Characterizing the relationship between MRI radiomics and AHR expression and deriving a predictive model for prognostic assessment in glioblastoma.

PURPOSE: Aryl hydrocarbon receptor (AHR), a crucial molecular marker associated with glioma, is a potential therapeutic target. We aimed to establish a non-invasive predictive model for AHR through radiomics. METHODS: Contrast-enhanced T1-weighted (T1W) MRI and the corresponding and clinical variables of glioblastoma patients from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) were obtained for analysis. KM curves and Cox regression analyses were used to assess the prognostic value of AHR expression. The radiomics features were screened by Max-Relevance and Min-Redundancy (mRMR) and recursive feature elimination (RFE), followed by the construction of two predictive models using logistic regression (LR) and a support vector machine (SVM). RESULTS: The expression levels of AHR in tumour patients were significantly higher than those in the control group, and higher AHR expression was associated with worse prognosis (P<0.05). AHR remained a risk factor for poor prognosis in glioblastoma after multivariate adjustment (HR: 1.61, 95% CI: 1.085-2.39, P<0.05). The radiomics models constructed using LR and SVM based on three selected features achieved area under the curve (AUC) values of 0.887 and 0.872, respectively. Radiomics score emerged as a key factor influencing overall survival (OS) after multivariate adjustment in the Cox model (HR: 3.931, 95% CI: 1.272-12.148, P < 0.05). CONCLUSION: The radiomics models could effectively distinguish the expression levels of AHR and predict prognosis in patients with glioblastoma, which may serve as a powerful tool to assist clinical assessment and precision treatment.

Spliceosome component PHD finger 5A is essential for early B lymphopoiesis.

The spliceosome, a multi-megadalton ribonucleoprotein complex, is essential for pre-mRNA splicing in the nucleus and ensuring genomic stability. Its precise and dynamic assembly is pivotal for its function. Spliceosome malfunctions can lead to developmental abnormalities and potentially contribute to tumorigenesis. The specific role of the spliceosome in B cell development is poorly understood. Here, we reveal that the spliceosomal U2 snRNP component PHD finger protein 5A (Phf5a) is vital for early B cell development. Loss of Phf5a results in pronounced defects in B cell development, causing an arrest at the transition from pre-pro-B to early pro-B cell stage in the bone marrow of mutant mice. Phf5a-deficient B cells exhibit impaired immunoglobulin heavy (IgH) chain expression due to defective V-to-DJ gene rearrangement. Mechanistically, our findings suggest that Phf5a facilitates IgH gene rearrangement by regulating the activity of recombination-activating gene endonuclease and influencing chromatin interactions at the Igh locus.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.

Nonpharmacological Interventions for Management of the Pain-Fatigue-Sleep Disturbance Symptom Cluster in Breast Cancer Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: The pain-fatigue-sleep disturbance symptom cluster is commonly experienced by breast cancer patients, and a variety of nonpharmacological interventions are used to treat this symptom cluster. Objective: To compare the efficacy of nonpharmacological interventions in improving the symptoms of the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Methods: A comprehensive literature search was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, CNKI, and Wanfang databases to identify randomized controlled studies from database inception to May 2022. Two reviewers independently performed data retrieval and risk of bias assessments. The consistency model was used to conduct network meta-analyses (NMA) based on the frequentist framework to assess the interventions, which were ranked by the surface under the cumulative ranking curve (SUCRA). Finally, the CINeMA application was used to evaluate the results of the NMA and the evidence of quality. The results Twenty-three eligible studies assessing 14 interventions were included. According to SUCRA values, among the management effects of the three symptoms, the effect of progressive muscle relaxation (PMR) ranked first, followed by mindfulness-based stress reduction (MBSR). The overall evidence quality of our study ranges from very low to moderate. Conclusion: PMR and MBSR were effective interventions for the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Clinical recommendations prioritize PMR for symptom management, followed by MBSR. However, this should be interpreted cautiously, as the confidence in the evidence was not high.

Long-term outcomes of transarterial embolization with lipiodol-bleomycin emulsion plus polyvinyl alcohol particles versus the particles alone for large symptomatic focal nodular hyperplasia: a propensity score-matched analysis.

OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.

Intravoxel Incoherent Motion Combined With Dynamic Contrast-Enhanced Perfusion MRI of Early Cervical Carcinoma: Correlations Between Multimodal Parameters and HIF-1α Expression.

BACKGROUND: The identification of hypoxia inducible factor (HIF-1α) expression is helpful for the quantitative assessment of tumor hypoxia. The application of multimodal imaging techniques may play a part in the assessment of HIF-1α expression of cervical carcinoma. PURPOSE: To investigate the correlations between multiple imaging parameters and HIF-1α expression of early cervical carcinoma and to determine whether tumor hypoxia can be predicted using multisequence imaging parameters. STUDY TYPE: Prospective observational. POPULATION: One hundred patients with early cervical carcinoma. FIELD STRENGTH/SEQUENCES: 3.0 T MRI including intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) perfusion MRI sequences. ASSESSMENT: DCE-MRI and IVIM DWI were performed for all patients. The imaging parameters included volume transfer constant (Ktrans ), rate constant (Kep ), extravascular extracellular volume fraction (Ve ), D, D*, and f. STATISTICAL TESTS: The comparisons of imaging parameters between two independent groups were performed using the Mann-Whitney U-test. Multiple linear regression analysis was performed to determine the correlation between multiple imaging parameters and HIF-1α expression. The diagnostic ability of DCE-MRI, IVIM DWI, and the combination of two techniques for discriminating high-expression and low-expression groups were analyzed. RESULTS: The high-expression group had a lower Ktrans or Kep value than the low-expression group (P = 0.03; 0.02), while the high-expression group had a higher Ve value than the low-expression group (P = 0.03). The high-expression group had a higher D or f value than the low-expression group (P = 0.02; 0.02). Ktrans , Kep , D, Ve , and f values were independently correlated with HIF-1α expression. The sensitivity or accuracy of a combined method was higher than that of DCE-MRI or IVIM DWI individually (P = 0.03, 0.02; 0.04, 0.03). DATA CONCLUSION: The combination of DCE-MRI and IVIM DWI can improve the diagnostic ability of discriminating different HIF-1α expression levels for early cervical tumors. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:918-929.

Consensus in Identification and Stability of Symptom Clusters Using Different Symptom Dimensions in Newly Diagnosed Acute Myeloid Leukemia Patients Undergoing Induction Therapy.

CONTEXT: An unresolved issue in symptom cluster (SC) research is that the numbers and types of SCs vary based on the multiple dimensions of the experienced symptoms that are used for SC identification. OBJECTIVE: This study aimed to identify SCs using the ratings of occurrence, severity, and distress in newly diagnosed acute myeloid leukemia (AML) patients at three stages of their induction therapy (i.e., T1, T2, and T3). Then, we evaluated the consensus among the numbers and types of symptoms in each SC identified by multiple dimensions over time. METHOD: The Chinese version of the Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, and distress ratings of 32 symptoms in patients newly diagnosed with AML during their induction therapy. Exploratory factor analysis was used for SCs identification. RESULTS: Using the three dimensions in the AML patients (n = 126), four SCs were identified at T1 and T3 and three SCs were identified at T2. The number of symptoms in individual SCs varied over time, whereas the specific symptoms in SCs remained similar over time. The severity ratings fit the data better than did the ratings of occurrence and distress. CONCLUSION: These findings provided insights into the most common SCs in AML patients undergoing induction therapy by multidimensional evaluation and could lay the foundation for future targeted symptom interventions. Further studies are needed to explore the mechanisms of SCs in AML patients undergoing the chemotherapy.

Preference of cancer patients and family members regarding delivery of bad news and differences in clinical practice among medical staff.

OBJECTIVES: To study the preferences of cancer patients and their families in way of being informed of their condition and, by comparing their preferences with the medical staff's clinical practices, explore the factors underlying the latter's preferences. METHODS: A survey was conducted with 216 cancer patients, 242 families, and 176 clinical staff members with the Medical Status Communication questionnaire (Simplified Chinese edition). RESULTS: The clinical staff scored lower than the cancer patients and their families in terms of the total score, way of communication, emotional support, and additional information (F = 16.134, p < .001; F = 28.604, p < .001; F = 13.839, p < .001; F = 16.745, p < .001). Factors underlying the medical staff's clinical practices included, as revealed by the multiple linear regression analysis, gender (p = .03), and willingness to improve the way of communication about cancer (p = .006). CONCLUSIONS: A gap existed between the medical staff's clinical practice and the preferences of the cancer patients and their families. The medical staff should receive adequate training in cancer communication skills and techniques for improvement in this respect. When designing training for skills in delivering bad news to cancer patients, the well-being of cancer patients and their families must be thoroughly considered, and patient demands for information should be satisfied in the context of the information explosion of the current age.

Intravoxel incoherent motion MR imaging of early cervical carcinoma: correlation between imaging parameters and tumor-stroma ratio.

OBJECTIVES: To investigate if intravoxel incoherent motion (IVIM) MR imaging can predict the tumour-stroma ratio (TSR) in patients with early cervical carcinoma. METHODS: Fifty-four patients with early cervical carcinoma were prospectively enrolled into this study. All patients underwent IVIM imaging and parameters including D, D* and f value were measured. The tumours were classified into stroma-rich and stroma-poor group according to TSR, and comparisons of IVIM parameters between two groups were performed. The relationships between IVIM parameters and TSR were analysed by using a multivariate multi-regression analysis. RESULTS: D and f values were significantly lower in stroma-poor tumours than in stroma-rich tumours (p=0.02, 0.04), while the difference in D* value between two groups didn't achieve statistical significance (p=0.09). The areas under ROC curves of D and f values in discriminating stroma-rich and stroma-poor tumours were 0.835 (95%CI=0.616~0.905) and 0.686 (95%CI=0.575~0.798). In multiple linear regression analysis, D value, pathologic type, histologic grade, tumour size and f value were independently correlated with TSR of cervical carcinoma. CONCLUSIONS: D and f values are independently correlated with TSR of cervical carcinoma and have the potential for quantitative measurement of TSR. KEY POINTS: • TSR is a recognized independent prognostic factor in many solid tumours. • D and f values measured by IVIM MRI are independently correlated with TSR while D* is not. • IVIM offers the potential to predict TSR.

The stratification of severity of acute radiation proctopathy after radiotherapy for cervical carcinoma using diffusion-weighted MRI.

OBJECTIVE: To determine whether diffusion-weighted imaging (DWI) can be used for quantitatively evaluating severity of acute radiation proctopathy after radiotherapy for cervical carcinoma. MATERIALS AND METHODS: One hundred and twenty-four patients with cervical carcinoma underwent MR examination including DWI before and after radiotherapy. Acute radiation proctopathy was classified into three groups (grade 0, grade I-II and grade III-IV) according to Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG). The pretreatment ADC (ADCpre), ADC after treatment (ADCpost) and ADC change (ΔADC) were compared among three groups. In addition, acute radiation proctopathy was classified into good-prognosis group and poor-prognosis group. ADCpre, ADCpost and ΔADC were compared between two groups. For DWI parameter that had significant difference, discriminatory capability of the parameter was determined using receiver operating characteristics (ROC) analysis. RESULTS: ADCpost and ΔADC were higher in grade I-II group than in grade 0 group (p<0.05), yielding a sensitivity of 79.3% and specificity of 69.4% for ADCpost, and 85.1%, 72.3% for ΔADC for discrimination between two groups. ADCpost and ΔADC were higher in grade III-IV group than in grade I-II group (p<0.05), yielding a sensitivity of 80.3% and specificity of 72.5% for ADCpost, and 84.1%, 74.5% for ΔADC for discrimination between two groups. ADCpost and ΔADC were higher in poor-prognosis group than in good-prognosis group (p<0.05), yielding a sensitivity of 79.5% and specificity of 73.4% for ADCpost, and 87.2%, 78.3% for ΔADC for discrimination between two groups. CONCLUSION: Diffusion-weighted MRI can be used for quantitative stratification of severity of acute radiation proctopathy, which serves as an important basis for appropriate timely adjustment of radiotherapy for cervical carcinoma in order to maximally reduce the radiation injury of rectum.

The Inhibition of Oxidised Low-Density Lipoprotein-Induced Apoptosis of Macrophages by Recombinant Human Brain Natriuretic Peptide and the Underlying Mechanism.

OBJECTIVE: Macrophage apoptosis plays a key role in atherosclerotic plaque rupture. This study investigated the effects of recombinant human brain natriuretic peptide (BNP) on oxidised low-density lipoprotein (ox-LDL)-induced macrophage apoptosis and explored the underlying mechanism. METHODS: A model of ox-LDL-induced macrophage injury was established to evaluate the role of BNP. Flow cytometry was employed to detect apoptosis and changes in mitochondrial membrane potential (x0394;x03A8;m), and confocal microscopy was used to determine cellular reactive oxygen species (ROS) levels. Additionally, reverse transcription-polymerase chain reaction and colourimetry were used to detect the mRNA expression and activity, respectively, of superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS: Ox-LDL induced macrophage apoptosis in a concentration-dependent manner, and maximum apoptosis occurred at 100 µg/ml ox-LDL (45.62 ± 2.76 vs. 6.84 ± 1.94%; p < 0.05). Conversely, BNP suppressed macrophage apoptosis, with a maximal effect at 10-9 mol/l (18.56 ± 1.79%; p < 0.05). Compared with the control group, intracellular ROS levels increased, x0394;x03A8;m decreased, SOD mRNA expression and activity decreased and MDA mRNA expression and content increased in the 100-µg/ml ox-LDL group (527.30 ± 36.20 vs. 100.00 ± 0.00%, 3.01 ± 0.52 vs. 9.67 ± 0.51%, 0.53 ± 0.18 vs. 1.00 ± 0.00, 256.6 ± 8.20 vs. 355.8 ± 9.58 U/ml, 1.59 ± 0.23 vs. 1.00 ± 0.00 and 29.4 ± 1.68 vs. 5.94 ± 0.51 nmol/ml; p < 0.05); these effects were significantly counteracted by 10-9 mol/l BNP (237.30 ± 30.62%, 6.55 ± 1.57%, 0.90 ± 0.07, 310.4 ± 2.97 U/ml, 1.14 ± 0.10, 20.54 ± 1.55 nmol/ml; p < 0.05). CONCLUSION: BNP attenuates ox-LDL-induced macrophage apoptosis by suppressing oxidative stress and preventing x0394;x03A8;m loss.

[Expression of plasma miR-106a in colorectal cancer and its clinical significance].

OBJECTIVE: To detect plasma miR-106a level in patients with colorectal cancer (CRC) and analyze its correlation to the clinicopathological features and disease diagnosis. METHODS: miRNA expression profiling was performed using miRNA microarray chip for 3 colorectal adenocarcinoma samples and matched normal tissues. Plasma samples was collected from 50 colorectal cancer patients for quantitative analysis of miR-106a using real-time RT-PCR using 47 plasma samples from healthy volunteer as the control. Forty plasma samples were collected from these patients 7 days after operation to examine the changes in miR-106a expression. RESULTS: miR-106a was differentially expressed in colorectal adenocarcinoma compared to normal tissues. The plasma levels of miR-106a expression were significantly higher in the cancer patients than in the healthy control group (P=0.012). miR-106a expression significantly decreased after the operation compared with its preoperative level (P<0.01), and no correlation was found between preoperative plasma miR-106a and the clinicopathological features including lymph node metastasis and TNM stage (P>0.05). miR-106a showed a receiver operating characteristic (ROC) curve area of 66.1%, a sensitivity of 62.3%, and a specificity of 68.2% in discriminating colorectal cancer patients from the control subjects. CONCLUSION: plasma miR-106a is up-regulated in CRC patients, suggesting its potential value for the diagnosis of CRC.

Single-nucleotide polymorphism of the osteoprotegerin gene and its association with bone mineral density in Chinese postmenopausal women.

OBJECTIVE: Osteoporosis is a common complex and polygenic disease in postmenopausal women, which is characterized by a decrease in bone mineral density (BMD). The osteoprotegerin (OPG) is an important candidate gene in the pathogenesis of osteoporosis. The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in the OPG gene and BMD. METHODS: OPG gene polymorphisms and BMD were analyzed in 352 Chinese postmenopausal women. BMD was quantified at the lumbar spine (L2-4), femoral neck, and total hip. RESULTS: Through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, an allelic variant corresponding to the G→A mutations at position 23276 in exon 3 of the OPG gene could be detected. The association between g.23276 G>A polymorphisms and BMD was analyzed, and a significant association was found between g.23276 G>A and spine BMD. The mean of genotype GG was significantly higher than those of genotype GA and AA. There was no significant difference in neck hip BMD and total hip BMD among different genotypes. CONCLUSIONS: These findings suggested that g.23276 G>A genotypes in the OPG gene were associated with spine BMD in Chinese postmenopausal women. The A-allele was associated with lower BMD and an increased risk for osteoporosis.