term curative effect of the small particle size group was better than large particle size group, but the incidence of biliary tumors was high, and D-TACE of different particle sizes had no significant effect on long-term survival.

Objective:To test the validity and reliability of the Perceived Stress Scale-14 items (PSS-14) applied in cancer survivors.Methods:Totally 652 cancer survivors (patients who had finished active treatments and were in convalescence) were selected and a field questionnaire survey was conducted among them.Exploratory factor analysis and confirmatory factor analysis were performed to test the construct validity of PSS-14.Correlation between the two dimensions (discriminant validity) and correlation between stress and quality of life were analyzed to further test its validity.The intemal consistency reliability,split-half reliability,retest reliability and sensitivity analysis were adopted to test the reliability of PSS-14.Results:Two common factors were extracted in the exploratory factor analysis.The cumulative percentage of variance explained was 60.8％.The index of confirmatory factor analysis were:TLI =0.92,CFI =0.93,SRMR =0.07,RMSEA =0.08.The correlation coefficient between the two dimensions of PSS-14 was-0.16 (P ＜0.001).The correlation coefficients between the score of PSS-14 and each dimension of EORTC QLQ-C30 were 0.24-0.55 (P ＜ 0.001).The Cronbach α coefficients of the whole scale and the two dimensions named "perceived coping ability" and "perceived distress" were 0.78,0.91 and 0.88 respectively.After the scale was split into two parts,the Cronbach α coefficients of each part were 0.66 and 0.60.The Spearman-Brown coefficient was 0.79.The Guttman split-half coefficient was 0.79.After one item was removed from the scale each time,the Cronbach a coefficients of the remaining items varied from 0.75 to 0.77.The retest reliability of the whole scale and the two dimensions were 0.89,0.86 and 0.85 respectively.Conclusion:PSS-14 shows favorable validity and reliability,suggesting the utility to assess stress of cancer survivors as a self-administered inventory.

Objective: To study the coping styles and its relationship with quality of life among part of the female breast cancer patients in Shanghai in 2014. Methods: In August of 2014, 1-3 block groups affiliated to Shanghai Cancer Rehabilitation Club were selected from each of the 17 districts of Shanghai by convenient sampling method. Respondents were recruited from these block groups via putting up posters in the community or top three hospitals nearby. The inclusion criteria were as follows: female, aged from 18 to 80 years old; the initial diagnosis or primary tumor was breast cancer, and active treatments including surgery, radiotherapy and chemotherapy were finished; capable of basic reading and comprehension, and there was no communication disorder; daily activities were not limited, and with no mental disorder or dysgnosia. Totally 2 205 respondents were included. Questionnaire survey was conducted to collect the information of demographic characteristics, disease characteristics, result of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and result of the Ways of Coping Inventory-Cancer Version (WOC-CA). 1 968 valid questionnaires were withdrawn. The results of respondent characteristics and WOC-CA were under descriptive analysis, and the differences of coping styles among groups of different demographic characteristics were compared using t test. In addition, we analyzed the correlation between respondents' coping styles and quality of life using partial correlation analysis. Results: The average age of the 1 968 respondents was (58.7±7.4) years old, and BMI was (24.4±5.4) kg/m². The score of positive coping styles was 2.04±0.41, and the score of negative coping styles was 1.79±0.33. The scores of Physical Functioning (PF), Role Functioning (RF), Cognitive Functioning (CF), Emotional Functioning (EF), Social Functioning (SF), and Global Health (GH) were 83.40±12.18, 90.80±15.92, 80.72±16.29, 84.67±15.19, 80.99±20.91, 65.27±21.21, respectively. Positive coping styles correlated with PF, EF, and GH positively, and the correlation coefficients were separately 0.581 (P=0.046), 0.593 (P=0.045), 0.770 (P<0.001). Negative coping styles correlated with RF, CF, EF, and SF negatively, and the correlation coefficients were separately-0.672 (P=0.021),-0.815 (P=0.005),-0.121 (P<0.001),-0.123 (P<0.001). Conclusion Part of the female breast cancer patients in Shanghai in 2014 mainly adopted positive coping styles, and in general the positive coping styles correlated with quality of life positively and negative coping styles correlated with quality of life negatively.

Objective To explore the source of endothelial cells in tumor vessels by A 549 tumor model with GFP nude mouse.Methods To establish the A 549 lung cancer models with GFP nude mice, expression of CD 31 was determined by immunofluorescence to label tumor vessels; to observe and take a picture of the tumor frozen section by confocal microscopy and invert microscope;expression of GFP in tumor vessels was determined by immunohistochemistry. Result The results of immunofluorescence showed:Tumor interstitial vascular endothelial cells or endothelial cells clusters and micro-vascular lumen size and shape are clearly visible by immunofluorescence, and part of vessels with no obvious lumen or irregular lumen.We can see green fluorescent in tumor cells of tumor tissue and endothelial cells which form of tumor vessels.The results of immunohistochemistry showed: expression of GFP was determined in cytoplasm of tumor stromal cells and endothelial cells in tumor vessels.Conclusion The endothelial cells which formed tumor neovessels that derived from GFP nude mice partly and the other part derived from tumor cells.