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

In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

Objective To investigate the expression of angiopoietin 1 and 2(Ang1,Ang2)in diffuse large B-cell lymphoma(DLBCL)and its survival prognosis analysis.Methods Peripheral blood was collected from 32 patients with initially diagnosed DLBCL and 30 healthy volunteers(the health control group),and the serum Ang1 and Ang2 levels were detected by ELISA.The biopsy tissues from DLBCL patients and the resec-ted normal lymph node biopsy tissues in neck surgery of 25 patients with non-tumor lesions(the control group)were taken as the specimens.The immunohistochemistry was used to detect the expression of CD34 in lymphoid tissues and the microvessel density was calculated;the statistical analyses were carried out by combi-ning with the clinical characteristics of the DLBCL patients and the follow-up data.Results The serum Ang1 level in initially diagnosed DLBCL was higher than that in the healthy control group[(36.22±9.12)ng/mL vs.(30.92±13.37)ng/mL],and the serum Ang2 level in initially diagnosed DLBCL was higher than that in the healthy control group[(28.42±10.78)ng/mL vs.(23.81±3.68))ng/mL],and the differences were sta-tistically significant(P＜0.05).CD34 was highly expressed in the lymphoma tissues of the patients with DL-BCL,whereas CD34 in normal lymph node tissues was weakly expressed;the microvessel density count in the DLBCL group was increased compared with the normal lymph node group(25.5±4.4 vs.13.2±3.0,P＜0.05).The Ang1 expression level had no significant correlation with the gender,age,IPI score,clinical stage and COO subtype.The Ang2 expression was correlated with the clinical stage,Ang2 was lowly expressed in the patients with stage Ⅰ-Ⅱ DLBCL,while which was highly expressed in the patients with stage Ⅲ-Ⅳ(P＜0.05);Ang2 had no significant correlation with the gender,age,IPI score and COO subtype.The OS time had no significant difference between the patients with Ang1 low expression and the patients with Ang1 high expression(25.86 months vs.23.11 months,P=0.722);the OS time in the patients with Ang2 low ex-pression was significantly higher than in the patients with high Ang2 expression(32.24 months vs.17.66 months,P=0.002).In the univariate analysis,Ann Arbor stage,IPI score and Ang2 all were the prognostic factors affecting the patients'OS,while gender,age and Ang1 had no significant correlation with the patients'OS.In Cox multifactorial analysis,the Ann Arbor stage,IPI score and Ang2 all were the independent prog-nostic factors affecting the patients'OS.prognostic factors.Conclusion Ang1 and Ang2 are highly expressed in DLBCL patients and promote lymphoma angiogenesis;Ang2 affects the survival prognosis of DLBCL patients.

TCM dispensing is the most basic clinical pharmaceutical work of TCM.In recent years,based on the 9 key technologies of TCM dispensing,the TCM dispensing industry has ushered in great development,and innovative TCM dispensing information system and intelligent dispensing equipment have appeared.This article sorted out the current situation of TCM dispensing industry and looked forward to its future development route.The results showed that the introduction of new technology and new equipment in the key technical links of procurement acceptance,dispensing review,TCM decocting,medication guidance and so on have improved the quality of dispensing service and ensured the quality and safety of medication.In the development of modern TCM dispensing industry,it is necessary to improve the quality control standard system,service standard system and core equipment standard system in the standardization of dispensing technology;in terms of talent cultivation in the field of dispensing,it is necessary to focus on restructuring and building new educational models to cultivate new medical talents that intersect medical and engineering fields;in terms of informatization and intelligence,it is necessary to develop intelligent equipment that is more in line with the characteristics of TCM,and further promote and improve the"shared TCM pharmacy"model.Through improving the content of TCM clinical pharmaceutical care,developing new technology and equipment of TCM dispensing,and improving the level of dispensing service and education,it is expected to gradually realize the standardization,informatization and intelligent development of modern TCM dispensing industry.

Objective: To prospectively compare single-shot (SS) echo-planar imaging (EPI) and field-of-view optimized and constrained undistorted single-shot multiplexed sensitivity-encoding (FOCUS MUSE) for diffusion-weighted imaging (DWI) in evaluating thyroid-associated ophthalmopathy (TAO). Materials and Methods: SS EPI and FOCUS MUSE DWIs were obtained from 39 patients with TAO (18 male; mean ± standard deviation: 48.3 ± 13.3 years) and 26 healthy controls (9 male; mean ± standard deviation: 43.0 ± 18.5 years). Two radiologists scored the visual image quality using a 4-point Likert scale. The image quality score, signal-to-noise ratio (SNR), contrast-tonoise ratio (CNR), and apparent diffusion coefficient (ADC) of extraocular muscles (EOMs) were compared between the two DWIs. Differences in the ADC of EOMs were also evaluated. The performance of discriminating active from inactive TAO was assessed using receiver operating characteristic curves. The correlation between ADC and clinical activity score (CAS) was analyzed using Spearman correlation. Results: Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated significantly higher image quality scores (P < 0.001), a higher SNR and CNR on the lateral rectus muscle (LRM) and medial rectus muscle (MRM) (P < 0.05), and a non-significant difference in the ADC of the LRM and MRM. Active TAO showed higher ADC than inactive TAO and healthy controls with both SS EPI and FOCUS MUSE DWIs (P < 0.001). Inactive TAO and healthy controls did not show a significant ADC difference with both DWIs. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated better discrimination of active from inactive TAO (AUC:0.925 vs. 0.779; P = 0.007). The ADC was significantly correlated with CAS in SS EPI DWI (r = 0.391, P < 0.001) and FOCUS MUSE DWI (r = 0.645, P < 0.001). Conclusion FOCUS MUSE DWI provides better images for evaluating EOMs and better performance in diagnosing active TAO than SS EPI DWI. The application of FOCUS MUSE will facilitate the DWI evaluation of TAO.

‍Hepatitis E virus （HEV） infection can cause acute， fulminant， and chronic hepatitis and is thus a worldwide health problem. The general population has no obvious symptoms or only mild symptoms after HEV infection， and most symptoms are self-limited and are easily ignored in clinical diagnosis. Previous reports have shown that HEV infection can cause dysfunction in multiple systems， especially the blood system， in which it often leads to a series of adverse outcomes. Comprehensive evaluation， early diagnosis， and early intervention of these HEV-related diseases will greatly reduce the medical burden of individuals and society. With reference to the previous reports， this article reviews the blood system diseases associated with HEV infection.

Objective:To analyze the clinical characteristics of elderly patients with papillary thyroid cancer(PTC)by age grouping.Methods:The patients were divided into three groups according to age at diagnosis: old(≥60 years, 90 cases), middle(40-59 years, 359 cases)and young patients(<40 years, 203 cases). The clinical data of 652 patients with PTC who were admitted to the Department of Thyroid Surgery of Beijing Hospital from December 2019 to December 2021 were retrospectively analyzed.The patients were divided into elderly group(≥60 years old, 90 cases), middle-aged group(40-59 years old, 359 cases)and young group(<40 years old, 203 cases). The clinical characteristics, ultrasound characteristics and invasion-related factors of patients in different groups were analyzed by statistical methods.Results:Compared with the young and middle-aged group, the elderly patients with PTC had a higher proportion of microcarcinoma(75.6%, 75.2%, 61.4%, χ2=13.054, P=0.001), less cervical lymph node metastasis(24.4%, 34.3%, 58.1%, χ2=41.650, P<0.001), and lower proportion of metastatic lymph nodes(0.08, 0.14, 0.24, χ2=40.618, P<0.001). There was no significant difference in tumor location and extra glandular invasion among the three age groups(35.56%, 36.2%, 38.4%, χ2=0.959, P=0.545). Conclusions:Compared with the young and middle-aged groups, PTC showed low invasiveness in the elderly population.In addition to surgical treatment, for elderly patients with low-risk clinical characteristics, it is worth performing a further study on whether careful observation or palliative treatment can be selected after comprehensive evaluation.

【Objective】 To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. 【Methods】 The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. 【Results】 From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P<0.05); There was no difference in the financial expenditure required for collecting 10 000U blood among blood stations with different scales. 【Conclusion】 From 2017 to 2020, the blood stations with an annual collection volume more than 50 000 U demonstrated a higher financial expenditure and the per capita cost of serving population than those <50 000 U. The blood collection volume of blood stations is significantly correlated with the annual total expenditure and the per capita cost of serving population.

【Objective】 To explore the psychological experience of blood donors with blood donation-related vasovagal reaction (DRVR), so as to provide basis for improving the quality of blood donation services. 【Methods】 The real experience of 9 DRVR blood donors was analyzed using the phenomenological research method in qualitative research. 【Results】 The occurrence of DRVR caused distinct psychological conflict among blood donor. Blood donors lacked knowledge about blood donation and expected professional evaluation and continuous support. The occurrence of DRVR was an important reason for blood donor lapsing. 【Conclusion】 By resolving the distinct psychological conflicts of DRVR blood donors, establishing DRVR early warning evaluation and feedback system, as well as strengthening the construction of support system, blood collection and supply institutions can create a good humanistic and social environment for sustainable development of voluntary blood donation.

IDEAL framework and recommendations provide a scientific and integrated evaluation pathway for surgical innovations and other complex therapeutic interventions, and underline that the preliminary studies are needed to prepare for a successful randomized controlled trial. IDEAL framework provides a series of recommendations in terms of nature stages of surgical innovation. We have reported the introduction and reporting guidelines of the IDEAL framework and recommendations in our IDEAL series paper. This paper aimed to provide some empirical evidence, focusing specifically on stages 2a and 2b, to help surgeons and researchers to understand how to imply IDEAL framework and recommendations into their clinical practice.