1.The analysis of risk factors of early rebleeding after ruptured intracranial aneurysm embolization surgery
Sichen TAO ; Hua WANG ; Kun FU ; Yunan BAI
Chinese Journal of Postgraduates of Medicine 2012;35(20):10-12
ObjectiveTo investigate the risk factors of early rebleeding after ruptured intracranial aneurysm embolization surgery.MethodsForty-two patients with early postoperative rebleeding after ruptured intracranial aneurysm embolization surgery(study group) were enrolled,and 40 patients without early postoperative rebleeding after ruptured intracranial aneurysm embolization surgery at the same period was selected randomly as control group.Single factor and multiple factors were analyzed by non-condition Logistic regression model.ResultsThe single factor analysis result showed that age ≥50,history of hypertension,diabetes history,ruptured frequency number ≥2,combined with vasospasm,postoperative anticoagulation therapy,postoperative blood pressure fluctuation ≥ 30 mm Hg (1 mm Hg =0.133 kPa),pseudoaneurysm,fatal embolism and most embolism in study group [81.0%(34/42),76.2%(32/42),66.7%(28/42),76.2% (32/42),81.0% (34/42),76.2% (32/42),66.7% (28/42),66.7% (28/42),66.7% (28/42) ]had statistical differences compared with those in control group [57.5% (23/40),50.0% (20/40),37.5%( 15/40 ),50.0% ( 20/40 ),57.5% ( 23/40 ),47.5% ( 19/40 ),37.5% ( 15/40 ),37.5% (15/40),37.5% ( 15/40) ](P <0.05).Further multiple factors analysis showed that age ≥50,history of hypertension,ruptured frequency number ≥ 2,combined with vasospasm,postoperative anticoagulation therapy,postoperative blood pressure fluctuation ≥ 30 mm Hg were the independent risk factors of early postoperative rebleeding after ruptured intracranial aneurysm embolization surgery (P <0.05).ConclusionsAge ≥50,history of hypertension,ruptured frequency number ≥ 2,combined with vasospasm,postoperative anticoagulation therapy,postoperative blood pressure fluctuation ≥ 30 mm Hg are the independent risk factors of early postoperative rebleeding after ruptured intracranial aneurysm embolization surgery.The necessary interventions to these risk factors have important significance,and can lower the incidence of early postoperative ruptured rebleeding after ruptured intracranial aneurysm embolization surgery and improve the prognosis.
2.Study on the inhibitory effect of UBE2T on radiosensitivity of lung adenocarcinoma
Mengjia WU ; Yunan WANG ; Bo HE ; Yanyi LU ; Junzhu XU ; Zixuan SU ; Fengmin YIN ; Shujun LIU ; Yuju BAI ; Wei HU
Chinese Journal of Radiation Oncology 2023;32(6):519-525
Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.
3.Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia.
Bing-Jie GUO ; Yi RUAN ; Ya-Jing WANG ; Chu-Lan XIAO ; Zhi-Peng ZHONG ; Bin-Bin CHENG ; Juan DU ; Bai LI ; Wei GU ; Zi-Fei YIN
Journal of Integrative Medicine 2023;21(5):474-486
OBJECTIVE:
Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment.
METHODS:
The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.
RESULTS:
According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.
CONCLUSION
JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals
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Mice
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Humans
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Carcinoma, Hepatocellular/genetics*
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beta Catenin/pharmacology*
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Liver Neoplasms/genetics*
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Drugs, Chinese Herbal/therapeutic use*
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RNA, Messenger/therapeutic use*
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Cell Line, Tumor
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Cell Proliferation
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Cell Movement
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Gene Expression Regulation, Neoplastic