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

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.

Objective To explore the clinical characteristics and prognosis of patients with malignant tumor of digestive system combined with venous thromboembolism(VTE).Methods The clinical data of 77 patients admitted in Beijing Hospital from January 2003 to April 2013 with digestive system malignant tumor complicated with VTE were retrospectively analyzed.The incidence,clinical features and prognosis of the patients with digestive system cancer were analyzed.Results Among 77 patients,57 cases of male and 20 cases of female were involved,with an average age of(68.7 ± 12.4)years,including 60 cases(77.9 ％)of adenocarcinoma.The pathological results showed that differentiated tumors accounted for 61.0％ (47/77).Among the 77 patients,pulmonary thromboembolism (PTE) accounted for 33.8 ％ (26 cases) and deep vein thrombosis(DVT)in the low extremities accounted for 66.2 ％ (51 cases).Among all the patients,the most common symptoms were dyspnea and swelling or pain in the extremities.The incidence of VTE was 24.7％ (19/77),13.0％(10/77),19.5％(15/77),5.2％(4/77),5.2％ (4/77),32.5％ (25/77) at 1,3,6,9,12,＞ 12 months after diagnosis of digestive system malignancies,respectively.By April 2013,the 54.5 ％ (42/77) patients died,among which 73.8 ％ (31/42) died of digestive system malignancies,11.9 ％ (5/42) died of PTE,14.3 ％ (6/42) died of other causes.The mortality rates at 1,3,6,9,12,＞ 12 months after the diagnosis of VTE were 20.8％ (16/77),6.5 ％ (5/77),13.0 ％ (10/77),5.2 ％ (4/77),2.6 ％ (2/77),6.5 ％ (5/77),respectively.The difference in VTE incidence between the group aged ≥65 years and group aged ＜65 years at 1,3,6,9 and 12 months after the diagnosis of tumors was not statistically significant(P =0.309).The differences in mortality(P =0.357) and in the median survival time(x2 =0.290,P =0.591) between the two groups were not statistically significant at 1,3,6,9 and 12 months after the diagnosis of VTE.Conclusions The risks for VTE are high in patients with digestive tract malignant tumor,advanced malignant tumor,poor histologic grade(poorly or moderately differentiation),and chemotherapy or surgery,which mostly occurs within 3-6 months after diagnosis.Most deaths occur within the 1st year after the diagnosis of VTE.

Objective To compare the diagnostic value of sound velocity(SV) and real-time ultrasonic elastography in differentiating benign or malignant of breast lesions.Methods 75 patients with 99 lesions were examined with the zone speed index technique and real-time ultrasonic elastography respectively.Then the SVs of the lesions were calculated and elastography of the lesions were scored with 5-scoring method.The ROC curves were constructed with histology as the golden standard.Results There was significant difference between the SVs of benign and malignant breast lesions(P =0.0001).1561 m/s was the best cufoff point.And the areas under the curves (AUC) of SV and real-time ultrasonic elastography were 0.842 and 0.968,respectively.There was significant difference between the two methods of AUC (P =0.023).The sensitivity,specificity and accuracy for SV were 81.5％,91.7％,88.9％,respectively.There was no significant difference between sensitivity,specificity and accuracy of the two methods(P =1.0,P =0.125,P =0.146).Conclusions Both SV method and real-time ultrasonic elastography are helpful in the evaluation of benign or malignant of breast lesions.

Objective To explore the application of contrast-enhanced scoring system in the diagnosis of breast tumor.Methods 249 patients with 260 lesions were examined by elastography and contrastenhanced ultrasound before surgery.All the lesions were scored according to the two different methods.Pathological results were made the golden criteria.The diagnosis accuracy of the two methods were compared.Results There were 145 benign and 115 malignant tumors.The diagnosis accuracy,specificity and sensibility of elastography were 85.0％,88.3％,80.1 ％ respectively.The critical value of contrastenhanced ultrasound was between 3 and 4.The diagnosis accuracy,specificity and sensibility of contrastenhanced ultrasound were 88.9％,87.6％,90.4％ respectively.Area under ROC curve of the two methods were 0.901 and 0.910,the difference was not statistically significant.Conclusions Contrast-enhanced ultrasound 5-point scoring system was an initial quantitative criterion for breast tumor diagnosis.The diagnosis accuracy was parallel to that of elastography.

Objective To investigate the mechanisms involved in cucurmosin-induced apoptosis of pancreatic cancer cell SW1990.Methods The expression of EGFR,PI3K,Akt,Bad,Caspase -9,mTOR,P70S6K-α,and 4E BP1 at the protein level were detected by western blot analysis,and RTPCR was used to determine EGFR mRNA expression.Results An increased concentration of cucurmosin showed a subsequent decrease in the expression of EGFR,PI3K,Akt,mTOR,P70S6Kα,and 4E -BP1,whereasthe expression of Bad and Caspase-9 were elevated.However,the mRNA expression of EGFR was unchanged.Conclusion Cucurmosin is shown to induce the apoptosis of pancreatic cancer cell SW1990 by down regulating the expression of EGFR and thus inactivating the PI3K/Akt/mTOR signaling pathway.

Objective To investigate the diagnostic value of strain ratio for differentiation breast benign and malignant solid lesions. Methods Two hundred and sixty-nine patients with 377 lesions (278 benign, 99 malignant) were included in the study. Ultrasonography found the lesions, then ultrasonic elastography got the strain images. By the strain ratio measure method equipped with the ultrasonic machine, strain ratio of the lesion was calculated. Compared with the pathologic diagnosis, the cut-off point of strain ratio was determined with receiver operating characteristic curve. Results There was significant difference between the strain ratio of benign and malignant lesions( P <0. 05). The cut off point of strain ratio was determined as 3. 08, Youden's index was 0. 88,sensitivity was 97. 38% ,and specificity was 91. 33%. Conclusions Strain ratio could be used to differentiate benign and malignant lesions in breast and would be a new diagnostic standard in future.

Objective To explore the value of improved elasticity scores in differentiating malignant and benign breast lesions. Methods A prospective study was done in 394 patients with 508 breast lesions confirmed by pathology and the elastographic images of the lesions were evaluated by using old and improved elasticity scores respectively. Results The elastographic images of the lesions could be evaluated and classified in all patients by improved elasticity scores but could not be evaluated and classified in 82 lesions by old elasticity scores. The accuracy of ultrasonic elastography for diagnosing benign and malignant breast lesions was 88.8% and 78.1%, respectively by old elasticity scores and improved elasticity scores. Conclusions The elastographic images of breast lesions were accurately evaluated by using improved elasticity scores, and the use of improved elasticity scores is helpful to reduce the biopsy which is not necessary.

Objective To analyze the value of color Doppler ultrasound in the diagnosis of lower extremity arterial disease in patients with type 2 diabetes mellitus.Methods A total of 800 patients with type 2 diabetes mellitus underwent color Doppler ultrasonography to examine anterior tibial artery (ATA),dorsalis pedis artery (DPA) and posterior tibial artery (PTA).Ultrasonic findings including vascular diameter,stenosis ratio and hemodynamics of lower extremity arterial disease were analyzed retrospectively.Results ATA and DPA had more plaques and stenosis than PTA.There was no statistical difference of vascular diameter,stenosis ratio and hemodynamics between left and right lower extremity artery in patients with type 2 diabetes mellitus including diabetic foot.Conclusion Color Doppler ultrasound is a useful method in the diagnosis of lower extremity arterial disease in patients with type 2 diabetes mellitus,providing information of stenosis ratio and hemodynamics of lower extremity artery,so as contributing to the clinical therapy of this disease.