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*

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

Objective:To compare the differences in chemical compositions before and after processing by different processing methods; To optimize the processing method of Atractylodes lancea Rhizoma.Methods:Atractylodes lancea Rhizoma was processed by stir-frying with bran and treating with rice washing water. The volatile and non-volatile components of raw Atractylodes lancea Rhizoma, bran-fried Atractylodes lancea Rhizoma and rice washing water treated Atractylodes lancea Rhizome were qualitatively analyzed by headspace gas chromatography-mass spectrometry (HS-GC-MS) and ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), and the differences in chemical composition before and after processing were compared.Results:The volatile components of the three different products were determined to have 18 common components, such as agarospirol, β-eudesol, etc. In addition, 86 non-volatile components were determined. The peak area response value of atractylodin, the index component prescribed by pharmacopoeia, decreased after processing, but there was little difference in bran stir-frying and rice-washed water frying.Conclusions:Different processing methods have certain effects on the chemical composition of Atractylodes lancea Rhizoma. Among them, the bran-frying method is superior in improving the quality of preparations, reducing production costs and improving production efficiency. The bran-fried product can be used as raw material for preparation production.

Public health laboratory testing involves a wide range of sample types,complex matrices,diverse target analytes with varying concentrations,and multiple application contexts with different analytical requirements.As a critical step in public health laboratory analysis and testing,sample pretreatment plays a decisive role in ensuring the reproducibility and efficiency of the analytical methods.It directly affects the accuracy,sensitivity,and reliability of testing results,as well as the feasibility of downstream analyses.Traditional sample pretreatment techniques face persistent challenges,including low efficiency,limited throughput,restricted universal applicability,high organic solvent consumption,and poor compatibility with downstream analytical procedures.These limitations constrain their capacity to meet the evolving demands of research and practice in public health and preventive medicine.In recent years,technological advances have focused on improving efficiency and automation,enhancing selectivity and sensitivity,facilitating online testing capabilities,and promoting environmental sustainability.Sample pretreatment techniques in public health laboratory testing have been undergoing progressive upgrades,and numerous novel technologies have emerged.The paper provides a comprehensive review of new technologies and applications in the field.We focused on the development of new materials,the application of artificial intelligence,connections for online processing,and the approaches tailored to the demands of specific testing settings.We also discussed sample processing for omics analyses and mass spectrometry imaging methods relevant to public health laboratory testing.These advances are expected to support the development of greener and higher-throughput sample pretreatment and foster innovation in the public health laboratory testing system.

Gastric cancer is one of the most common malignant tumors of the digestive tract globally, causing a heavy burden on society due to its high incidence and mortality rates. Patients with gastric cancer and peritoneal metastasis suffer poor prognosis, and peritoneal metastasis is a major factor in the recurrence and metastasis of gastric cancer. Currently, the diagnosis of peritoneal metastasis mainly relies on contrast-enhanced CT, PET-CT, and other imaging techniques, but these technologies have a limited capability to detect small lesion of peritoneal metastases. Laparoscopic exploration is still considered as the most reliable method to diagnose peritoneal metastasis of gastric cancer. It allows direct visualization of the abdominal cavity and peritoneal regions, facilitating the detection of metastases. Furthermore, it enables the collection of histological or cytological specimens for definitive pathological diagnosis. However, the area formed by the parietal peritoneum and visceral peritoneum is large and has many folds in space. To explore the tumor and peritoneum as comprehensively as possible, our team has proposed the "Four-Step Procedure" of laparoscopic exploration for gastric cancer to standardize the operation process of laparoscopic exploration, which is characterized by its safety, comprehensiveness, precision and ease of implementation. This article primarily discusses the limitation of routine clinical techniques in diagnosing peritoneal metastasis in gastric cancer and introduce the significant value of the "Four-Step Procedure" in diagnosing peritoneal metastasis in gastric cancer.

Gastric cancer is one of the most common malignant tumors of the digestive tract globally, causing a heavy burden on society due to its high incidence and mortality rates. Patients with gastric cancer and peritoneal metastasis suffer poor prognosis, and peritoneal metastasis is a major factor in the recurrence and metastasis of gastric cancer. Currently, the diagnosis of peritoneal metastasis mainly relies on contrast-enhanced CT, PET-CT, and other imaging techniques, but these technologies have a limited capability to detect small lesion of peritoneal metastases. Laparoscopic exploration is still considered as the most reliable method to diagnose peritoneal metastasis of gastric cancer. It allows direct visualization of the abdominal cavity and peritoneal regions, facilitating the detection of metastases. Furthermore, it enables the collection of histological or cytological specimens for definitive pathological diagnosis. However, the area formed by the parietal peritoneum and visceral peritoneum is large and has many folds in space. To explore the tumor and peritoneum as comprehensively as possible, our team has proposed the "Four-Step Procedure" of laparoscopic exploration for gastric cancer to standardize the operation process of laparoscopic exploration, which is characterized by its safety, comprehensiveness, precision and ease of implementation. This article primarily discusses the limitation of routine clinical techniques in diagnosing peritoneal metastasis in gastric cancer and introduce the significant value of the "Four-Step Procedure" in diagnosing peritoneal metastasis in gastric cancer.

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 paracan-cerous 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 immunohis-tochemistry 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 xeno-transplantation 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 hepatocel-lular 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 infec-tion,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 ex-pression levels and activity of HDAC2,as well as enhanced cell proliferation,clone formation,migra-tion,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 regula-tion of malignant behaviors in liver cancer cells through H3K27ac,the PI3K activator 740Y-P was intro-duced.Compared with the iHDAC2 group,the iHDAC2+740Y-P group exhibited increased prolifera-tion,clone formation,migration,invasion ability,tumor volume and mass in vivo,and elevated expres-sion 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 me-diating H3K27 acetylation,which promotes the occurrence and development of hepatocellular carcinoma.

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

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.

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.