Objective To examine the immunoregulation of Celastrus orbiculatus extracts(COE),a traditional Chinese medicine,on maturation and function of dendritic cells(DCs)in vitro and in vivo.Methods In vitro,after treated with COE indifferent nontoxic concentrations(0,10,20,40,80,and 160 μg/mL)for 5 d,the surface immunological molecules andcytokine secretion of mice bone marrow-derived DCs in response to COE were analyzed by flow cytometric analysis(FACS)and enzyme linked immunosorbent assay(ELISA),respectively.In vivo,mouse hepatoma cells(Hepal-6,1 ×106)were injected sc and were treated with different dosages of COE(10,20 or 40 mg/kg/d).Effects on tumor growth were determined by tumor volume and histology analysis after 28 d administration of COE.The relative proportions ofmature DCs and CD8+ T cells were measured in mononuclear cells that had been isolated from spleen by FACS.Results COE stimulated IL-2 and IFN-γ secretion of DCs,simultaneously enhanced the maturation of DCs byenhancing immunological molecule(CD40,CDS0,CD86,H-2Kb,and I-Ab)expression in a dose-dependent manner.Furthermore,the chcmotactic responses of DCs were significantly higher in COE-treated than untreated DCs,in association with higher chcmokine receptor 7 expression.Furthermore,COE increased DCs produce IFN-γ and IL-2 ina dose-dependent manner when the concentration of COE less than 40 μg/mL,decreased DCs produce IL-10 and IL-4also in a dose-dependent manner.In in vivo studies,COE can not only suppress growth of malignant hepatocellularcarcinomas but also stimulate maturation of DCs,associated with strongly enhanced CD8+ CTL responses.ConclusionThese data provide new insight into the mechanism of action of COE and indicate that the stimulation of maturation andfunction of DCs by COE contributes to its immunoregulatory effects.

Heat shock protein 27 ( HSP27 ) is an endogenous protein that plays an important role in a great variety of physio-logical and pathological processes. It can express a large number under body stress conditions. Recent studies have shown estro-gen upregulates the expression of HSP27 through a number of ways, playing a perfect “triple protection” role. In the early stage of atherosclerosis, estrogen induces the phosphorylation of HSP27 via PI3K/Akt signaling pathway. Phosphorylation of HSP27 can resist the injury of vascular endothelial cells( VECs) through an antioxidant and anti-apoptotic pathway as well as the inhibition of cytochrome C. In the stage of forming foam cells, estrogen induces the expression and release of HSP27 from mac-rophages by stimulating the estrogen receptor β ( ERβ) , then HSP27 inhibits the LDL uptake and the release of proinflammato-ry cytokine by binding scavenger receptor A ( SR-A) . During the proliferation and migration of vascular smooth muscle cells ( VSMCs) , estrogen induces estrogen receptor α ( ERα) and protein phosphatase 2 ( PP2A) to form a complex that enhances the activity of PP2A, then it can lead to the dephosphorylation of HSP27 and finally inhibit cells proliferation and migration. In summary, the anti-atherosclerotic effect of estrogen is closely re-lated to the role of HSP27. Given the side effects of estrogen re-placement therapy( MHT) , regulating HSP27 may provide a no-vel therapy for the prevention and treatment of cardiovascular dis-eases in menopausal women clinically.

Objective To observe the effect of electroacupuncture on back three-acupoints ( namely bilateral Dazhu, Fengmen, Feishu) on the protein and mRNA expression of transforming growth factor-beta 1 (TGF-β1) and Smad3 in asthmatic rat airway remodeling model, and to explore its therapeutic efficacy and molecular mechanism. Methods Rat asthma model was established by inhalation of ovalbumin. After sensitization for 6 weeks, rats were killed. And then the airway morphological parameters of rats were measured by image analysis. The protein and mRNA expression of TGF-β1 and Smad3 in lung tissues were detected by immunohistochemistry and real-time quantitative polymerase chain reaction (qRT-PCR) respectively. Results Compared with the blank group, the standardized values of muscle cross-sectional area including airway smooth muscle area (WAm) /perimeter of the basement membrane (Pbm), and bronchial inner wall area (WAi)/Pbm were increased in the model group. The protein and mRNA expression levels of TGF-β1 and Smad3 were also increased in the model group. In electroacupuncture group, the above observation indexes were decreased, and the differences were statistically significant ( P<0.05 compared with the model group). Conclusion The experimental results indicated that back three-acupoint electroacupuncture has an effect on remodeling airway, and one of the mechanisms is probably associated with the regulation of TGF-β1/Smad3 signaling pathway.

Objective To explore the effects of an aerobic exercise of different durations on the binding capacity of NF-E2-related factor 2(Nrf2)/Kelch-like ECH-associated protein-1(Keap1) in skeletal muscle of mice.Methods Thirty C57BL/6J mice were divided into a control(0h) group,an acute exercise for 3 hours (3h) group and an acute exercise for 6 hours(6h) group.The mice ran on treadmill at the speed of 15 m/min for different durations.The mice were sacrificed immediately after exercise and collected skeletal muscles of legs.The high quality fluorescence assay was done to detect the reactive oxygen species(ROS) level in the skeletal muscles of mice.The binding capacity of Nrf2/Keap1 was detected using co-immunoprecipitation.The expression of Nrf2 and Keap1 was analyzed using the Western blotting.Result Compared with group 0h,the Nrf2/Keap1 binding capacity in skeletal muscles of group 3h and 6h decreased significantly(P＜0.05),but the total Nrf2 in skeletal muscles increased significantly(P＜0.05).No significant differences were observed in the expression of total Keapl.The expression of Nrf2 protein of group 3h and 6h increased significantly compared with 0h,with that of group 6h significantly higher than group 3h(P＜0.05).The ROS level in skeletal muscles of group 6h increased significantly compared with group 0h(P＜0.05).Conclusion The effect of acute aerobic exercise on Nrf2/Keap1 binding capacity in skeletal muscle of mice depends on its duration.

This study was aimed to investigate whether the extracts of Celastrus orbiculatus enhanced the invasion function of maspin tumor inhibitor gene through the construction of maspin overexpression human gastric carcinoma MGC803 cell line. Maspin was cloned into plasmid GV208-EGFP eukaryotic expression vector. And then, the recombinant plasmid GV208-maspin-EGFP was transfected into human gastric carcinoma MGC803 cells. After the maspin overexpression MGC803 cell were treated with Celastrus orbiculatus extracts in different concentrations (10, 20, 40 μg·mL-1), the invasion effects were detected by Transwell chamber assay. The results showed that after the successful construction of maspin overexpression cell line, the number of cells invading through Matrigel was obviously decreased in the Transwell chamber assay. It also showed drug concentration dependency. It was concluded that maspin gene can inhibit invasion of gastric carcinoma MGC803 cells. Simultaneously, the extracts of Celastrus orbiculatus can enhance the function of maspin gene.

Objective:To investigate the clinical features,therapeutic methods,therapeutic efficacy,and prognostic characteristics of older patients with acute myeloid leukemia(AML).Methods:We collected data from 134 older patients with AML treated at Peking University International Hospital between January 2015 and February 2023.White blood cell count,bone marrow primitive cell count,cytogen-etic and molecular characteristics,and European LeukemiaNet(ELN)risk stratification at initial diagnosis were retrospectively ana-lyzed.Patients were assigned into two groups according to treatment plan―high-intensity chemotherapy and low-dose treatment―to determine whether intensive chemotherapy would yield survival benefits during treatment and the factors affecting survival.Results:Among 36 patients treated with high-intensity chemotherapy,22(61.1%)achieved complete response(CR);among 90 treated with low-intensity therapy,46(51.1%)achieved CR;and among 19 treated with azacitidine(AZA)+ venecra(VEN),14(73.7%)achieved CR.Medi-an overall survival(OS)was 15 months for high-intensity chemotherapy and 14.5 months for low-intensity treatment(P=0.226).According to ELN risk stratification,patients in the low,medium,and high risk groups exhibited OS of 18,14,and 9 months,respectively(P=0.009).OS for high-intensity chemotherapy and low-dose therapy was 22 and 15 months in the low-risk group(P=0.745),9 and 15 months in the medium-risk group(P=0.783),and 9 and 8 months in the high-risk group(P=0.739),respectively.Patients in the intensive chemotherapy group(n=36)had an OS of 15 and 17 months(P=0.689)compared with AZA+VEN treatment(n=19).The prognosis of six patients with TP53 mutation was significantly worse than those without the mutation,and the median OS was 2 months and 14 months,respectively(P=0.004).One-and 3-year survival rates for the low-,medium-and high-risk groups were 79%,53%,and 44%,and 41%,20%,and 3%,respectively.Multivariate analysis revealed that high peripheral blood white blood cell count(P=0.034),ELN risk stratification(P=0.002),and complications(P=0.017)were correlated with OS,while treatment intensity,age,sex,and bone marrow primitive cell count were not significantly correlated with OS.Conclusions:High-intensity chemotherapy did not yield a significant survival benefit in older patients with AML;however,this result needs to be confirmed in patients at low risk.Patients with TP53 mutations had a poor prognosis.Multivariate analyses revealed that baseline mo-lecular characteristics,leukocyte count,and comorbidities were more important than treatment intensity in predicting survival among older patients with AML.

【Objective】 To investigate the relationship between hepatitis B virus X （HBx） protein and EGFR promoter， and the role of HBx protein in activating EGFR/PI3K/p-Akt signaling pathway and inhibiting apoptosis. 【Methods】 EGFR promoter plasmids were constructed and the relationship between HBx and EGFR promoters was characterized using a luciferase reporter assay. EGFR-overexpressing trophoblast cells were constructed， and EGFR expression in the overexpressing cells was knocked down using EGFR shRNA. The expression and localization of EGFR/PI3K/p-Akt were detected by Western blotting and confocal laser microscopy. Cell apoptosis was analyzed using flow cytometry. HBV plasmids carrying either full-length HBx or HBx with a deletion mutation （ΔHBx） and HBx plasmids were transfected into two types of trophoblast cells； HBx and PI3K/p-Akt protein expressions were detected by Western blotting. Cell apoptosis was analyzed using flow cytometry. 【Results】 Co-transfection of HBx and EGFR promoter plasmids in JEG-3 and HTR-8/Svneo cells significantly elevated the expression of EGFR promoter driven luciferase compared with the control group （P<0.01）. In EGFR-overexpressing cells， the expression of PI3K/p-Akt was significantly increased （P<0.01）， whereas the apoptosis rate was significantly decreased for JEG-3 cells and HTR-8/Svneo cells （both P<0.01）. These results were reversed in the EGFR-knock down group. When the intracellular HBx protein was expressed in JEG-3 and HTR-8 cells， PI3K/p-Akt protein expression was significantly increased （both P<0.05）， and the proportion of apoptosis was significantly decreased （both P<0.05）. 【Conclusion】 In placental trophoblast cells， HBx protein activates the expression of EGFR by acting on the EGFR promoter， and inhibits the apoptosis of trophoblast cells via the downstream EGFR/PI3K/p-Akt signaling pathway.