The comparison of anatomical and functional features between patients with ischemic with non-obstructive coronary artery disease and obstructive coronary artery disease by CT / 中华放射学杂志

Objective:To explore the difference of the vessel and plaque characteristics, myocardial perfusion and cardiac function between patients with ischemia with non-obstructive coronary artery disease (INOCA) and obstructive coronary artery disease (CAD).Methods:From July 2021 to June 2022, 101 patients with angina were referred to dynamic computed tomography myocardial perfusion (CTP) and coronary computed tomography angiography (CCTA) and retrospectively included in our hospital. Based on the results of CTP and CCTA, patients were divided into INOCA (27 cases), moderate obstructive CAD (26 cases) and severe obstructive CAD (48 cases). The anatomical coronary artery stenosis, plaque characteristics and myocardial perfusion features of all patients were analyzed. Furthermore, left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained on full-phase reconstruction CCTA image by using Medis Suite 3.2 postprocessing software. Multigroup analysis used one way ANOVA or Kruskal Wallis H test. Results:Patients with INOCA were younger than patients with moderate and severe obstructive CAD ( P<0.001). INOCA patients (7.4%, 2/27) had lower rate of positive remodeling than both moderate (57.7%, 15/26, P<0.001) and severe obstructive CAD patients (33.3%, 16/48, P=0.017). The percentage of ischemic myocardium volume in patients with INOCA were similar with those in patients with severe CAD (all P>0.05), but significantly higher than those in patients with moderate CAD (all P<0.05). No significant difference in terms of GLS was detected between patients with INOCA [-17.4% (-21.6%, -11.6%)] and severe CAD [-17.6% (-21.9%, -14.8%), P=0.536], however, patients both with INOCA and severe CAD also had higher GLS than patients with moderate obstructive CAD [-22.3% (-29.8%, -19.0%), all P<0.05]. Conclusions:Based on"one-stop-shop"CTP combined with CCTA imaging, early cardiac functional changes including abnormal myocardial perfusion and myocardial strain in INOCA patients were similar to those in patients with severe obstructive CAD and more severe than those in patients with moderate obstructive CAD.

Machine Learning Model for Predicting CVD Risk on NHANES Data.

Cardiovascular disease (CVD) is a major health problem throughout the world. It is the leading cause of morbidity and mortality and also causes considerable economic burden to society. The early symptoms related to previous observations and abnormal events, which can be subjectively acquired by self-assessment of individuals, bear significant clinical relevance and are regularly preserved in the patient's health record. The aim of our study is to develop a machine learning model based on selected CVD-related information encompassed in NHANES data in order to assess CVD risk. This model can be used as a screening tool, as well as a retrospective reference in association with current clinical data in order to improve CVD assessment. In this form it is planned to be used for mass screening and evaluation of young adults entering their army service. The experimental results are promising in that the proposed model can effectively complement and support the CVD prediction for the timely alertness and control of cardiovascular problems aiming to prevent the occurrence of serious cardiac events.

Analysis of nipple-areola blood supply in patients with breast hypertrophy and normal population / 中华整形外科杂志

Objective@#To explore the nipple-areola complex blood supply mode in hypertrophic breasts, and to obtain the pertinent knowledge of vascular anatomy for breast reduction surgery as well as the analysis of similarities and differences between hypertrophic and normal breasts. Comparing the blood supply of nipples-areola complex between these two groups for analyzing their similarities and differences.@*Methods@#Three dimensional reconstruction of the arteries in breast were performed in 50 patients between September 2015 and August 2017 with breast hypertrophy by computed tomographic angiography (CT angiography). The distribution pattern and the source direction of each main blood vessel was observed, counted and analyzed. Then, the data of breast hypertrophy patients were compared with the previous data about nipple-areola blood supply in normal population (the definition of main vessel: entering the breast gland or reaching the nipple-areola surrounding area, and diameter larger than 1 mm). Statistical description was taken for comparison.@*Results@#135 main vessels were observed in 100 breasts (50 patients). They mainly originate from the internal thoracic artery (69, 51.1%), lateral thoracic artery (37, 27.4%) and thoracoacromial artery(16, 11.9%), as well as a small amount from the brachial artery (7, 5.2%) and axillary artery(6, 4.4%). No main supply vessels from the posterior intercostal artery have been found. The patterns of breast blood supply varied among individuals, and high asymmetry ratio in the same individual was also observed. The internal superior (left: 30.7%, right: 34.2%) and superior lateral quadrant (Left: 29.2%, Right: 20%) of the breast was the most likely area for the main vessel to pass, followed by the breast lateral (Left: 16.9%, Right: 18.5%), lower inner (Left: 4.6%, Right: 5.7%), central (Left: 4.6%, Right: 4.2%), and superior (Left: 1.5%, Right: 2.8%). Differences existed in main vessels between normal breasts and hypertrophic breasts, either for source arteries or the distribution of breast. There was no main blood supply from the intercostal arteries or across the outer inferior quadrant.@*Conclusions@#The blood supply of the nipple-areola is not completely consistent between the hypertrophic breast and the normal size breast, and the blood supply pattern of the hypertrophic breasts is complex and diverse. CT angiography might be used before breast reduction surgery for clarifying the direction of the main vessels, so as to preserve more blood supply for nipple-areola, and to prevent nipple-areola necrosis.

Computed Tomographic Angiography-Based Characterization of Source Blood Vessels for Nipple-Areola Complex Perfusion in Hypertrophic Breasts.

BACKGROUND: Current knowledge about the blood supply of the nipple-areola complex (NAC) has largely been derived from studies on cadavers or persons with breasts of normal size. The aim of this study was to identify and classify the NAC blood supply by computed tomographic angiography (CTA) examination in female volunteers with breast hypertrophy. METHODS: CTA examination was performed on hypertrophic breasts of 23 female subjects. The main blood supplies were revealed through image data analyses. The dominant blood supply of the NAC and its vascular sources were identified and sorted. The detectable diameter threshold of blood vessels was set beyond 1.0 mm. RESULTS: A total of 61 dominant blood vessels were identified. The source arteries were traced as the internal thoracic artery (ITA, 50.8%), lateral thoracic artery (LTA, 27.8%), thoracoacromial artery (TA, 14.8%), brachial artery (BA, 3.3%), and axillary artery (AA, 3.3%), and the corresponding reproducibility of these source vessels was 31, 37, 9, 4.3, and 4.3%, in all breasts. The intercostal artery (IA) was not identified as a dominant NAC supplying vessel in any CTA scan image. Twenty-six breasts had only one dominant artery, whereas 17 breasts showed multiple dominant blood supplies. Three breasts showed no dominant blood vessels of the NAC, with diameters greater than the detectable threshold of 1.0 mm, and 52.2% of the breasts demonstrated anatomically symmetrical patterns of blood supply for the NAC. CONCLUSIONS: The ITA, LTA, and TA are likely to be the main vessel sources, whereas the IA is unlikely to be the dominant vessel for NAC perfusion, on the basis of the studied breasts. An asymmetrical pattern of bilateral breast blood supply was demonstrated in a considerable portion of the females with breast hypertrophy in this study. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Biclustering strategies for genetic marker selection in gynecologic tumor cell lines.

Over the past few decades great interest has been focused on cell lines derived from tumors, because of their usability as models to understand the biology of cancer. At the same time, advanced technologies such as DNA-microarrays have been broadly used to study the expression level of thousands of genes in primary tumors or cancer cell lines in a single experiment. Results from microarray analysis approaches have provided valuable insights into the underlying biology and proven useful for tumor classification, prognostication and prediction. Our approach utilizes biclustering methods for the discovery of genes with coherent expression across a subset of conditions (cell lines of a tumor type). More specifically, we present a novel modification on Cheng & Church's algorithm that searches for differences across the studied conditions, but also enforces consistent intensity characteristics of each cluster within each condition. The application of this approach on a gynecologic panel of cell lines succeeds to derive discriminant groups of compact bi-clusters across four types of tumor cell lines. In this form, the proposed approach is proven efficient for the derivation of tumor-specific markers.

Extracting reliable gene expression signatures through Stable Bootstrap Validation.

Identification of candidate genes responsible for specific phenotypes, such as cancer, has been a major challenge in the field of bioinformatics. Given a DNA Microarray dataset, traditional feature selection methods produce lists of candidate genes which vary significantly under variations of the training data. That instability hinders the validity of research findings and raises doubts about the reliability of such methods. In this study, we propose a framework for the extraction of stable genomic signatures. The proposed methodology enforces stability at the validation step, independent of the feature selection and classification methods used. The statistical significance of the selected gene set is also assessed. The results of this study demonstrate the importance of stability issues in genomic signatures, beyond their prediction capabilities.

Temporal and spatial patterns of gene profiles during chondrogenic differentiation.

Clustering analysis based on temporal profile of genes may provide new insights in particular biological processes or conditions. We report such an integrative clustering analysis which is based on the expression patterns but is also influenced by temporal changes. The proposed platform is illustrated with a temporal gene expression dataset comprised of pellet culture-conditioned human primary chondrocytes and human bone marrow-derived mesenchymal stem cells (MSCs). We derived three clusters in each cell type and compared the content of these classes in terms of temporal changes. We further considered the induced biological processes and the gene-interaction networks formed within each cluster and discuss their biological significance. Our proposed methodology provides a consistent tool that facilitates both the statistical and biological validation of temporal profiles through spatial gene network profiles.

Nonparametric network design and analysis of disease genes in oral cancer progression.

Biological networks in living organisms can be seen as the ultimate means of understanding the underlying mechanisms in complex diseases, such as oral cancer. During the last decade, many algorithms based on high-throughput genomic data have been developed to unravel the complexity of gene network construction and their progression in time. However, the small size of samples compared to the number of observed genes makes the inference of the network structure quite challenging. In this study, we propose a framework for constructing and analyzing gene networks from sparse experimental temporal data and investigate its potential in oral cancer. We use two network models based on partial correlations and kernel density estimation, in order to capture the genetic interactions. Using this network construction framework on real clinical data of the tissue and blood at different time stages, we identified common disease-related structures that may decipher the association between disease state and biological processes in oral cancer. Our study emphasizes an altered MET (hepatocyte growth factor receptor) network during oral cancer progression. In addition, we demonstrate that the functional changes of gene interactions during oral cancer progression might be particularly useful for patient categorization at the time of diagnosis and/or at follow-up periods.

Identification of altered MET network in oral cancer progression based on nonparametric network design.

Oral cancer is characterized by multiple genetic events such as alterations of a number of oncogenes and tumour suppressor genes. The aim of this study is to identify genes and their functional interactions that may play a crucial role on a specific disease-state, especially during oral cancer progression. We examine gene interaction networks on blood genomic data, obtained from twenty three oral cancer patients at four different time stages. We generate the gene-gene networks from sparse experimental temporal data using two methods, Partial Correlations and Kernel Density Estimation, in order to capture genetic interactions. The network study reveals an altered MET (hepatocyte growth factor receptor) network during oral cancer progression, which is further analyzed in relation to other studies.

Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.

Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis.

Phosphorylation status of glucocorticoid receptor, heat shock protein 70, cytochrome c and Bax in lymphocytes of euthymic, depressed and manic bipolar patients.

Bipolar disorder (BD), a severe mental illness, has been correlated with alterations in glucocorticoid receptor (GR) signaling. Since it is phosphorylated GR that contributes to receptor function and determines its transcriptional activity, the Ser211 being a biomarker for activated GR in vivo, it is pertinent that we seek to determine the putative role of the total phosphorylation status of GR and site-specific phosphorylation at serine 211 (S211) in BD and their possible association with parameters of apoptosis. In lymphocytes from 48 BD patients under multiple psychotropic therapy and 20 healthy subjects, we measured whole cell GR, total GR phosphorylation, and phosphorylation of GR at serine 211 in nucleus, using immunoprecipitation, phosphospecific antibody and Western-blot analysis. Cytosolic cytochrome c and Bax and whole cell HSP70 were determined by immunoblot analysis. One-way ANOVA statistical analysis was carried out. Total phosphorylated GR was lower (P<0.001) while the GR S211 was higher (P<0.001) in all BD patients as compared to healthy subjects. HSP70 was reduced in euthymic (P<0.05), depressed (P<0.001) and manic (P<0.001) as compared to healthy subjects. Cytochrome c was higher in all-patient groups as compared to healthy subjects, however without reaching statistical significance (P>0.05). Bax levels were lower in the cytosolic fraction of all three BD groups. We provide the first evidence of altered GR phosphorylation joined with signs of apoptosis in lymphocytes of BD patients and suggest that the phosphorylation status of GR may play a role in the pathophysiology of bipolar disorder.

Cirrhosis and muscle cramps: evidence of a causal relationship.

The aim of the study was to define the features, prevalence, and pathophysiology of therapy for muscle cramps in cirrhotic patients. The first protocol study included 294 cirrhotic patients and 194 age- and sex-matched controls. Controls were defined as inpatients or outpatients without any clinical and laboratory evidence of liver disease. Features and prevalence of muscle cramps were defined on the basis of a standard questionnaire. As far as the pathophysiological associations of muscle cramps were concerned, the following parameters were evaluated: mean arterial pressure (MAP), nutritional status, liver function tests, plasma volume (PV), plasma renin activity (PRA), and electrolyte, mineral, and acid-base status. The prevalence of cramps was higher in cirrhotic patients than in controls, and it was related to the duration of recognized cirrhosis and to the severity of liver function impairment. At a multiple regression analysis, the presence of ascites, low values of MAP, and high values of PRA were the independent predictive factors for the occurrence of cramps in cirrhosis. In the second protocol study, the effects of a sustained expansion of the effective circulating volume induced by intravenous infusion of human albumin were compared with those of a placebo in 12 cirrhotic patients with more than three cramp crises a week. Compared with the placebo, albumin reduced the cramp frequency (P < .01). In conclusion, an increased prevalence of true muscle cramps occurs in patients with cirrhosis. Our data indicate that the pathophysiological link between cirrhosis and cramps may be represented by the reduction of the effective circulating volume. They also indicate that weekly infusion of human albumin may be an effective treatment for cramps in cirrhosis.

Randomized clinical study of the efficacy of amiloride and potassium canrenoate in nonazotemic cirrhotic patients with ascites.

Although some clinical studies seem to prove the efficacy of nonantialdosteronic potassium-sparing diuretics in the treatment of ascites, no controlled study has compared the efficacy of these drugs with that of antialdosteronic diuretics. Forty nonazotemic cirrhotic patients were randomized to receive amiloride (group A, n = 20) or potassium canrenoate (group B, n = 20). The initial doses of amiloride and potassium canrenoate were 20 mg and 150 mg, respectively. The doses were increased in stepwise fashion to 60 and 500 mg/day, respectively, if no response ensued. Nonresponders to the highest doses of each drug were later treated with potassium canrenoate and amiloride, respectively. Seven of 20 group A patients responded to amiloride, whereas 14 of 20 group B patients responded to potassium canrenoate (p < 0.025). Seven of 13 nonresponders to amiloride later responded to potassium canrenoate, whereas only two of the nonresponders to potassium canrenoate later responded to amiloride. The diuretic responses to amiloride and potassium canrenoate were related to the activity of the renin-aldosterone system. All responders to amiloride (n = 9) had normal values of plasma aldosterone. All nonresponders to amiloride who later responded to potassium canrenoate (n = 7) had increased levels of plasma aldosterone. Moreover, on comparison of all responders (n = 21) and nonresponders (n = 12) to potassium canrenoate, a higher degree of renal proximal sodium reabsorption (with consequent limitation of sodium delivery to the distal tubule) was found to be the main difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of amiloride on renal lithium handling in nonazotemic ascitic cirrhotic patients with avid sodium retention.

The reliability of lithium clearance as an index of distal fluid delivery in cirrhosis with ascites and in other clinical conditions characterized by low fractional sodium excretion has not yet been proven. In particular, lithium reabsorption in the amiloride-sensitive segment of the distal tubule, as evidenced in experimental studies, has not been excluded in such clinical conditions. Thus the acute effect of amiloride on renal lithium handling in 15 nonazotemic ascitic cirrhotic patients with avid sodium retention was evaluated after at least 5 days of controlled sodium intake. Renal plasma flow, glomerular filtration rate, fractional sodium excretion, fractional lithium excretion, fractional potassium excretion, fractional excretion of uric acid, plasma renin activity, plasma aldosterone and human atrial natriuretic peptide were evaluated before and for 6 hr after the administration of amiloride (20 mg/os). After amiloride administration a volume replacement scheme was enacted with intravenous amounts of saline solution, determined by the diuretic and natriuretic effect of the drug, to avoid volume depletion. Amiloride induced a prompt and sustained increase in fractional sodium excretion (from 0.28% +/- 0.09% to 1.0% +/- 0.41%, p less than 0.001) and a decrease in fractional potassium excretion (from 9.38% +/- 5.98% to 3.28% +/- 2.24%, p less than 0.0025), whereas it did not affect fractional lithium excretion and fractional excretion of uric acid. No change was observed in renal plasma flow, glomerular filtration rate, plasma renin activity, plasma aldosterone and human atrial natriuretic peptide. It was concluded that lithium is not reabsorbed in the amiloride-sensitive segment of the distal tubule in nonazotemic ascitic cirrhotic patients with avid sodium retention.

Distribution of axillary node metastases by level of invasion. An analysis of 539 cases.

Five hundred and thirty-nine patients with carcinoma of the breast treated with total axillary dissection and with positive axillary nodes were evaluated. The total number of lymph nodes removed was 11,082, with an average of 20.5 nodes per patient. The average number of lymph nodes at the first level was 13.8, at the second level 4.5, at the third level 2.2. The average number of nodes was 20.7 in cases treated with Halsted mastectomy, 20.9 with total mastectomy and axillary dissection, 20.3 with quadrantectomy and axillary dissection. Of 3259 metastatic nodes, 64 were site of micrometastases; 797 were partially involved, 441 were totally involved and 1957 were site of metastases with extracapsular invasion. In 314 (58.2%) the first level only was involved, in 117 cases (21.7%) metastases were present at the first and second level, whereas in 88 cases (16.3%) all the three levels were sites of metastases. Only 20 cases showed skipping distribution. In 1.5% of the cases the first level was skipped by metastases, in 0.4% the first nodes of the first level are clear the chances that metastatic nodes are present at the second and third levels are negligible. When the nodes at the first level are positive, the chances that metastases are also present at the higher levels are of the order of 40.0%.