1.HDAC2-mediated H3K27 acetylation promotes the proliferation and migration of hepatocellular carcinoma cells.
Shaohai TANG ; Baoming YANG ; Jiankun LI ; Lili ZHAO ; Yifan WANG ; Shunxiang WANG
Journal of Peking University(Health Sciences) 2025;57(5):884-894
OBJECTIVE:
To explore the specific mechanism of histone deacetylase 2 (HDAC2) mediated histone H3 lysine 27 acetylation (H3K27ac) modification in promoting the proliferation and migration of hepatocellular carcinoma cells.
METHODS:
Samples of 40 cases of hepatocellular carcinoma and paracancerous tissues resected from January 2021 to January 2023 were collected. The expressions of HDAC2 and H3K27ac in hepatocellular carcinoma, paracancerous tissues and cell lines were detected by immunohistochemistry and Western blotting. The correlation between the expression levels of HDAC2 and H3K27ac and the relationship between HDAC2 expression and clinicopathological characteristics of patients with hepatocellular carcinoma were analyzed. The proliferation, migration and invasion of Hep3B and HepG2 cells were determined by MTS, clone formation, scratch and Transwell experiments. The acetylation of H3K27 mediated by HDAC2 was verified by Western blotting, real-time fluorescence quantitative PCR (qRT-PCR) and chromatin immunoprecipitation high-throughput sequencing (ChIP-seq). In vivo xenotransplantation experiment, the tumorigenicity of cells in each group was measured, and the expression of proteins related to phosphoinositide 3-kinases/phosphatase and tensin homolog deleted on chromosome ten/protein kinase B/mammalian target of rapamycin (PI3K/PTEN/AKT/mTOR) signal pathway was detected.
RESULTS:
High expression of HDAC2 and low expression of H3K27ac were found in hepatocellular carcinoma tissues and cell lines (P < 0.05), and there was a negative correlation between them (r=-0.477, P=0.002). The expression of HDAC2 was related to tumor size, hepatitis B virus infection, TNM stage and portal vein tumor thrombus (P < 0.05). Compared with the sh-NC group of Hep3B and HepG2 cells, the proliferation, clone formation, migration and invasion ability of sh-HDAC2 group were decreased (P < 0.05). Compared with the Empty group, the HDAC2 group exhibited increased expression levels and activity of HDAC2, as well as enhanced cell proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and elevated expression levels of p-PI3K, p-AKT, and p-mTOR (P < 0.05). Conversely, the enrichment and expression levels of H3K27ac, along with the expression level of PTEN, were decreased (P < 0.05). In the iHDAC2 group, the expression levels and activity of HDAC2, as well as the proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and expression levels of p-PI3K, p-AKT, and p-mTOR were reduced (P < 0.05). Additionally, the expression levels of H3K27ac and PTEN were increased (P < 0.05). To validate the involvement of the PI3K/PTEN/AKT/mTOR signaling pathway in HDAC2-mediated regulation of malignant behaviors in liver cancer cells through H3K27ac, the PI3K activator 740Y-P was introduced. Compared with the iHDAC2 group, the iHDAC2+740Y-P group exhibited increased proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and elevated expression levels of p-PI3K, p-AKT, and p-mTOR (P < 0.05). Conversely, the expression level of PTEN was decreased (P < 0.05).
CONCLUSION
HDAC2 initiates PI3K/PTEN/AKT/mTOR signal pathway by mediating H3K27 acetylation, which promotes the occurrence and development of hepatocellular carcinoma.
Humans
;
Carcinoma, Hepatocellular/metabolism*
;
Liver Neoplasms/metabolism*
;
Histone Deacetylase 2/physiology*
;
Cell Proliferation
;
Acetylation
;
Cell Movement
;
Histones/metabolism*
;
Animals
;
Hep G2 Cells
;
Male
;
Female
;
Mice
;
Cell Line, Tumor
;
Signal Transduction
;
Mice, Nude
;
PTEN Phosphohydrolase/metabolism*
;
Lysine/metabolism*
;
Middle Aged
2.Pre-action Neuronal Encoding of Task Situation Uncertainty in the Medial Prefrontal Cortex of Rats.
Qiulin HUA ; Yu PENG ; Jianyun ZHANG ; Baoming LI ; Jiyun PENG
Neuroscience Bulletin 2025;41(11):2036-2048
Humans and animals have a fundamental ability to use experiences and environmental information to organize behavior. It often happens that humans and animals make decisions and prepare actions under uncertain situations. Uncertainty would significantly affect the state of animals' minds, but may not be reflected in behavior. How to "read animals' mind state" under different situations is a challenge. Here, we report that neuronal activity in the medial prefrontal cortex (mPFC) of rats can reflect the environmental uncertainty when the task situation changes from certain to uncertain. Rats were trained to perform behavioral tasks under certain and uncertain situations. Under certain situations, rats were required to simply repeat two nose-poking actions that each triggered short auditory tone feedback (single-task situation). Whereas under the uncertain situation, the feedback could randomly be either the previous tone or a short musical rhythm. No additional action was required upon the music feedback, and the same secondary nose-poking action was required upon the tone feedback (dual-task situation); therefore, the coming task was uncertain before action initiation. We recorded single-unit activity from the mPFC when the rats were performing the tasks. We found that in the dual task, when uncertainty was introduced, many mPFC neurons were actively engaged in dealing with the uncertainty before the task initiation, suggesting that the rats could be aware of the task situation change and encode the information in the mPFC before the action of task initiation.
Animals
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Prefrontal Cortex/cytology*
;
Uncertainty
;
Neurons/physiology*
;
Male
;
Rats
;
Rats, Long-Evans
;
Action Potentials/physiology*
;
Acoustic Stimulation
3.Summary of best evidence for nursing management of percutaneous external bone fixation needle paths
Liling SU ; Xiaojie LIAN ; Baoming LI ; Yan SUN
Chinese Journal of Practical Nursing 2024;40(23):1809-1816
Objective:To search and evaluate the relevant evidence of percutaneous external fixation needle care management, and integrate the evidence to provide the best nursing management strategy for clinical needle care.Methods:BMJ best clinical practice, UpToDate, PubMed, CINAHL, ProQuest, CNKI, Wanfang database and other domestic and foreign databases related to clinical practice guidelines, evidence summary, expert consensus, systematic evaluation, randomized controlled trial were searched. The search period was from database inception to November 2023. Evaluated the quality of the included literatures, and conduct evidence extraction, level evaluation and evidence summary analysis.Results:A total of 11 articles were included, including 1 guideline, 1 evidence summary, 3 systematic reviews, 2 expert consensus, and 4 randomized controlled trials. The 10 pieces of best evidence were summarized in 5 categories, including needle evaluation, cleaning management, scab management, disinfection management, and dressing management.Conclusions:This study summarized the best evidence on the management of percutaneous external fixation needle care, and provides evidence- based basis for clinical nurses to perform needle care. In clinical practice, evidence should be selectively and reasonably applied in combination with clinical situations and relevant factors to promote the improvement and development of clinical nursing work.
4.Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats.
Hongyu SUN ; Siyu HE ; Li WU ; Zeying CAO ; Xian SUN ; Mingwei XU ; Shan LU ; Mingdi XU ; Baoming NING ; Huimin SUN ; Tiqiao XIAO ; Peter YORK ; Xu XU ; Xianzhen YIN ; Jiwen ZHANG
Acta Pharmaceutica Sinica B 2022;12(1):326-338
Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.
5.Automatic three-dimensional segmentation of liver and tumors regions based on conditional generative adversarial networks.
Zelin ZHANG ; Baoming LI ; Jun XU
Journal of Biomedical Engineering 2021;38(1):80-88
The three-dimensional (3D) liver and tumor segmentation of liver computed tomography (CT) has very important clinical value for assisting doctors in diagnosis and prognosis. This paper proposes a tumor 3D conditional generation confrontation segmentation network (T3scGAN) based on conditional generation confrontation network (cGAN), and at the same time, a coarse-to-fine 3D automatic segmentation framework is used to accurately segment liver and tumor area. This paper uses 130 cases in the 2017 Liver and Tumor Segmentation Challenge (LiTS) public data set to train, verify and test the T3scGAN model. Finally, the average Dice coefficients of the validation set and test set segmented in the 3D liver regions were 0.963 and 0.961, respectively, while the average Dice coefficients of the validation set and test set segmented in the 3D tumor regions were 0.819 and 0.796, respectively. Experimental results show that the proposed T3scGAN model can effectively segment the 3D liver and its tumor regions, so it can better assist doctors in the accurate diagnosis and treatment of liver cancer.
Humans
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Image Processing, Computer-Assisted
;
Liver Neoplasms/diagnostic imaging*
;
Tomography, X-Ray Computed
6.The expression of C1q/TNF-related protein-1 in patients with acute ischemic stroke and its predictive value for the severity of neurological deficits
Suping LI ; Yan XIE ; Fei XU ; Yi LIANG ; Baoming HE ; Hong-Bin SUN
The Journal of Practical Medicine 2018;34(10):1672-1675
Objective To investigate the expression of C1q/TNF-related protein-1(CTRP1)in patients with acute ischemic stroke and its predictive value for the severity of neurological deficits. Methods A total of 452 patients with newly diagnosed ischemic stroke(IS)from February 2014 to February 2017 in our hospital were selected as the study subjects,and 403 healthy subjects were selected as control group in the physical examination center. The National Institutes of Health Stroke Scale(NIHSS)was used to evaluate the neurological status of pa-tients at admission and at 6 months after discharge. The expression of CTRP1 in plasma was detected by enzyme-linked immunosorbent assay(ELISA). Multiple linear regression was used to analyze the relationship between neu-rological deficit and CTRP1. Results The expression level the CTRP1in the healthy control group[(119.53 ± 17.62)ng/mL],unexplained causes IS[(145.81 ± 18.96)ng/mL],large atherosclerotic IS[(153.17 ± 19.21) ng/mL],cardiac IS[(156.56 ± 20.96)ng/mL]and small artery occlusion IS[(169.23 ± 22.34)ng/mL]in-creased gradually with statistically significant difference(P < 0.05). The level of CTRP1in the healthy control group[(119.53 ± 17.62)ng/mL],mild neurologic impairment group[(156.29 ± 19.86)ng/mL],moderate neuro-logic impairment group[(168.74 ± 18.53)ng/mL]and severe neurologic impairment group[(175.96 ± 19.15)ng/mL]increased gradually with statistically significant difference (P < 0.05). Multiple linear regression analysis showed that CTRP1,age,diabetes,Hs-CRP and LDL-C were independent factors of neurological deficits at 6 months after discharge in IS patients. Conclusion CTRP1 can effectively predict the severity of neurological defi-cits in patients with acute IS.
7.The comparison of CT features and pathologic changes of pulmonary sclerosing pneumocytoma
Zhengjun LI ; Baoming DONG ; Dingping CAI ; Peng YE ; Yongqian QIANG
Journal of Practical Radiology 2016;32(10):1525-1528
Objective To analyze CT morphologic features and pathologic changes of pulmonary sclerosing pneumocytoma (PSP) and to improve preoperative diagnostic accuracy of PSP.Methods The clinical and CT data of 12 cases with PSP (with total 13 lesions)confirmed by surgery and pathology were collected and analyzed retrospectively.All cases performed CT plain scan,9 cases had contrast CT scan.Results 1 1 cases had isolated lesions,and 1 case multiple lesions.The long-axis diameter ranged from 1.10 cm to 8.03 cm, with an average of (3.53±0.78)cm.Of 13 lesions,3 located in left lung (23.1%,1 in the upper lobes,2 in lower lobe),and 10 in right lung (76.9%,2 in upper lobe,2 in the middle lobe and 6 in lower lobe);8 lesions located in the lower lobe (61.5%),and 5 in upper and middle lobe (38.5%).There were center type of 4 lesions (30.8%),and peripheral type of 9 lesions (69.2%);The shapes of 8 lesions wereovoid or similar round (61.5%),irregular type of 1 case (7.7%),shallow lobe of 4 cases (30.8%);Smooth edge of 10 cases (76.9%), burr edge in 3 cases (23.1%).With contrast CT scan,7 cases (53.8%)had vascular welt sign,6 cases (46.2%)had air crescent sign,6 cases (46.2%)had halo sign,and 6 cases (46.2%)had tail sign.3 lesions (23.1%)had scattered spot calcification,and the other lesions had uniform density.The CT value ranged from 28 HU to 47 HU,with the average of 35 HU;Of 9 cases (with 10 lesions)with contrast CT scan,2 lesions had mild enhancement,5 cases had obvious enhancement,and 3 case had non-uniform enhancement.Enhanced CT value was 60-1 10 HU,with the average of 77.2 HU,and with the maximum of 75 HU.Conclusion If the pulmonary nodules or masses in middle-aged females had single round or ovoid shape,with about 3 cm diameters,soft-tissue density,smooth edge,and with obvious enhancement after contrast CT scan,and accompanied by vascular welt sign,air crescent sign,halo sign,or tail sign, the diagnosis of PSP should be considered.
8.Effect of zein/chitosan composite membrane on the osteogenic differentiation of bone marrow mesenchymal stem cells
Chunliang LI ; Feng QIN ; Linchang LI ; Baoming TANG ; Zhaowei LI
Chinese Journal of Tissue Engineering Research 2016;20(21):3071-3079
BACKGROUND:Some scholars have prepared zein/chitosan composite membrane based on blending methods, and preliminary evaluation ofitsphysical and chemical properties showsthat chitosan partly improvesthe mechanical properties and hydrophilic properties of zein. Therefore, zein/chitosan composite membrane presumably has good cytocompati bility, which is beneficial to osteogenic differentiation of bone marrow mesenchymal stem cels.
OBJECTIVE:To explore the effect of zein/chitosan composite membrane on the differentiation of bone marrow mesenchymal stem cels into osteoblasts and its feasibility asabone tissue-engineered material.
METHODS:With 60% acetic acid as solvent, zein/chitosan composite membrane was prepared by blending and casting method. The structure and physicochemical properties of the composite membrane were investigated by Fourier transform infrared spectroscopy, tensile testing, water absorption testing and scanning electron microscopy. And the cytocompatibility of the membrane was evaluated byin vitrocel cufture. Besides,bone marrow mesenchymal stem celsfrom Sprague-Dawley ratwere isolatedvia adherence screening method, andthe effects of thecompositemembrane on theosteogenic differentiation ofthese celswere observedby scanning electron microscopy, fluorescent labeling and alkaline phosphatase assay.
RESULTS AND CONCLUSION:The tensile strength, water absorption and hydrophilicity of the films were improved with the chitosan increased; chitosan could promote cel proliferation indicating the good cytocompatibility of the composite films. Moreover, osteogenic induction occurredin bone marrow mesenchymal stem cels cultured on the compositem embrane, and with an increase of chitosan, the induction was promoted. In conclusion, zein/chitosan composite membrane can be applied widely in the field of bone tissue engineering.
9.Rapid measurement of 210Po in seafood with large area grid ionization chamber α spectrometry
Yucheng LI ; Liangliang YIN ; Fei CHEN ; Xianzhang SHAO ; Baoming SHEN ; Xiangyin KONG ; Yanqin JI
Chinese Journal of Radiological Medicine and Protection 2015;35(5):367-370
Objective To develop a rapid and reliable method for determination of 210Po using large-area grid ionization chamber α spectrometry.Methods Samples were digested using a microwave digestion system.After preparation of sample source,the concentration of 210Po in clam was detected by large-area grid ionization chamber (φ 25 cm).209Po tracer was used to obtain the recovery.Results Large-area grid ionization chamber could achieve better counting and α spectrum resolution when the optimized thickness was 250 μg/cm2.By spiking 209Po tracer in clam,the minimum detectable activity was 9.870 × 10 4 Bq and the recovery of 210Po was 98%.Conclusions Compared with the traditional method,the developed method can avoid separation process,using less quantity of sample (0.2-0.5 g dry) and simplify the measurement process.This method may be has broad application prospects.
10.Determination of α-radionuclides in environmental samples by large area grid ionization chamber
Liangliang YIN ; Xianzhang SHAO ; Baoming SHEN ; Yucheng LI ; Yanqin JI
Chinese Journal of Radiological Medicine and Protection 2015;35(6):461-464
Objective To develop the method of analyzing α-radionuclides using large area grid ionization chamber.Methods Ultrasonic dispersion and vacuum drying system was used to prepare sample source,large standard thin source and plutonium plane source were used to optimize the working condition of spectrometer,and calibrate the instrument for analyzing α emitters.The certified reference materials (GBW04127) were used to verify the accuracy of the method.Results The non-linearity of calibration curve for standard thin sources of neptunium,plutonium and americium was less than 0.2%,and the resolution were 112,84 and 106 keV,respectively.The counting efficiency was 31.2% for the large standard thin source.The values of specific activity measured in this way were in good agreement with those of the certified reference materials.232Th,238U,230Th,234U/226Ra,210Po,222Rn and 218Po were analyzed in a uranium mineral sample,and their specific radioactivity values were 5.3,3.8,35.6,21.4,27.0,19.6 and 11.1 Bq/g,respectively.Conclusions The method can be used to analyze α spectrum quickly in low-level radioactive environmental samples.

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