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Results of the IMbrave150 clinical study showed that atezolizumab plus bevaci-zumab have better overall survival and progression-free survival than sorafenib in the treatment of hepatocellular carcinoma patients. However, hepatocellular carcinoma patients with esophageal varices were not included in the IMbrave150 clinical study mainly considering the bleeding risk of patients undergoing treatment of bevacizumab. The authors introduce the atezolizumab plus bevaci-zumab treatment of an advanced hepatocellular carcinoma patient with moderate esophageal varices. By reducing the dose of bevacizumab, the patient achieved an excellent curative effect.
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Aim To assess the effects of Banqiao Codonopisis Pilosula(BCP)decoction on learning and memory dysfunction in AD model rats induced by high activity GSK-3β and its possible mechanism.Methods The SD rats(4 months old,♂)were divided into five groups,namely,sham-operated group(blank group),AD model group,BCP high-dose(2.16 g·kg-1·d-1)group,BCP medium-dose(1.08 g·kg-1·d-1)group,and BCP lower-dose(0.54 g·kg-1·d-1)group.Treatment group received BCP decoction by gavage once a day for 14 days,while other groups were offered drinking water by gavage once a day for 14 days.The autonomous behavior activities of all rats were observed and recorded after gavage.In the last seven days by gavage,Morris water maze test was used to test the spatial learning and memory ability of the five groups.After five days training,treatment groups and AD model group were injected wortmannin(WT,PI3K specific inhibitor)and GF-109203X(GFX,PKC specific inhibitor)(100 μmol·L-1 of each,total volume of 10 μL)into the right lateral ventricle of the rats.The blank group was only injected 2％DMSO.The spatial memory retention was detected by water maze 24 hours after lateral ventricle injection.Then,changes in the spatial learning memory of rats were observed.The level of Tau phosphorylation in SD rat hippocampus and the expression and activity changes of related protein kinase GSK-3β were detected by Western blot and immunohistochemistry.The changes of Nissl bodies in SD rat hippocampus were observed by Nissl′s staining.Results After intragastric administration of BCP,the rat autonomous behavior activities in each group all showed a declining trend,and the differences in low-dose and middle-dose groups had statistical significance compared with blank group.The Morris water maze tests showed that the latency navigation of model group was significantly longer than that of blank group(P<0.01),while that of the BCP three doses groups was shorter than that of model group(P<0.05).Compared with the same group,the latency navigation of the three groups after gavage BCP low,middle and high dose was significant shorter than that without gavage(P<0.05).Western blot results showed that the activity of GSK-3β in AD model group was up-regulated compared with the blank group.However,BCP inhibited activity of GSK-3β.Western blot and immunohistochemistry results showed the level of Tau phosphorylation in AD model group was increased compared with the blank group in the area of CA3(P<0.05).Compared with AD model group,the level of Tau phosphorylation was decreased in treatment group.Nissl′s staining results showed that dendritic spines in AD model group was significantly attenuated compared with the blank group(P<0.05).Far more dendritic spines were observed in treatment group than in AD model group.The number of Nissl′s bodies in neuron cells of hippocampus in hippocampal CA3 was obviously larger in treatment groups than in AD model group.These effect of BCP was dose-dependent.Conclusions BCP can prevent the learning and memory dysfunction in AD model rats induced by high activity of GSK-3β.The mechanism may be related to inhibiting GSK-3β activity and then reducing the level of phosphorylation of Tau and improving neural development.
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Objective To investigate the influence of classically activated macrophage (M1) on the proliferation of rheumatoid arthritis (RA) fibroblast-like synovial (FLS) and osteoarthritis (OA) FLS proliferation.Methods Human monocytes leukemia cells (THP)-1 were induced into M1 by lipopolysaccharides (LPS) and interferon gamma (IFN-γ),M1 specific surface molecular markers human leukocyte antigen (HLA)-DR and CD197 were detected by flow cytometry (FCM).RA-FLS and OA-FLS were co-cultured with M1 by transwell chambers,the proliferation of RA-FLS and OA-FLS were observed by crystal violet staining assay.MTS was used to detect cytokines secreted from M1 on the multiplication of RA-FLS and OA-FLS.TNF-α and IL-12 were detected by enzyme linked immunosorbent assay (ELISA).Paried student t test was used for statistical analysis.Results THP-1 were induced into M1 by LPS and IFN-γ,the expression rates of M1 surface specific molecular markers HLA-DR and CD197 were 78.25％ and 87.96％.Crystal violet staining showed that RA-FLS and OA-FLS proliferation were significantly inhibited after co-cultured with M1 48 h,RA-FLS and OA-FLS of each vision under microscope in co-culture groups were (64 ±30) and (85 ±23) respectively,while the RA-FLS and OA-FLS in separate culture groups were (467±87) and (263±78) respectively,the difference was statistically significant (t=7.459,3.791;P＜0.05).MTS assay indirectly reflected that the cytokines from M1 suppressed RA-FLS and OA-FLS proliferation (t=-7.155,-8.111;P＜0.05).The concentration of TNF-α in cell culture supernatants secreted from RA-FLS group and RA-FLS/M1 co-culture group respectively were (0.024±0.01 1) ng/ml and (0.832±0.241) ng/ml respectively,the concentration of IL-12 from the two groups were (0.033±0.015) ng/ml and (0.372±0.122) ng/ml respectively.TNF-α from OA-FLS and OA-FLS/M1 co-culture group respectively were (0.031±0.017) ng/ml and (0.852±0.323) ng/ml,IL-12 were (0.012±0.009) ng/ml,(0.373±0.144) ng/ml.Compared with FLS separate culture group,the concentration of TNF-α and IL-12 were obviously elevated (t=-4.997,-4.777,-4.407,-4.334;P were all ＜0.05).Conclusion M1 can significantly inhibite RA-FLS and OA-FLS proliferation,this may be related to the increased concentration of TNF-α and IL-1 β in from cell culture supernatant.
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Objective This study was performed to investigate the effect of hypoxia on glucose-6-phosphate isomerase (G6PI) expression and cell cycle of fibroblast-like synoviocytes from synovium of rheumatoid arthritis (RA) and osteoarthritis (OA) under hypoxia or normoxia.Methods Fibroblast-like synoviocytes were cultured with either of hypoxia (3％ oxygen) or normoxia (21％ oxygen) for 24 hours.The mRNA expression of G6PI and HIF-1α was tested by PCR quantification,while the protein levels of G6PI and HIF-1α were measured by western blot.Cell cycle was performed by FACS.T-test and Mann-Whitney U were used for statistical analysis.Results The expression levels of G6PI mRNA under hypoxia in RA were higher than those of OA (2.6±0.4 vs 1.5±0.4,P＜0.05).The protein levels of G6PI in RA were higher than those of OA (P＜0.05).The expression levels of HIF-1α mRNA under hypoxia in RA were higher than those of OA (2.9±0.8vs 1.4 ±0.4,P＜0.05).The protein levels of HIF-1α in RA were higher than those of OA (P＜0.05).The G1 phase ratio of cell cycle was decreased significantly under hypoxia than those of normoxia in RA ELs (t=1 1.31,P＜0.05).The S and G2 phase ratio of cell cycle were increased.Conclusion Hypoxia upregulates G6PI and HIF-1α expression and improves proliferation in fibroblast-like synoviocytes.
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Objective To investigate the clinical significance of IL-27 in hepatocellular carcinoma ( HCC) in the early stage , and to compare it with alpha-fetoprotein ( AFP) in diagnostic performance .Methods Enzyme-linked immunosorbent assay was used to detect the serum level of IL-27 in the HCC group and control group .Receiver operator characteristic ( ROC) curve was used to ana-lyze two indicators and the logistic regression model predicted value ( PRE) was obtained .Results The study indicated the concentra-tion of IL-27 in HCC group [(364.19 ±177.55)pg/ml] was significantly higher than the control group [(255.49 ±94.33)pg/ml], the area under the curve (AUC) of IL-27 and AFP were (0.804) and (0.818), respectively.Logistic regression obtained the regres-sion model PRE that contains AFP and IL-27, with a predicted area under the ROC curve for HCC (0.901), while the diagnostic sen-sitivity (84.8%) and specificity (96.7%) were significantly higher than the capability of individual diagnosis of each indicator .Con-clusions In this study we obtained the model which can be used for clinical diagnosis of hepatocellular carcinoma in future .
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OBJECTIVE@#To explore the effect of myeloid leukemia-1 (Mcl-1) gene on the proliferation and apoptosis of Hela cells and the sensitivity of cervical cancer chemotherapy by antisense technology.@*METHODS@#Mcl-1 antisense oligonucleotide(AS-ODN)was transfected into Hela cells with lipofectamine 2000. The expression of Mcl-1 was analyzed by Western blot, the cell viability was detected by MTT assay, and apoptosis was evaluated by flow cytometry.@*RESULTS@#Mcl-1 AS-ODN arrested the cell cycle at G1/S,greatly inhibited the cell growth and induced apoptosis. The sensitivity of Hela cells on chemotherapy was low. There was obvious increase in the apoptosis rate by chemotherapy drugs and growth inhibition rate after inhibiting the expression of Mc1-1.@*CONCLUSION@#Mcl-1 AS-ODN can not only inhibit Hela cell proliferation and induce apoptosis, but also increase the sensitivity of chemotherapy. Mcl-1 may be a potential target gene for cervical cancer chemotherapy.