Repurposing of the FGFR inhibitor AZD4547 as a potent inhibitor of necroptosis by selectively targeting RIPK1.

Necroptosis is a form of regulated necrosis involved in various pathological diseases. The process of necroptosis is controlled by receptor-interacting kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase domain-like protein (MLKL), and pharmacological inhibition of these kinases has been shown to have therapeutic potentials in a variety of diseases. In this study, using drug repurposing strategy combined with high-throughput screening (HTS), we discovered that AZD4547, a previously reported FGFR inhibitor, is able to interfere with necroptosis through direct targeting of RIPK1 kinase. In both human and mouse cell models, AZD4547 blocked RIPK1-dependent necroptosis. In addition, AZD4547 rescued animals from TNF-induced lethal shock and inflammatory responses. Together, our study demonstrates that AZD4547 is a potent and selective inhibitor of RIPK1 with therapeutic potential for the treatment of inflammatory disorders that involve necroptosis.

Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1 pathway.

Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.

Iron-Based Metal-Organic Frameworks as Platform for H2S Selective Conversion: Structure-Dependent Desulfurization Activity.

Three classical Fe-MOFs, viz., MIL-100(Fe), MIL-101(Fe), and MIL-53(Fe), were synthesized to serve as platforms for the investigation of structure-activity relationship and catalytic mechanism in the selective conversion of H2S to sulfur. The physicochemical properties of the Fe-MOFs were characterized by various techniques. It was disclosed that the desulfurization performances of Fe-MOFs with well-defined microstructures are obviously different. Among these, MIL-100(Fe) exhibits the highest catalytic performance (ca. 100% H2S conversion and 100% S selectivity at 100-180 °C) that is superior to that of commercial Fe2O3. Furthermore, the results of systematic characterization and DFT calculation reveal that the difference in catalytic performance is mainly because of discrepancy in the amount of Lewis acid sites. A plausible catalytic mechanism has been proposed for H2S selective conversion over Fe-MOFs. This work provides critical insights that are helpful for rational design of desulfurization catalysts.

The dentin permeability of anti-inflammatory and antibacterial drugs: In vitro study.

BACKGROUND/PURPOSE: Stimuli from the oral cavity may penetrate through exposed dentinal tubules and evoke inflammatory pulp response. Anti-bacterial and anti-inflammatory drugs applied to exposed dentin may infiltrate through the dentinal tubules and cause pulp recovery. This study investigated the dentin permeability of anti-bacterial and anti-inflammation drugs via an in-vitro transwell dentin disc tube model. METHODS: Twenty-seven dentin discs prepared from extracted human molars were collected. Nine kinds of drugs were investigated with three dentin discs in each group. These nine drugs included two anti-bacterial drugs (ampicillin sodium and clindamycin phosphate), two corticosteroids (betamethasone sodium phosphate and hydrocortisone sodium succinate), three non-steroidal anti-inflammatory drugs (NSAIDs, piroxicam, lysine acetylsalicylate, and diclofenac sodium), and two natural extracts with anti-inflammatory effect (Ginsenoside Rg1 and Hinokitol). The drugs were introduced to the transwell dentin disc tube model and the 4-hour cumulative release of the drug was detected and recorded by UV-visible spectroscopy. RESULTS: We found that ampicilin sodium had better dentin permeability than clindamycin phosphate. Betamethasone sodium phosphate revealed better dentin permeability than hydrocortisone sodium succinate. Lysine acetylsalicylate showed the best dentin permeability among the three NSAIDs. Ginsenoside Rg1 had the best dentin permeability among the nine drugs tested. However, Hinokitiol could not penetrate the dentin disc after 4 h. CONCLUSION: Regarding the dentin permeability, Ginsenoside Rg1 is the best among the seven anti-inflammatory drugs tested and ampicilin sodium is the better one between the two anti-bacterial drugs tested. Therefore, these two drugs may have high potential for treating exposed dentinal tubule diseases.

Amino-Modified Fe-Terephthalate Metal-Organic Framework as an Efficient Catalyst for the Selective Oxidation of H2S.

Classical amino-functionalized Fe-terephthalate metal-organic framework NH2-MIL-53(Fe) and its parent framework MIL-53(Fe) were prepared via simple hydrothermal methods. The catalytic performaces of these two Fe-MOFs were explored for the selective oxidation of H2S. The physicochemical properties of the fresh and used Fe-MOFs catalysts were investigated by XRD, BET, SEM, FT-IR, CO2-TPD, and XPS techniques. It was found that the introduction of amino groups reduces the activation energies for H2S oxidation and endows this catalyst surface with moderate basic sites. As a result, the NH2-MIL-53(Fe) catalyst displays high H2S conversion and near 100% S selectivity in the temperature range of 130-160 °C, outperforming commercial Fe2O3 and activated carbon. Moreover, a plausible reaction route for H2S selective oxidation over NH2-MIL-53(Fe) is proposed. This work opens up the possibility of utilizing MOFs as efficient catalyst for desulfuration reactions.

Burden of biliary tract carcinoma in China (1990-2021): Findings from the 2021 Global Burden of Disease Study.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.

Use of the cardiopulmonary coupling index based on refined composite multiscale entropy for prognostication of acute type A aortic dissection.

Objectives: The aim of this study is to assess the influence of cardiopulmonary coupling (CPC) based on RCMSE on the prediction of complications and death in patients with acute type A aortic dissection (ATAAD). Background: The cardiopulmonary system may be nonlinearly regulated, and its coupling relationship with postoperative risk stratification in ATAAD patients has not been studied. Methods: This study was a single-center, prospective cohort study (ChiCTR1800018319). We enrolled 39 patients with ATAAD. The outcomes were in-hospital complications and all-cause readmission or death at 2 years. Results: Of the 39 participants, 16 (41.0%) developed complications in the hospital, and 15 (38.5%) died or were readmitted to the hospital during the two-year follow-up. When CPC-RCMSE was used to predict in-hospital complications in ATAAD patients, the AUC was 0.853 (p < 0.001). When CPC-RCMSE was used to predict all-cause readmission or death at 2 years, the AUC was 0.731 (p < 0.05). After adjusting for age, sex, ventilator support (days), and special care time (days), CPC-RCMSE remained an independent predictor of in-hospital complications in patients with ATAAD [adjusted OR: 0.8 (95% CI, 0.68-0.94)]. Conclusion: CPC-RCMSE was an independent predictor of in-hospital complications and all-cause readmission or death in patients with ATAAD.

[Pollution Characteristics of Carbonaceous Components in PM10 and PM2.5 of Road Dust Fall and Soil Dust in Xi'an].

To investigate the pollution characteristics of carbonaceous components in PM10 and PM2.5 of road dust fall and soil dust in Xi'an and enrich their source profiles, samples from five sites of road dust fall and 16 sites of soil dust were collected in Xi'an from April to May 2015. The ZDA-CY01 particulate matter resuspension sampler was used to obtain PM10 and PM2.5 samples, and the Model5L-NDIR OC and EC analyzer were used to determine the concentrations of organic carbon (OC) and elemental carbon (EC) in PM10 and PM2.5. The pollution and sources of carbonaceous aerosol in PM10 and PM2.5 were investigated by analyzing OC and EC characteristics, ratio, and the principal component analysis statistical model. The results showed that the proportions of OC in PM10 and PM2.5 at the various dust fall sites differed, ranging from 6.0% to 19.4% and 7.6% to 29.8%, respectively. The ratios of EC in PM10 and PM2.5at the different dust fall sites were relatively small, accounting for 0.6%-2.2% and 0.2%-3.6% in urban sites, respectively; however, EC was almost undetectable in most peripheral soil dust. The proportions of carbonaceous components in PM10 and PM2.5 followed the order of urban road dust fall>external control dust>river beach soil dust>soil dust and urban road dust fall>soil dust>external control dust>river beach soil dust, respectively. OC dominated the carbonaceous aerosols at the different sites, which was relatively low in urban road dust fall. The OC to total carbon (TC) ratios in PM10 and PM2.5 at urban road dust fall were 85.2%-95.3% and 87.9%-98.9%, respectively. The OC to TC ratios in PM10 and PM2.5 of soil dust were relatively high, exceeding 99%. Carbonaceous components were primarily concentrated in fine particles. The pollution distribution of carbonaceous components in the urban road dust fall sites was consistent, whereas that in the different soil dust sites were quite different. The carbonaceous components in urban road dust fall and soil dust were primarily affected by pollutant source emissions such as biomass burning, coal burning, gasoline, and diesel vehicle exhaust. There were differences in the source contribution rates of carbonaceous aerosols in PM10 and PM2.5.

GRB10 is a novel factor associated with gastric cancer proliferation and prognosis.

GRB10 and its family members GRB7 and GRB14 were important adaptor proteins. They regulated many cellular functions by interacting with various tyrosine kinase receptors and other phosphorus-containing amino acid proteins. More and more studies have shown that the abnormal expression of GRB10 is closely related to the occurrence and development of cancer. In our current research, expression data for 33 cancers from the TCGA database was downloaded for analysis. It was found that GRB10 was up-regulated in cholangiocarcinoma, colon adenocarcinoma, head and neck squamous carcinoma, renal chromophobe, clear renal carcinoma, hepatocellular carcinoma, lung adenocarcinoma, lung squamous carcinoma, gastric adenocarcinoma and thyroid carcinoma. Especially in gastric cancer, the high GRB10 expression was closely associated with poorer overall survival. Further research showed that the knockdown of GRB10 inhibited proliferation and migration ability in gastric cancer. Also, there was a potential binding site for miR-379-5p on the 3'UTR of GRB10. Overexpression of miR-379-5p in gastric cancer cells reduced GRB10-regulated gastric cancer proliferation and migration capacity. In addition, we found that tumor growth was slower in a mice xenograft model with knock down of GRB10 expression. These findings suggested that miR-379-5p suppresses gastric cancer development by downregulating GRB10 expression. Therefore, miR-379-5p and GRB10 were expected to be potential targets for the treatment of gastric cancer.

Nrf2/PHB2 alleviates mitochondrial damage and protects against Staphylococcus aureus-induced acute lung injury.

Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2-/- mice after 6 h of intraperitoneal injection. A cell model simulating SA-ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA-sepsis patients, negatively correlated with the severity of ALI. In SA-ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation-induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA-ALI. The p-Nrf2/total-Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA-treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual-luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA-ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.

[The effects of p38MAPK and HBxAg on cell proliferation and apoptosis in human hepatocarcinogenesis].

OBJECTIVE: To investigate the effects of host-derived p38 mitogen-activated protein kinase subunit 38 (p38MAPK) and the hepatitis B virus X antigen (HbxAg) on cell proliferation and apoptosis in human hepatocellular carcinoma (HCC), and to study the mechanism underlying hepatocarcinogenesis. METHODS: Liver tissues were biopsied from healthy individuals and patients with chronic hepatitis B (CHB), liver cirrhosis, paratumor cirrhosis, and HCC. Immunohistochemical staining was used to detect expressions of HBxAg, p38MAPK, cell cycle G2/M phase-related factors (cdc25B, p34cdc2, cyclin B1), and cell proliferation factor ki-67.The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method (known as TUNEL) was used to detect apoptosis. RESULTS: The highest rates of HBxAg were detected in CHB (65.0%) and HCC (44.4%) liver samples, and the antigen was mainly expressed in nuclei. Increasingly higher rates of p38MAPK, cdc25B, cyclin B1, and p34cdc2 expression were detected with increases in disease severity: normal liver (40.0%, 20.0%, 20.0%, and 30.0%, respectively), chronic hepatitis B (60.0%, 65.0%, 40.0%, and 50.0%, respectively), liver cirrhosis (65.0%, 75.0%, 70.0%, and 55.0%, respectively), paratumor cirrhosis (66.7%, 75.0%, 75.0%, and 63.9%, respectively), and HCC (77.8%, 80.6%, 80.6%, and 72.2%, respectively). In addition, the intracellular location of p38MAPK expression was different under different disease conditions, showing nuclear expression in CHB and liver cirrhosis samples and cytoplasmic expression in paratumor cirrhosis and HCC samples (x2 = 1.11, P more than 0.05). The proliferation index (PI) and the apoptosis index (AI) were both increased along with disease severity (normal more than CHB more than paratumor cirrhosis more than HCC) (PI: 0.0000+/-0.000, 0.0502+/-0.011, 0.0411+/-0.009, 0.0762+/-0.017; AI: 0.0351+/-0.024, 0.0607+/-0.022, 0.0562+/-0.013, 0.0716+/-0.011), with the notable exception for liver cirrhosis (PI: 0.1810+/-0.036 and AI: 0.1200+/-0.018). PI in poorly-differentiated HCC (0.2285+/-0.062) was significantly higher than in well-differentiated HCC (0.1216+/-0.032, t = 2.082, P = 0.044). AI in well-differentiated HCC (0.152+/-0.026) was significantly higher than in poorly-differentiated HCC (0.081+/-0.022, t = 2.129, P = 0.041). CONCLUSIONS: In the process of hepatocarcinogenesis, HBxAg may cause a series of abnormal changes in cell cycle, proliferation and apoptosis by affecting the expression of p38MAPK.

[Temporal and Spatial Variations in Black Carbon Aerosol in Different Atmospheric Background Stations in China from 2006 to 2020].

Black carbon (BC) aerosol emissions are complex and have important environmental and meteorological effects. In China, the temporal and spatial variations in BC in different atmospheric environmental conditions need to be fully understood. Based on the long-term observational BC data in seven atmospheric background stations in China from 2006 to 2020, combined with meteorological data, emission source data, enhanced vegetation index (EVI) data, and aerosol optical depth (AOD) data, we comprehensively analyzed the characteristics of temporal and spatial variations, long-term evolution, and influencing factors of BC in China. The results showed that the BC and AOD values of different atmospheric environments in China were quite different, and BC positively contributed to AOD. The spatial distribution was high in the east and low in the west owing to the differences in emission sources and meteorological conditions. The ρ(BC) and AOD values were higher to the east of the "Hu Huanyong" line, such as at the Mt. Longfeng, Shangdianzi, Lin'an, and Jinsha stations, where the average values were (1699±2213)-(3392±2131) ng·m-3 and 0.36±0.32-0.72±0.37, respectively. These values were lower to the west of the "Hu Huanyong" line, such as at the Akedala, Mt. Waliguan, and Shangri-La stations, where the average values were (287±226)-(398±308) ng·m-3 and 0.20±0.13-0.22±0.19, respectively. The interannual variability in BC included differences between different atmospheric background stations, which could be divided into four categories:low interannual variability, such as at the Akedala station; an initial increase followed by a decrease and subsequent stabilization, such as at the Mt. Waliguan station; an initial decrease followed by stabilization, such as at the Shangri-La station; and an initial stabilization followed by a decrease, such as at the Mt. Longfeng, Shangdianzi, Jinsha, and Lin'an stations. Seasonal variations in BC included differences in different atmospheric background stations. The BC mass concentrations were lowest in autumn and higher in winter and spring west of the "Hu Huanyong" line and were highest in winter and lowest in summer east of the "Hu Huanyong" line. BC contributed to the AOD being larger in all stations in the spring and summer and contributed less at the stations west of the "Hu Huanyong" line in autumn and the stations east of the "Hu Huanyong" line in winter. The diurnal variations in BC were mainly bimodally distributed in the different atmospheric background stations, but the peak times varied in different stations and seasons.

Crocin Alleviates Intracerebral Hemorrhage-Induced Neuronal Ferroptosis by Facilitating Nrf2 Nuclear Translocation.

Intracerebral hemorrhage (ICH) is the deadliest type of stroke. Oxidative stress was considered to play an important role in ICH-induced secondary injury. Crocin, the main compound isolated from Crocus sativus L., possesses a potential anti-oxidative function in many types of diseases including ICH. In the current study, the protective role of crocin in ICH-induced brain injury was investigated in the ICH model. The ICH-induced brain edema and neurological deficits were analyzed by brain edema measurement and neurological testing. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity and the content of malondialdehyde (MDA) were assessed by a total superoxide dismutase assay kit. The expressions of ferroptosis-related genes were verified by quantitative real-time PCR (qPCR) and western blotting. The ICH-induced brain edema and neurological deficits were significantly decreased after treatment with crocin. Moreover, the SOD and GSH-px activities were obviously increased in the ICH with crocin-treated group compared with the ICH group, while the content of MDA was markedly decreased after treatment with crocin. Crocin inhibited ferroptosis of neuron cells, as evidenced by increased Fe2+ concentration and the expression of GPX4, FTH1, and SLC7A11. Mechanistically, crocin treatment increased the expression and nuclear translocation of Nrf2. Our data suggest that crocin alleviates intracerebral hemorrhage-induced neuronal ferroptosis by facilitating Nrf2 nuclear translocation.

Systematic chemical characterization of Xiexin decoctions using high performance liquid chromatography coupled with electrospray ionization mass spectrometry.

Xiexin decoctions (XXDs) display beneficial anti-inflammatory and anti-diabetic effects, which raises interests on this group of formulae for broad clinical applications. However, there was no report about systematic analysis of XXDs to elucidate the constitution of chemical components, which hampers further investigations on the therapeutic values of XXDs. In this work, crude herbs were extracted and prepared to obtain the XXDs for systemic analysis on their chemical compositions, according to the information described in the ancient Zhang Zhongjing's herbal formulae. LC-MS analysis of five XXDs was carried out to facilitate recognition of the source herbs for compounds in the mixture. A total number of 93 compounds were identified through our methods and their chemical classes encompassed five major groups, including protoberberine alkaloids, flavonoids, stilbenes, anthraquinones and saponins. Our current work provided important information about material basis for pharmacological studies on XXDs and would help shed light on relationships between chemical compositions and therapeutic effects.

[Role of p38MAPK in apoptosis of human paratumor cirrhosis hepatocellular cell line QSG-7701 induced by cisplatin].

OBJECTIVE: To investigate the roles of p38 MAPK in apoptosis of the normal liver cell, the paratumor cirrhosis hepatocellular cell and the hepatocellular carcinoma cell. METHODS: Three cell lines were adopted (the normal liver cell line HL-7702, the paratumor cirrhosis hepatocellular cell line QSG-7701 and the hepatocellular carcinoma cell line QGY-7703) and treated with Diamminedichloroplatin (DDP, cisplatin) and p38MAPK inhibitor SB203580. The apoptosis and cell cycles were detected by flow cytometry and electromicroscopy. The expressions of p38MAPK, CDC25B, p34cdc2 and cyclinB1 were detected by immunocytochemical staining , confocal microscopy and western blot. RESULTS: The apoptotic rates in all three cell lines pretreated with DDP increased obviously and the rates in normal liver cells and HCC cells increased continuously even after SB203580 treatment, whereas in paratumor cirrhosis cells the rate decreased and the cell cycle stopped at S phase. CONCLUSION: Cisplatin induces apoptosis in the paratumor cirrhosis hepatocellular cell line QSG-7701 via activation of p38MAPK pathway and it differs in the normal liver cells from the hepatocellular carcinoma cells.

Type 1 myocardial infarction rapid screening scale for emergency triage in patients with non-traumatic chest pain: A study of 1928 cases with coronary angiography.

INTRODUCTION: The effectiveness of treatment and prognosis of patients with type 1 myocardial infarction are highly correlated with time of diagnosis. This study aimed to develop a type 1 MI rapid screening scale (T1MIrs scale) suitable for emergency pre-diagnosis. METHODS: A total of 1928 patients who underwent coronary angiography were enrolled. Multivariate regression analysis was used to identify the independent risk factors of type 1 MI. And the T1MIrs scale was developed and evaluated according to the multivariate regression result. RESULTS: The incidence of type 1 MI was 23.3% in the population with suspected acute coronary syndrome. After 5 adjusting for relevant factors, MEWS score (OR = 1.809, 95%CI 1.623-2.016, P < .001), typical symptoms (OR = 9.826, 95%CI 7.379-13.084, P < .001), male (OR = 2.184, 95%CI 1.602-2.979, P < .001), age (OR = 1.021, 95%CI 1.009-1.033, P = .001), history of diabetes (OR = 2.174, 95%CI 1.594-2.963, P < .001) and current smoker (OR = 2.498, 95%CI 1.550-4.026, P < .001) were the independent risk factors for type 1 MI. The T1MIrs scale is established based on risk factors, with a range of 0-8 points. The incidence of type 1 MI is ascending with the scale (0.3% vs. 3.7% vs. 14.3% vs. 34.9% vs. 57% vs. 76.4% vs. 84.2% vs. 87.5% vs. 100%, P for trend <0.001). CONCLUSIONS: Type 1 MI is common in patients with suspected acute coronary syndrome in emergency department. The T1MIrs scale could act as a rapid pre-examination triage of suspected population in emergency department, which is meaningful to screen out type 1 MI patients as soon as possible.

Graves' disease treated with thyroid arterial embolization.

PURPOSE: To study pathological changes in the thyroid gland of patients with Graves' disease (GD) treated with thyroid arterial embolization. METHODS: Thirty-seven patients with GD were treated through transcatheter thyroid arterial embolization. Of these patients, twenty-two had biopsy of the thyroid gland at different time points before and after the embolization for the study of pathology. Serum thyroid hormones, TSH and TRAb were also studied at these time points. Thyroid size was evaluated in all patients using color Doppler ultrasound or CT scan. RESULTS: Thyroid size decreased immediately or several days following embolization. Pathological study demonstrated mainly acute infarction and necrosis at 7 days post embolization. At 6 months, chronic inflammation and fibrous hyperplasia were the primary findings in the gland, and at 3 years following embolization, mesenchyma hyperplasia and follicle atrophy were primarily present in the embolized thyroid tissue. The thyroid hormones and TSH gradually resumed to normal range after embolization while TRAb decreased significantly. CONCLUSION: Thyroid arterial embolization can cause GD thyroid gland a series of pathological changes of acute ischemia and necrosis and later, chronic inflammation, fibroplasia and atrophy to decrease secretion of thyroid. The pathological changes within the thyroid gland after embolization form the basis of thyroid arterial embolization in treating GD hyperthyroidism.

Angiogenic study in Graves' disease treated with thyroid arterial embolization.

PURPOSE: To investigate angiogenesis in the thyroid of Graves' disease (GD) treated with thyroid arterial embolization through analysis of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and microvessel density (MVD). MATERIALS AND METHODS: Forty-two GD patients were treated with thyroid arterial embolization and followed up for 1-68 months after embolization. Before embolization and at 7 days, 3, 6, 12, 36 and 48 months following embolization, TT3, TT4, FT3, FT4, TSH and thyroid stimulating antibody (TSAb) were tested respectively. Thyroid biopsy was performed under the guidance of computed tomography for immunohistochemical staining of VEGF and bFGF, and MVD within the thyroid gland was marked by CD34. RESULTS: VEGF and bFGF were mostly expressed in the cytoplasm and on the cell membrane. The expression of VEGF was increased (P < 0.05) at < or = 6 months compared with before embolization and decreased (P < 0.05) at > or = 1 year compared with either at < or = 6 months or before embolization. The expression of bFGF was not statistically different at < or = 6 months compared with before embolization but was decreased (P < 0.05) at > or = 1 year compared with either at ?6 months or before embolization. Thyroid MVD marked by CD34 had similar changes to those of the VEGF expression after embolization. There was a positive correlation between VEGF and bFGF (P < 0.05) and between VEGF or bFGF and MVD (P < 0.05). Thyroid hormones mostly returned to normal and TSAb was decreased in longer follow-up. CONCLUSION: Thyroid arterial embolization can decrease the expression of VEGF, bFGF and MVD. Consequently, angiogenesis within the GD thyroid will be decreased in the long term after embolization and may serve as the basis for reduced thyroid size and function.

Apoptotic study in Graves disease treated with thyroid arterial embolization.

OBJECTIVE: To investigate apoptosis in the thyroid of Graves disease (GD) induced by thyroid arterial embolization. MATERIALS AND METHODS: Forty one patients with clinically and laboratorily ascertained GD were treated with thyroid arterial embolization and followed up for 3-54 months following embolization. Prior to embolization and at 1, 3, 6, 12 and 36 months following embolization, thyroid autoimmunue antibodies were tested respectively, including thyroid stimulating antibody (TSAb), thyroglobulin antibody (TGAb) and thyroid microsomal antibody (TMAb). Thyroid biopsy was performed under the guidance of computed tomography for immunohistochemistry examination using semi-quantity analysis. RESULTS: The positive staining of Fas and FasL was mostly in the cytoplasma and cell membrane, the positive expression of Bax was mainly in the cytoplasma, and no positive expression of P53 was detected in the thyroid cells before embolization. After arterial embolziation, the positive cell number and staining degree of these genes were both greater than before embolization. CONCLUSION: The treatment method of thyroid arterial embolization can effectively enhance the positive expression of pro-apoptotic genes of Fas, FasL, Bax, Bcl-2 and P53 in GD thyroid, thus promoting apoptosis of GD thyroid and helping restore the thyroid size and function to normal conditions.