Prediction value of pericoronary fat attenuation index for coronary in-stent restenosis.

OBJECTIVES: As a novel imaging marker, pericoronary fat attenuation index (FAI) reflects the local coronary inflammation which is one of the major mechanisms for in-stent restenosis (ISR). We aimed to validate the ability of pericoronary FAI to predict ISR in patients undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Patients who underwent coronary CT angiography (CCTA) before PCI within 1 week between January 2017 and December 2019 at our hospital and had follow-up invasive coronary angiography (ICA) or CCTA were enrolled. Pericoronary FAI was measured at the site where stents would be placed. ISR was defined as ≥ 50% diameter stenosis at follow-up ICA or CCTA in the in-stent area. Multivariable analysis using mixed effects logistic regression models was performed to test the association between pericoronary FAI and ISR at lesion level. RESULTS: A total of 126 patients with 180 target lesions were included in the study. During 22.5 months of mean interval time from index PCI to follow-up ICA or CCTA, ISR occurred in 40 (22.2%, 40/180) stents. Pericoronary FAI was associated with a higher risk of ISR (adjusted OR = 1.12, p = 0.028). The optimum cutoff was - 69.6 HU. Integrating the dichotomous pericoronary FAI into current state of the art prediction model for ISR improved the prediction ability of the model significantly (△area under the curve = + 0.064; p = 0.001). CONCLUSION: Pericoronary FAI around lesions with subsequent stent placement is independently associated with ISR and could improve the ability of current prediction model for ISR. CLINICAL RELEVANCE STATEMENT: Pericoronary fat attenuation index can be used to identify the lesions with high risk for in-stent restenosis. These lesions may benefit from extra anti-inflammation treatment to avoid in-stent restenosis. KEY POINTS: • Pericoronary fat attenuation index reflects the local coronary inflammation. • Pericoronary fat attenuation index around lesions with subsequent stents placement can predict in-stent restenosis. • Pericoronary fat attenuation index can be used as a marker for future in-stent restenosis.

Residual Risk in Non-ST-Segment Elevation Acute Coronary Syndrome: Quantitative Plaque Analysis at Coronary CT Angiography.

Background Lipid-rich plaques detected with intravascular imaging are associated with adverse cardiovascular events in patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). But evidence about the prognostic implication of coronary CT angiography (CCTA) in NSTE ACS is limited. Purpose To assess whether quantitative variables at CCTA that reflect lipid content in nonrevascularized plaques in individuals with NSTE ACS might be predictors of subsequent nonrevascularized plaque-related major adverse cardiovascular events (MACEs). Materials and Methods In this multicenter prospective cohort study, from November 2017 to January 2019, individuals diagnosed with NSTE ACS (excluding those at very high risk) were enrolled and underwent CCTA before invasive coronary angiography (ICA) within 1 day. Lipid core was defined as areas with attenuation less than 30 HU in plaques. MACEs were defined as cardiac death, myocardial infarction, hospitalization for unstable angina, and revascularization. Participants were followed up at 6 months, 12 months, and annually thereafter for at least 3 years (ending by July 2022). Multivariable analysis using Cox proportional hazards regression models was performed to determine the association between lipid core burden, lipid core volume, and future nonrevascularized plaque-related MACEs at both the participant and plaque levels. Results A total of 342 participants (mean age, 57.9 years ± 11.1 [SD]; 263 male) were included for analysis with a median follow-up period of 4.0 years (IQR, 3.6-4.4 years). The 4-year nonrevascularized plaque-related MACE rate was 23.9% (95% CI: 19.1, 28.5). Lipid core burden (hazard ratio [HR], 12.6; 95% CI: 4.6, 34.3) was an independent predictor at the participant level, with an optimum threshold of 2.8%. Lipid core burden (HR, 12.1; 95% CI: 6.6, 22.3) and volume (HR, 11.0; 95% CI: 6.5, 18.4) were independent predictors at the plaque level, with an optimum threshold of 7.2% and 10.1 mm3, respectively. Conclusion In NSTE ACS, quantitative analysis of plaque lipid content at CCTA independently predicted participants and plaques at higher risk for future nonrevascularized plaque-related MACEs. Chinese Clinical Trial Registry no. ChiCTR1800018661 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tavakoli and Duman in this issue.

[Arsenic trioxide induces the apoptosis of prostate cancer PC-3 cells via the P38 signaling pathway].

OBJECTIVE: To explore the role of the P38 signaling pathway in the apoptosis of arsenic trioxide (As2 O3)-induced androgen-independent prostate cancer PC-3 cells. METHODS: Androgen-independent prostate cancer PC-3 cells were treated with different concentrations of As2 O3 for 24, 48 and 72 hours. The inhibitory effect of As2 O3 on the cell growth was measured by MTT, the expression of p- P38 detected by Western blot, and the rate of cell apoptosis determined by Annexin V and PI double staining before and after interfering the P38 signaling pathway by SB203580, a highly selective P38 inhibitor. RESULTS: As2 O3 inhibited the proliferation of PC-3 cells in a concentration- and time-dependent manner, and quickly activated P38 phosphorylation, thus giving full play to its biological activities. After 24 hours of treatment with As2 O3 at the concentrations of 2, 10 and 20 micromol/L, the apoptosis rates of the PC-3 cells were (18.9 +/- 0.43), (24.7 +/- 0.29) and (49.7 +/- 1.79)%, respectively, which were reduced to (14.8 +/- 0.81), (22.1 +/- 0.51) and (39.6 +/- 1.74)% after interfering the P38 pathway with SB203580. Inhibition of the P38 pathway significantly reduced the apoptosis of the PC-3 cells induced by As2 O3 (P < 0.05). CONCLUSION: As2 O3 can induce the apoptosis of prostate cancer PC-3 cells by activating the P38 signaling pathway, and interfering the P38 signaling pathway can reduce their apoptosis, which suggests that the P38 signaling pathway is involved in the apoptosis of As2 O3-induced androgen-independent prostate cancer PC-3 cells.

[Pituitary prolactinoma with severe erectile dysfunction as the initial symptom: diagnosis and treatment of 4 cases].

OBJECTIVE: Pituitary prolactinoma with severe erectile dysfunction (ED) as the initial symptom is often misdiagnosed. This article explores the diagnosis and treatment of severe ED caused by pituitary prolactinoma. METHODS: We retrospectively analyzed the diagnosis and treatment of 4 cases of pituitary prolactinoma with severe ED (IIEF-5 score 5 - 7) as the initial clinical symptom confirmed by MRI. RESULTS: The 4 cases of pituitary prolactinoma-induced severe ED, with serum prolactin 10 times above the maximum normal level, were misdiagnosed for 2 years. All failed to respond to the PDE5 inhibitor therapy, and then 3 of them underwent transnasal hypophysectomy. Twenty-four months of follow-up found the level of prolactin restored to normal in 1 case (IIEF-5 = 19), and reduced to 600 and 768 IU/L respectively (IIEF-5 = 15) in the other 2. Then administration of the PDE5 inhibitor was followed, which produced satisfactory efficacy. One case was treated with oral bromocriptine, which restored the prolactin level to normal at 12 months (IIEF-5 > 21). CONCLUSION: Prolactin detection and brain MRI can help to confirm pituitary prolactinoma with severe ED at the onset. As for its treatment, in case of an extremely high level of prolactin, simple administration of the PDE5 inhibitor is ineffective. When the prolactin level is reduced after surgery or medication, the symptom of ED can be improved and, in case of no obvious relief, administration of the PDE5 inhibitor can be followed, which may achieve satisfactory results.

Effect of miR-145 on intracardiac thrombosis in patients with rheumatic heart disease complicated with atrial fibrillation: A retrospective analysis.

Patients with rheumatic heart disease (RHD) and atrial fibrillation (AF) often have a risk of intracardiac thrombosis. Exfoliated thrombus is easy to cause embolic diseases. This study revealed the risk of intracardiac thrombosis in patients with RHD with AF by exploring the expression of plasma microRNA miR-145. The expression of plasma miR-145 in 58 patients with RHD complicated with AF was detected by real-time quantitative polymerase chain reaction [28 cases in thrombus (TH) group and 30 cases in non-thrombus (NTH) group]. At the same time, a healthy control group (33 cases) was established. The correlation between miR-145 and thrombosis in RHD was analyzed. The expression of plasma miR-145 in TH group and NTH group decreased significantly, especially in TH group (P < .01). In TH group and NTH group, the expression of miR-145 was negatively correlated with D-Dimer level, Factor XI concentration and tissue factor level as well as left atrial diameter (all P < .01, respectively). The receiver operating curve analysis showed that the expression of miR-145 had diagnostic significance for RHD and its intracardiac thrombosis. In this study, we suggest that the change of plasma miR-145 expression in patients with RHD is related to coagulation activity and fibrinolysis, which can predict the risk of intracardiac thrombosis.

[Determination of 18 caine anesthetics in animal meat using solid phase extraction combined with ultra-performance liquid chromatography-tandem mass spectrometry].

Because of the widespread application of anesthetic drugs in the fields of animal breeding and transportation, demand for the rapid, sensitive detection of anesthetic drugs in animal meat is increasing. The complex animal meat matrix contains various interfering substances, such as proteins, fats, and phospholipids, along with anesthetic drug residues at very low concentrations. Therefore, adopting appropriate pretreatment methods is necessary to improve the sensitivity of detection. In this study, a rapid, accurate analytical method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and solid phase extraction (SPE) was established to determine the contents of 18 caines in animal meat. The MS parameters, such as the collision energies of 18 caines, were optimized. Furthermore, the chromatographic separation conditions and response intensities of the caine in different mobile phases were compared. The effects of different pretreatment conditions on the extraction efficiencies of the 18 caines in meat samples and those of different purification conditions, such as extraction solvent, SPE column, and dimethylsulfoxide (DMSO) dosage, on their recoveries were investigated. Combined with the external standard method, the 18 caines in meat were successfully quantified. Sample pretreatment is a three-step process. First, in ultrasound-assisted extraction, 2.0 g samples were added to 2.0 mL water and extracted using 10 mL 0.1% (v/v) formic acid in acetonitrile under ultrasound conditions for 10 min. SPE was then performed using an Oasis PRIME HLB column. Finally, DMSO-assisted concentration was employed: the organic layer was collected and dried at 40 ℃ under a stream of N2 gas with the addition of 100 µL DMSO. Acetonitrile-water (1∶9, v/v) was added to the residue to yield a final volume of 1.0 mL for use in UPLC-MS/MS. The 18 caines were separated using an HSS T3 (100 mm×2.1 mm, 1.8 µm) column with 0.1% (v/v) formic acid in water (containing 0.02 mmol/L ammonium acetate) and methanol as mobile phases. Samples were detected using an electrospray ion source (ESI) in the positive ion and multiple reaction monitoring (MRM) modes during UPLC-MS/MS. Under the optimized conditions, the 18 target caine anesthetics displayed good linearities in the range of 1.00-50.0 µg/L, and the correlation coefficients (R2) were >0.999. The respective limits of detection (LODs) and quantification (LOQs) were 0.2-0.5 µg/kg, and 0.6-1.5 µg/kg. In pork, beef, and mutton samples, the recoveries obtained at three spiked levels were 83.4%-100.4% with relative standard deviations (RSDs) of 3.1%-8.5%. This simple, rapid, sensitive method may be applied in the detection of 18 caine anesthetics in animal meat and may provide technical support to the food safety department in China in monitoring the residues of caine anesthetics in animal meat.

[Expressions of E-cadherin and alpha-catenin in benign, malignant and metastatic prostate tumors].

OBJECTIVE: To investigate the expressions of E-cadherin (E-cd) and alpha-catenin (alpha-cat) proteins in benign and malignant prostate tumors, and determine whether they could be used as molecular markers for the prognosis of prostate cancer (PCa). METHODS: We detected the expressions of E-cd and alpha-cat in the prostatic tissues from 45 cases of PCa and 10 cases of benign prostatic hyperplasia (BPH) by immunohistochemical Elivision staining, and analyzed the relationships of E-cd and alpha-cat expressions with the PCa stage, PCa grade, preoperative PSA, results of endocrine therapy and prognosis. RESULTS: The E-cd protein was abnormally expressed in 86.7% of the PCa and 10.0% of the PSA patients, and the E-cd expression was significantly lower in the former than in the latter (P < 0.05). The abnormal expressions of E-cd in the PCa patients with metastasis, non-metastasis, Gleason score < or = 7 and > 7 were 85.0, 87.5, 100.0 and 86.7%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 97.1%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 93.8 and 72.7%, respectively, with no significant differences between the two groups (P > 0.05). The alpha-cat protein was abnormally expressed in 93.3% of the PCa and 30.0% of the BPH patients, respectively, and the alpha-cat expression was significantly lower in the former than in the latter (P < 0.05). The abnormal alpha-cat expressions in the PCa patients with metastasis, non-metastasis, Gleason score > 7 and < or = 7 were 90.0, 100.0, 90.0 and 100.0%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 94.3%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 100.0 and 81.8%, respectively, with no significant differences between the two groups (P > 0.05). CONCLUSION: The expressions of E-cd and alpha-cat are significantly lower in PCa than in BPH, and they are not associated with cancerous metastasis, but negatively correlated with the PSA level in PCa patients.

The effects of hypoxia on mitochondrial function and metabolism in gastric cancer cells.

BACKGROUND: A number of studies have found that metabolic disorders are the characteristic manifestations of tumor cells. However, the effects of hypoxic environment on mitochondrial function and glucose metabolism of tumor cells were still unclear. The study wanted to explore the regulatory mechanism of hypoxic environment on mitochondrial function and metabolism in gastric cancer cells. METHODS: The animal model of gastric cancer and MKN45 were treated in a hypoxic environment. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were analyzed by flow cytometry, qPCR was used to detect the expression levels of glycose metabolism key enzymes, damage repair genes and mitochondrial DNA (mtDNA) copy numbers in gastric cancer. RESULTS: Compared with 2,000 m normal gastric cancer tissue, the decreased of mitochondrial membrane potential and the production of ROS reduced, the expressions of glucose metabolism genes [the M1 isoform of Hexokinase (HK1), pyruvate kinase (PKM), Succinate dehydrogenase (SDHA), Glucose-6-phosphate dehydrogenase (G6PD)], homologous recombination repair gene (RAD51) and repair DNA double-stranded broken gene (ASTCT2) increased, and aerobic respiration reduced in gastric cancer cells. In the hypoxic environment, the decreased of mitochondrial membrane potential reduced, the production of ROS and mtDNA copies increased, HK1 expression increased, the expressions of SDHA, G6PD, RAD51 and ASCT-2 decreased, and the aerobic respiration decreased. CONCLUSIONS: Hypoxia plays an important role in maintaining mitochondrial functions in gastric cancer cells by promoting glycolysis and inhibiting mitochondrial aerobic respiration capacity.

Practical multi-component synthesis of di- or tri-aryl (Heteraryl) substituted 2-(pyridin-2-yl)imidazoles from simple building blocks.

A convenient and highly efficient multicomponent protocol has been developed for the synthesis of various poly-substituted 2-(pyridin-2-yl)imidazoles from 2-cyanopyridine, corresponding aromatic aldehydes, and NH(4)OAc/primary amine. Notably, tri-substituted 2-(pyridin-2-yl)imidazoles were highly yielded when aromatic primary amines were used as substrates, but both di- and tri-substituted 2-(pyridin-2-yl)imidazoles were obtained in one pot when some aliphatic primary amines were used as substrates.

Ionizing radiation promotes migration and invasion of cancer cells through transforming growth factor-beta-mediated epithelial-mesenchymal transition.

PURPOSE: To examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-ß)-mediated epithelial-mesenchymal transition (EMT). METHODS AND MATERIALS: Six cancer cell lines originating from different human organs were irradiated by 60Co γ-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-ß in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-ß signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. RESULTS: After irradiation with γ-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-ß were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-ß signaling. CONCLUSIONS: These results suggest that EMT mediated by TGF-ß plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.