Perfusion of hepatocellular carcinomas measured by diffusion-derived vessel density biomarker: Higher hepatocellular carcinoma perfusion than earlier intravoxel incoherent motion reports.

Diffusion-derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2. Pathohistological studies and contrast-enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0-T magnet. Diffusion-weighted images with b-values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty-two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(-)). Fifty-eight patients had Edmondson-Steiner grade I or II HCC, and 14 patients had Edmondson-Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419-3.522), of MVI(-) HCCs was 2.699 (2.030-3.522), of MVI(+) HCCs was 2.988 (2.423-3.990), of Edmondson-Steiner grade I/II HCCs was 2.873 (2.277-3.465), and of Edmondson-Steiner grade III/IV HCCs was 3.403 (2.008-4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(-) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson-Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson-Steiner grade I and II).

Repeatability and reproducibility comparisons of liver IVIM imaging with free-breathing or respiratory-triggered sequences.

For liver intravoxel incoherent motion (IVIM) data acquisition, respiratory-triggering (RT) MRI is commonly used, and there are strong motivations to shorten the scan duration. For the same scan duration, more b values or higher numbers of excitations can be allowed for free-breathing (FB) imaging than for RT. We studied whether FB can be used to replace RT when careful IVIM image acquisition and image processing are conducted. MRI data of 22 healthy participants were acquired using a 3.0 T scanner. Diffusion imaging was based on a single-shot spin-echo-type echo-planar sequence and 16 b values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, and 600 s/mm2 . Each subject attended two scan sessions with an interval of 10-20 days. For each scan session, a subject was scanned twice, first with RT and then with FB. The mean image acquisition time was 5.4 min for FB and 10.8 min for RT. IVIM parameters were calculated with bi-exponential model segmented fitting with a threshold b value of 60 s/mm2 , and fitting started from b = 2 s/mm2 . There was no statistically significant difference between IVIM parameters measured with FB imaging or RT imaging. Perfusion fraction ICC (intraclass correlation coefficient) for FB imaging and RT imaging in the same scan session was 0.824. For perfusion fraction, wSD (within-subject standard deviation), BA (Bland-Altman) difference, BA 95% limit, and ICC were 0.022, 0.0001, -0.0635~0.0637, and 0.687 for FB and 0.031, 0.0122, -0.0723~0.0967, and 0.611 for RT. For Dslow (×10-3  s/mm2 ), wSD, BA difference, BA 95% limit, and ICC were 0.057, 0.0268, -0.1258~0.1793, and 0.471 for FB and 0.073, -0.0078, -0.2170-0.2014, and <0.4 for RT. The Dfast coefficient of variation was 0.20 for FB imaging and 0.28 for RT imaging. All reproducibility indicators slightly favored FB imaging.

Magnetic Resonance Deep Learning Radiomic Model Based on Distinct Metastatic Vascular Patterns for Evaluating Recurrence-Free Survival in Hepatocellular Carcinoma.

BACKGROUND: The metastatic vascular patterns of hepatocellular carcinoma (HCC) are mainly microvascular invasion (MVI) and vessels encapsulating tumor clusters (VETC). However, most existing VETC-related radiological studies still focus on the prediction of VETC status. PURPOSE: This study aimed to build and compare VETC-MVI related models (clinical, radiomics, and deep learning) associated with recurrence-free survival of HCC patients. STUDY TYPE: Retrospective. POPULATION: 398 HCC patients (349 male, 49 female; median age 51.7 years, and age range: 22-80 years) who underwent resection from five hospitals in China. The patients were randomly divided into training cohort (n = 358) and test cohort (n = 40). FIELD STRENGTH/SEQUENCE: 3-T, pre-contrast T1-weighted imaging spoiled gradient recalled echo (T1WI SPGR), T2-weighted imaging fast spin echo (T2WI FSE), and contrast enhanced arterial phase (AP), delay phase (DP). ASSESSMENT: Two radiologists performed the segmentation of HCC on T1WI, T2WI, AP, and DP images, from which radiomic features were extracted. The RFS related clinical characteristics (VETC, MVI, Barcelona stage, tumor maximum diameter, and alpha fetoprotein) and radiomic features were used to build the clinical model, clinical-radiomic (CR) nomogram, deep learning model. The follow-up process was done 1 month after resection, and every 3 months subsequently. The RFS was defined as the date of resection to the date of recurrence confirmed by radiology or the last follow-up. Patients were followed up until December 31, 2022. STATISTICAL TESTS: Univariate COX regression, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier curves, log-rank test, C-index, and area under the curve (AUC). P < 0.05 was considered statistically significant. RESULTS: The C-index of deep learning model achieved 0.830 in test cohort compared with CR nomogram (0.731), radiomic signature (0.707), and clinical model (0.702). The average RFS of the overall patients was 26.77 months (range 1-80 months). DATA CONCLUSION: MR deep learning model based on VETC and MVI provides a potential tool for survival assessment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Single-cell RNA sequencing of mouse left ventricle reveals cellular diversity and intercommunication.

Previous studies have revealed the diversity of the whole cardiac cellulome but not refined the left ventricle, which was essential for finding therapeutic targets. Here, we characterized single-cell transcriptional profiles of the mouse left ventricular cellular landscape using single-cell RNA sequencing (10× Genomics). Detailed t-distributed stochastic neighbor embedding (tSNE) analysis revealed the cell types of left ventricle with gene markers. Left ventricular cellulome contained cardiomyocytes highly expressed Trdn, endothelial cells highly expressed Pcdh17, fibroblast highly expressed Lama2, and macrophages highly expressed Hpgds, also proved by in situ hybridization. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis (ListHits > 2, P < 0.05) were employed with the DAVID database to investigate subtypes of each cell type with the underlying functions of differentially expressed genes (DEGs). Endothelial cells included 5 subtypes, fibroblasts comprising 7 subtypes, and macrophages contained 11 subtypes. The key representative DEGs (P < 0.001) were Gja4 and Gja5 in cluster 3 of endothelial cells, Aqp2 and Thbs4 in cluster 2 of fibroblasts, and Clec4e and Trem-1 in cluster 3 of macrophages perhaps involved in the occurrence of atherosclerosis, heart failure, and acute myocardial infarction proved by literature review. We also revealed extensive networks of intercellular communication in left ventricle. We suggested possible therapeutic targets for cardiovascular disease and autocrine and paracrine signaling underpins left ventricular homeostasis. This study provided new insights into the structure and function of the mammalian left ventricular cellulome and offers an important resource that will stimulate studies in cardiovascular research.

Streptococcus strain C17T as a potential probiotic candidate to modulate oral health.

In the microbiome, probiotics modulate oral diseases. In this study, Streptococcus strain C17T was isolated from the oropharynx of a 5-year-old healthy child, and its potential probiotic properties were analysed using human bronchial epithelial cells (16-HBE) used as an in vitro oropharyngeal mucosal model. The results demonstrated that the C17T strain showed tolerance to moderate pH ranges of 4-5 and 0·5-1% bile. However, it was more tolerant to 0·5% bile than 1% bile. It also demonstrated an ability to accommodate maladaptive oropharyngeal conditions (i.e. tolerating lysozyme at 200 µg ml-1 ). It was also resistant to hydrogen peroxide at 0·8 mM. In addition, we found out that the strain possesses inhibitory activities against various common pathogenic bacteria. Furthermore, C17T was not cytotoxic to 16-HBE cells at different multiplicities of infection. Scanning electron microscopy disclosed that C17T adhesion to 16-HBE cells. Competition, exclusion and displacement assays showed that it had good anti-adhesive effect against S. aureus. The present study revealed that Streptococcus strain C17T is a potentially efficacious oropharyngeal probiotic.

Method to Calculate the Retention Index in Hydrophilic Interaction Liquid Chromatography Using Normal Fatty Acid Derivatives as Calibrants.

Hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) is a complementary technique to reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and has been widely used to expand the coverage of the metabolome in MS-based metabolomics. However, the use of HILIC retention time (HILIC RT) in metabolites annotation is quite limited because of its poor reproducibility. Here, we developed a method to calculate the retention index in HILIC (HILIC RI) for calibration of HILIC RT. In this method, a mixture of 2-dimethylaminoethylamine (DMED)-labeled fatty acid standards with carbon chain length from C2 to C22 were selected as calibrants to establish a linear calibration equation between HILIC RT and carbon number for the calculation of HILIC RI. The calculated HILIC RIs based on a regression equation could efficiently calibrate the retention time shifts for 28 DMED-labeled carboxyl standards and DMED-labeled carboxyl metabolites in rat urine, serum and feces on a HILIC column with different gradient elution conditions. Furthermore, the developed HILIC RI strategy was applied to RT calibration of screened metabolites, the annotation of isomers in HILIC-MS-based metabolomics analysis for real samples, and the correction of isotope effects in chemical isotope labeling HILIC-MS analysis. Taken together, the resulting HILIC RI strategy is a promising analytical technique to improve the accuracy of metabolite annotation; it would be widely used in HILIC-MS-based metabolome analysis.

SOX2-mediated inhibition of miR-223 contributes to STIM1 activation in phenylephrine-induced hypertrophic cardiomyocytes.

Stromal interaction molecule 1 (STIM1) is the key molecule responsible for store-operated Ca2+ entry (SOCE). Numerous studies have demonstrated that STIM1 levels appeared to be enhanced during cardiac hypertrophy. However, the mechanism underlining this process remains to be clarified. In this study, phenylephrine (PE) was employed to establish a model of hypertrophic neonatal rat cardiomyocytes (HNRCs) in vitro, and low expression of primary and mature miR-223 was detected in PE-induced HNRCs. Our results have revealed that downregulation of miR-223 by PE contributed to the increase of STIM1, which in turn induced cardiac hypertrophy. As expected, overexpression of miR-223 could prevent the increase in cell surface and reduce the mRNA levels of ANF and BNP in cardiomyocytes. To address the mechanism triggering downregulation of miR-223 under PE, we demonstrated that PE-induced inhibition of GSK-3ß activity led to the activation of ß-catenin, which initiates the transcription of SOX2. Increased expression of SOX2 occupied the promoter region of primary miR-223 and suppressed its transcription. Therefore, miR-223 appears to be a promising candidate for inhibiting cardiomyocyte hypertrophy, and miR-223/STIM1 axis might be one of interesting targets for the clinical treatment of hypertrophy.

[Biochemical regulatory mechanism of asiaticoside in preventing and treating stent restenosis].

OBJECTIVE: To discuss whether asiaticosides could effectively reduce the endothelial cell damage as a biochemical modulator, so as to further inhibit the post-stenting intima-media membrane hyperplasia. METHOD: Human aortic smooth muscle cells and aortic fibroblasts were selected and divided into the blank group, the rapamycin group and the asiaticoside group and the rapamycin and asiaticoside group. The expressions of muscle cells and fibroblasts TGF-beta1, Smad7 and I-collagen gene were determined by RT-PCR. The expression quantity of I-collagen protein was assayed by ELISA. The coefficient of drug interaction (CDI) between rapamycin and asiaticoside was calculated. Additionally, 16 Chinese mini-swines were randomly divided into group A and group B. One sirolimus drug-eluting stent of the same type was implanted after the high-pressure pre-expansion of anterior descending artery balloon. After the operation, the group A was intravenously injected with normal saline 30 mL x d(-1). Whereas the group B was intravenously injected with asiaticoside 30 mg x kg(-1) x d(-1)(diluted to 30 mL). The expressions of plasma vWF of the two groups were measured at the 7th and 14th days after the operation. At the 28th day after the operation, tissues of the stented vessel segments were sliced and stained to calculate the vessel area, inner stent area, lumen area and neointima area RESULT: Compared with the control group, the combination group showed significant up-regulation in smooth muscle cells and fibroblast Smad7 gene, down-regulation in TGF-beta, and obvious inhibition of I-collagen gene expression (P < 0.01). As for smooth muscle cells, there was no difference in the expression of I-collagen between the combination group and the rapamycin group, with CDI at 0. 83. As for fibroblasts, there was a significant difference in the expression of I-collagen between the combination group and the rapamycin group (P < 0.05), with CDI at 0.77. Plasma vWF of the group B was significantly lower than that of the group A (P < 0.05) at the 7th and 14th days after the operation. At the 28th day after the operation, no difference was observed in vessel area and stent area between the two groups. However, the lumen area in the group B was significantly larger than that of the group A(P < 0.05), and the neointima area of the group B was significantly smaller than that of the group A (P < 0.05). CONCLUSION: As an effective biochemical modulator for rapamycin, asiaticosides could inhibit TGF-beta expression, significantly decrease the synthesis and secretion of extracellular matrix, further inhibit the post-stenting intima-media membrane hyperplasia and reduce the endothelial cell damage by effectively up-regulate the expression of Smad7 protein.

Age and gender differences of normative values of spleen diffusion MRI parameters.

This study investigates age and gender differences of normative values of spleen diffusion MRI parameters.We recruited 124 volunteers with MRI conducted at 1.5T. Diffusion imaging had b-values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, 600 s/mm2. ADC, IVIM-Dslow, IVIM-PF, IVIM-Dfast, and DDVD (diffusion-derived vessel density) were computed. DDVD is the signal difference between the b=0 s/mm2 image and b=2, 4 s/mm2 image. Only images without apparent artifacts and with good curving fitting were included in the analysis. Finally, 34 females (age: 20-71 years) and 69 males (22-70 years) were measured with ADC; 20 females (20-71 years) and 48 males (22-67 years) were measured with IVIM; 32 females (20-71 years) and 65 males (22-70 years) were measured with DDVD parameter.An age-related decrease in ADC was noted for females, while such a trend was not noted for males. A very high level of heterogeneity was noted for the data for the males, with the highest ADC value being 1.710 × 10-3mm 2/s and the lowest ADC value being 0.705 × 10-3 mm2/s when b=0 and 600 s/mm 2 were used for ADC calculation. A male-female data comparison did not show a statistically significant difference between the ADC median value. However, ADCs > 1.3 × 10-3 mm2/s were only seen among males. A very high level of heterogeneity was also noted for males' Dslow, with the highest value being 1.468 × 10-3 mm2/s and the lowest value being 0.600 × 10-3 mm2/s. Both PF and Dfast demonstrated a trend of age-related increase for older subjects. PF values were higher among males than females. However, no difference was noted for Dfast between males and females. DDVD did not show an age-related trend both for females and males. No difference was noted in DDVD values between males and females.Interpreting normal spleen diffusion MRI parameters should consider age and gender factors. · An age-related decrease in spleen ADC and IVIM-Dslow was seen for healthy females.. · There is a high level of heterogeneity for spleen ADC and IVIM-Dslow data for healthy males.. · IVIM modelled perfusion fraction and Dfast demonstrate an artificial trend of age-related increase for older subjects.. · Vessel density measured on diffusion imaging does not show an age-related trend.. · Yu W, Ma FZ, Huang H et al. Age and gender differences of normative values of spleen diffusion MRI parameters. Fortschr Röntgenstr 2024; DOI 10.1055/a-2357-9741.

[Factors associated with psychological distress after surgery and quality of life before and after radiotherapy in 216 patients with oral squamous cell carcinoma].

PURPOSE: To investigate the degree of psychological distress of patients with oral squamous cell carcinoma after operation and its influencing factors, and the impact of radiotherapy on their quality of life. METHODS: Univariate analysis and regression analysis were used to evaluate the relationship between psychological distress and socio-economic and therapeutic factors. The quality of life of the subjects before and after radiotherapy was evaluated by paired t-test using the Chinese version of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/ Head and Neck 35. SPSS 22.0 software package was used to deal with the data. RESULTS: Age, AJCC stage and median incision of lower lip were the main factors affecting psychological distress. In addition, there were significant differences in scores of most functional areas and specific items before and after radiotherapy. CONCLUSIONS: Clinicians should select individualized treatment programs and procedures for patients of different ages and stages, and screen high-risk groups for psychological distress and provide additional psychological and social support. In addition, radiotherapy can improve or aggravate some special symptoms of patients. Clinicians should take targeted preventive measures.

[Novel GATA4 mutations identified in patients with congenital heart disease].

OBJECTIVE: To identify the novel genetic determinants in patients with congenital heart disease (CHD). METHODS: The clinical data and peripheral venous blood samples from 120 unrelated individuals with idiopathic CHD were collected and evaluated compared to 100 unrelated healthy controls. The complete coding exons and the partial flanking introns of GATA4 gene were amplified by polymerase chain reaction and sequenced by di-deoxynucleotide chain termination. The generated sequences were aligned with those retrieved from GenBank with the aid of programme BLAST to identify the sequence variations. The software Clustal W was utilized to analyze the conservation of altered amino acids. RESULTS: Three novel heterozygous missense GATA4 mutations were identified in 3 of 120 CHD cases. Namely, the triplet substitutions of AGA for AGC at codon 90, GAG for GAC at codon 95, and AAT for AAG at codon 329, predicting the conversions of serine into arginine at amino acid residue 90 (S90R), aspartic acid into glutamic acid at amino acid residue 95 (D95E) and lysine into asparagine at amino acid residue 329 (K329N), were detected. None of these three mutations were probed in 100 controls. A cross-species alignment of GATA4 encoded protein sequences displayed that the lysine at amino acid residue 329 was completely conserved evolutionarily. Additionally, a single nucleotide polymorphism c. 99G>T was observed. However, the polymorphic frequency distribution in CHD patients was not statistically different from that in controls (for genotypes, chi(2) = 0.2640, P = 0.6074; for alleles, chi(2) = 0.2514, P = 0.6161). CONCLUSION: The idiopathic CHD has a marked heterogeneity and the mutated GATA4 gene may be responsible for CHD in a subset of patients.

[Genetic screening for novel GATA4 mutations associated with congenital atrial septal defect].

OBJECTIVE: To screen the gene GATA4 for novel mutations associated with congenital atrial septal defect (ASD). METHODS: The clinical data and peripheral venous blood specimen from 85 unrelated subjects with congenital ASD were collected and analyzed in contrast to 200 healthy individuals. The coding exons and the exon/intron boundaries of GATA4 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination procedure. The obtained sequences were aligned with those publicized in GenBank with the help of programme BLAST to identify the sequence variations. The software Clustal W was applied to analysis of the conservation of altered amino acids. RESULTS: Three novel heterozygous missense GATA4 mutations were identified in 3 of 85 ASD patients, respectively. Namely, the triplet substitutions of ATG for GTG at codon 267, GCC for ACC at codon 354, and CAA for CCA at codon 407, predicting the conversions of valine into methionine at amino acid residue 267 (V267M), threonine into alanine at amino acid residue 354 (T354A), and proline into glutamine at amino acid residue 407 (P407Q), were identified. No mutation was detected in 200 healthy controls. A cross-species alignment of GATA4 encoded protein sequences showed that the valine at amino acid residue 267 and proline at amino acid residue 407 were completely conserved evolutionarily. CONCLUSION: Three novel heterozygous missense GATA4 mutations were identified in patients with congenital ASD, which reveals new molecular etiology responsible for ASD, and contributes to the early prophylaxis and therapy for ASD.

[Effect of long chain non-coding RNA H19 on the migration and invasion of oral cancer cells and its molecular mechanism].

OBJECTIVE: To investigate the effect of the long chain non-coding RNA H19 (lncRNA H19) on the invasion and migration of oral cancer cells and its related molecular mechanism. METHODS: The expression levels of lncRNA H19, miR-107, and cyclin-dependent kinase 6 (CDK6) in the immortalized oral epithelial cell line HIOEC and the oral cancer cell line CAL27 were detected by real-time quantitative polymerase chain reaction. CAL27 cells were transfected with siRNA H19, miR-107 mimics, pcDNA H19, or anti-miR-107, and the effects of H19 and miR-107 on the invasion and migration of cells were examined via Transwell assay. The TargetScan database predicted the targeting of H19, miR-107, and CDK6. Double luciferase reporter gene assay was performed to detect interactions among H19, miR-107, and CDK6. Western blot analysis was conducted to examine the effects of H19 and miR-107 on the protein level of the target gene CDK6. RESULTS: Compared with that in HIOEC cells, the expression of H19 was significantly increased in CAL27 cells (P<0.05). After transfection with siRNA H19, the expression of H19 decreased, and the invasion and migration ability of CAL27 cells were inhibited (P<0.05). H19 could bind specifically to the 3'-UTR of miR-107 to modulate the expression of miR-107. Compared with that in HIOEC cells, the expression of miR-107 significantly decreased in CAL27 cells (P<0.05). The expression of miR-107 increased after transfection with siRNA H19, and anti-mir-107 co-transfection could promote the invasion and migration ability of siRNA H19 in CAL27 cells (P<0.05). Compared with that in HIOEC cells, CDK6 expression significantly increased in CAL27 cells (P<0.05), and the expression level of the gene was coregulated by H19 and miR-107 (P<0.05). CONCLUSIONS: lncRNA H19 plays an important role in the development of oral cancer. It can regulate the invasion and migration of oral cancer cells by targeting the miR-107/CDK6 signaling axis.

Clinical analysis of percutaneous computed tomography-guided injection of cyanoacrylate for localization of 115 small pulmonary lesions in 113 asymptomatic patients.

OBJECTIVE: This study was performed to assess the clinical feasibility, safety, and effectiveness of a computed tomography (CT)-guided cyanoacrylate injection system and investigate the relationship between clinical features and pathologic characteristics of diminutive pulmonary lesions. METHODS: In total, 115 pulmonary nodules from 113 patients (63 female, 50 male) with a diameter of <20 mm were percutaneously localized with a CT-guided cyanoacrylate injection system and then resected. RESULTS: Of the pure ground-glass opacities (GGOs), 16.0% were atypical adenomatous hyperplasia (AAH), 18.7% were adenocarcinoma in situ (AIS), 49.3% were lung adenocarcinoma (ADC), and 16.0% were benign inflammatory fibrosis/fibrotic scars. Of the mixed GGOs, 18.2% were AAH, 22.7% were AIS, 22.7% were ADC, and 36.4% were benign lesions. Lesions of >10 mm and those located in relation to vessels were significantly more likely to be malignant. The success rate of both the cyanoacrylate injection system and video-assisted thoracoscopic surgery was 100% with no severe complications. CONCLUSIONS: Preoperative localization of small pulmonary nodules using a cyanoacrylate injection system is a safe, simple, and useful technique.

Effect of protein degradation on spot M(r) distribution in 2-D gels--a case study of proteolysis during development of Streptomyces coelicolor cultures.

Proteolysis, a regulated biological process, is reflected by protein spot molecular weight distribution in 2-D gel electrophoretograms. Here we report studies of Streptomyces cultures as they undergo two different developmental processes involving proteolysis. Systematic changes in protein molecular weight distribution between the control samples and those with high activity of proteases were demonstrated. The observations were supported by a numerical model of degradation and its influence on the M(r) distribution. Simple statistics could be used to distinguish between normal and degradative 2-D gel electrophoretic patterns.

Comparison of coronary plaque composition among patients with acute coronary syndrome and stable coronary artery disease.

BACKGROUND: The identification of vulnerable plaques before rupture is an important clinical goal. The purpose of the present study was to assess the difference in plaque composition among patients with acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) by intravascular ultrasound virtual histologic analysis. METHODS: One hundred and thirty-nine patients were divided into ACS group and SCAD group according to clinical presentation. A total of 229 de novo lesions with >50% stenosis in native coronary arteries with diameters >2.5 mm were studied with intravascular ultrasonography. Geometric and compositional data were obtained using intravascular ultrasound virtual histology software. RESULTS: There were no significant differences in overall lesions for fibrous ((52.0+/-11.9)% vs (54.3+/-8.5)%, P>0.05), fibrolipidic ((12.3+/-10.1)% vs (13.8+/-9.5)%, P > 0.05), calcium ((14.0+/-9.1)% vs (19.3+/-13.1)%, P>0.05), or necrotic core ((22.0+/-11.1)% vs (19.7 +/- 5.4)%, P > 0.05) percentages in ACS and SCAD patients, respectively. There were also no significant differences in culprit lesions for fibrous ((46.4+/-12.0)% vs (53.6+/-8.8)%, P>0.05), fibrolipidic ((9.1+/-9.0)% vs (12.9+/-9.7)%, P>0.05), calcium ((16.6+/-9.7)% vs (21.8+/-26.3)%, P>0.05), or necrotic core ((28.0+/-12.6)% vs (20.6+/-5.2)%, P>0.05) percentages in ACS and SCAD patients, respectively. High density lipoprotein-cholesterol levels >1.04 mmol/L were associated with more fibrolipidic ((14.5+/-10.4)% vs (7.1+/-6.5)%, P<0.05) and less necrotic core ((20.6+/-9.7)% vs (27.9+/-12.6)%, P<0.05) percentages in the cohort with ACS. CONCLUSIONS: In this study, coronary plaque composition assessed by intravascular ultrasound virtual histologic analysis was not significantly different between ACS and SCAD patients. The anatomic relationship of the specific plaque components to the lumen of the vessel was more important than the quantitative information of plaque composition for plaque stability.

Molecular mechanisms of action of imatinib mesylate in human ovarian cancer: a proteomic analysis.

BACKGROUND: Imatinib mesylate (Gleevec, Novartis, Basel, Switzerland) is a small-molecule tyrosine kinase inhibitor with activity against ABL, BCR-ABL, c-KIT, and PDGFR alpha. Several clinical trials have evaluated the efficacy and safety of imatinib in patients with ovarian carcinoma who have persistent or recurrent disease following front-line platinum/taxane based chemotherapy. However, there is limited pre-clinical and clinical data on the molecular targets and action of imatinib in ovarian cancer. MATERIALS AND METHODS: Human ovarian cancer cells (A2780) were treated with imatinib mesylate for either 6 or 24 h. We employed a 2D (two-dimensional) gel electrophoresis and mass spectrometry-based proteomics approach to identify protein expression patterns and signaling pathways that were altered in response to imatinib. Cells were analyzed for PDGFR alpha and AKT expression, which were then correlated with imatinib sensitivity. RESULTS: Using 2D gel electrophoresis of overlapping pH ranges from pH 4 to 11, about 4,000 protein spots could be analyzed reproducibly. Proteins whose levels changed between twofold to 30 fold were grouped according to whether changes were in the same direction at both time points of treatment with respect to the control, or changed their levels only at one of the time points. CONCLUSION: Differentially regulated proteins following imatinib treatment of A2780 cells involved the regulation of actin cytoskeleton, metabolic pathways, cell cycle, cell proliferation, apoptosis, cell junctions, and signal transduction. Thus, exposure of cells to imatinib produces complex changes in the cell that require further investigation.

[Comparison of coronary plaque composition between patients with acute coronary syndrome and stable coronary artery disease].

OBJECTIVE: The purpose of the present study was to compare the plaque composition between patients with acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) by intravascular ultrasound virtual histological analysis. METHODS: Two hundred and ten patients were divided into ACS group (n = 131, 188 diseased vessels) and SCAD group (n = 79, 158 diseased vessels). A total of 346 de novo lesions with > 50% stenosis in native coronary arteries with diameters > 2.5 mm were studied with intravascular ultrasonography. Geometric and compositional data were obtained using intravascular ultrasound virtual histology software. RESULTS: There were no significant differences in overall lesions for fibrous (51.2% +/- 12.5% vs. 52.6% +/- 9.6%), fibrolipidic (11.3% +/- 10.6% vs. 12.9% +/- 9.4%), calcium (15.1% +/- 8.9% vs. 20.5% +/- 12.5%) or necrotic core (23.1% +/- 9.8% vs. 20.4% +/- 6.8%, all P > 0.05) components between ACS and SCAD patients. Culprit lesions for fibrous (49.1% +/- 11.2% vs. 50.3% +/- 9.7%), fibrolipidic (10.2% +/- 9.5% vs. 12.7% +/- 9.5%), calcium (15.4% +/- 8.9% vs. 17.4% +/- 24.8%), or necrotic core (24.0% +/- 11.5% vs. 19.7% +/- 5.3%, all P > 0.05) components were also similar between ACS and SCAD patients. High density lipoprotein-cholesterol (HDL) levels > 1.04 mmol/L was associated with more fibrolipidic (15.6% +/- 9.6% vs. 7.4% +/- 5.9%) and less necrotic core (19.4% +/- 8.6% vs. 28.6% +/- 11.2%, all P < 0.05 vs. patients with HDL < or = 1.04 mmol/L) components in ACS patients. CONCLUSION: Coronary plaque composition was similar between ACS and SCAD patients.

[Influencing factors on the quality of life and medical coping style of patients with oral cancer].

OBJECTIVE: To evaluate the influencing factors on the postoperative quality of life and to analyze the coping styles of patients with oral cancer. METHODS: A total of 131 oral cancer cases confirmed through diagnostic criteria were investigated to analyze the influencing factors on the quality of life (QOL) and the relationship between coping style and QOL of these patients by using the fourth edition of the University of Washington Quality of Life Questionnaire (UWQOL) and medical coping modes questionnaires (MCMQ), respectively. RESULTS: Among the 131 questionnaires collected, only 126 were valid with a recovery rate of 96.18% (126/131). Single factor analysis showed that age, marital status, educational level, other systemic diseases, personal income level, tooth loss, operation times, adjuvant radiotherapy, cancer staging, cervical lymph node dissection, recurrence, and jaw resection yielded different UWQOL scale scores (P<0.05). Multiple regression analysis showed that the loss of teeth, cancer staging, recurrence, and jaw resection yielded statistically significant differences in the total score of UWQOL (P<0.05). Among the coping styles, the average scores of  "confrontation", "avoidance", and "yielding" were 17.54±4.97, 17.79±2.19, and 12.97±5.70, respectively. Compared with the norm, the difference was statistically significant (P<0.05). Correlation analysis showed that "confrontation" and "avoidance" were positively correlated, whereas "yielding" was negatively correlated to QOL (P<0.05). CONCLUSIONS: Age, marital status, educational level, other systemic diseases, personal income level, tooth loss, operation times, adjuvant radiotherapy, cancer staging, cervical lymph node dissection, recurrence, and jaw resection have different effects on the quality of QOL. Tooth loss, cancer staging, recurrence, and jaw resection are the main causative factors affecting the patients' perceived QOL. Personalized treatment and nursing care should be strengthened to improve the coping style and quality of life of patients.