[Exploration and practice of cardio-oncology].

With the improvement of oncology diagnosis and treatment, the survival time of cancer patients has been significantly prolonged, and the cancer therapy-related cardiovascular toxicity such as radiotherapy, chemotherapy, immunotherapy, and surgery are becoming more and more prominent, and it is in this context that the germ of Cardio-Oncology exploration has come into being. The multidisciplinary Cardio-Oncology team aims to establish a multidisciplinary prevention and control system to assess patients' baseline risk factors, individualized monitoring, and weighing the risk-benefit ratio of cancer therapy. At present, the connotation of the discipline of Cardio-Oncology has been expanded horizontally and deepened vertically in China, and Cardio-Oncology treatment centers have blossomed all over the country. Moreover, international and domestic scholars continue to improve Cardio-Oncology guidelines and consensus through their own practice, and develop artificial intelligence software to help the development of the discipline. It is believed that in the future, with the training of Cardio-Oncologists and the output of high-quality clinical research evidence, cardiovascular safety of cancer patients can be ensured more scientifically and effectively.

Selective vulnerability of brainstem and cervical spinal cord regions in people with non-progressive multiple sclerosis of Black or African American and European ancestry.

BACKGROUND: We evaluated imaging features suggestive of neurodegeneration within the brainstem and upper cervical spinal cord (UCSC) in non-progressive multiple sclerosis (MS). METHODS: Standardized 3-Tesla three-dimensional brain magnetic resonance imaging (MRI) studies were prospectively acquired. Rates of change in volume, surface texture, curvature were quantified at the pons and medulla-UCSC. Whole and regional brain volumes and T2-weighted lesion volumes were also quantified. Independent regression models were constructed to evaluate differences between those of Black or African ancestry (B/AA) and European ancestry (EA) with non-progressive MS. RESULTS: 209 people with MS (pwMS) having at least two MRI studies, 29% possessing 3-6 timepoints, resulted in 487 scans for analysis. Median follow-up time between MRI timepoints was 1.33 (25th-75th percentile: 0.51-1.98) years. Of 183 non-progressive pwMS, 88 and 95 self-reported being B/AA and EA, respectively. Non-progressive pwMS demonstrated greater rates of decline in pontine volume (p < 0.0001) in B/AA and in medulla-UCSC volume (p < 0.0001) for EA pwMS. Longitudinal surface texture and curvature changes suggesting reduced tissue integrity were observed at the ventral medulla-UCSC (p < 0.001), dorsal pons (p < 0.0001) and dorsal medulla (p < 0.0001) but not the ventral pons (p = 0.92) between groups. CONCLUSIONS: Selectively vulnerable regions within the brainstem-UCSC may allow for more personalized approaches to disease surveillance and management.

Deficient chaperone-mediated autophagy in macrophage aggravates inflammation of nonalcoholic steatohepatitis by targeting Nup85.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.

[Analyze of the correlation and corresponding value of serum C-peptide and insulin in adult population].

Objective: To investigate the correlation between serum C-peptide and in adult population, and establish the corresponding insulin values of serum C-peptide levels. Methods: Cross-sectional study. The clinical data of the adults who underwent physical examination in the Second Medical Center of PLA General Hospital from January 2017 to December 2021 were retrospectively included. The participants were divided into type 2 diabetes group, prediabetes group and normal plasma glucose group according to the diagnostic criteria for diabetes. The correlation between serum C-peptide and insulin was explored by Pearson correlation analysis, linear regression analysis, and nonlinear regression analysis, and the corresponding insulin values of serum C-peptide were established. Results: A total of 48 008 adults were enrolled, including 31 633 males (65.9%) and 16 375 females (34.1%), aged (50.1±9.9) years (18-89 years). There were 8 160 subjects (17.0%) with type 2 diabetes, 13 263 subjects (27.6%) with prediabetes, and 26 585 subjects (55.4%) with normal plasma glucose. The serum fasting C-peptide (FCP, M(Q1, Q3)] of the three groups were 2.76(2.18, 3.47), 2.54(1.99, 3.21) and 2.18(1.71, 2.79)µg/L, respectively. The fasting insulin [FINS, M(Q1,Q3)] of the three groups were 10.98(7.57, 16.09), 10.06(6.95, 14.47) and 8.43(5.86,12.12)mU/L, respectively. FCP was positively correlated with FINS (r=0.82), and 2 h postprandial C-peptide (2 h CP) was positively correlated with 2 h postprandial insulin (2 h INS) (r=0.84) (both P<0.001). FCP was linearly associated with FINS (R2=0.68), and 2 h CP was linearly associated with 2 h INS (R2=0.71) (both P<0.001). There was a power function correlation between FCP and FINS (R2=0.74), and 2 h CP and 2 h INS (R2=0.78) (both P<0.001). The results of the statistical analysis were similar in various glucose metabolism subgroups. Since the fitting degree of the power function model was higher than that of the linear model, the power function model was the best model. The power function equation was FINS=2.96×FCP1.32, and 2 h INS=1.64×(2 h CP)1.60, respectively. Multivariate linear regression analysis demonstrated that FCP was a related factor of FINS (R2=0.70, P<0.001) and 2 h CP was a related factor of 2 h INS (R2=0.73, P<0.001), after adjusting for related confounders. Conclusions: There was a power function correlation between FCP and FINS, 2 h CP and 2 h INS in adult population. The insulin values corresponding to C-peptide levels were established in the study.

[Relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status].

Objective: To investigate the relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status. Methods: The demographic data and biochemical indicators of the adult population who had received physical examination in the Second Medical Center of the PLA General Hospital from January 2018 to December 2021 were collected. The subjects were divided into two groups according to the level of serum uric acid: the normal uric acid group and the hyperuricemia group. The relationship between hemoglobin (stratified into four levels of Q1 to Q4 by the quartile) and serum uric acid was quantified by using Pearson correlation and logistic regression analysis. The effects of age and glucose metabolism status on the relationship between hemoglobin and serum uric acid were analyzed. Results: A total of 33 183 adults were enrolled with age (50.6±10.0) years. The level of hemoglobin in the normal uric acid group (142.61±14.24) g/L was significantly lower than that in the hyperuricemia group [(151.79±11.24) g/L, P<0.001]. Univariate Pearson correlation analysis showed that hemoglobin was positively associated with serum uric acid (r=0.444, P<0.001). After adjusting for related confounding factors, multivariate logistic regression analysis showed that hemoglobin was associated with serum uric acid, and the OR values (95%CI) of hemoglobin Q2 to Q4 group were 1.29 (1.13-1.48), 1.42 (1.24-1.62) and 1.51 (1.32-1.72), respectively (Ptrend<0.001) when compared with hemoglobin Q1 group. Subgroup analysis and hierarchical interaction analysis suggested that with the increase of hemoglobin, the serum uric acid in the age<60 years subgroup, normal glucose subgroup and prediabetes subgroup increased gradually (Ptrend<0.05 and Pinteraction<0.001). Conclusion: The association between hemoglobin and serum uric acid in adults is affected by age and glucose metabolism status.

[Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years].

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.

Cancer risk in individuals with autism spectrum disorder.

BACKGROUND: Whether individuals with autism spectrum disorders (ASDs) have a higher-than-expected risk of cancer remains unknown. PATIENTS AND METHODS: We carried out a population-based cohort study including 2.3 million individuals live-born to mothers from Nordic countries during 1987-2013 in Sweden with follow-up through 2016 (up to age 30 years). Individuals with ASD were ascertained through the Swedish National Patient Register. We estimated the relative risk of cancer in relation to ASD by odds ratios (ORs) and associated 95% confidence intervals (CIs) derived from logistic regression, after detailed adjustment for potential confounders. We also carried out a sibling comparison to address familial confounding and a genetic correlation analysis using the genome-wide association study summary statistics to address confounding due to potential polygenetic pleiotropy between ASD and cancer. RESULTS: We observed an overall increased risk of any cancer among individuals with ASD (OR 1.3, 95% CI 1.2-1.5), compared with individuals without ASD. The association for any cancer was primarily noted for narrowly defined autistic disorder (OR 1.7, 95% CI 1.3-2.1) and ASD with comorbid birth defects (OR 2.1, 95% CI 1.5-2.9) or both birth defects and intellectual disability (ID; OR 4.8, 95% CI 3.4-6.6). An association was also suggested for ASD with comorbid ID (OR 1.4; 95% CI 0.9-2.1), but was not statistically significant. ASD alone (i.e. without comorbid ID or birth defects) was not associated with an increased risk of any cancer (OR 1.0, 95% CI 0.8-1.2). Sibling comparison and genetic correlation analysis showed little evidence for familial confounding or confounding due to polygenetic pleiotropy between ASD and cancer. CONCLUSIONS: ASD per se is not associated with an increased risk for cancer in early life. The increased cancer risk among individuals with ASD is likely mainly attributable to co-occurring ID and/or birth defects in ASD.

Probing

The isomer depletion of ^{93m}Mo was recently reported [Chiara et al., Nature (London) 554, 216 (2018)NATUAS0028-083610.1038/nature25483] as the first direct observation of nuclear excitation by electron capture (NEEC). However, the measured excitation probability of 1.0(3)% is far beyond the theoretical expectation. In order to understand the inconsistency between theory and experiment, we produce the ^{93m}Mo nuclei using the ^{12}C(^{86}Kr,5n) reaction at a beam energy of 559 MeV and transport the reaction residues to a detection station far away from the target area employing a secondary beam line. The isomer depletion is expected to occur during the slowdown process of the ions in the stopping material. In such a low γ-ray background environment, the signature of isomer depletion is not observed, and an upper limit of 2×10^{-5} is estimated for the excitation probability. This is consistent with the theoretical expectation. Our findings shed doubt on the previously reported NEEC phenomenon and highlight the necessity and feasibility of further experimental investigations for reexamining the isomer depletion under low γ-ray background.

Diagnostic Utility of Hippocampal Volumetric Data in a Memory Disorder Clinic Setting.

BACKGROUND: Hippocampal volumetric data are widely used in research but are rarely examined in clinical populations in regard to aiding diagnosis or correlating with objective memory test scores. OBJECTIVE: To replicate and expand on the few prior clinical examinations of the utility of hippocampal volumetric data. We evaluated MRI volumetric data to determine (a) the degree of hippocampal loss across diagnostic groups compared with a cognitively intact group, (b) if total or lateralized hippocampal volumes predict diagnostic group membership, and (c) how total and lateralized volumes correlate with memory tests. METHOD: We retrospectively examined hippocampal volumetric data and memory test scores for 294 individuals referred to a memory clinic. RESULTS: Individuals with mild cognitive impairment or Alzheimer disease had smaller hippocampal volumes compared with cognitively intact individuals. The raw and normalized total and lateralized hippocampal volumes were essentially equal for predicting diagnostic group membership, and notably low hippocampal volumes evidenced greater specificity than sensitivity. All of the volumetric data correlated with the memory test scores, with the total and left hippocampal volumes accounting for the slightly more variance in the diagnostic groups. CONCLUSION: The diagnostic groups exhibited hippocampal volume loss, which can be a potential biomarker for neurodegenerative disease in clinical practice. However, solely using hippocampal volumetric data to predict diagnostic group membership or memory test failure was not supported. While extreme hippocampal volume loss was rare in the cognitively intact group, the sensitivity of these volumetric data suggests a need for supplementation by other tools when making a diagnosis.

Limonitum Ameliorates Castor Oil-Induced Diarrhoea in Mice by Modulating Gut Microbiota.

Diarrhoea is a common clinical condition; its pathogenesis is strongly associated with gut microbiota dysbiosis. Limonitum is a well-known traditional Chinese medicine that exerts appreciable benefits regarding the amelioration of diarrhoea. However, the mechanism through which Limonitum ameliorates diarrhoea remains unclear. Here, the efficacy and underlying mechanism of Limonitum decoction (LD) regarding diarrhoea were explored from the aspect of gut microbiota. Castor oil (CO) was used to induce diarrhoea in mice, which were then used to evaluate the effects of LD regarding the timing of the first defecation, diarrhoea stool rate, degree of diarrhoea, diarrhoea score, intestinal propulsive rate, and weight of intestinal contents. The concentrations of short-chain fatty acids (SCFAs), including acetic, propionic, isobutyric, butyric and valeric acids, were analysed by gas chromatography-mass spectrometry (GC-MS). The 16S rRNA high-throughput sequencing technology was applied to evaluate changes in the gut microbiota under exposure to LD. LD was found to effectively ameliorate the symptoms of diarrhoea, and the diversity and relative abundance of gut microbiota were restored to normal levels following LD treatment. Additionally, LD significantly restored the observed reductions in SCFAs. These results provide strong evidence that LD can sufficiently ameliorate diarrhoea in mice by regulating their gut microbiota. The findings presented here highlight that Limonitum may constitute a prospective remedy for diarrhoea.

[Correlation between glycemic variability and glycosylated hemoglobin level during follow-up in elderly male patients with type 2 diabetes in Beijing].

Objective: To investigate the relationship between glycemic variability and glycosylated hemoglobin (HbA1c) level during follow-up in elderly male patients with type 2 diabetes. Methods: Retrospective cohort study. A total of 200 elderly male patients who received continuous glucose monitoring from January 2007 to January 2011 were recruited in the Second Medical Center of PLA General Hospital. The subjects were divided into two groups according to baseline mean amplitude of glycaemic excursion (MAGE) level, including MAGE <3.9 mmol/L group (n=114) and MAGE ≥3.9 mmol/L group (n=86). The correlation between baseline MAGE and mean HbA1c during follow-up were evaluated by univariate Pearson correlation analysis and multivariate linear regression analysis. Results: Baseline characteristics including age, body mass index, waist circumference, smoking, drinking, fasting blood glucose, blood lipid and blood pressure were comparable between MAGE <3.9 mmol/L group and MAGE ≥3.9 mmol/L group. The average follow-up period was 12.5 years. The mean HbA1c during follow-up in MAGE ≥3.9 mmol/L group was significantly higher than that in MAGE <3.9 mmol/L group (7.23%±0.72% vs. 6.91%±0.77%, t=-2.94, P=0.004). The proportion of mean HbA1c <7.0% during follow-up in MAGE ≥3.9 mmol/L group was 44.2% (38/86), which was significantly lower than that in MAGE <3.9 mmol/L group [60.5% (69/114), χ2=5.26, P=0.022]. In univariate analysis, MAGE at baseline was correlated with the mean HbA1c during follow-up (r=0.306, P<0.001). Multivariate linear regression analysis suggested that the baseline MAGE remained an independent influential factor of mean HbA1c (ß=0.09, 95%CI: 0.03 to 0.15, P=0.006, R2=0.31) after several confounding factors were adjusted. Conclusions: With the increased glycemic variability at baseline, mean HbA1c level during follow-up is accordingly elevated. The glycemic variability at baseline is independently related to mean HbA1c level during follow-up in elderly male patients with type 2 diabetes.

[Cardiovascular events and risk factors in hematological neoplasms patients treated with anthracyclines].

Objective: To explore the incidence and risk factors of cardiovascular events in hematological neoplasms patients treated with anthracyclines in the real world. Methods: A total of 408 patients with lymphoma and leukemia, who were treated with anthracyclines during hospitalization in the First Affiliated Hospital of Dalian Medical University from January 1, 2018 to July 31, 2021, were included in this retrospective study. Patients were divided into cardiovascular event group (n=74) and non-cardiovascular event group (n=334). The primary endpoint was cardiovascular events (arrhythmia, heart failure, acute myocardial infarction etc.) after anthracyclines therapy. The secondary endpoint was all-cause mortality, cardiovascular-cause death, discontinued chemotherapy due to cardiovascular events. Multivariate regression analysis was used to investigate the risk factors of cardiovascular events. Kaplan-Meier was performed to calculate the incidence of all-cause mortality. Results: The mean age was (55.6±14.9) years, and there were 227 male patients (55.6%) in this cohort. The median follow-up time was 45 months. During follow-up, cardiovascular adverse events occurred in 74 patients (18.1%), including 45 heart failure (38 were heart failure with preserved ejection fraction), 30 arrhythmia, 4 acute myocardial infarction and 2 myocarditis/pericarditis. Multivariate regression analysis showed age (OR=1.024, 95%CI 1.003-1.045, P=0.027) and history of hypertension over 10 years (OR=2.328, 95%CI 1.055-5.134, P=0.036) were independent risk factors for the cardiovascular events. Kaplan-Meier survival curve showed mortality was significantly higher in cardiovascular event group than in non-cardiovascular event group (47.3% vs. 26.6%, P=0.001). In the cardiovascular event group, chemotherapy was discontinued in 9 cases (12.2%) due to cardiovascular events and cardiovascular death occurred in 7 cases (9.5%). Conclusions: Although heart failure is the main cardiovascular event in lymphoma and leukemia patients post anthracyclines therapy, other cardiovascular events especially arrhythmias are also common. The presence of cardiovascular events is associated with higher risk of all-cause mortality in these patients. Age and long-term hypertension are independent risk factors for cardiovascular events in lymphoma and leukemia patients after anthracyclines treatment.

Fully Automated Volumetric Breast Density Estimation from Digital Breast Tomosynthesis.

Background While digital breast tomosynthesis (DBT) is rapidly replacing digital mammography (DM) in breast cancer screening, the potential of DBT density measures for breast cancer risk assessment remains largely unexplored. Purpose To compare associations of breast density estimates from DBT and DM with breast cancer. Materials and Methods This retrospective case-control study used contralateral DM/DBT studies from women with unilateral breast cancer and age- and ethnicity-matched controls (September 19, 2011-January 6, 2015). Volumetric percent density (VPD%) was estimated from DBT using previously validated software. For comparison, the publicly available Laboratory for Individualized Breast Radiodensity Assessment software package, or LIBRA, was used to estimate area-based percent density (APD%) from raw and processed DM images. The commercial Quantra and Volpara software packages were applied to raw DM images to estimate VPD% with use of physics-based models. Density measures were compared by using Spearman correlation coefficients (r), and conditional logistic regression was performed to examine density associations (odds ratios [OR]) with breast cancer, adjusting for age and body mass index. Results A total of 132 women diagnosed with breast cancer (mean age ± standard deviation [SD], 60 years ± 11) and 528 controls (mean age, 60 years ± 11) were included. Moderate correlations between DBT and DM density measures (r = 0.32-0.75; all P < .001) were observed. Volumetric density estimates calculated from DBT (OR, 2.3 [95% CI: 1.6, 3.4] per SD for VPD%DBT) were more strongly associated with breast cancer than DM-derived density for both APD% (OR, 1.3 [95% CI: 0.9, 1.9] [P < .001] and 1.7 [95% CI: 1.2, 2.3] [P = .004] per SD for LIBRA raw and processed data, respectively) and VPD% (OR, 1.6 [95% CI: 1.1, 2.4] [P = .01] and 1.7 [95% CI: 1.2, 2.6] [P = .04] per SD for Volpara and Quantra, respectively). Conclusion The associations between quantitative breast density estimates and breast cancer risk are stronger for digital breast tomosynthesis compared with digital mammography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Yaffe in this issue.

Disruption of the Atrophy-based Functional Network in Multiple Sclerosis Is Associated with Clinical Disability: Validation of a Meta-Analytic Model in Resting-State Functional MRI.

Background In multiple sclerosis (MS), gray matter (GM) atrophy exhibits a specific pattern, which correlates strongly with clinical disability. However, the mechanism of regional specificity in GM atrophy remains largely unknown. Recently, the network degeneration hypothesis (NDH) was quantitatively defined (using coordinate-based meta-analysis) as the atrophy-based functional network (AFN) model, which posits that localized GM atrophy in MS is mediated by functional networks. Purpose To test the NDH in MS in a data-driven manner using the AFN model to direct analyses in an independent test sample. Materials and Methods Model fit testing was conducted with structural equation modeling, which is based on the computation of semipartial correlations. Model verification was performed in coordinate-based data of healthy control participants from the BrainMap database (https://www.brainmap.org). Model validation was conducted in prospectively acquired resting-state functional MRI in participants with relapsing-remitting MS who were recruited between September 2018 and January 2019. Correlation analyses of model fit indices and volumetric measures with Expanded Disability Status Scale (EDSS) scores and disease duration were performed. Results Model verification of healthy control participants included 80 194 coordinates from 9035 experiments. Model verification in healthy control data resulted in excellent model fit (root mean square error of approximation, 0.037; 90% CI: 0.036, 0.039). Twenty participants (mean age, 36 years ± 9 [standard deviation]; 12 women) with relapsing-remitting MS were evaluated. Model validation in resting-state functional MRI in participants with MS resulted in deviation from optimal model fit (root mean square error of approximation, 0.071; 90% CI: 0.070, 0.072), which correlated with EDSS scores (r = 0.68; P = .002). Conclusion The atrophy-based functional network model predicts functional network disruption in multiple sclerosis (MS), thereby supporting the network degeneration hypothesis. On resting-state functional MRI scans, reduced functional network integrity in participants with MS had a strong positive correlation with clinical disability. © RSNA, 2021 Online supplemental material is available for this article.

Combining inhomogeneous magnetization transfer and multipoint Dixon acquisition: Potential utility and evaluation.

PURPOSE: The recently introduced inhomogeneous magnetization transfer (ihMT) method has predominantly been applied for imaging the central nervous system. Future applications of ihMT, such as in peripheral nerves and muscles, will involve imaging in the vicinity of adipose tissues. This work aims to systematically investigate the partial volume effect of fat on the ihMT signal and to propose an efficient fat-separation method that does not interfere with ihMT measurements. METHODS: First, the influence of fat on ihMT signal was studied using simulations. Next, the ihMT sequence was combined with a multi-echo Dixon acquisition for fat separation. The sequence was tested in 9 healthy volunteers using a 3T human scanner. The ihMT ratio (ihMTR) values were calculated in regions of interest in the brain and the spinal cord using standard acquisition (no fat saturation), water-only, in-phase, and out-of-phase reconstructions. The values obtained were compared with a standard fat suppression method, spectral presaturation with inversion recovery. RESULTS: Simulations showed variations in the ihMTR values in the presence of fat, depending on the TEs used. The IhMTR values in the brain and spinal cord derived from the water-only ihMT multi-echo Dixon images were in good agreement with values from the unsuppressed sequence. The ihMT-spectral presaturation with inversion recovery combination resulted in 24%-35% lower ihMTR values compared with the standard non-fat-suppressed acquisition. CONCLUSION: The presence of fat within a voxel affects the ihMTR calculations. The IhMT multi-echo Dixon method does not compromise the observable ihMT effect and can potentially be used to remove fat influence in ihMT.

Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

Mammographic Variation Measures, Breast Density, and Breast Cancer Risk.

OBJECTIVE. Our previous work showed that variation measures, which represent breast architecture derived from mammograms, were significantly associated with breast cancer. For replication purposes, we examined the association of three variation measures (variation [V], which is measured in the image domain, and P1 and p1 [a normalized version of P1], which are derived from restricted regions in the Fourier domain) with breast cancer risk in an independent population. We also compared these measures to volumetric density measures (volumetric percent density [VPD] and dense volume [DV]) from a commercial product. MATERIALS AND METHODS. We examined 514 patients with breast cancer and 1377 control patients from a screening practice who were matched for age, date of examination, mammography unit, facility, and state of residence. Spearman rank-order correlation was used to evaluate the monotonic association between measures. Breast cancer associations were estimated using conditional logistic regression, after adjustment for age and body mass index. Odds ratios were calculated per SD increment in mammographic measure. RESULTS. These variation measures were strongly correlated with VPD (correlation, 0.68-0.80) but not with DV (correlation, 0.31-0.48). Similar to previous findings, all variation measures were significantly associated with breast cancer (odds ratio per SD: 1.30 [95% CI, 1.16-1.46] for V, 1.55 [95% CI, 1.35-1.77] for P1, and 1.51 [95% CI, 1.33-1.72] for p1). Associations of volumetric density measures with breast cancer were similar (odds ratio per SD: 1.54 [95% CI, 1.33-1.78] for VPD and 1.34 [95% CI, 1.20-1.50] for DV). When DV was included with each variation measure in the same model, all measures retained significance. CONCLUSION. Variation measures were significantly associated with breast cancer risk (comparable to the volumetric density measures) but were independent of the DV.

Fundamentals of Radiation Oncology for Treatment of Vertebral Metastases.

The fields of both radiology and radiation oncology have evolved considerably in the past few decades, resulting in an increased ability to delineate between tumor and normal tissue to precisely target and treat vertebral metastases with radiation therapy. These scientific advances have also led to improvements in assessing treatment response and diagnosing toxic effects related to radiation treatment. However, despite technological innovations yielding greatly improved rates of palliative relief and local control of osseous spinal metastases, radiation therapy can still lead to a number of acute and delayed posttreatment complications. Treatment-related adverse effects may include pain flare, esophageal toxic effects, dermatitis, vertebral compression fracture, radiation myelopathy, and myositis, among others. The authors provide an overview of the multidisciplinary approach to the treatment of spinal metastases, indications for surgical management versus radiation therapy, various radiation technologies and techniques (along with their applications for spinal metastases), and current principles of treatment planning for conventional and stereotactic radiation treatment. Different radiologic criteria for assessment of treatment response, recent advances in radiologic imaging, and both common and rare complications related to spinal irradiation are also discussed, along with the imaging characteristics of various adverse effects. Familiarity with these topics will not only assist the diagnostic radiologist in assessing treatment response and diagnosing treatment-related complications but will also allow more effective collaboration between diagnostic radiologists and radiation oncologists to guide management decisions and ensure high-quality patient care. ©RSNA, 2021.

[Preoperative treatment of uterine fibroids with low-dose mifepristone: a multicenter, randomized, double-blind, placebo-controlled, parallel-group study].

Objective: To evaluate the clinical efficacy and safety of oral mifepristone (10 mg/day) versus placebo in the preoperative treatment of uterine fibroids. Methods: This study was a multi-center, randomized, double-blind, placebo, parallel controlled trial. A total of 132 patients with uterine fibroids were randomly divided into study group and control group, with 66 cases in each group. The patients in the study group orally took 1 tablet/day of mifepristone (dose of 10 mg/tablet), the patients in the control group orally took 1 tablet/day of placebo, and both groups were treated for 3 months. The primary efficacy evaluation indicators were the change rate of maximum fibroid volume; the secondary efficacy evaluation indicators included amenorrhea rate, improvement of subjective symptoms and anemia; the safety evaluation indicators included the analysis of adverse events and changes in laboratory biochemical indicators. Results: At the end of treatment, the maximum leiomyoma volume was reduced by 25.97% (95%CI: -34.79%--15.95%) in the study group and reduced by 1.51% (95%CI: -13.03%-11.54%) in the control group. The change rate of the maximum leiomyoma volume before and after treatment in the study group was significantly greater than that in the control group, and the difference in the change rate of the maximum leiomyoma volume between the two groups was -24.84% (95%CI: -36.56%--10.94%), which was much higher than the 10% superiority threshold goal set by this study within the 95%CI interval. At the end of treatment, the complete amenorrhea rate [84% (52/62)], dysmenorrhea elimination rate [98% (61/62)], and menstrual blood loss disappearance rate [87% (54/62)] in the study group were significantly higher than those in the control group (all P<0.05). At the end of treatment, the mean hemoglobin [(131±13) g/L], red blood cell count [(4.5±0.4)×1012/L] and hematocrit (0.39±0.03) in the study group were significantly increased compared with the baseline, and the differences had statistical significance (all P<0.05); after treatment, the differences in the above three indicators between the two groups had statistical significance (all P<0.01). The serum estradiol level in the study group was significantly lower than that in the control group at the end of treatment, and the difference was statistically significant (P<0.01). There were no significant differences in follicle-stimulating hormone and cortisol levels before and after treatment between the two groups (P>0.05). The overall incidences of any adverse event were not significantly different between the two groups (all P>0.05). Abdominal pain was the most common adverse event in the study group [9% (6/65)], but the incidence was not significantly increased compared with the control group [3% (2/64); P>0.05]. Conclusion: Compared with placebo, oral mifepristone 10 mg/day is significantly superior to placebo in reducing the size of uterine fibroids and improving anemia, without significant adverse reactions, and could be used as a drug treatment for patients with of uterine fibroids before surgery.

[Screening of candidate genes related to low-dose ionizing radiation based on transcriptome-proteome correlation research techniques].

Objective: To identify the related genes of low-dose ionizing radiation on basis of association analysis of transcriptome and proteome data, and provide new clues for the molecular mechanism of low-dose radiation (LDR) effect. Methods: In March 2018, healthy human peripheral blood was used as materials for transcriptome sequencing and proteome analysis after exposure to radiation at 150 mGy (treatment group) and no radiation (control group) , with three samples in each group. The total RNA and protein were extracted and then correlation analysis of transcriptomic and proteomic were performed to determine LDR effect-related genes, and after that, the biological process and molecular function were analyzed. Results: A total of 486 genes and 266 proteins were identified differentially expressed between treatment group and control group, respectively. Twelve genes and related proteins were found correlated (P<0.05) . The overall correlation between quantitative protein and gene was low (rs=0.0034) , the differential gene with the same change trend was positively correlated with protein expression (rs=0.6786) , and the differential gene with the opposite change trend was negatively correlated with protein expression (rs=-0.1000) . Seven differentially expressed genes (DEGs) showed the same trend as proteins, among which FBXO7 and SNCA were up-regulated as well as ORM1, ORM2, HIST1H4J, HBZ and LYZ were down-regulated. Five DEGs showed the opposite trend as proteins, including SLC4A1, BCAM, C4B_2, KEL, TGM2 up-regulated in transcription level and down-regulated in protein expression level. These DEGs were involved in various biological processes such as immune system regulation, signal transduction, enzyme activity regulation, transmembrane transport, defense, transcription and DNA repair, which indicated their important roles in response to LDR in human peripheral blood. Conclusion: Twelve candidate genes related to LDR effect and their corresponding expressed proteins are screened by the correlation research of transcriptome and proteome data, which provides new clues for the further study of the mechanism of LDR effect.