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
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Hep G2 Cells
;
Male
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Female
;
Mice
;
Cell Line, Tumor
;
Signal Transduction
;
Mice, Nude
;
PTEN Phosphohydrolase/metabolism*
;
Lysine/metabolism*
;
Middle Aged
2.Emergency single drainage tube and dual target thalamic hematoma ventricular drainage surgery based on body surface marker localization for the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus
Baoming JIA ; Jiankai ZHAO ; Lizhen WANG ; Xiguang ZHOU ; Hongsha PEI ; Yanli ZHANG ; Guo-Qiang FENG ; Hongbin KU
Chinese Journal of Nervous and Mental Diseases 2024;50(1):23-29
Objective To explore the application value of emergency temporal body surface positioning for single drain dual-target thalamic hematoma ventricular drainage in the treatment of thalamic hemorrhage breaking into ventricle with hydrocephalus.Methods A retrospective analysis was conducted on 223 patients with thalamic hemorrhage breaking into the ventricles with hydrocephalus,including a study group of 115 cases who underwent emergency single drain dual-target thalamic hematoma ventricular drainage surgery with temporal body surface positioning,and a control group of 108 cases who underwent emergency ventricular drainage first and then underwent stereotactic thalamic hematoma drainage surgery after the condition stabilized.Compare the differences in postoperative complications and treatment outcomes between two groups of patients,and evaluate the application value of temporal surface positioning for single drain dual-target thalamic hematoma ventricular drainage surgery in the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus.Results The postoperative rebleeding rates,hematoma clearance and death were 5.2%,87.5%±7.3%and 13.9%in the study group and 4.7%,90.2%±8.5%and 15.7%in control group,respectively.There was no significant difference between the two groups(P>0.05).The tube time,postoperative intracranial infection,Shunt dependent hydrocephalus,effective treatment and favorable prognosis of and the control group were(75.5±18.4)h,3.5%,19.1%,53.9%and 51.3%in the study group and(130.8±22.9)h,13.9%,35.1%,38.7%and 38.0%,respectively.The difference between the two groups was statistically significant(P<0.05).Conclusion Body surface landmark-guided emergency single drain dual-target thalamic hematoma ventricular drainage surgery for the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus is safe and reliable,and can improve the patient's prognosis.
3.Comparison of short-term outcomes between fluorescence method versus modified inflation-deflation method on thoracoscopic anatomical segmentectomy: a study based on propensity score matching
Baoming WANG ; Feng WU ; Dongchun MA ; Mingming WANG ; Tangbin LIU ; Congshu HUA ; Chaodong ZHANG ; Wensheng WANG ; Xiang DING ; Jian ZHAO ; Chen DAI
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(3):134-141
Objective:To investigate the application value of fluorescence imaging in single-port thoracoscopic anatomic segmentectomy.Methods:The clinical data of 280 patients (145 patients with fluorescence method and 135 patients with modified inflation-deflation method) who underwent thoracoscopic anatomic segmentectomy were retrospectively studied in the Anhui Chest Hospital from June 2020 to June 2021. There were 113 patients in the simple segmentectomy group and 167 patients in the complex segmentectomy group. The baseline data of the fluorescence method and the modified inflation-deflation method in the complex segmentectomy group were corrected by propensity score matching, and the perioperative results were compared between the groups.Results:There were no significant differences in segmental resection time, intraoperative blood loss, postoperative drainage, postoperative pain, postoperative extubation time, length of hospital stay, incidence of complications and cost of hand-holding between the fluorescence method and the modified method of the simple segmentectomy group.In the complex segmentectomy group, the time of segmental resection with the fluorescence method was significantly shorter than that with the modified inflation-deflation method( P<0.05), and other indexes had no significant difference. Conclusion:Fluorescence method single-port thoracoscopic anatomic segmentectomy has the same perioperative safety and short-term efficacy as modified inflation-deflation method, which can significantly shorten the operative time and improve the operative efficiency in complex anatomic segmentectomy.
4.Evaluation on measurement uncertainty of correction factors of fluconazole impurities determined by HPLC standard curve method
Ting XIAO ; Bufang MA ; Chen WANG ; Shangchen YAO ; Yanchun FENG ; Baoming NING
Journal of China Pharmaceutical University 2022;53(3):306-313
In this paper, the uncertainties of correction factors of fluconazole impurities determined by HPLC standard curve method were evaluated, and the main common factors affecting the accuracy of standard curve method were found, so as to improve the accuracy of the method.In this study, the corresponding fitting lines of fluconazole and its impurities A, B, C, D, F and I were established respectively, and the ratio of the slope of fitting lines of each impurity and its corresponding principal component was calculated as the correction factor of the impurity.Then on the basis of GUM method, the uncertainty of each impurity correction factor determined by standard curve method was evaluated according to the established uncertainty evaluation scheme of correction factor determination process.The correction factor and uncertainty of fluconazole impurities A, B, C, D, F and I were 1.068 ± 0.046, 0.102 ± 0.005, 0.0582 ± 0.0031, 1.382 ± 0.121, 0.802 ± 0.067 and 1.383 ± 0.119, respectively, and the coverage factor k was 2.Finally, the contribution rate of each uncertainty component was calculated.In the relative combined standard uncertainties urel(f) of fluconazole impurities A, B, C, D, F and I correction factors, the sum of contribution rate of slope uncertainty urel(K) of the linear equation of principal component and its impurity is more than 85%; in the slope uncertainties urel(K) of linear equation, the contribution rates of uncertainties of solution concentration in 8 of 12 data groups are more than 80%, and the contribution rates of uncertainties introduced by reference substance content in solution concentration are about 80%.It can be seen that the preparation of linear solution concentration is the most influential factor in the determination of impurity correction factor by standard curve method, followed by the linear fitting process.In the preparation process of linear solution concentration, the purity of reference substance is the most influential factor, followed by weighing and pipetting times.The conclusion can help the experimenters to better formulate experimental plans and ensure the accuracy of the results when doing similar work.
5.Diagnosis and treatment of 112 patients with solid pseudopapillary neoplasm of the pancreas
Zhikai JIAO ; Ningning FENG ; Yan DING ; Jionghui FU ; Yueshan ZHANG ; Baoming YANG ; Xi KANG ; Shunxiang WANG
Chinese Journal of General Surgery 2021;36(11):831-834
Objective:To study the clinicopathological features, diagnosis, treatment and prognosis of patients with solid pseudopapillary neoplasm of the pancreas (SPN).Methods:From Jan 2008 to Dec 2017, 112 pathology confirmed SPN patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University were followed up. The clinicopathological characteristics and diagnosis were analyzed.Results:Most SPN patients were young women, the ratio of male to female is 1∶7. SPN patients have no typical clinical symptoms. The preoperative diagnostic accuracy of SPN was 57.14% with imaging examination. Pathological diagnosis depends mainly on immunohistochemical staining. All patients underwent surgical resection. Follow-up ranged from 4 to 123 months. The mean follow-up time was 49 months. All patients were doing well and no recurrence or metastasis was found.Conclusions:SPN is a rare tumor with low malignant potential. Surgical resection is effective.
6.Diagnosis and treatment of multiple liver myopericytoma
Han GAO ; Heng CAO ; Yueshan ZHANG ; Baoming YANG ; Shunxiang WANG
Chinese Journal of Digestive Surgery 2019;18(10):998-1000
7.Development of Terahertz Imaging Technology in the Assessment of Burn Injuries.
Xinjian ZHU ; Xuan HE ; Pin WANG ; Dandan GAO ; Yan QIU ; Qinghua HE ; Baoming WU
Journal of Biomedical Engineering 2016;33(1):184-187
Terahertz waves have unique properties and advantages, which makes it gain increasing attention and applications in the biomedical field. Burns is a common clinical trauma. Since the water-sensitive and non-destructive characteristics of terahertz, terahertz imaging techniques can be used to detect burns. So far, terahertz imaging technology in the assessment of burn injuries has been developed from ex vivo to in vivo, and high-resolution images can be obtained through the gauzes and plasters. In this paper, we mainly introduces the application of terahertz imaging technology and development in the assessment of burn injuries.
Bandages
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Burns
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diagnosis
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Humans
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Terahertz Imaging
8.Dual source CT coronary angiography and selective coronary angiography for evaluation of coronary artery stenosis: a control study
Feng XU ; Yuanyuan BO ; Baoming ZOU ; Qinyan HU ; Zhengyi BAO ; Jingwu WANG ; Min XU
Journal of Interventional Radiology 2015;24(12):1044-1046
Objective To evaluate the diagnostic accuracy of dual source CT angiography (DSCTA) for coronary artery stenosis.Methods During the period from November 2012 to November 2013, a total of 210 patients with coronary artery disease underwent DSCTA and selective coronary arteriography (CAG). Taking CAG as the gold standard, the diagnostic accuracy of DSCTA for coronary artery stenosis was evaluated. Thirty patients receiving DSCTA and 30 patients receiving CAG were selected, and all of them underwent stent implantation in the anterior descending branch after imaging examination. The angiography positions, the used time of PCI and the used dosage of contrast agent were compared between the two groups. Results DSCTA was performed in 210 patients and a total of 2 630 segments of coronary stenosis or occlusion were detected. Compared with CAG, the diagnostic sensitivity, specificity, positive predictive value and negative predictive value of DSCTA were 95.4%, 96.2%, 91.3%and 100%respectively, which were not significantly different from those obtained by CAG (P=0.066). In performing DSCTA, 2-3 angiography positions were used (2-4 positions less than that of CAG), the used time of PCI was about 15 min (about 10 min less than that of CAG), and the mean used dosage of contrast agent was 48 ml (30-150 ml) (about half less than that of CAG). Conclusion DSCTA has higher accuracy in diagnosing coronary artery stenosis, quite similar to that of CAG. DSCTA is a safe, reliable and noninvasive examination method. Preoperative DSCTA can reduce exposure positions during angiography, can reduce the dosage of contrast agent, and can shorten the time of PCI as well, thus, iatrogenic radioactive radiation dose can be reduced.
9.Reliability and validity of Professional Quality of Life Scale among government staff in earthquake - stricken areas in China.
Weimin DANG ; Wenhong CHENG ; Hong MA ; Jin LIN ; Baoming WU ; Ning MA ; Rongke WANG ; Junting XU ; Tianhang ZHOU ; Xin YU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(6):440-443
OBJECTIVETo evaluate the reliability and validity of Professional Quality of Life Scale (ProQOL-30, 4th version, 30 items) among government staff in the Wenchuan earthquake-stricken areas
METHODSA total of 1,175 members of government staff in the Wenchuan earthquake-stricken areas were selected by convenience sampling and required to complete the ProQOL and Self-Reporting Questionnair (SRQ). The reliability and validity of the scale was evaluated by correlation analysis, t-test, and confirmatory factor analysis.
RESULTSItem-total correlation coefficients of the three subscales were 0.590 - 0.752, 0.389 - 0.603, and 0.340 - 0.647, respectively (P<0.05), and the average coefficients were 0.672, 0.482, and 0.555 respectively (P<0.05). The Cronbach's α coefficients of the three subscales were 0.864, 0.569, and 0.742 respectively, and the split-half reliabilities were 0.829, 0.490, and 0.677, respectively. P value was 0.88 in thE chi-square test of confirmatory factor analysis model. Goodness-of-fit indices of ProQOL-30 included GFI=0.895 NFI=0.856, CFI=0.895, RMSEA=0.063, and AGFI=0.912. For the ProQOL-28 as an optimized version o ProQOL-30, the Cronbach's a coefficients for burnout and trauma/compassion fatigue increased to 0.616 and 0.757, respectively. P value was 0.91 in the chi-square test of confirmatory factor analysis model test. Goodness-of-fit indices of ProQOL-28 were GFI =0.913, AGFI =0.924, NFI =0.900, CFI =0.913, and RMSEA =0.031 CONCLUSION: ProQOL-28 has good reliability and validity among government staff in the earthquake-stricker areas in China.
China ; Disasters ; Earthquakes ; Factor Analysis, Statistical ; Government ; Humans ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires
10.Effects of lead exposure on placental cellular apoptosis and endoplasmic reticulum stress in rats.
Yunying WANG ; Haiyan HU ; Hong LI ; Haiyan MA ; Fengsen XU ; Baoming QU
Chinese Medical Journal 2014;127(9):1744-1748
BACKGROUNDLead exposure during pregnancy contributes to fetal abortion and/or teratogenesis. Endoplasmic reticulum (ER) apoptosis can be induced by various pathological conditions when ER function is disturbed. However, it is unclear whether ER stress and apoptosis play a role in the etiology of lead-exposed disease status. We aimed to investigate whether lead induced placental apoptosis and subsequent toxicity is initiated by ER apoptosis via caspase-12.
METHODSSixty-three female Wistar rats were exposed to lead in drinking water during various gestational periods. Blood lead level was determined by atomic absorption spectrophotometry. Placental cytoplasmic organelles were examined by electronic microscopy. Placental caspase-12 mRNA expression was evaluated by qRT-PCR. TUNEL assay was used to determine the placental apoptosis.
RESULTSLead exposure significant induced ER apoptosis compared to that of the controls (P < 0.05), accompanied with increased caspase-12 mRNA expression. Significant differences of caspase-12 mRNA expression levels were observed among the four groups (F = 13.78, P < 0.05). Apoptotic index (AI) was significantly increased in experimental groups compared to that of the controls (F = 96.15, P < 0.05). In lead-exposed groups, trophoblast cells underwent degeneration and fibrin deposition; Mitochondria were swollen and decreased in number; ER swelling, expansion, and vacuolization were observed.
CONCLUSIONLead exposure contributes to placental apoptosis, as well as increased caspase-12 mRNA expression, which in turn promoted ER stress.
Animals ; Apoptosis ; drug effects ; Endoplasmic Reticulum Stress ; drug effects ; Female ; Lead ; toxicity ; Placenta ; cytology ; ultrastructure ; Pregnancy ; Rats ; Rats, Wistar

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