NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Quantitative diffusion weighted imaging in patients with hepatocellular carcinoma: effects of simultaneous multi-slice acceleration and gadoxetic acid administration.

PURPOSE: To investigate whether simultaneous multi-slice (SMS) acceleration and gadoxetic acid administration affect the quantitative apparent diffusion coefficient (ADC) and signal-to-noise ratio (SNR) measurement of DWI in patients with HCC. METHODS: This prospective study initially enrolled 208 patients with clinically suspected HCC. Free breathing SMS-DWI and conventional DWI (CON-DWI) were performed before and after gadoxetic acid administration. Lesion conspicuity, ADCs and SNRs of the HCC lesion and normal liver parenchyma were independently measured by two radiologists. The paired t test or Wilcoxon signed rank test was used to evaluate the differences of lesion conspicuity, ADCs and SNRs between SMS-DWI and CON-DWI, as well as those before and after gadoxetic acid administration. RESULTS: A total of 102 HCC patients (90 men and 12 women; mean age, 54.6 ± 11.7 years) were finally included for analysis. SMS-DWI and CON-DWI demonstrated comparable lesion conspicuity (P = 0.081-0.566). For the influence of SMS acceleration, the SNRs of liver parenchyma on enhanced SMS-DWI were significantly higher than enhanced CON-DWI (P = 0.015). For the influence of gadoxetic acid administration, the mean ADCs were significantly higher on enhanced SMS-DWI than unenhanced SMS-DWI (HCC, P = 0.013; liver parenchyma, P = 0.032). CONCLUSION: Quantitative ADC measurements of HCC and liver parenchyma were not affected by SMS acceleration, and SMS-DWI can provide higher SNR than CON-DWI. However, the ADC measurements can be affected by gadoxetic acid administration on SMS-DWI, so it is recommended to perform SMS-DWI before gadoxetic acid administration.

Characteristics and prognostic implications of peripheral blood lymphocyte subsets in patients with anti-MDA5 antibody positive dermatomyositis-interstitial lung disease.

OBJECTIVES: To examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients. METHODS: Data were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5+ DM-ILD) and anti-MDA5 antibody negative group (MDA5- DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5+ DM-ILD. RESULTS: Out of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5+ and 194 were anti-MDA5-. Peripheral blood lymphocyte count, CD3+ count, percentage of CD3+, CD3+CD4+ count, and CD3+CD8+ count was lower in MDA5+ DM-ILD than in MDA5- DM-ILD- (all P < 0.001) as well as CD3-CD19+ count (P = 0.04). In MDA5+ DM-ILD, CD3+CD8+ count ≤ 49.22 cell/µL (HR = 3.81, 95%CI [1.20,12.14]) and CD3-CD19+ count ≤ 137.64 cell/µL (HR = 3.43, 95%CI [1.15,10.24]) were independent predictors of mortality. CD3+CD8+ count ≤ 31.38 cell/µL was associated with a higher mortality risk in all DM-ILD patients (HR = 8.6, 95%CI [2.12,31.44]) after adjusting for anti-MDA5 and other clinical characteristics. CONCLUSION: Significant lymphocytes decrease was observed in MDA5+ DM-ILD patients. CD3+CD8+ cell count was associated with worse prognosis in both MDA5+ DM-ILD and all DM-ILD patients.

Multiple mycotoxins in commonly used edible oils: Occurrence and evaluation of potential health risks.

In this study, the contamination of 51 mycotoxins in 416 edible oils were determined by UPLC-MS/MS. Totally, twenty-four mycotoxins were detected and nearly half of the samples (46.9%, n = 195) were contaminated simultaneously with six to nine kinds of mycotoxins. The predominant mycotoxins and contamination characteristics varied depending on the type of oils. More specifically, four enniatins, alternariol monomethyl ether (AME) and zearalenone were the most frequent combination. Overall, peanut and sesame oils (10.7-11.7 mycotoxins on average) were found to be the most contaminated matrices whereas camellia and sunflower seed oils (1.8-2.7 species) were the opposite. Dietary exposure risks of mycotoxins were acceptable in most cases, however, the ingestion of aflatoxins (especially aflatoxin B1) through peanut and sesame oil (margin of exposure: 239.4-386.3 < 10000) exceeded the acceptable carcinogenic risk level. Meanwhile, the risks of cumulative ingestion through the food chain should be of great concern, especially sterigmatocystin, ochratoxin A, AME and zearalenone.

Hormonal regulation of non-cystic fibrosis transmembrane conductance regulator ion channels in the endocervix.

OBJECTIVE: To characterize ion channel expression and localization in the endocervix under different hormonal conditions using a nonhuman primate primary endocervical epithelial cell model. DESIGN: Experimental. SETTING: University-based, translational science laboratory. INTERVENTIONS: We cultured and treated conditionally reprogrammed primary rhesus macaque endocervix cells with estradiol and progesterone and measured gene expression changes for several known ion channel and ion channel regulators of mucus secreting epithelia. Using both rhesus macaque endocervical samples and human samples, we localized channels in the endocervix using immunohistochemistry. MAIN OUTCOME MEASURES: The relative abundance of transcripts was evaluated using real-time polymerase chain reaction. Immunostaining results were evaluated qualitatively. RESULTS: Compared with controls, we found that estradiol increased gene expression for ANO6, NKCC1, CLCA1, and PDE4D. Progesterone down-regulated gene expression for ANO6, SCNN1A, SCNN1B, NKCC1, and PDE4D (P≤.05). Immunohistochemistry confirmed endocervical cell membrane localization of ANO1, ANO6, KCNN4, LRR8CA, and NKCC1. CONCLUSIONS: We found several ion channels and ion channel regulators that are hormonally sensitive in the endocervix. These channels, therefore, may play a role in the cyclic fertility changes in the endocervix and could be further investigated as targets for future fertility and contraceptive studies.

Intravoxel incoherent motion diffusion weighted imaging for preoperative evaluation of liver regeneration after hepatectomy in hepatocellular carcinoma.

OBJECTIVES: To explore whether intravoxel incoherent motion (IVIM) parameters could evaluate liver regeneration preoperatively. METHODS: A total of 175 HCC patients were initially recruited. The apparent diffusion coefficient, true diffusion coefficient (D), pseudodiffusion coefficient (D*), pseudodiffusion fraction (f), diffusion distribution coefficient, and diffusion heterogeneity index (Alpha) were measured by two independent radiologists. Spearman's correlation test was used to assess correlations between IVIM parameters and the regeneration index (RI), calculated as 100% × (the volume of the postoperative remnant liver - the volume of the preoperative remnant liver) / the volume of the preoperative remnant liver. Multivariate linear regression analyses were used to identify the factors for RI. RESULTS: Finally, 54 HCC patients (45 men and 9 women, mean age 51.26 ± 10.41 years) were retrospectively analyzed. The intraclass correlation coefficient ranged from 0.842 to 0.918. In all patients, fibrosis stage was reclassified as F0-1 (n = 10), F2-3 (n = 26), and F4 (n = 18) using the METAVIR system. Spearman correlation test showed D* (r = 0.303, p = 0.026) was associated with RI; however, multivariate analysis showed that only D value was a significant predictor (p < 0.05) of RI. D and D*showed moderate correlations with fibrosis stage (r = -0.361, p = 0.007; r = -0.457, p = 0.001). Fibrosis stage showed a negative correlation with RI (r = -0.263, p = 0.015). In the 29 patients who underwent minor hepatectomy, only the D value showed a positive association (p < 0.05) with RI, and a negative correlation with fibrosis stage (r = -0.360, p = 0.018). However, in the 25 patients who underwent major hepatectomy, no IVIM parameters were associated with RI (p > 0.05). CONCLUSIONS: The D and D* values, especially the D value, may be reliable preoperative predictors of liver regeneration. KEY POINTS: • The D and D* values, especially the D value, derived from IVIM diffusion-weighted imaging may be useful markers for the preoperative prediction of liver regeneration in patients with HCC. • The D and D* values derived from IVIM diffusion-weighted imaging show significant negative correlations with fibrosis, an important predictor of liver regeneration. • No IVIM parameters were associated with liver regeneration in patients who underwent major hepatectomy, but the D value was a significant predictor of liver regeneration in patients who underwent minor hepatectomy.

Predictive models and early postoperative recurrence evaluation for hepatocellular carcinoma based on gadoxetic acid-enhanced MR imaging.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is still poor largely due to the high incidence of recurrence. We aimed to develop and validate predictive models of early postoperative recurrence for HCC using clinical and gadoxetic acid-enhanced magnetic resonance (MR) imaging-based findings. METHODS: In this retrospective case-control study, 209 HCC patients, who underwent gadoxetic acid-enhanced MR imaging before curative-intent resection, were enrolled. Boruta algorithm and backward stepwise selection with Akaike information criterion (AIC) were used for variables selection Random forest, Gradient-Boosted decision tree and logistic regression model analysis were used for model development. The area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis were used to evaluate model's performance. RESULTS: One random forest model with Boruta algorithm (RF-Boruta) was developed consisting of preoperative serum ALT and AFP levels and six MRI findings, while preoperative serum AST and AFP levels and four MRI findings were included in one logistic regression model with backward stepwise selection method (Logistic-AIC).The two predictive models demonstrated good discrimination performance in both the training set (RF-Boruta: AUC, 0.820; Logistic-AIC: AUC, 0.853), internal validation set (RF-Boruta: AUC, 0.857, Logistic-AIC: AUC, 0.812) and external validation set(RF-Boruta: AUC, 0.805, Logistic-AIC: AUC, 0.789). Besides, in both the internal validation and external validation sets, the RF-Boruta model outperformed Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.05). CONCLUSIONS: The RF-Boruta and Logistic-AIC models with good prediction performance for early postoperative recurrence may lead to optimal and comprehensive treatment approaches, and further improve the prognosis of HCC after resection.

Diffusion Weighted Imaging of the Abdomen and Pelvis: Recent Technical Advances and Clinical Applications.

Diffusion weighted imaging (DWI) serves as one of the most important functional magnetic resonance imaging techniques in abdominal and pelvic imaging. It is designed to reflect the diffusion of water molecules and is particularly sensitive to the malignancies. Yet, the limitations of image distortion and artifacts in single-shot DWI may hamper its widespread use in clinical practice. With recent technical advances in DWI, such as simultaneous multi-slice excitation, computed or reduced field-of-view techniques, as well as advanced shimming methods, it is possible to achieve shorter acquisition time, better image quality, and higher robustness in abdominopelvic DWI. This review discussed the recent advances of each DWI approach, and highlighted its future perspectives in abdominal and pelvic imaging, hoping to familiarize physicians and radiologists with the technical improvements in this field and provide future research directions.

The association between vision impairment and cognitive outcomes in older adults: a systematic review and meta-analysis.

OBJECTIVES: To provide a quantitative synthesis of studies on the relationship between vision impairment (VI) and cognitive outcomes in older adults. METHOD: A systematic search was undertaken of relevant databases for original articles published before April 2020. Random effect models were used to obtain pooled estimates of the associations between VI and cognitive outcomes (cognitive impairment and dementia) with subgroup analyses of VI measures, cross-sectional associations of VI with cognitive impairment, and longitudinal associations of baseline VI with incident cognitive impairment and dementia. Potential sources of heterogeneity were explored by meta-regression. Publication bias was evaluated with Egger's test. RESULTS: Sixteen studies including 76,373 participants were included in this meta-analysis, with five cross-sectional studies and eleven longitudinal studies. There was a significantly increased risk of cognitive outcomes with VI identified by subjective measures (odds ratio (OR)=1.63; 95% confidence interval (CI): 1.26-1.99) and objective measures (OR = 1.59; 95% CI: 1.40-1.78). The odds of baseline cognitive impairment were 137% higher in older adults with VI compared with those without VI (OR = 2.37, 95% CI: 1.84-3.03) at baseline. Compared with older adults without VI at baseline, those with baseline VI had a higher relative risk (RR) of incident cognitive impairment (RR = 1.41; 95% CI: 1.31-1.51) and dementia (RR = 1.44, 95% CI: 1.19-1.75). CONCLUSIONS: VI was associated with increased risks of cognitive impairment and dementia across cross-sectional and longitudinal studies. Additional research and randomized clinical trials are warranted to examine the implications of treatment for VI, such as wearing glasses and cataract surgery, to avoid cognitive impairment and dementia.

Preoperative evaluation of liver regeneration following hepatectomy in hepatocellular carcinoma using magnetic resonance elastography.

Background: For patients with hepatocellular carcinoma (HCC) undergoing hepatectomy, insufficient remnant liver regenerative capacity can lead to liver failure. The aim of this study was to evaluate the potential role of magnetic resonance elastography (MRE) for the preoperative prediction of liver regeneration in patients with HCC after partial hepatectomy (PH). Methods: A total of 54 patients with HCC undergoing MRE prior to PH were retrospectively included. The total functional liver, volume of preoperative future liver remnant (LVpre), and volume of postoperative liver remnant (LVpost), respectively, were measured, and the regeneration index (RI) and parenchymal hepatic resection rate (PHRR) were manually calculated. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with a high RI, and receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the liver stiffness (LS) values. Patients were classified into three subgroups based on the value of PHRR: low PHRR (<30%), intermediate PHRR (30-50%), and high PHRR (>50%). Subsequently, Spearman correlation analysis was used to investigate the relationship between LS values and RI in the subgroups. Results: Multivariable analysis revealed a low LS value was associated with greater odds of a high RI [odds ratio (OR), 0.049; 95% confidence interval (CI): 0.002 to 0.980]. An optimal cutoff value of 3.30 kPa was used to divide all patients into a low RI group and a high RI group with an area under the curve (AUC) value of 0.882 (95% CI: 0.767 to 0.996). A significant negative relationship between RI and LS values (r=-0.799; P<0.001) was observed in the intermediate PHRR subgroup. Conclusions: The LS values based on MRE may serve as a potential preoperative predictor of liver regeneration for patients with HCC undergoing PH.

Using arterial phase hyperenhancement on CT instead of gadoxetic acid arterial phase enhancement may improve the diagnostic performance for hepatocellular carcinoma.

Background: The diagnostic performance for hepatocellular carcinoma (HCC) is hampered using gadoxetic acid-enhanced magnetic resonance (MR) imaging due to the high incidence of transient severe motion in arterial phase (AP). Dynamic contrast enhanced computed tomography (CT) imaging yield high detection rate for hepatic nodules in AP, and the combined use of CT arterial phase (CTAP) imaging with gadoxetic acid-enhanced MR imaging may improve the diagnostic performance for HCC. Thus, this study aimed to determine whether the combined use of CTAP and gadoxetic acid-enhanced MR imaging can improve the diagnostic performance for HCC based on various imaging diagnostic criteria. Methods: A total of 169 surgically histologically confirmed hepatic nodules (137 HCCs and 32 non-HCC-nodules) were retrospectively enrolled. Two different imaging protocol sets were reviewed: (I) full gadoxetic acid-enhanced magnetic resonance imaging (MRI) sequences; and (II) CTAP imaging combined with the gadoxetic acid-enhanced MRI but excluding the MR imaging AP images. Three independent reviewers followed the 2018 Liver Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), and 2018 Korean guidelines to characterize these heaptic nodules by reviewing the two imaging protocol sets and the diagnostic peformance were compared by using McNemar test. Results: The detection rate of AP hyperenhancement (APHE) was higher in CTAP than in the MR arterial phase (MRAP) for hepatic nodules (87.57% vs. 75.15%) and HCCs (97.08% vs. 82.48%) (all P<0.001). For the LI-RADS criteria, the Protocol-II increased the sensitivity to 75.91% from 70.80% of Protocol-I (P=0.016), with a minimal decrease of the specificity to 71.88% from 75.00% (P=1.000). For the EASL criteria, the numerical increases were found of Protocol-II than Protocol-I in both sensitivity (81.02% vs. 78.10%) and specificity (75.00% vs.71.88%), but with no statistical significance. For the Korean criteria, the Protocol-II increased the sensitivity to 94.89% from 83.21% of Protocol-I (P<0.001). The specificity increased to 65.63% from 62.50%, with no statistical significance (P=1.000). Conclusions: Using CTAP instead of gadoxetic acid-enhanced MRAP can improve the diagnostic sensitivity for HCC and also yields a comparable specificity. Thus, the combined use of CTAP and gadoxetic acid-enhanced MR imaging may improve the diagnostic performance for HCC.

Systemic polidocanol from intravenous or pressurized intrauterine administration produces reversible cardiovascular toxicity.

Objective: Fatal allergic responses and cardiac arrhythmias have been reported with the intravenous (IV) administration of polidocanol. We sought to identify the physiologic mechanism of systemic cardiovascular response after transcervical (TC) and IV administration of polidocanol. Methods: We continuously monitored blood pressure (BP) and heart rate using an arterial line during IV and intraperitoneal (IP) administration of polidocanol solution (PS) and polidocanol doxycycline solution in female rats and TC and IP administration of polidocanol foam (PF) and PDF (TC only) in female baboons. We performed TC procedures using a catheter with (pressurized) and without (nonpressurized) balloon inflation. Baboons also underwent monitoring during IV PS administration with and without pretreatment with antihistamines. We performed cardiac echo and electrocardiograms during selected experiments. We defined a refractory hypotension as a sustained decrease of more than 30% from baseline that prevented delivery of the target dose. Results: We found a dose-related increase in the proportion of baboons that developed refractory hypotension during TC administration of 5% PDF and PF, an effect confined to pressurized administration. The infusion of 0.5% PS in rats induced a rapid and dramatic refractory hypotension. The inclusion of doxycycline did not improve or deteriorate these outcomes, and doxycycline solution or saline (control) alone did not affect BP. All five female baboons that received up to 20 mL of 1% PS (200 mg) developed refractory hypotension. Pretreatment with diphenhydramine, ranitidine, or both did not block the refractory hypotension induced by IV administration of 1% PS (100 mg). In contrast, only one of the six female baboons treated with IP PF 400 mg developed a decrease of more than 30% in BP, and this response was not sustained. Cardiac echocardiography done in four baboons during TC treatment demonstrated a decrease in cardiac output as the physiologic mechanism of hypotension. We did not observe important changes on the electrocardiograms. Conclusions: Adverse cardiovascular effects of polidocanol treatment occur owing to a direct myocardial effect of polidocanol and not as a result of a hypersensitivity reaction. Pressurized TC administration of PF results in refractory hypotension owing to endometrial vascular uptake of polidocanol and not as a result of uptake from peritoneal surfaces.

Effect of aerobic exercise on cardiotoxic outcomes in women with breast cancer undergoing anthracycline or trastuzumab treatment: a systematic review and meta-analysis.

PURPOSE: We aimed to assess the impact of aerobic exercise (AE) on parameters related to cardiotoxicity in breast cancer (BC) patients receiving anthracycline or trastuzumab. METHODS: We performed a systematic review and meta-analysis of comparative studies on AE via the screening of standard databases from their inception to January 18, 2022. The risk of bias was assessed qualitatively using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data were analyzed quantitatively using fixed effects meta-analysis and subgroup analysis in RevMan software. Notable outcomes included imaging outcomes of cardiotoxicity, cardiorespiratory fitness, and cardiac biomarkers. RESULTS: A meta-analysis of the pooled evidence obtained from seven studies revealed that AE significantly increased peak oxygen consumption (VO2 peak) and E/A values, compared to the values observed during usual care. Moreover, AE was safe and feasible, and was associated with a lower risk of adverse effects, a higher participation rate, and better results, when combined with resistance exercise. CONCLUSION: In BC patients receiving anthracyclines or trastuzumab, the effects of AE on the levels of cardiotoxicity were mixed; the diastolic functions and VO2 peak values were improved, biomarkers were not affected, and the overall improvements in the levels of cardiotoxicity were promising, despite the use of different exercise parameters.

Multi-nuclear magnetic resonance spectroscopy: state of the art and future directions.

With the development of heteronuclear fluorine, sodium, phosphorus, and other probes and imaging technologies as well as the optimization of magnetic resonance imaging (MRI) equipment and sequences, multi-nuclear magnetic resonance (multi-NMR) has enabled localize molecular activities in vivo that are central to a variety of diseases, including cardiovascular disease, neurodegenerative pathologies, metabolic diseases, kidney, and tumor, to shift from the traditional morphological imaging to the molecular imaging, precision diagnosis, and treatment mode. However, due to the low natural abundance and low gyromagnetic ratios, the clinical application of multi-NMR has been hampered. Several techniques have been developed to amplify the NMR sensitivity such as the dynamic nuclear polarization, spin-exchange optical pumping, and brute-force polarization. Meanwhile, a wide range of nuclei can be hyperpolarized, such as 2H, 3He, 13C, 15 N, 31P, and 129Xe. The signal can be increased and allows real-time observation of biological perfusion, metabolite transport, and metabolic reactions in vivo, overcoming the disadvantages of conventional magnetic resonance of low sensitivity. HP-NMR imaging of different nuclear substrates provides a unique opportunity and invention to map the metabolic changes in various organs without invasive procedures. This review aims to focus on the recent applications of multi-NMR technology not only in a range of preliminary animal experiments but also in various disease spectrum in human. Furthermore, we will discuss the future challenges and opportunities of this multi-NMR from a clinical perspective, in the hope of truly bridging the gap between cutting-edge molecular biology and clinical applications.

One kind of challenging tetrapeptide biomimetic chromatographic resin for antibody separation.

Short peptide biomimetic chromatography technology as a developing protein separation technology has huge potential for antibody purification. In this study, four tetrapeptide ligands (Ac-FYKH, Ac-YEHF, Ac-YFLH and Ac-FYHI) with high potential binding ability to antibody were selected for the optimal ligand to antibody purification. The results showed that Ac-YEHF-4FF resin had higher binding capacity and selectivity for hIgG among the four resins. And at pH 7.0 and 0.3 ml/min, the highest Q10%-hIgG of Ac-YEHF-4FF resin was 26.2 mg/ml resin while its Q10%-BSA was just 2.2 mg/ml resin. Further, Ac-YEHF-4FF resin was used to purify protein mixtures. By binding at pH 7.0 and being eluted at pH 5.0 and pH 4.0, Ac-YEHF-4FF resin was well used to separate hIgG from BSA containing feedstock, HSA containing feedstock and human serum with the purity and yield both more than 95 %. And the screened resin could also separate mAb from CHO cell culture supernatant with purity 94.3 % and yield 97.5 %. The adsorption and separation results of Ac-YEHF-4FF resin indicated that the goal of getting the efficacy of critical residues from protein A to biomimetic its structure and function could be achieved, which had great significance to the establishment and improvement of tetrapeptide biomimetic chromatography, and also provided a new method for the field of antibody separation and purification.

Providing higher value care for hepatocellular carcinoma rather than diagnosis: What can current radiologists do?

Medical imaging is of great value for the comprehensive evaluation of hepatocellular carcinoma from diagnosis to prognosis, which contributes to optimal clinical management making.

Comparison of a preoperative MR-based recurrence risk score versus the postoperative score and four clinical staging systems in hepatocellular carcinoma: a retrospective cohort study.

OBJECTIVES: To establish a risk score integrating preoperative gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and clinical parameters to predict recurrence after hepatectomy for patients with hepatocellular carcinoma (HCC) and to compare its performance with that of a postoperative score and four clinical staging systems. METHODS: Consecutive patients with surgically confirmed HCC who underwent preoperative EOB-MRI between July 2015 and November 2020 were retrospectively included. Two recurrence risk scores, one incorporating only preoperative variables and the other incorporating all preoperative and postoperative variables, were constructed via Cox regression models. RESULTS: A total of 214 patients (derivation set, n = 150; test set, n = 64) were included. Six preoperative variables, namely tumor number, infiltrative appearance, corona enhancement, alpha-fetoprotein (AFP) level, aspartate aminotransferase (AST) level, and sex, were independently associated with recurrence. After adding postoperative features, microvascular invasion and tumor differentiation were additional significant variables in lieu of corona enhancement and AFP level. Using the above variables, the preoperative score achieved a C-index of 0.741 on the test set, which was comparable with that of the postoperative score (0.729; p = 0.235). The preoperative score yielded a larger time-dependent area under the receiver operating characteristic curve at 1 year (0.844) than three existing systems (0.734-0.742; p < 0.05 for all). Furthermore, the preoperative score stratified patients into two prognostically distinct risk strata with low and high risks of recurrence (p < 0.001). CONCLUSION: The preoperative score integrating EOB-MRI features, AFP and AST levels, and sex improves recurrence risk estimation in HCC. KEY POINTS: • The preoperative risk score incorporating three EOB-MRI findings, AFP and AST levels, and sex achieved comparable performance with that of the postoperative score for predicting recurrence after hepatectomy in patients with HCC. • Two risk strata with low and high risks of recurrence were obtained based on the preoperative score. • The preoperative score may help tailor pretreatment decision-making and facilitate candidate selection for adjuvant clinical trials.

New Liver MR Imaging Hallmarks for Small Hepatocellular Carcinoma Screening and Diagnosing in High-Risk Patients.

Objective: Early detection and diagnosis of hepatocellular carcinoma (HCC) is essential for prognosis; however, the imaging hallmarks for tumor detection and diagnosis has remained the same for years despite the use of many new immerging imaging methods. This study aimed to evaluate the detection performance of hepatic nodules in high risk patients using either hepatobiliary specific contrast (HBSC) agent or extracellular contrast agent (ECA), and further to compare the diagnostic performances for hepatocellular carcinoma (HCC) using different diagnostic criteria with the histopathological results as reference standard. Methods: This prospective study included 247 nodules in 222 patients (mean age, 53.32 ± 10.84 years; range, 22-79 years). The detection performance and imaging features of each nodule were evaluated in all MR sequences by three experienced abdominal radiologists. The detection performance of each nodule on all MR sequences were compared and further the diagnostic performance of various diagnostic criteria were evaluated. Results: For those patients who underwent ECA-MRI, the conventional imaging hallmark of "AP + PVP and/or DP" was recommended, as 60.19% diagnostic sensitivity, 80.95% specificity and 100% lesion detection rate. Additionally, for those patients who underwent HBSC-MRI, the diagnostic criteria of "DWI + HBP" was recommended. This diagnostic criteria demonstrated, both in all tumor size and for nodules ≤2 cm, higher sensitivity (93.07 and 90.16%, all p <0.05, respectively) and slightly lower specificity (64.71 and 87.50%, all p >0.05, respectively) than that of the European Association for the Study of the Liver (EASL) criteria. Conclusions: Different abbreviated MR protocols were recommended for patients using either ECA or HBSC. These provided imaging settings demonstrated high lesion detection rate and diagnostic performance for HCC.

Multiparametric Magnetic Resonance Imaging Improves the Prognostic Outcomes in Patients With Intrahepatic Cholangiocarcinoma After Curative-Intent Resection.

Purpose: The prognosis of patients with intrahepatic cholangiocarcinoma remains unclear. Thus, this study aimed at investigating whether additional multiparametric magnetic resonance imaging (mpMRI) would guide additional treatment and improve the prognostic outcomes of intrahepatic cholangiocarcinoma patients. Methods and Materials: This retrospective study included 256 patients undergoing dynamic enhanced computed tomography scan only (CT group) and 31 patients undergoing both mpMRI and computed tomography scans (CT+MR group). Propensity score matching (PSM) was used to minimize the potential selection bias and confounding effects. The overall survival (OS) and recurrence-free survival (RFS) rates were compared between the two groups. Results: More nodules (n = 6), additional biliary dilation (n = 4), and peritumoral parenchymal arterial phase hyperenhancement (n = 18) were found with the additional mpMRI scan, which led to treatment modification. Cox regression analysis revealed the survival advantage of additional mpMRI imaging based on the OS (HR 0.396, 95% CI 0.239-0.657, p < 0.001; PSM HR 0.400, 95% CI 0.218-0.736, p = 0.003) and RFS (HR 0.558, 95% CI 0.352-0.882, p = 0.013; PSM HR 0.508, 95% CI 0.288-0.897, p = 0.020). Conclusions: Additional mpMRI helps clinicians to select better treatment options, lower the risk of tumor recurrence, and improve the overall survival.

An autophagy-related lncRNA prognostic risk model for thyroid cancer.

PURPOSE: Thyroid cancer (TC) is the most common malignancy of the endocrine system and its incidence is gradually rising. Research has demonstrated a close link between autophagy and thyroid cancer. We constructed a prognostic model of autophagy-related long non-coding RNA (lncRNA) in thyroid cancer and explored its prognostic value. METHODS: The data used in this study were all obtained from The Cancer Genome Atlas (TCGA) database and the Human Autophagy Database (HADb). We construct a co-expression network by autophagy-related genes and lncRNA to obtain autophagy-related lncRNAs. After univariate Cox regression analysis and multivariate Cox regression analysis, autophagy-related lncRNAs significantly associated with prognosis were identified. Based on the risk score of lncRNA, thyroid cancer patients are divided into high-risk group and low-risk group. RESULTS: A total of 14,142 lncRNAs and 212 autophagy-related genes (ATGs) were obtained from the TCGA database and the HADb, respectively. We performed lncRNA-ATGs correlation analysis and finally obtained 1,166 autophagy-associated lncRNAs. Subsequently, we conducted univariate Cox regression analysis and multivariate Cox regression analysis, nine autophagy-related lncRNAs (AC092279.1, AC096677.1, DOCK9-DT, LINC02454, AL136366.1, AC008063.1, AC004918.3, LINC02471 and AL162231.2) significantly associated with prognosis were identified. Based on these autophagy-related lncRNAs, a risk model was constructed. The area under the curve (AUC) of the risk score was 0.905, proving that the accuracy of risk signature was superior. In addition, multiple regression analysis showed that risk score was a significant independent prognostic risk factor for thyroid cancer. CONCLUSION: In this study, nine autophagy-related lncRNAs in thyroid cancer were established to predict the prognosis of thyroid cancer patients.