Five compounds were isolated and purified from the water extract of Elaeagnus oxycarpa Schlechtend leaf by multi-dimensional reversed-phase preparative liquid chromatographic system based on the separation and enrichment model. Their structures were identified by spectral analysis such as NMR, MS, UV, IR and by comparison with literature information as 2,4(1H,3H)-pyrimidinedione (1), elaeagnussugarester B (2), elaeagnussugarester A (3), elaeagnussugarester C (4), gallic acid (5). Compounds 2-4 are new compounds, compound 1 was isolated from Elaeagnus oxycarpa Schlechtend for the first time. The antioxidant and anti-tyrosinase activities of these compounds were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical method, the potassium ferricyanide reduction method and the colorimetric method with L-tyrosine as substrate. The results showed that compounds 2-5 have good antioxidant activities and inhibitory effect on tyrosinase. Compound 4 exhibited the most strong antioxidant activities, with IC₅₀ = 3.59 ± 0.06 μmol·L^-1 for DPPH free radical scavenging ability, IC₅₀ = 10.04 ± 0.20 μmol·L^-1 for ABTS free radical scavenging ability, and total reduction capacity of compound 4 was better than vitamin C respectively. Compound 3 possessed better inhibitory effect on tyrosinase with IC₅₀ = 0.25 ± 0.06 mmol·L^-1.

Objective: To determine the heterogeneity for caries prevention service preferences among children in Anhui Province, so as to provide reference for the promotion and popularization of caries prevention services for school age children. Methods: Based on a discrete selection experiment, a face to face questionnaire survey was administered using a multi stage sampling method among 785 parents with children 3-12 years of age who were hospitalized in the stomatology clinics of 7 prefectures and cities in Anhui Province from October 2021 to October 2022. A mixed Logit model was used to evaluate caries prevention service preferences for children. Results: Four discrete choice experiment attributes included in the study were statistically significant for choice preference ( P <0.05). Compared with the control group, parents with a high school education or above preferred caries prevention services with 70%-<80% preventive effectiveness, 2-<5 and <2 km from the service point, and a high service cost ( β =0.38, 1.66, 1.64, 0.00); female parents preferred preventive services with 70%-<80% preventive effectiveness and a high service cost ( β =0.35, 0.01 ); parents of children <7 years of age preferred services with 70%-<80% preventive effectiveness ( β =0.75); parents of children with oral health preferred preventive services during winter and summer vacations ( β =-0.28); parents of children with caries preferred preventive services with a high cost per denticle ( β =0.00)( P <0.05). Conclusions Parents with different education levels, gender, child age, and oral health status have heterogeneity in dental caries prevention service preferences. The provision of targeted and precise services can improve the participation and coverage of caries prevention services for school age children.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

ObjectiveGQDs has become a superstar among zero-dimensional carbon-based materials. As one of the most abundant and important biological elements, its unique optical properties, high dispersion and biocompatibility have attracted extensive attention from scientists. This paper aims to investigate the effect of GQDs on cell viability, apoptosis and inflammatory factor expression in RAW264.7 macrophages and evaluate cell imaging capability of GQDs in vitro, which could provide theoretical basis for the safe application of GQDs in biomedical field. MethodsGraphene oxide was prepared by modified Hummer’s method. H₂O₂ and W₁₈O₄₉ interacted with each other under hydrothermal conditions to produce hydroxyl radicals, which can cut graphene oxide into GQDs using a top-down approach. The microstructure of GQDs was analyzed in detail by X-ray powder diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, atomic force microscopy, scanning electron microscopy and Fourier infrared transform. The biocompatibility of GQDs on macrophage was evaluated by CCK-8 and dead/alive staining. Flow cytometry results showed the apoptosis of RAW264.7 macrophages induced by GQDs. mRNA expression of inflammatory factors was evaluated byRT-qPCR. Cell imaging was exhibited by laser scanning confocal. ResultsHydroxyl radicals are produced by H₂O₂ and W₁₈O₄₉ under hydrothermal conditions, which contribute to cut graphene oxide into 3-5 nm GQDs in one step. The quantum yield of this method is 43%. Fluorescence lifetime of these blue GQDs is 1.67 ns. The Zigzag-type site and defect state of the triplet carbene radical lead to the excitation wavelength dependence of GQDs, and the optimal excitation and emission wavelengths are 330 nm and 400 nm, respectively. The boundary effect and amphiphilicity of quantum dots make GQDs possess abundant functional groups, vacancy defects and high dispersion, which results in GQDs exhibits good water solubility. RAW264.7 macrophages are incubated with different concentration in DEME medium for 24 h, 48 h and 72 h to evaluate cell. The survival rate of RAW264.7 cells is significantly dependent on the concentration and time of GQDs. CCK-8 and dead/alive staining show that GQDs have high biocompatibility. The effect of 200 mg/L GQDs on apoptosis of RAW264.7 cells is revealed by the scatter plot of bivariate flow cytometry. Under the stimulation of LPS+INF‑γ, the expression of TNF-α was increased in RAW264.7 cells, which co-acted with other cytokines to participate in the immune response of RAW264.7 cells in vitro, and mediated the production of IL-1β inflammatory factor in RAW264.7 cells, thereby inducing apoptosis of RAW264.7 cells. The results of RT-qPCR showed that GQDs can inhibit the growth of RAW264.7 cells in vitro, and stimulate them to increase TNF-α expression in RAW264.7 cells, which make cell membrane rupture and produce IL-1β inflammatory factors to induce cell apoptosis. The high biocompatibility of GQDs is attributed to the rich oxygen-containing functional groups (―COOH, ―OH, and CO) on the surface of GQDs, which makes its surface negatively charged and easy to be swallowed into the cell interior when interacting with the cell membrane with low affinity. Transmission electron microscopy (TEM) observed that the GQDs were swallowed into the cells. Furthermore, laser confocal results displayed that blue GQDs has certain ability of cell imaging in vitro. ConclusionThe water solubility, low toxicity, fluorescence properties and the induction effect of inflammatory factors of GQDs provide broad prospects for their application in the field of immunotherapy and cell imaging in the future.

Objective This study is to explore the clinical efficacy and common adverse reactions of PEG-IFN α-2b combined with TMF and TDF in the treatment of hepatitis B liver fibrosis,and provide more clinical reference for the treatment of chronic hepatitis B.Methods From January 2022 to December 2023,we selected 130 patients with chronic hepatitis B liver fibrosis who were admitted to Kunming Third People's Hospital.Divided into TMF combined group and TDF combined group,the virus reduction level,virus response rate,liver fibrosis four items,instantaneous elastography(FibroScan)and other indicators were compared between the two groups of patients after 48 weeks of treatment.The changes in liver fibrosis grading and adverse reactions before and after treatment were also compared.Results After 48 weeks of treatment,the TMF combined group showed a significant increase in HBV DNA seroconversion rate and HBeAg seroconversion rate compared to the TDF combined group,with statistical significance(P<0.05).However,there was no statistically significant difference in HBsAg seroconversion rate between the two groups of patients(P>0.05).After 48 weeks of treatment,the TMF combined group showed more significant efficacy in reducing the levels of HA,PC Ⅲ,Ⅳ-C,and LN,with a significant difference(P<0.05);After 48 weeks of treatment,both groups of patients showed improvement in the degree of liver tissue fibrosis.Compared with the TDF combined group,the TMF combined group had a more significant effect on tissue improvement.After 48 weeks of treatment,the incidence of dyslipidemia,hypothyroidism,and diarrhea was higher in the TMF combined group than in the TDF combined group(P<0.05);After 48 weeks of treatment,there was no statistically significant difference in the incidence of gingival bleeding,anemia,and thrombocytopenia between the two groups of patients(P>0.05);The incidence of elevated uric acid and joint pain in the TDF combined group was higher than that in the TMF combined group after 48 weeks of treatment(P<0.05).Conclusion TMF combined with PEG-IFN α-2b has better clinical efficacy in treating chronic hepatitis B,strong antiviral ability,greater inhibition of liver fibrosis,good drug safety,better prognosis,and can provide more effective medication basis for clinical cure of hepatitis B.

Objective To explore the value of the combination of serum hemoglobin A1c(HbA1c),Alarin and Ficolin-3 in predicting adverse pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods From March 2021 to March 2023,129 GDM patients who underwent prenatal examination and hospital delivery in Yantai Yeda Hospital were collected as the GDM group,while 133 pregnant women with normal glucose tolerance test results were regarded as the control group.Fully automated glycated hemoglobin analyzer was applied to detect serum HbA1c level.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum Alarin and Ficolin-3 levels.Pearson method was used to analyze the correlation between serum HbA1c,Alarin,Ficolin-3 levels and 2 hour postprandial glucose(2 h PG),fasting blood glucose(FBG)and homeostasis model assessment method for insulin resistance(HOMA-IR)in GDM patients.Logistic regression was applied to analyze the relationship between HbA1c,Alarin,Ficolin-3 levels and adverse pregnancy outcomes in GDM patients.Receiver operating characteristic(ROC)curve was plotted to analyze the value of serum HbA1c,Alarin and Ficolin-3 levels in predicting adverse pregnancy outcomes in GDM patients.Results The 2 h PG,FBG,HOMA-IR,and serum HbA1c,Alarin,and Ficolin-3 levels were significantly higher in the GDM group than those in the control group(P＜0.05).The serum levels of HbA1c,Alarin and Ficolin-3 were positively correlated with 2 h PG,FBG and HOMA-IR in GDM patients(P＜0.05).The serum HbA1c,Alarin and Ficolin-3 levels were greatly higher in GDM patients with poor blood glucose control than those in GDM patients with good blood glucose control(P＜0.05).The above levels of three indicators in GDM patients with adverse pregnancy outcomes were significantly higher than those in GDM patients without adverse pregnancy outcomes(P＜0.05).Elevated levels of HbA1c,Alarin and Ficolin-3 were independent risk factors for adverse pregnancy outcomes in GDM patients(P＜0.05).The area under the curves of HbA1c,Alarin and Ficolin-3 alone and in combination were 0.840,0.865,0.815 and 0.979,respectively in predicting adverse pregnancy outcomes in GDM patients.Conclusion The serum HbA1c,Alarin and Ficolin-3 levels are abnormally elevated in GDM patients,and the combined detection of the three can improve the value in predicting adverse pregnancy outcomes.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.